Efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis: a phase II trial.
BACKGROUND
This study aimed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis (TB).


METHODS
A 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.


RESULTS
The 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.


CONCLUSIONS
Recombinant 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.
Department of Infectious Diseases, Third Affiliated Hospital to Wenzhou Medical College, Ruian, Zhejiang, P.R. China.
Qing-Feng
QF
Sun
Miao
M
Xu
Jin-Guo
JG
Wu
Bao-Wen
BW
Chen
Wei-Xin
WX
Du
Ji-Guang
JG
Ding
Xiao-Bing
XB
Shen
Cheng
C
Su
Jin-Sheng
JS
Wen
Guo-Zhi
GZ
Wang
D000328:Adult; D000704:Analysis of Variance; D000942:Antigens, Bacterial / Q000009:adverse effects / Q000235:genetics; D019540:Area Under Curve; D001426:Bacterial Proteins / Q000009:adverse effects / Q000235:genetics; D002681:China; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D011994:Recombinant Proteins / Q000009:adverse effects / Q000235:genetics; D012882:Skin Tests; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011994:Recombinant Proteins