Modern immunodiagnostics of tuberculosis infection in adults

Despite the steady decline in the main epidemiologically significant indicators of tuberculosis in Russia, the problem remains of choosing an affordable and informative diagnostic test for the timely detection of latent tuberculosis infection (LTI).

The aim of this study was to evaluate the compatibility of various methods of immunological diagnosis in adult patients with LTI with a high (LTI-HR) and low (LTI-LR) risk of developing tuberculosis, as well as in patients with established tuberculosis of the respiratory system.

Methods. A cross-sectional open single-center study was conducted, which included 100 adult patients. The first group included 50 conditionally healthy individuals with LTI-LR. The second group of patients consisted of 25 people with LTI-HR. The third group of patients included 25 patients with tuberculosis of the respiratory system (TRS). All participants were examined once using six immunological diagnostic tests: Mantoux test with 2 units PPD-L, Diaskintest, T-SPOT®.TB, QuantiFERON®-TB Gold Plus, Standard E TB-Feron IGRA and IGRA-TB. The end point of the study was the overall percentage consistency of the results, that is, the ability of the tests to correctly predict the condition assumed by the combination of clinical signs.

Results. The proportion of “correct results” (positive in the TRS and LTI-HR group and negative in the LTI-LR group) was 83% for the IGRA-TB test, 80% for the Diaskintest, 80% for the QuantiFERON®-TB Gold Plus test, 78% for the Standard E TB-Feron IGRA test, 67% for the T-SPOT®.TB test (p > 0.05). Only the Mantoux test with 2 units PPD-L showed significantly lower “accuracy” in our study (53%; p < 0.05).

Conclusion. The new Russian test IGRA-TB is not inferior to its foreign counterparts and can be recommended in practical healthcare as a diagnosis of latent tuberculosis infection in adults. It seems fundamentally important to continue studying the informative value of tests in adult patients in real clinical practice without applying strict selection criteria. The immunological features of the patients, which determine the different sensitivity of the tests, need to be further studied.

1. Guinn K., Hickey M., Mathur S. et al. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol. Microbiol. 2004; 51 (2): 359–370. DOI: 10.1046/j.1365-2958.2003.03844.x.

2. Metcalfe J.Z., Everett C.K., Steingart K.R. et al. Interferon-gamma release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis. J. Infect. Dis. 2011; 204 (Suppl. 4): S1120–1129. DOI: 10.1093/infdis/jir410.

3. Shubina A.T., Borodulina E.A., Kudlay D.A. et al. [Test with recombinant tuberculo-sis allergen (Diaskintest®) in the diagnosis of pulmonary tuberculosis in pulmonological practice]. Pul'monologiya. 2022; 32 (4): 576–584. DOI: 10.18093/0869-0189-2022-32-4-576-584 (in Russian).

4. Collins J.M., Onwubiko U., Holland D.P. QuantiFERON-TB gold versus tuberculin screening and care retention among persons experiencing homelessness: Georgia, 2015-2017. Am. J. Public Health. 2019; 109 (7): 1028–1033. DOI: 10.2105/AJPH.2019.305069.

5. Kiselev V.I., Baranovskiy P.M., Pupyshev S.A. et al. [A new skin test for the diagno-sis of tuberculosis based on the recombinant protein ESAT-CFP]. Molekulyarnaya med-itsina. 2008; 4: 28–34 (in Russian).

6. Russkih O.E., Savintseva E.V., Kudlay D.A. et al. [Skin test based on Mycobacte-rium tuberculosis antigens (ESAT-6 and CFP-10) for the detection of tuberculosis infec-tion in world practice]. Pul'monologiya. 2023; 33 (4): 559–567. DOI: 10.18093/0869-0189-2023-33-4-559-567 (in Russian).

7. Global tuberculosis report 2018. Geneva: World Health Organization; 2018 Available at: https://www.challengetb.org/reportfiles/WHO_TB_Report_2018.pdf [Accessed: March 26, 2025].

8. Smerdin S.V., Makarova N.Yu., Aksenova V.A. et al. [Tuberculosis in the Russian Federation, 1991–2021]. Moscow: GEOTAR-Media, 2025 (in Russian).

9. Aksenova V.A., Baronova O.D., Baryshnikova L.A. et al. [Latent tuberculosis infection in children. Clinical recommendations]. Moscow: Zdorov'e cheloveka; 2024. Available at: https://tbinfo.ru/klin.rekomendacii-lti-deti-2024.pdf (in Russian).

10. [Latent tuberculosis infection: updated and consolidated guidelines for program-matic management]. Geneva: World Health Organization; 2018. Available at: https://iris.who.int/bitstream/handle/10665/312059/9789245550235-rus.pdf?ua=1 [Ac-cessed: March 26, 2025] (in Russian).

11. Carranza C., Pedraza-Sanchez S., de Oyarzabal-Mendez E. et al. Diagnosis for la-tent tuberculosis infection: new alternatives. Front. Immunol. 2020: 11: 2006. DOI: 10.3389/fimmu.2020.02006.

12. Landry J., Menzies D. Preventive chemotherapy. Where has it got us? Where to go next? Int. J. Tuberc. Lung Dis. 2008; 12 (12):1352–1364. Available at: https://www.ingentaconnect.com/contentone/iuatld/ijtld/2008/00000012/00000012/art00005

13. Dheda K., Schwander S.K., Zhu B. et al. The immunology of tuberculosis: from bench to bedside. Respirology. 2010; 15 (3): 433–450. DOI: 10.1111/j.1440-1843.2010.01739.x.

14. Barry C.E. 3rd, Boshoff H.I., Dartois V. et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat .Rev. Microbiol. 2009; 7 (12): 845–855. DOI: 10.1038/nrmicro2236.

15. Glants S. [Medical and biological statistics]. Moscow: Praktika; 1998 (in Russian).

16. Venkatappa T.K., Punnoose R., Katz D.J. et al. Comparing QuantiFERON-TB gold plus with other tests to diagnose mycobacterium tuberculosis infection. J. Clin. Mi-crobiol. 2019; 57 (11): e00985-19. DOI: 10.1128/JCM.00985-19.

17. Krutikov M., Faust L., Nikolayevskyy V. et al. The diagnostic performance of novel skin-based in-vivo tests for tuberculosis infection compared with purified protein deriva-tive tuberculin skin tests and blood-based in vitro interferon-γ release assays: a systemat-ic review and meta-analysis. Lancet Infect. Dis. 2020; 22 (2): 250–264. DOI: 10.1016/S1473-3099(21)00261-9 14.

18. Prakash Babu S., Ezhumalai K., Raghupathy K. et al. Comparison of IGRA and TST in the diagnosis of latent tuberculosis among women of reproductive age in South India. Indian J. Tuberc. 2023; 70 (1): 12–16. DOI: 10.1016/j.ijtb.2022.03.011.

19. Zhang Y., Zhou G., Shi W. et al. Comparing the diagnostic performance of QuantiFERON-TB gold plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis. BMC Infect. Dis. 2023; 23 (1): 40. DOI: 10.1186/s12879-023-08008-2.

20. Nikitina I.Y., Karpina N.L., Kasimceva O.V. et al. Comparative performance of QuantiFERON-TB gold versus skin test with tuberculosis recombinant allergen (Di-askintest) among patients with suspected pulmonary tuberculosis in Russia. Int. J. Infect. Dis. 2019; 86: 18–24. DOI: 10.1016/j.ijid.2019.06.014.

21. Starshinova A., Zhuravlev V., Dovgaluk I. et al. Comparison of intradermal test with recombinant tuberculosis allergen (Diaskintest) with other immunologic tests in the diagnosis of tuberculosis infection. Int. J. Mycobacteriol. 2018; 7 (1): 32–39. DOI: 10.4103/ijmy.ijmy_17_18.