Efficiency of screening for tuberculosis infection in children and adolescents in Moscow in 2019 based on the new procedure for using the intradermal test with tuberculosis recombinant allergen (ESAT-6/CFP-10)

The objective of the study: to compare two approaches to mass screening for tuberculosis infection in children and adolescents in Moscow.

Subjects and methods. Two periods have been assessed. Period 1 (2014), when a pilot screening project was implemented in two stages: Stage 1 -all children and adolescents had Mantoux test with 2 TU PPD-L (1,429,395 people were tested), Stage 2 - a skin test with TRA (tuberculosis recombinant allergen - ESAT protein-6/CFP-10) was used in those with increasing induration as a response to Mantoux test (219,888 people were tested). Period 2 (2019): children from 0 to 7 years old (711,869 children were tested) were screened by the same two-stage scheme, and those 8-17 years old (904,757 people were tested) had the test with TRA only.

Results. It has been demonstrated that the test with TRA can be used as a screening tool and effectively identify patients with a high risk of tuberculosis development. At the same time, the rate of detection of tuberculosis patients, persons with post-tuberculosis changes and latent infection is tens times higher among persons with positive reactions to TRA test versus Mantoux test. The preventive therapy received by those positively responding to TRA test resulted in almost no disease in them. Over the past 7 years, the number of people newly diagnosed with tuberculosis, latent tuberculosis infection (LTBI) and post-tuberculosis changes has decreased. Preventive therapy in those with a positive result of TRA test helps to stop the progression of tuberculosis infection and reduce the pool of LTBI among children and adolescents.

TRA test versus Mantoux test, allows more effective selection patients with a high risk of developing tuberculosis, thus it is possible to carry out additional examination only of this target group and save resources.

1. Kiselev V.I., Baranovskiy P.M., Pupyshev S.A. et al. The new skin test for tuberculosis diagnostics based on recombinant protein of ESAT-CFP. Molekulyarnaya Meditsina, 2008, no. 4, pp. 4-6. (In Russ.)

2. Kudlay D.A. Biomarkers and immunological tests. Experimental and clinical parallels of latent tuberculosis infection. Tuberculosis and Lung Diseases, 2020, vol. 98, no. 8, pp. 63-74. (In Russ.) http://doi.org/10.21292/2075-1230-2020-98-8-63-74.

3. Kudlay D.A., Starshinova А.А., Dovgalyuk I.F. Tuberculous recombinant allergen: 10-year experience of using this test in children and adolescents in the Russian Federation (data of meta analysis). Pediatriya. Journal im. G.N. Speranskogo, 2020, vol. 99, no. 3, pp. 121-129. (In Russ.)

4. Edict no. 124n as of March 03, 2017 by the Russian Ministry of Health On the Approval of Procedure and Time Frames of Preventive Mass Screening of Population for Tuberculosis. (In Russ.)

5. Edict no. 951 by RF MoH as of 29.12.2014 On Approval of Guidelines for Improvement of Respiratory Tuberculosis Diagnostics and Treatment. (In Russ.) M-vo Zdravookhraneniya Rossii Publ., Moscow, 2014. Available: https://www.garant.ru/products/ipo/prime/doc/70749840/.

6. Edict no. 855 as of October 29, 2009 by Russian Ministry of Health and Social Development. On Changes to Appendix no. 4 to Edict no. 109 as of March 21, 2003 by the Russian Ministry of Health. (In Russ.)

7. Slogotskaya L.V., Bogorodskaya E.M., Sinitsyn M.V., Kudlay D.A., Shamuratova L.F., Sevostyanova T.A. Screening of tuberculosis infection with various options for the use of recombinant tuberculosis allergen in children and adolescents in Moscow. Pediatriya im. G.N. Speranskogo, 2020, vol. 99, no. 2, pp. 136-146. (In Russ.)

8. Slogotskaya L.V., Kochetkov Ya.A., Senchikhina O.Yu., Seltsovskiy P.P., Litvinov V.I. Changes in skin test (diaskintest) in children when assessing the activity of tuberculosis infection. Tuberculosis and Lung Diseases, 2011, no. 2, pp. 59-63. (In Russ.)

9. Starshinova А.А., Kudlay D.A., Dovgalyuk I.F., Basantsova N.Yu., Zinchenko Yu.S., Yablonskiy P.K. Efficacy of new methods of immunodiagnostics of tuberculous infection in the Russian Federation. Pediatriya, 2019, vol. 98, no. 4, pp. 229-235. (In Russ.) doi: 10.24110/0031-403X-2019-98-4-229-235.

10. Affronti L., Lind A., Ouchterlony O. et al. An evaluation of the polyacrylamide gel electrophoresis fractionation method for the production of Mycobacterium tuberculosis skin test preparations. I. Production, physiochemical characterization and serological analyses. J. Biol., 1986, vol. 26, pp. 1-18.

11. Auguste P., Tsertsvadze A., Pink J., Courtney R., Seedat F., Gurung T., Accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation. Health Technology Assessment, 2016, vol. 20, no. 38, pp. 1-678. doi: 10.3310/hta20380.

12. Barry С., Boshoff H.I., Dartois V., Dick T., Ehrt S., Flynn J. et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat. Rev. Microbiol., 2009, vol. 7, pp. 845-855.

13. Boussiotis V., Tsai E., Yunis E. et al. IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J. Clin. Invest., 2000, vol. 105, no. 9, pp. 1317-1325.

14. Cobat A., Gallant C., Simkin L., Black G., Kim S., Hughes J. et al.Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis. J. Exp. Med., 2009, vol. 206(12), 2583-91. doi: 10.1084/jem.20090892.

15. Cole S., Brosch R., Parkhill J. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature, 1998, vol. 393, pp. 537-544.

16. Consensus meeting report: development of a Target Product Profile (TPP) and a framework for evaluation for a test for predicting progression from tuberculosis infection to active disease / World Health Organization. Geneva, 2017 (WHO/HTM/TB/2017.18). Licence: CC BY-NC-SA3.0 IGO.

17. Dillon D., Alderson М., Day Н. et al. Molecular and immunological character izationof Mycobacterium tuberculosis CFP-10, an immunodiagnostic antigen missing in Mycobacterium bovis BCG. J. Clin. Microbiol., 2000, vol. 38, pp. 3285-3290.

18. Implementing the endTB strategy: the essentials. World Health Organization, Geneva, 2015. (WHO/HTM/TB/2015.31; http://www.who.int/tb/publications/2015/end_tb_essential.pdf?ua=1, Accessed 18 July 2017).

19. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. World Health Organization. Geneva, 2018.

20. Lin P., Ford C., Coleman M., Myers A., Gawande R., Ioerger T. et al. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nature Med., 2014, vol. 20, no. 1, pp. 75-79.

21. Mahairas G., Sabo P., Hickey M. et al. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J. Bacteriol., 1996, vol. 178, pp. 1274-1282.

22. Marais B., Gie R., Schaaf H., Hesseling A., Obihara C., Starke J. et al. The natural history of childhood intra-thoracic tuberculosis - a critical review of literature from the pre-chemotherapy era. Int. J. Tuberc. Lung Dis., 2004, no. 8, pp. 392-340.

23. Pai M. Innovations in tuberculosis diagnostics: progress and translational challenges. EBioMedicine, 2015, vol. 2, no. 3, pp. 182-183. doi: 10.1016/j.ebiom.2015.01.018.

24. Pai M., Behr M., Dowdy D., Dheda K., Divangahi M., Boehme C. et al. Tuberculosis. Nat. Rev. Dis. Primers, 2016, vol. 2. doi: 10.1038/nrdp.2016.76.

25. Palmer C., Edwards L. Tuberculin test in retrospect and prospect. Arch. Environ. Health., 1967, vol. 15, no. 6, pp. 792-808.

26. Report on BCG vaccine use for protection against mycobacterial infections including tuberculosis, leprosy, and other nontuberculous mycobacteria (NTM) infections Prepared by the SAGE Working Group on BCG Vaccines and WHO Secretariat 22. September 2017.

27. Simmons J., Stein C., Chetan S., Campo M., Alter G., Fortune S. et al. Immunological mechanisms of human resistance to persistent Mycobacterium tuberculosis infection. Nat. Rev. Immunol., 2018, vol. 18, no. 9, pp. 575-589. doi:10.1038/s41577-018-0025-3.

28. Slogotskaya L., Bogorodskaya E., Ivanova D., Sevostyanova T. 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. Plos ONE, 2018, vol. 13, no. 12, pp. e0208705.

29. Thye T., Browne E., Chinbuah M. et al. IL10 Haplotype associated with tuberculin skin test response but not with pulmonary TB. PLoS ONE, 2009, vol. 4, no. 5, pp. e5420.

30. Vukmanovic-Stejic M., Reed J., Lacy K. et al. Mantoux Test as a model for a secondary immune response in humans. Immunol. Lett., 2006, vol. 107, no. 2, pp. 93-100.

31. World Health Organization. Global tuberculosis report. 2018. http://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?ua=1 (Accessed Nov. 2020).