Dataset Information

Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials.

ABSTRACT:

Background

Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults.

Methods

We conducted 2 randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received an EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A bacillus Calmette Guerin (BCG) model was established to assess the diagnosis of tuberculosis infection using an EC skin test.

Results

In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive EC skin test at 1.0 μg/0.1 mL or 0.5 μg/0.1 mL. The area under the curve was 0.95 (95% confidence interval [CI], .91-.97) for the EC skin test at 1.0 μg/0.1 mL at 24-72 hours. Compared with the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI, 77.8-97.2 vs 86.5, 95% CI, 79.5-93.4) and specificity (98.9, 95% CI, 96.0-99.9 vs 96.1, 95% CI, 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed.

Conclusions

The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0 μg/0.1 mL, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination.

Clinical trials registration

NCT02389322 and NCT02336542.

SUBMITTER: Xu M

PROVIDER: S-EPMC8886919 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials.

Xu Miao M Lu Wei W Li Tao T Li Jingxin J Du Weixin W Wu Qi Q Liu Qiao Q Yuan Baodong B Lu Jinbiao J Ding Xiaoyan X Li Feng F Liu Min M Chen Baowen B Pu Jiang J Zhang Rongping R Xi Xiuhong X Zhou Rongguang R Mei Zaoxian Z Du Ronghui R Tao Lifeng L Martinez Leonardo L Lu Shuihua S Wang Guozhi G Zhu Fengcai F

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20220301 4

<h4>Background</h4>Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults.<h4>Methods</h4>We conducted 2 randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received an EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at ...[more]

PMID: 34021314

Similar Datasets

Project description:BackgroundThis study aimed to evaluate the diagnostic performance of ESAT6-CFP10 (EC) skin test in healthy population and determine the factors influencing the booster effect.MethodsWe conducted a randomized, double-blind, parallel controlled trial in healthy population. The experiment was divided into two stages. In the first stage, all participants underwent T-SPOT, TB-PPD, and EC tests. In the second stage, to evaluate whether BCG vaccination affected the efficacy of skin tests, the participants with three negative results in the first stage were randomly assigned to the BCG and placebo groups at a ratio of 2:1 and underwent three tests. The positivity rates and concordance of the three tests were calculated in both stages, and a logistic regression model was constructed to determine the factors influencing the booster effect of EC in the second stage. Safety observations were continued until the skin test results were available.ResultsIn the first stage, 1,564 participants were enrolled in the study. The positivity rates of the T-SPOT, EC, and TB-PPD tests in all the participants were 18.89%, 10.37%, and 53.96%, respectively. The concordance between the EC and T-SPOT tests was 88.97% (kappa = 0.56), and that between the TB-PPD and T-SPOT tests was 58.19% (kappa = 0.20). In the second stage, 585 participants were assigned to the BCG or placebo group. In the BCG group, the positivity rates for the T-SPOT, EC, and TB-PPD tests were 4.76%, 7.30%, and 73.65%, respectively. The concordance between the EC and T-SPOT tests was 94.92% (kappa = 0.55), and that between the TB-PPD and T-SPOT tests was 29.84% (kappa = 0.02). In the placebo group, the positivity rates for the T-SPOT, EC, and TB-PPD tests were 6.88%, 11.88%, and 39.38%, respectively. The concordance between the EC and T-SPOT tests was 91.25% (kappa = 0.49), and that between the TB-PPD and T-SPOT tests was 66.25% (kappa = 0.17). The logistic regression model showed that age ≥ 60 years (odds ratio [OR] = 5.42, 95% confidence interval [CI]: 2.05-14.26) and retest positivity of T-SPOT test (OR = 44.87, 95% CI: 16.58-135.21) were stimulative factors of EC booster effect. Adverse reactions occurred in 168 (10.74%) and 33 participants (5.64%) in the first and second stage, respectively. Most of these were local adverse reactions, including injection site pain, pruritus, and rash.ConclusionsThe diagnostic performance of the EC skin test was similar to that of the T-SPOT test in the healthy population and was unaffected by BCG vaccination. The booster effects were more inclined to occur in population with retest positivity of T-SPOT or age ≥ 60 years.Clinical trials registrationNCT02795260, Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 on Healthy People Aged 18-65(III-healthy), Registration Date: June 10, 2016.

Project description:BACKGROUND:A group of Russian scientists has developed Diaskintest, which comprises Mycobacterium tuberculosis-specific recombinant proteins CFP10-ESAT6, for skin testing (0.2 μg/0.1 ml). STUDY PURPOSE:To evaluate the comparative sensitivity of TST with 2 TU PPD-L and a skin test with tuberculous recombinant allergen (Diaskintest) containing the ESAT6-CFP10 protein in children and adolescents with newly diagnosed active tuberculosis during mass screening in the primary medical service in Moscow. MATERIALS AND METHODS:The trial was a comprehensive retrospective group study of children and adolescents diagnosed in Moscow with active tuberculosis in 2013-2016, aged 0 to 17 years inclusive. RESULTS:From 441 patients selected for analysis 408 patients had both tests (TST with 2 TU PPD-L and Diaskintest) performed, in 193 patients both tests were given simultaneously, of them 162 patients were BCG-vaccinated. Comparative results of both tests in 408 patients with tuberculosis: at cut-off ≥ 5 mm, both tests has similar sensitivity: Diaskintest 98.3% (95% CI 97.0-99.6%), TST 98.0% (95% CI 96.7-99.4%), at cut-off ≥10 mm, the sensitivity decreases for both tests: Diaskintest 90.0% (95% CI 87.0-93.0%), TST 88.7% (95% CI 85.6-91.9%), but at cut-off ≥ 15 mm, the decrease in sensitivity is statistically significant: for Diaskintest 61.5% (95% CI 56.7-66.3%), and for TST 46.3% (95% CI 41.4-51.3%), p <0.0001. The results of simultaneous setting of tests on different hands in 193 people (including 162 BCG-vaccinated), do not differ from the results for 408 people. The correlation between the results of Diaskintest and TST was significant in all groups. CONCLUSION:In children and adolescents with active tuberculosis, Diaskintest of 0.2 μg/ml and the Mantoux test with 2 TU PPD-L have high sensitivity (98%) at a cut-off of 5 mm; however, at cut-off ≥ 15 mm sensitivity is significantly reduced, and the decrease is more pronounced in the Mantoux test. The advantage of Diaskintest is that, unlike the Mantoux test, it has high specificity under the conditions of mass BCG vaccination. The test is simple to carry out, and can be used in mass screening.

Project description:BackgroundRecombinant fusion protein ESAT6-CFP10 (EC) is a newly developed skin test reagent for detecting Mycobacterium tuberculosis (M. tuberculosis) infection. In this study, we evaluated whether induration and erythema could be used as diagnostic indicators for EC skin test to detect M. tuberculosis infection.MethodsA total of 743 tuberculosis patients and 1514 healthy volunteers underwent an EC skin test. The diameters of induration and erythema were measured with Vernier caliper, 24 h, 48 h, and 72 h after skin testing. Related indicators of EC reagent diagnostic test were tested, and the diagnostic effects of the four diagnostic indicators for EC skin test were compared.ResultsThe sensitivity of induration / erythema measurement was lower at 24 h after EC skin test than at 48 h or 72 h (P<0.01). There was no difference in consistency (P = 0.16) between induration with clinical diagnosis, and erythema with clinical diagnosis at 48 h (88.88 and 90.16%, Kappa value was 0.75 and 0.78, respectively). In patients, the sensitivity of erythema measurement was higher than induration measurement (P<0.01). In healthy volunteers, the specificity of erythema measurement was lower than induration at 24 h after skin test, but there was no difference at 48 h after skin test (P = 0.22). In BCG vaccination volunteers, the specificity of induration and erythema were higher than 90%. In addition, there was a high consistency of induration and erythema. When induration or erythema was used as a positive diagnostic indicator, the sensitivity of the EC skin test was improved, and was no different from the other three indicators in terms of specificity and consistency with clinical diagnosis.ConclusionsInduration or erythema diameter not less than 5 mm could be used as a diagnostic indicator for detecting M. tuberculosis infection.Trial registrationPhase III clinical trial of recombinant Mycobacterium tuberculosis ESAT6-CFP10 allergen; CTR20150695 ; registered in December 16, 2015.

Dataset Information

Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials.

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials.

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