Herd immunity to diphtheria in the population of several russian regions

Diphtheria is a serious infection, often characterized by a pronounced toxic component, which can be accompanied by severe complications of the cardiovascular and nervous systems. The primary method of infection prevention is immunization (primarily in children) with diphtheria toxoid, which induces effective and long-lasting antitoxic immunity. Objective of the study: evaluation of collective immunity to the causative agent of diphtheria among the population of several regions (Amur, Irkutsk, Nizhny Novgorod, Kaliningrad) and the Republic of Crimea. Materials and methods. The cross-sectional cohort randomized study involved 18,207 people uniformly stratified by age (1–5, 6–11, 12–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70+ years), including: 3,576 in Amur; 3,657 in Irkutsk; 3,580 in Nizhny Novgorod; 3,613 in Kaliningrad regions; and 3,781 in the Republic of Crimea. All studies were conducted in strict accordance with the requirements of the Declaration of Helsinki. Immunoglobulin G Abs to the C. diphtheriae toxin were determined in the examined volunteers by enzyme immunoassay using a Russian-made test system. Data analysis and statistical processing were carried out using a web application. Results. The average cohort regional seroprevalence levels were: Amur Region - 82.3% (95% CI: 81.0 - 83.5); Irkutsk - 87.6% (95% CI: 87.6-88.9); Nizhny Novgorod - 86.5% (85.3-87.6); Kaliningrad - 74.2% (95% CI: 72.8 - 75.6); and the Republic of Crimea - 74.8% (95% CI: 73.4-76.1). In some cases, seropositivity did not reach 60%, namely: among individuals aged ≥60 in the Kaliningrad Region and the Republic of Crimea; and among individuals aged ≥70 in the Amur and Nizhny Novgorod Regions. Most volunteers had serum IgG Abs to diphtheria toxin at concentrations of 0.1–1.0 IU/ml, regardless of age, region, or vaccine type. Conclusion. The level of collective immunity mandated by current Russian documents (95% in children, 90% in adults) was practically not achieved in any region or age group (except children aged 1–5 years in the Irkutsk and Nizhny Novgorod Regions). In all regions, the least protected group were individuals aged 60 and older, among whom the seronegative value reached 30–45%.

1. Basov A.A., Maksimova N.M., Vysochanskaya S.O., Tsvirkun O.V., Yatskovsky K.A., Aduguzelov S.E. Assessment of the State of Antidiphtheria Immunity in Different Age Groups of the Population of the Russian Federation Based on Seromonitoring Data for 2015–2021. Epidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccine Prevention, 2023, Vol. 22, no. 5, pp. 63-73. (In Russ.)

2. From the history of the calendar of preventive vaccinations in the USSR/Russia. [Electronic resource]. Available at: https:// cgon.rospotrebnadzor.ru/naseleniyu/vaktsinatsiya/natsionalnyy-kalendar-profilakticheskikh-privivok/iz-istoriikalendarya-profilakticheskikh-privivok-v-sssr-rossii/ (date of access: December 3, 2025).

3. Radar Calculators [Electronic resource]. Available at: https://radarresearch.ru/instruments/calculators (date of access: April 29, 2024).

4. Kovalev E.V., Kharseeva G.G., Nenadskay S.A., Ryabova A.M., Alutina E.L., Vorotnykova I.S., Myroshnichenko G.A., Shvager M.M., Zanina M.Ya. Anti-diphtheria antitoxic immunity in the population of rostov-on-don and the rostov region. Epidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccine Prevention, 2019, Vol. 18, no. 2, pp. 68-73. (In Russ.)

5. Maksimova N.M., Yakimova T.N., Markina S.S., Yatskovsky K.A., Aduguzelov S.E. Diphtheria in Russia in the 21st century. Epidemiologiya i vaktsinop rofilaktika = Epidemiology and Vaccine Prevention, 2017, Vol, 16, no. 5, pp. 4-15. (In Russ.)

6. Markina S.S., Maksimova N.M., Kotova E.A., Zhilina N.Ya. Diphtheria incidence in Russia in 1993-1995. Epidemiologiya i infektsionnyye bolezni = Epidemiology and Infectious Diseases, 1997, no. 4, pp. 8-10. (In Russ.)

7. Medical statistics [Electronic resource]. Available at: https://medstatistic.ru/ (date of access: June 1, 2025).

8. Nosov S.D., Kostyukova N.N. Diphtheria. In: Great Medical Encyclopedia]. Moscow: Sovetskaya entsiklopediya, 1977. Vol. 7, pp. 1193-1220.

9. On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2024: State report [Electronic resource]. Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 2025. 424 p. Available at: www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=30171 (date of access: January 25, 2026).

10. Organization and implementation of serological monitoring of the state of collective immunity to infections controlled by specific prophylaxis (diphtheria, tetanus, whooping cough, measles, rubella, mumps, poliomyelitis, hepatitis B): Methodological guidelines [Electronic resource]. Moscow: Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, 2011. 19 p. Available at: https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=4852 (date of access: January 25, 2026)

11. Popova A.Yu., Totolyan A.A. Methodology for assessing population immunity to the SARS-CoV-2 virus in the context of the COVID-19 pandemic. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2021, Vol. 11, no. 4, pp. 609-616. (In Russ.) doi: 10.15789/2220-7619-MFA-1770.

12. Popova A.Yu., Smirnov V.S., Egorova S.A., Milichkina A.M., Turov V.M., Drozd I.V., Vasilyeva Z.V., Zhimbaeva O.B., Gubanova A.V., Buts L.V., Glazkova E.S., Zotkin N.N., Arbuzova T.V., Demidyuk O.I., Ivanov V.A., Dymchenko G.B., Totolyan A.A. Population immunity to measles, rubella, mumps and diphtheria in the population of some districts of the Kherson region. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2025, Vol. 15, no. 6, pp. 1159-1178. (In Russ.) doi: 10.15789/2220-7619-MRM-18042.

13. Order of the Ministry of Health of the Russian Federation dated December 6, 2021 No. 1122n (as amended on December 12, 2023) “On approval of the National Immunization Schedule, the Immunization Schedule for epidemic indications, and the Procedure for administering preventive vaccinations” (Registered on December 20, 2021 No. 66435). [Electronic resource]. Available at: http://publication.pravo.gov.ru/Document/ View/0001202112200070 (date of access: January 25, 2026).

14. Ryabenko Yu.N., Ryabenko E.B. Diphtheria and its prevention. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy, 2025, Vol. 27, no. 1, pp. 23-26. (In Russ.)

15. Decree of the Chief State Sanitary Doctor of the Russian Federation dated January 28, 2021 No. 4 “On approval of Sanitary Rules and Regulations SanPiN 3.3686-21 ‘Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases’” (Registered February 15, 2021 No. 62500). [Electronic resource]. Available at: http://publication.pravo.gov.ru/Document/View/0001202102180019 (date of access: December 27, 2025).

16. Semenenko T.A., Rusakova E.V., Shcherbakov A.G., Gaidarenko A.D., Gotvyanskaya T.P., Evseeva L.F., Sipacheva N.B., Guseva E.V., Nikitina G.Yu., Shaposhnikov A.A. State of population immunity against vaccine-preventable infections (based on blood serum bank data). Epidemiologiya i infektsionnye bolezni. Aktualnye voprosy = Epidemiology and Infectious Diseases. Current Issues, 2021, no. 6, pp. 10–15. (In Russ.)

17. Serological methods for diagnosis and monitoring of diphtheria infection: Methodological recommendations [Electronic resource]. Moscow: Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, 2016. 16 p. Available at: https://meganorm.ru/Data2/1/4293755/4293755688.pdf (date of access: January 15, 2026).

18. Shmeleva E.A., Popova T.N., Safronova A.V. Features of the formation of natural and post-vaccination anti-diphtheria antitoxic immunity. Epidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccine Prevention, 2021, Vol. 20, no. 1, pp. 100-113. (In Russ.)

19. Shmeleva E.A., Melekhova A.V., Saphronova A.V. Population and Epidemiological Aspects of Carriage of Toxigenic (Cd tox+) and Non-toxigenic (Cd tox-) Diphtheria corynebacteria. Epidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccine Prevention, 2023, Vol. 22, no. 3, pp. 85-92. (In Russ.)

20. Epidemiological surveillance of diphtheria: Methodological guidelines [Electronic resource]. Moscow: Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, 2012. 27 p. Available at: https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=4862 (date of access: January 27, 2026).

21. Abdulrasheed N., Lawal L., Mogaji A.B., Abdulkareem A.O., Shuaib A.K., Adeoti S.G., Amosu O.P., Muhammad-Olodo A.O., Lawal A.O., Jaji T.A., Abdul-Rahman T. Recurrent diphtheria outbreaks in Nigeria: A review of the underlying factors and remedies. Immun. Inflamm. Dis., 2023, vol. 11, no 11, e1096. doi: 10.1002/iid3.1096.

22. Adegboye O.A., Alele F.O., Pak A., Castellanos M.E., Abdullahi M.A.S., Okeke M.I., Emeto T.I., McBryde E.S. A resurgence and re-emergence of diphtheria in Nigeria, 2023. Ther. Adv. Infect. Dis., 2023, Vol. 10, 20499361231161936. doi: 10.1177/20499361231161936.

23. Agresti A., Coull B.A. Approximate is better than “exact” for interval estimation of binomial proportions. Am. Stat., 1998, vol. 52, no. 2, pp. 119-126.

24. Balasubramanian C. Understanding the Basic Reproduction Number (R0): The Key to Tracking Disease Spread. 2024. Available at: https://www.gideononline.com/blogs/understanding-the-basic-reproduction-numberr0-the-key-to-tracking-disease-spread.

25. Begg N. Manual for the management and control of Diphtheria in the European Region. The Expanded Programme on Immunization in the European Region of WHO. Copenhagen: WHO Regional Office for Europe; 1994. Available at: https://iris.who.int/handle/10665/108107.

26. Cherri Z., Lau K., Nellums L.B., Himmels J., Deal A., McGuire E., Mounier-Jack S., Norredam M., Crawshaw A., Carter J., Seedat F., Clemente N.S., Bouaddi O., Friedland J.S., Edelstein M., Hargreaves S.. The immune status of migrant populations in Europe and implications for vaccine-preventable disease control: a systematic review and meta-analysis. J. Travel Med., 2024, Vol. 31, no. 6, taae033. doi: 10.1093/jtm/taae033.

27. Djaafara B.A., Adrian V., Eriawati E., Elyazar I.R.F., Hamers R.L., Baird J.K., Thwaites G.E., Clapham H.E. Modeling the transmission dynamics and control strategies during the 2017 diphtheria outbreak in Jakarta, Indonesia. Infect. Dis. Model. 2025, Vol. 11, no. 1 pp. 1-15.

28. Dittmann S. Epidemic diphtheria in the Newly Independent States of the former USSR – situation and lessons learned. Biologicals, 1997, Vol. 25, no. 2, pp. 179-186.

29. European Centre for Disease Prevention and Control. Increase of reported diphtheria cases among migrants in Europe due to Corynebacterium diphtheriae, 2022. Available at: https://www.ecdc.europa.eu/en/publicationsdata/increase-reported-diphtheria-cases-among-migrants-europe-due-corynebacterium.

30. Karyanti M.R., Nelwan E.J., Assyidiqie I.Z., Satari H.I., Hadinegoro S.R. Diphtheria Epidemiology in Indonesia during 2010-2017. Acta Med. Indones, 2019, Vol. 51, no. 3, pp. 205-213.

31. Lamichhane A., Radhakrishnan S. Diphtheria. In: StatPearls. Treasure Island (FL): StatPearls Publishing, 2025. Available at: https://www.ncbi.nlm.nih.gov/books/NBK560911/.

32. Liang J.L., Tiwari T., Moro P., Messonnier N.E., Reingold A., Sawyer M., Clark T.A. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep., 2018, Vol. 67, no. 2, pp. 1-44.

33. Matsuyama R., Akhmetzhanov A.R., Endo A., Lee H., Yamaguchi T., Tsuzuki S., Nishiura H. Uncertainty and sensitivity analysis of the basic reproduction number of diphtheria: a case study of a Rohingya refugee camp in Bangladesh, November-December 2017. PeerJ, 2018, Vol. 6, e4583. doi: 10.7717/peerj.4583.

34. Plans-Rubió P. Evaluation of the establishment of herd immunity in the population by means of serological surveys and vaccination coverage. Hum. Vaccin. Immunother., 2012, Vol. 8, no. 2, pp. 184-188.

35. Popova A.Yu., Egorova S.A., Smirnov V.S., Ezhlova E.B., Milichkina A.M., Melnikova A.A., Bashketova N.S., Istorik O.A., Buts L.V., Ramsay E.S., Drozd I.V., Zhimbaeva O.B., Drobyshevskaya V.G., Danilova E.M., Ivanov V.A., Totolian A.A. Herd immunity to vaccine preventable infections in Saint Petersburg and the Leningrad region: serological status of measles, mumps, and rubella. Russian Journal of Infection and Immunity, 2024, Vol. 14, no. 6, pp. 1187-1208. doi: 10.15789/2220-7619-HIT-17797.

36. Staehelin C., Chernet A., Sydow V., Piso R.J., Suter-Riniker F., Funez S., Nickel B., Paris D.H., Labhardt N.D. Seroprotection rates of vaccine-preventable diseases among newly arrived Eritrean asylum seekers in Switzerland: a cross-sectional study. J. Travel Med., 2019, Vol. 26, no. 6, taz035. doi: 10.1093/jtm/taz035.

37. Truelove S.A., Keegan L.T., Moss W.J., Chaisson L.H, Macher E., Azman A.S., Lessler J. Clinical and epidemiological aspects of diphtheria: a systematic review and pooled analysis. Clin. Infect. Dis., 2020, Vol. 71, iss. 1, pp. 89-97.

38. Wald A., Wolfowitz J. Confidence limits for continuous distribution functions. Ann. Math. Statist., 1939, Vol. 10, no. 2. pp. 105-118.

39. Weinberger B. Adult vaccination against tetanus and diphtheria: the European perspective. Clin. Exp. Immunol., 2017, Vol. 187, no. 1, pp. 93-99.

40. White L.F., Pagano M. A likelihood-based method for real-time estimation of the serial interval and reproductive number of an epidemic. Stat. Med., 2008, Vol. 27, no. 16, pp. 2999-3016.

41. World Health Organization. Diphtheria vaccine: WHO position paper. Wkly Epidemiol Rec., 2017, Vol. 92, pp. 31. Available at: https://www.who.int/publications/i/item/diphtheria-vaccines-who-position-paper-august-2017.

42. World Health Organization. Recommendations to assure the quality, safety and efficacy of diphtheria vaccines (adsorbed), Annex 4, TRS No 980. Available at: https://www.who.int/publications/m/item/annex4-trs-980-diphtheria.

43. Zwizwai R. Infectious disease surveillance update. Lancet Infect. Dis., 2017, Vol. 17, no 8, 809. doi: 10.1016/S1473-3099(17)30415-2.