Recombinant fusion ESAT6-CFP10 immunogen as a skin test reagent for tuberculosis diagnosis: an open-label, randomized, two-centre phase 2a clinical trial. (October 2016)

• Record Type: Journal Article
• Authors: Li, F.; Xu, M.; Qin, C.; Xia, L.; Xiong, Y.; Xi, X.; Fan, X.; Gu, J.; Pu, J.; Wu, Q.; Lu, S.; Wang, G.
• Is Part Of: Clinical microbiology and infection. Volume 22:Number 10(2016)
• Page Start: 889.e9
• Page End: 889.e16
• Publication Date: 2016-10
• Subjects: CFP10 -- Diagnosis -- ESAT6 -- Phase 2a clinical trial -- Tuberculosis; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2016.07.015
• Languages: English
• ISSNs: 1198-743X

Abstract

Abstract: We sought to assess the accuracy and safety of the ESAT6-CFP10 reagent in diagnosing tuberculosis (TB) disease. An open-label, randomized phase 2a trial was conducted in 56 healthy adults and 88 TB patients at one medical centre and one teaching hospital in China. All participants received 0.1, 0.5, 1 or 2 μg ESAT6-CFP10 in their right forearm. Moreover, 56 healthy volunteers and 56 patients were given tuberculin-purified protein derivative (TB-PPD) in their left forearm. The remaining 32 patients were administered placebo. The main outcome measure was induration diameter. An enzyme-linked immunospot (ELISPOT) assay was conducted before the skin test. The ESAT6-CFP10 test caused a higher positivity rate than placebo (81.2% (26/32) vs. 3.1% (1/32); p <0.001). The median maximum induration diameter after ESAT6-CFP10 injection was 17.0 (interquartile range (IQR), 14.0–21.7) mm, similar to that for TB-PPD (17.5 (IQR, 7.0–30.5) mm). The diagnostic accuracy of ESAT6-CFP10 was superior to that of TB-PPD (area under the receiver operating characteristic curve (AUC), 0.870 (95% confidence interval (CI), 0.796–0.944) vs. 0.686 (95% CI, 0.585–0.786); p <0.001). When analysed in all participants, ESAT6-CFP10 had comparable AUC values to the ELISPOT assay (0.849 (95% CI, 0.835–0.952) vs. 0.908 (95% CI, 0.852–0.965)). Local itching (12/144, 8.3%) and pain (26/144, 18.1%) were the main side effects of ESAT6-CFP10. No serious adverse events were reported. The ESAT6-CFP10 skin test appears to be a safe and promising tool; further testing will confirm its efficacy in identifying TB disease.