Cytomegalovirus Infection in Adolescents of Russian Federation: Results of Cross-Sectional Population Analysis of Seroprevalence

Background. Cytomegalovirus infection (CMVI) is the reason of high mortality in perinatal period, disability in children from risk groups with further development of congenital malformations and chronic diseases. Clear understanding of epidemiology and determination of focus population groups is crucial for development of measures and algorithms of congenital CMVI prevention.

Objective. The aim of the study is to study CMVI seroprevalence among immunocompetent adolescents in Russian Federation with reference to the gender, regional, social and economic, and age factors.

Methods. We have used for our study data from the survey of senior schoolchildren from 7 municipalities representing various regions of Russian Federation: group 1 (10–12 years old) and group 2 (14–16 years old). The study of CMVI seroprevalence and immune response was performed via the analysis of the level of IgG antibodies to cytomegalovirus (CMV) in blood serum. The social and economic well-being of the region was determined by "RIA Rating" experts.

Results. Serological prevalence of CMVI in the study group of adolescents (n = 1403) was 70.6% (n = 990). There were no statistically significant gender differences in the distribution of seropositive children in regions (p = 0.525). Infection in boys (72.6%; n = 455; median age — 12.9 (11.0; 14.9)) did not prevail over the infection in girls (68.8%; n = 535; median age — 13.1 (11.0; 14,9)); p = 0,117. The overall prevalence of CMVI increased statistically significant with age — from 68% (n = 486) in group 1 to 73% (n = 504) in group 2 (p = 0.036). The prevalence of CMVI varied statistically significant by region (p = 0.003). There was no correlation between the regional seropositive level and the social and economic situation in the region (r = 0.034, p = 0.192). Immune response intensity did not differ by age, gender, and region with the antibody median of 88.9 CU/ml.

Conclusion. More than half of adolescents (by the age of 10) in Russian Federation are infected, and infection increases with approaching to childbearing age, however, age is not the only aspect associated with serological status. Factors affecting immune response intensity require further study. Understanding of the CMV prevalence among children is crucial for determining future prevention approaches in target groups.

1. Tsinzerling VA. Intrauterine Infections: Modern View upon the Problem. Journal Infectology. 2014;6(4):5–10. (In Russ).

2. Voigt S, Schaffrath Rosario A, Mankertz A. Cytomegalovirus Seroprevalence Among Children and Adolescents in Germany: Data From the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), 2003–2006. Open Forum Infect Dis. 2015;3(1):ofv193. doi: 10.1093/ofid/ofv193

3. Tuktarova AYu, Vasilev VV, Ivashchenko IA, Ushakova GM. Congenital cytomegalovirus infection (clinical report). Journal Infectology. 2014;6(4):93–97. (In Russ).

4. Griffiths PD. Burden of disease associated with human cytomegalovirus and prospects for elimination by universal immunization. Lancet Infect Dis. 2012;12(10):790–798. doi: 10.1016/S1473-3099(12)70197-4

5. Lancini D, Faddy HM, Flower R, Hogan C. Cytomegalovirus disease in immunocompetent adults. Med J Aust. 2014;201(10):578–580. doi: 10.5694/mja14.00183

6. Manicklal S, Emery VC, Lazzarotto T, et al. The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev. 2013;26(1):86–102. doi: 10.1128/CMR.00062-12

7. Kinney JS, Kumar ML. Should we expand the TORCH complex? A description of clinical and diagnostic aspects of selected old and new agents. Clin Perinatol. 1988;15(4):727–744.

8. Cytomegalovirus: Appendix 4. In: Stratton KR, Durch JS, Lawrence RS, eds. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington (DC): National Academies Press (US); 2000. doi: 10.17226/5501

9. Arvin AM, Fast P, Myers M, et al. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis. 2004;39(2):233–239. doi: 10.1086/421999

10. Mardanly S.G., Avdonina A.S., Rotanov S.V., Gotvyanskaja T.P. The detection rate of serological markers for torch infections in the population of the Moscow city. Èpidemiologiâ i infekcionnye bolezni. Aktual’nye voprosy = Epidemiology and Infectious Diseases. Current Items. 2015;(4):44–49. (In Russ).

11. Zuhair M, Smit GSA, Wallis G, et al.. Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and metaanalysis. Rev Med Virol. 2019;29(3):e2034. doi: 10.1002/rmv.2034

12. Lanzieri TM, Dollard SC, Bialek SR, Grosse SD. Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries. Int J Infect Dis. 2014;22:44–48. doi: 10.1016/j.ijid.2013.12.010

13. Babachenko IV, Mel’nik OV, Levina AS. Tsitomegalovirusnaya infektsiya u chasto boleyushchikh detei. Disease Treatment and Prevention. 2012;(4):19–24. (In Russ).

14. Zhebrun AB, Kulyashova LB, Ermolenko KD, Zakrevskaya AV. Spread of herpesvirus infections in children and adults in St. Petersburg according to seroepidemiologic study data. Žurnal mikrobiologii, èpidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology. 2013;(6):30–36. (In Russ).

15. Stadler LP, Bernstein DI, Callahan ST, et al. Seroprevalence and Risk Factors for Cytomegalovirus Infections in Adolescent Females. J Pediatric Infect Dis Soc. 2013;2(1):7–14. doi: 10.1093/jpids/pis076

16. Mardanly SG, Arseneva VA, Mardanly SS, Rotanov SV. The prevalence rate of human herpes viruses among different age populations. Žurnal mikrobiologii, èpidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology. 2019;(2):50–55. (In Russ). doi: 10.36233/0372-9311-2019-2-50-55

17. Smirnova AI, Rossikhina EV. Tsitomegalovirus — vozbuditel’ opportunisticheskikh infektsii. Medical Newsletter of Vyatka. 2011;(1):36–44. (In Russ).

18. Eletskaya KA, Namazova-Baranova LS, Kaytukova EV, et al. The Correlation Between Body Weight and Arterial Blood Pressure in 11 and 15 Years Old Children: Retrospective Cross-Sectional Study. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2019;16(4):211–215. (In Russ). doi: 10.15690/pf.v16i4.2050

19. Namazova-Baranova LS, Yeletskaya KA, Kaytukova EV, Маkarova SG. Evaluation of the Physical Development of Children of Secondary School Age: аn Analysis of the Results of a Cross-Sectional Study. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2018;15(4):333–342. (In Russ). doi: 10.15690/pf.v15i4.1948

20. Mukozheva RA, Kulichenko TV, Brzhozovskaya EA, et al. Serological monitoring of antibodies levels to measles, rubella, and mumps pathogens in schoolchildren aged 11–17 years in seven regions of the Russian Federation. Rossiyskiy Pediatricheskiy Zhurnal (Russian Pediatric Journal). 2019;22(6):332–337. (In Russ). doi: 10.18821/1560-9561-2019-22-6-332-337

21. Mayansky NA, Mukozheva RA, Kulichenko TV, et al. Serological monitoring of levels of antibodies to pathogens of tetanus, diphtheria and pertussis in schoolchildren aged of 11–17 years in seven regions of the Russian federation. Rossiyskiy Pediatricheskiy Zhurnal (Russian Pediatric Journal). 2019;22(2):81–87. (In Russ). doi: 10.18821/1560-9561-2019-22-2-81-87

22. Bolehan VN, Emelyanov VN, Orlova ES. Early sexual activity as a model of risk behavior. Bulletin of the Russian Military Medical Academy. 2017;(4):56–58. (In Russ).

23. Bates M, Brantsaeter AB. Human cytomegalovirus (CMV) in Africa: a neglected but important pathogen. J Virus Erad. 2016;2(3):136–142.

24. https://riarating.ru/infografika/20190604/630126280.html. 12.05.2021.

25. Korndewal MJ, Mollema L, Tcherniaeva I, et al. Cytomegalovirus infection in the Netherlands: seroprevalence, risk factors, and implications. J Clin Virol. 2015;63:53–58. doi: 10.1016/j.jcv.2014.11.033

26. Stadler LP, Bernstein DI, Callahan ST, et al. Seroprevalence of cytomegalovirus (CMV) and risk factors for infection in adolescent males. Clin Infect Dis. 2010;51(10):e76–e81. doi: 10.1086/656918

27. Ataman S, Colak D, Günseren F, et al. Investigation of cytomegalovirus seroepidemiology in Antalya with a populationbased cross-sectional study and review of related data in Turkey. Mikrobiyol Bul. 2007;41(4):545–555.

28. Zhang Q, Gao Y, Peng Y, et al. Epidemiological survey of human cytomegalovirus antibody levels in children from Southeastern China. Virol J. 2014;11:123. doi: 10.1186/1743-422X-11-123

29. Mussi-Pinhata MM, Yamamoto AY. Natural History of Congenital Cytomegalovirus Infection in Highly Seropositive Populations. J Infect Dis. 2020;221(Suppl 1):S15–S22. doi: 10.1093/infdis/jiz443

30. Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202–213. doi: 10.1002/rmv.655

31. Swanson EC, Schleiss MR. Congenital cytomegalovirus infection: new prospects for prevention and therapy. Pediatr Clin North Am. 2013;60(2):335–349. doi: 10.1016/j.pcl.2012.12.008

32. Schleiss MR, Diamond DJ. Exciting Times for Cytomegalovirus (CMV) Vaccine Development: Navigating the Pathways toward the Goal of Protecting Infants against Congenital CMV Infection. Vaccines (Basel). 2020;8(3):526. doi: 10.3390/vaccines8030526

33. Hanson H, Leiser C, Bandoli G, et al. Charting the Life Course: Emerging Opportunities to Advance Scientific Approaches Using Life Course Research. J Clin Trans Sci. 2020:5(1):e9. doi: 10.1017/cts.2020.492

34. Plotkin SA, Wang D, Oualim A, et al. The Status of Vaccine Development Against the Human Cytomegalovirus. J Infect Dis. 2020;221(Suppl 1):S113–S122. doi: 10.1093/infdis/jiz447

35. Pinninti S, Hough-Telford C, Pati S, Boppana S. Cytomegalovirus and Epstein-Barr Virus Infections. Pediatr Rev. 2016;37(6): 223–234. doi: 10.1542/pir.2015-0072

36. Ivanov AA. Diagnostika i lechenie gerpesvirusnykh infektsii v real’noi klinicheskoi praktike: u strakha glaza veliki. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2021;18(2):146–152. (In Russ). doi: 10.15690/pf.v18i2.2254