The role of children and adults as a reservoir of pathogens during the seasonal rise in the incidence of upper respiratory tract infections

Infection caused by the Epstein-Barr virus (EBV) is more common in children and is transmitted through contact with saliva. The role of adults in the epidemic process has not been sufficiently studied.

The goal is to study the role of children and adults with catarrhal phenomena in the spread of EBV during the seasonal epidemic rise in the incidence of upper respiratory tract infections (URTI).

Materials and methods. In the epidemic season of 201 9—2020, 226 people with catarrhal symptoms (140 adults and 86 children) were examined by PCR for the presence of EBV and other URTI pathogens in their nasal and oropharyngeal smears.

Results. Significant differences in the frequency of detection of pathogens in children and adults have not been established. In both groups, EBV was detected as a single pathogen and in combination with other pathogens. The presence of a runny nose, sneezing and coughing is unusual for EBV, but occurs when EBV is combined with other URTI pathogens.

Discussion. The presence of EBV in the nasopharynx and oropharynx in children and adults plays an important role in the spread of the pathogen. The combination of EBV with other pathogens that cause runny nose, sneezing, and coughing contributes to the formation of a more concentrated infectious aerosol and its spread over long distances.

Conclusions. During the seasonal epidemic upsurge, children and adults are equally involved in URTI epidemic process and are sources of EBV infection with a frequency of 3 1.39 and 37.14 per 1 00 examined and an average concentration of the virus in smears of 31 199 and 33 074 copies/ ml, respectively. In children and adults, EBV was detected in combination with other U RTI pathogens with a frequency of 1 6.28 and 1 8.57 per 1 00 subjects, respectively. The presence of EBV in the upper respiratory tract, together with other pathogens, contributes to the active transmission of EBV during the seasonal epidemic rise of upper respiratory tract infections.

1. Rooney BV, Crucian BE, Pierson DL, Laudenslager ML, Mehta SK. Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth. Front Microbiol. 2019 Feb 7; 10:16. doi: 10.3389/fmicb.2019.00016.

2. Dunmire SK, Hogquist KA, Balfour HH. Infectious Mononucleosis. Curr Top Microbiol Immunol. 2015; 390(Pt 1):211—40. doi: 10.1007/978-3-319-22822-8_9.

3. Hui KF, Chan TF, Yang W, Shen JJ, Lam KP, Kwok H, Sham PC, Tsao SW, Kwong DL, Lung ML, Chiang AKS. High risk Epstein-Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma. Int J Cancer. 2019 Jun 15; 144(12):3031—3042. doi: 10.1002/ijc.32049.

4. Ishii T, Sasaki Y, Maeda T, Komatsu F, Suzuki T, Urita Y. Clinical dif ferentiation of infectious mononucleosis that is caused by Epstein-Barr virus or cytomegalovirus: A single-center case-control study in Japan. J Infect Chemother. 2019 Jun; 25(6):431—436. doi: 10.1016/j.jiac.2019.01.012.

5. Holden DW Gold J, Hawkes CH, Giovannoni G, Saxton JM, Carter A, Sharrack B. Epstein Barr virus shedding in multiple sclerosis: Similar frequencies of EBV in saliva across separate patient cohorts. Mult Scler Relat Disord. 2018 Oct; 25:197—199. doi: 10.1016/j.msard.2018.07.041

6. Baranova I.P., Kurmaeva AJu., Lesina O.N. Clinical features of infectious mononucleosis depending on the age and etiology of the disease. Detskie Infekcii=Children’s Infections. 2010; 4: 25—28. (In Russ.)

7. Visser E, Milne D, Collacott I, McLernon D, Counsell C, Vickers M. The epidemiology of infectious mononucleosis in Northern Scotland: a decreasing incidence and winter peak. BMC Infect Dis. 2014 Mar 20; 14:151. doi: 10.1186/1471-2334-14-151.

8. Kharlamova F.S., N.Yu. Egorova, O. V Shamsheva, VF Uchaikin, O.V. Molochkova, E.V. Novosad, T.M. Lebedeva, E.V Simonov. The role of herpesvirus infection types IV, V and VI in infectious and somatic pathology in children. Pediatriya=Pediatrics. 2017; 96(4): 42—47. (In Russ.) DOI: 10.24110/0031-403X-2017-96-4-42-47

9. Lossius A, Riise T, Pugliatti M, Bjornevik K, Casetta I, Drulovic J, Granieri E, Kampman MT, Landtblom AM, Lauer K, Magalhaes S, Myhr KM, Pekmezovic T, Wesnes K, Wolfson C, Holmoy T. Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the Env IMS Study. Mult Scler. 2014 May; 20(6):669—74. doi: 10.1177/1352458513505693.

10. Mihneva S.A., Martynov Ju.V, Kuhtevich E.V., Grishina JuJu. Infectious mononucleosis: spatio-temporal manifestation of the epidemic process. ZNiSO. 201 8; 10 (307):50—54. (In Russ.)

11. Downham C, Visser E, Vickers M, Counsell C. Season of infectious mononucleosis as a risk factor for multiple sclerosis: A UK primary care case-control study. Mult Scler Relat Disord. 2017 Oct; 17:103—106. doi: 10.1016/j.msard.2017.07.009.

12. Rostgaard K, Balfour HH Jr, Jarrett R, Erikstrup C, Pedersen O, Ullum H, Nielsen LP, Voldstedlund M, Hjalgrim H. Primary Epstein-Barr virus infection with and without infectious mononucleosis. PLoS One. 2019 Dec 17; 14(12):e0226436. doi: 10.1371/journal.pone.0226436.

13. Levine H, Mimouni D, Grotto I, Zahavi A, Ankol O, Huerta-Hartal M. Secular and seasonal trends of infectious mononucleosis among young adults in Israel: 1978—2009. Eur J Clin Microbiol Infect Dis. 2012 May; 31(5):757—60. doi: 10.1007/s10096-011-1371-2.

14. Solomay T.V. Dynamics of morbidity and territorial spread of infectious mononucleosis. ZdravookhranenieRossiiskoiFederatsii. Health Care of the Russian Federation. 2019; 63(4): 186—192. (In Russ.) dx.doi.org/10.18821/0044-197X-2019-63-4-186-192

15. Gralton J, Tovey E, McLaws ML, Rawlinson WD. The role of particle size in aerosolised pathogen transmission: a review. J Infect. 2011 Jan; 62(1):1—1 3. doi: 10.1016/j.jinf.2010.11.010.

16. Solomay T.V, Semenenko T.A. Viral hepatitis B, C and infectious mononucleosis: epidemiological similarities and differences. Vo-prosy Virusologii. 2020; 65(1): 27—34. (In Russ.) doi.org/10.36233/0507-4088-2020-65-1-27-34

17. Wainwright C.E., France M.W, O'Rourke P., Anuj S., Kidd TJ., Nis-sen M.D., et al. Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis. Thorax. 2009; 64: 926—931.

18. Kulikova M.M., Solomay T.V. Assessment of the epidemic situation in the diagnosis of infection caused by the Epstein-Barr virus in persons 15 years and older with a description of the clinical case. San-itarnyj Vrach=Sanitary Doctor. 2020; 2:20—27. (In Russ.)

19. Fabian P., McDevitt JJ., DeHaan W.H., Fung R.O.P., Cowling B.J., Chan K.H., et al. Influenza virus in human exhaled breath: an observational study. PLoS ONE. 2008; 3 (07/16): e2691

20. Stahlman S, Williams VF, Ying S. Infectious mononucleosis, active component, U.S. Armed Forces, 2002—2018. MSMR. 2019 Jul; 26(7):28—33.

21. Milton DK, Fabian MP, Cowling BJ, Grantham ML, McDevitt JJ. Influenza virus aerosols in human exhaled breath: particle size, cul-turability, and effect of surgical masks. PLoS Pathog. 2013 Mar; 9(3):e1003205. doi: 10.1371/journal.ppat.1003205.

22. Mbulaiteye SM, Walters M, Engels EA, Bakaki PM, Ndugwa CM, Owor AM, Goedert JJ, Whitby D, Biggar RJ. High levels of Epstein-Barr virus in saliva and peripheral blood from Ugandan mother-child pairs. J Infect Dis. 2006 Feb 1; 193(3):422—6. doi: 10.1086/499277.

23. Vieira Rda R, Ferreira LL, Biasoli ER, Bernabe DG, Nunes CM, Mi-yahara GI. Detection of Epstein-Barr virus in different sources of materials from patients with oral lichen planus: a case-control study. J Clin Pathol. 2016 Apr; 69(4):358—63. doi: 10.1136/jclinpath-2015-203325.

24. Imbronito AV, Grande SR, Freitas NM, Okuda O, Lotufo RF, Nunes FD. Detection of Epstein-Barr virus and human cytomegalovirus in blood and oral samples: comparison of three sampling methods. J Oral Sci. 2008 Mar; 50(1):25—31. doi: 10.2334/josnusd.50.25.

25. Hug M, Dorner M, Frohlich FZ, Gysin C, Neuhaus D, Nadal D, Berger C. Pediatric Epstein-Barr virus carriers with or without tonsillar enlargement may substantially contribute to spreading of the virus. J Infect Dis. 2010 Oct 15; 202(8):1192—9. doi: 10.1086/656335.

26. Fafi-Kremer S, Morand P, Brion JP, Pavese P, Baccard M, Germi R, Genoulaz O, Nicod S, Jolivet M, Ruigrok RW, Stahl JP, Seigneurin JM. Long-term shedding of infectious Epstein-Barr virus after infectious mononucleosis. J Infect Dis. 2005 Mar 15; 191(6):985—9. doi: 10.1086/428097.

27. Ikuta K, Satoh Y, Hoshikawa Y, Sairenji T. Detection of Epstein-Barr virus in salivas and throat washings in healthy adults and children. Microbes Infect. 2000 Feb; 2(2): 1 15—20. doi: 10.1016/s1286-4579(00)00277-x.

28. Fagin U, Nerbas L, Vogl B, Jabs WJ. Analysis of BZLF1 mRNA detection in saliva as a marker for active replication of Epstein-Barr virus. J Virol Methods. 2017; 244:11 — 16. doi: 10.1016/j.jviromet.2017.02.016

29. Van Roosbroeck K, Calin GA. When kissing (disease) counts. Blood. 2016 Apr 21;127(16): 1 947—8. doi: 10.1182/blood-2016-01-692087.

30. Ginsburg CM, Henle G, Henle W Outbreak of infectious mononucleosis among the personnel of an outpatient clinic. Am J Epidemiol. 1976 Nov; 104(5):571-5. doi: 10.1093/oxfordjournals.aje.a112332.

31. Gallone MS, Astuto L, Mastrorilli G, Tamma R, Ascatigno L, Sinesi D, Notarnicola A, Tafuri S. Risk of infectious mononucleosis among agonistic swimmers: a cross-sectional study. Ann Ig. 2016 Nov—Dec; 28(6):404—408. doi: 10.7416/ai.201 6.2122.

32. Ceraulo AS, Bytomski JR. Management in Athletes. Clin Sports Med. 2019 Oct; 38(4):555—561. doi: 10.1016/j.csm.2019.06.002.

33. Johnson KH et al. Epstein-Barr Virus Dynamics in Asymptomatic Immunocompetent Adults: An Intensive 6-month Study. Clin Transl Immunology. 2016; 5(5):e81. doi: 10.1038/cti.2016.28.

34. CederbergL. etal. Epstein-Barr Virus DNA in Parental Oral Secretions: A Potential Source of Infection for Their Young Children. Clin Infect Dis 2019; 68(2):306—31 2. doi: 10.1093/cid/ciy464.

35. Karazhas N.V, Feklisova L.V, Semenenko T.A., Kornienko M.N., Rybalkina T.N., Gotvyanskaya T.P., Veselovsky P.A., Lysenkova M.Yu., Kosenchuk V.V., Boshian R.E. Identification of markers of opportunistic infections in frequently ill children of North-Eastern regions of Russia. Detskie Infekcii=Children’s Infections. 2019; 1 8(4): 5—11. (In Russ.) doi.org/10.22627/2072-8107-2019-18-4-5-11

36. Dawson DR, Wang C, Danaher RJ, Lin Y, Kryscio RJ, Jacob RJ, Miller CS. Salivary levels of Epstein-Barr virus DNA correlate with subgingival levels, not severity of periodontitis. Oral Dis. 2009 Nov; 15(8):554—9. doi: 10.1111/j.1601-0825.2009.01585.x.

37. Rooney BV, Crucian BE, Pierson DL, Laudenslager ML, Mehta SK. Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth. Front Microbiol. 2019 Feb 7; 10:16. doi: 10.3389/fmicb.2019.00016.

38. Hui KF, Chan TF, Yang W, Shen JJ, Lam KP, Kwok H, Sham PC, Tsao SW, Kwong DL, Lung ML, Chiang AKS. High risk Epstein-Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma. Int J Cancer. 2019 Jun 15; 144(12):3031—3042. doi: 10.1002/ijc.32049.

39. Holden DW Gold J, Hawkes CH, Giovannoni G, Saxton JM, Carter A, Sharrack B. Epstein Barr virus shedding in multiple sclerosis: Similar frequencies of EBV in saliva across separate patient cohorts. Mult Scler Relat Disord. 2018 Oct; 25:197—199. doi: 10.1016/j.msard.2018.07.041

40. Visser E, Milne D, Collacott I, McLernon D, Counsell C, Vickers M. The epidemiology of infectious mononucleosis in Northern Scotland: a decreasing incidence and winter peak. BMC Infect Dis. 2014 Mar 20; 14:151. doi: 10.1186/1471-2334-14-151.

41. Lossius A, Riise T, Pugliatti M, Bjornevik K, Casetta I, Drulovic J, Granieri E, Kampman MT, Landtblom AM, Lauer K, Magalhaes S, Myhr KM, Pekmezovic T, Wesnes K, Wolfson C, Holmoy T. Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the Env IMS Study. Mult Scler. 2014 May; 20(6):669—74. doi: 10.1177/1352458513505693.

42. Downham C, Visser E, Vickers M, Counsell C. Season of infectious mononucleosis as a risk factor for multiple sclerosis: A UK primary care case-control study. Mult Scler Relat Disord. 2017 Oct; 17:103—106. doi: 10.1016/j.msard.2017.07.009.

43. Levine H, Mimouni D, Grotto I, Zahavi A, Ankol O, Huerta-Hartal M. Secular and seasonal trends of infectious mononucleosis among young adults in Israel: 1978—2009. Eur J Clin Microbiol Infect Dis. 2012 May; 31(5):757—60. doi: 10.1007/s10096-011-1371-2.

44. Gralton J, Tovey E, McLaws ML, Rawlinson WD. The role of particle size in aerosolised pathogen transmission: a review. J Infect. 2011 Jan; 62(1):1—1 3. doi: 10.1016/j.jinf.2010.11.010.

45. Wainwright C.E., France M.W, O'Rourke P., Anuj S., Kidd TJ., Nis-sen M.D., et al. Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis. Thorax. 2009; 64: 926—931.

46. Fabian P., McDevitt JJ., DeHaan W.H., Fung R.O.P., Cowling B.J., Chan K.H., et al. Influenza virus in human exhaled breath: an observational study. PLoS ONE. 2008; 3 (07/16): e2691

47. Milton DK, Fabian MP, Cowling BJ, Grantham ML, McDevitt JJ. Influenza virus aerosols in human exhaled breath: particle size, cul-turability, and effect of surgical masks. PLoS Pathog. 2013 Mar; 9(3):e1003205. doi: 10.1371/journal.ppat.1003205.