Dataset Information

Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow.

ABSTRACT: BACKGROUND:A group of Russian scientists has developed Diaskintest, which comprises Mycobacterium tuberculosis-specific recombinant proteins CFP10-ESAT6, for skin testing (0.2 ?g/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 ?g/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.

SUBMITTER: Slogotskaya L

PROVIDER: S-EPMC6303070 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow.

Slogotskaya Liudmila L Bogorodskaya Elena E Ivanova Diana D Sevostyanova Tatiana T

PloS one 20181221 12

<h4>Background</h4>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).<h4>Study purpose</h4>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 ser ...[more]

PMID: 30576322

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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.

Project description:Virulence effectors secreted by Mycobacterium tuberculosis (Mtb) help subvert host immune mechanisms and, therefore, are critical for establishing infection and pathogenesis. However, knowledge in terms of signaling mechanisms that modulate the secretion of virulence factors is sparse. We performed high-throughput secretome, phosphoproteome, and phospho-secretome analysis of Mtb. We combined the analysis with empirical validations to show regulation of mycobacterial secretion through protein phosphorylation. System level protein-protein interaction network analysis superimposed with the secretome, phosphoproteome, and phospho-secretome profile revealed an intricate relationship between phosphorylation and secretion. At the core of the network was a key virulence factor CFP10. We identified PknA to be the kinase responsible for phosphorylating CFP10. Using genetic tools, we show that phosphomimetic mutation of CFP10 negatively regulates the secretion of virulence mediator ESAT6. Significantly, the dynamics of CFP10 phosphorylation strongly influenced bacterial virulence and survival within macrophages and mice. Together, the results show that the dynamic phosphorylation status of the secretory protein CFP10 regulates the secretion of virulence factors and impacts virulence. IMPORTANCE Secreted virulence factors play a critical role in bacterial pathogenesis. Virulence effectors not only help bacteria to overcome the host immune system but also aid in establishing infection. Mtb, which causes tuberculosis in humans, encodes various virulence effectors. Triggers that modulate the secretion of virulence effectors in Mtb are yet to be fully understood. To gain mechanistic insight into the secretion of virulence effectors, we performed high-throughput proteomic studies. With the help of system-level protein-protein interaction network analysis and empirical validations, we unravelled a link between phosphorylation and secretion. Taking the example of the well-known virulence factor of CFP10, we show that the dynamics of CFP10 phosphorylation strongly influenced bacterial virulence and survival ex vivo and in vivo. This study presents the role of phosphorylation in modulating the secretion of virulence factors.

Dataset Information

Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow.

Publications

Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow.

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