Recombinant fusion ESAT6 CFP10 immunogen as a skin test reagent for tuberculosis diagnosis: an open label, randomized, two centre phase 2a clinical trial.
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 mg 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.
Clinical microbiology and infection the official publication of the European Society of Clinical Microbiology and Infectious Diseases