title: Recombinant fusion ESAT6-CFP10 immunogen as a skin test reagent for tuberculosis diagnosis: an open-label, randomized, two-centre phase 2a clinical trial.
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.
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute for Biological Products Control, National Institutes for Food and Drug Control, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.affiliation: Tianjin Haihe Hospital, Tianjin, China.
authors.forename: C
authors.initials: C
authors.lastname: Qin
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Xi
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.affiliation: Anhui Longcom Biologic Pharmacy Co. Ltd., Hefei, China.
authors.forename: J
authors.initials: J
authors.lastname: Pu
authors.affiliation: Tianjin Haihe Hospital, Tianjin, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: lushuihua66@126.com.
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.affiliation: Institute for Biological Products Control, National Institutes for Food and Drug Control, Beijing, China. Electronic address: vaccine2012@126.com.
authors.forename: G
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000276:immunology; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000379:methods*; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology
chemical_list: C505464:ESAT-6-CFP10 fusion protein; D011993:Recombinant Fusion Proteins
keywords: CFP10; Diagnosis; ESAT6; Phase 2a clinical trial; Tuberculosis