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

BackgroundA 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 purposeTo 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 methodsThe 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.ResultsFrom 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.ConclusionIn 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.

Latent tuberculosis infection in children and adolescents in Russia

“…Due to the complexity and sometimes the impossibility of observation, TB infection in children is established retrospectively by comparing tuberculin reactions over several years (Slogotskaya et al, 2018). Therefore, the issue of early detection of not only active TB, but especially of LTBI during mass screening of children remains relevant.…”

“…Positivity was defined as an induration of 5 mm (cut-off 5 mm) in accordance with Russian guidelines. Follow-up testing was performed using a skin test that includes two recombinant antigens, ESAT6 and CFP-10 (Diaskintest; CJSC GENERIUM, Russia), applied intradermally at a dose of 0.2 mg/0.1 ml, following the same procedures as for the TST; the induration was measured 72 h later (Slogotskaya et al, 2012;Slogotskaya et al, 2013;Slogotskaya et al, 2015;Shovkun et al, 2018;Slogotskaya et al, 2018;Nikitina et al, 2017). This recombinant tuberculosis antigen, RTA, skin test (Diaskintest) has been used in Russia since 2008 (Kiselev et al, 2008;Aksenova et al, 2011).…”

“…Due to the complexity and sometimes impossibility of observation in the differential diagnosis of infectious and postvaccination allergies in the initial stages, TB infection in children is established retrospectively by comparing tuberculin reactions over several years (Aksenova et al, 2017;Slogotskaya et al, 2018). Therefore, the issue of early detection of not only active TB, but especially latent TB infection (LTBI) during mass screening of children remains relevant (Slogotskaya et al, 2013).…”

Comparative performance of QuantiFERON-TB Gold versus skin test with tuberculosis recombinant allergen (Diaskintest) among patients with suspected pulmonary tuberculosis in Russia

“…Overall, the sensitivity of the Diaskintest for active TB was 68% in adults and 73% in children, which is lower compared to that reported in other studies. According to a review study by Slogotskaya et al, the sensitivity of the Diaskintest was 97% in children and 84% in adults (Slogotskaya et al, 2017), yet there were data suggesting a low sensitivity of Diaskintest (61%) for identifying TB in individuals with a hyperergic reaction to the injection of the recombinant allergen (Slogotskaya et al, 2018). The sensitivity of QFT for active TB was 82% in adults and 65% in children.…”

“…The performances of the TST and IGRAs have been compared in multiple studies and discussed in many reviews and meta-analyses (Menzies et al, 2007;Campbell et al, 2015). Diaskintest has been compared to the TST and demonstrated a significantly higher specificity, apparently due to the use of M. tuberculosis-specific antigens not reacting with BCG or non-tuberculous mycobacteria (Slogotskaya et al, 2011(Slogotskaya et al, , 2017(Slogotskaya et al, , 2018. However, publications on the comparative performances of Diaskintest and IGRAs are limited in number (Slogotskaya et al, 2012;Losovskaya et al, 2016;Starshinova et al, 2018).…”