PMID- 27451942
OWN - NLM
STAT- MEDLINE
DCOM- 20170301
LR  - 20170302
IS  - 1469-0691 (Electronic)
IS  - 1198-743X (Linking)
VI  - 22
IP  - 10
DP  - 2016 Oct
TI  - Recombinant fusion ESAT6-CFP10 immunogen as a skin test reagent for tuberculosis 
      diagnosis: an open-label, randomized, two-centre phase 2a clinical trial.
PG  - 889.e9-889.e16
LID - S1198-743X(16)30239-7 [pii]
LID - 10.1016/j.cmi.2016.07.015 [doi]
AB  - 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 mug 
      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.
CI  - Copyright (c) 2016 European Society of Clinical Microbiology and Infectious 
      Diseases. Published by Elsevier Ltd. All rights reserved.
FAU - Li, F
AU  - Li F
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Xu, M
AU  - Xu M
AD  - Institute for Biological Products Control, National Institutes for Food and Drug 
      Control, Beijing, China.
FAU - Qin, C
AU  - Qin C
AD  - Tianjin Haihe Hospital, Tianjin, China.
FAU - Xia, L
AU  - Xia L
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Xiong, Y
AU  - Xiong Y
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Xi, X
AU  - Xi X
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Fan, X
AU  - Fan X
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Gu, J
AU  - Gu J
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Pu, J
AU  - Pu J
AD  - Anhui Longcom Biologic Pharmacy Co. Ltd., Hefei, China.
FAU - Wu, Q
AU  - Wu Q
AD  - Tianjin Haihe Hospital, Tianjin, China.
FAU - Lu, S
AU  - Lu S
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 
      Electronic address: lushuihua66@126.com.
FAU - Wang, G
AU  - Wang G
AD  - Institute for Biological Products Control, National Institutes for Food and Drug 
      Control, Beijing, China. Electronic address: vaccine2012@126.com.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160721
PL  - England
TA  - Clin Microbiol Infect
JT  - Clinical microbiology and infection : the official publication of the European 
      Society of Clinical Microbiology and Infectious Diseases
JID - 9516420
RN  - 0 (ESAT-6-CFP10 fusion protein)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mycobacterium tuberculosis/*immunology
MH  - Recombinant Fusion Proteins/*administration & dosage/immunology
MH  - Sensitivity and Specificity
MH  - Tuberculin Test/*methods
MH  - Tuberculosis/*diagnosis/immunology
OTO - NOTNLM
OT  - CFP10
OT  - Diagnosis
OT  - ESAT6
OT  - Phase 2a clinical trial
OT  - Tuberculosis
EDAT- 2016/07/28 06:00
MHDA- 2017/03/03 06:00
CRDT- 2016/07/26 06:00
PHST- 2016/03/02 00:00 [received]
PHST- 2016/07/08 00:00 [revised]
PHST- 2016/07/13 00:00 [accepted]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2017/03/03 06:00 [medline]
PHST- 2016/07/26 06:00 [entrez]
AID - S1198-743X(16)30239-7 [pii]
AID - 10.1016/j.cmi.2016.07.015 [doi]
PST - ppublish
SO  - Clin Microbiol Infect. 2016 Oct;22(10):889.e9-889.e16. doi: 
      10.1016/j.cmi.2016.07.015. Epub 2016 Jul 21.