Abstract
Objective. The article presents the results of studies to determine the significance of the microbial flora of the nasal mucosa and oropharynx in the formation of the clinical course and immune response in children with infectious mononucleosis (IM). Materials and methods. Under the supervision were 93 children aged three to nine years, patients with mononucleosis. In 32 children (first group), Streptococcus pyogenes at concentrations of 10-5 and higher was isolated during bacteriological examination of the mucosa of the nasopharynx and oropharynx. 30 (second group) - 10-4 degrees or less. In 31 (the third group), Staphylococcus aureus, Spirochetae buccalis, E. Coli and other bacteria, except streptococcus, were sown in smears from the mucous membrane of the nasoropharynx. The immune status of patients was assessed by indicators of levels of lymphocytes CD3+, CD4+, CD8+, CD22+ and the content of interleukins 1β, 4, TNFα. Results. The acute period of the mononucleosis in children of the first group was characterized more severe symptoms of intoxication, more severe morphological changes in the tissues of the tonsils, lymph nodes, liver and spleen. Also a significant decrease in the relative amount of CD3+, CD4+, CD8+ was observed compared with the indicators of children of the second and third groups. The increase in blood CD22+ content was more significant in children of the first group. The content of pro-inflammatory IL-1β and TNF-α in patients of all groups was significantly higher than in healthy children. The IL-4 increased in children of the second and third groups. In the period of early convalescence in children of the second and third groups, the relative content of CD3+, CD4+, CD8+ cells approached the corresponding indices of the control group. This was not observed in children of the first group. CD22+ levels in all observation groups decreased by the convalescence period, but remained high compared with the control group. In children of the studied groups, by the period of reconvalescence, a decrease in the levels of IL-1β, TNF-α is noted, more significant in children of the second and third groups. At the same time, in children of the first group, the level of pro-inflammatory interleukins by the period of reconvalescence remained at high numbers. The content of IL-4 was a significant difference in the indicators of its content in comparison with the digital characteristics of healthy ones in children of the second and third groups. Conclusion. An analysis of the results of the study found that the presence of streptococcus in its high concentration on the mucosa of the nosopharynx of children with mononucleosis already contributes to the formation of cellular immunosuppression and a pronounced reaction of pro-inflammatory interleukins at the initial stage of the disease, which, in general, leads to aggravation of the clinical manifestations of the disease and, in our opinion, may be a causative factor of a possible unfavorable course of the disease.
References
Krasnov, M. V., Stekolschikova, I. A., Borovkova, M.G., Andreeva, L. V. (2015). Zhurnal: sovremennyie problemyi nauki i obrazovaniya. Infektsionnyiy mononukleoz u detey, 2, 63.
Dunmire , S. K., Hogquist , K. A., Balfour , H. H. (2015). Curr Top Microbiol Immunol. Infectious Mononucleosis, 1, 211–40.
Azzi, T, Luneman, N. A., Murer, A., Ueda, S., Beziat, V, Malmberg, K. J., Staubli, G., Gysin, C., Berger, C., Munz C, Chijioke, O., Nadal, D. (2014). Role for early-differentiated natural killer cells in infectious mononucleosis. Blood, 124, 2533–2543. doi: 10.1182/blood-2014-01-553024.
Bartlett, A., Williams, R., Hilton, M. (2016). Splenic rupture in infectious mononucleosis: A systematic review of published case reports. Injury, 3, 531–538.
Bobruk, S. V. (2017). The degree of indicators level violation of local immunity in children with infectious mononucleosis. Journal of Education, Health and Sport, 3, 576–585.
Chijioke, O., Muller, A., Feederle, R., Barros, M. H., Krieg, C., Emmel, V, Marcenar, O. E., Leung, C. S., Antsiferova, O., Landtwing, V, Bossar. t, W, Morett. a, A., Hassan, R., Boyman, O., Niedobitek, G., Delecluse, H.J, et al. (2013). Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection. Cell Rep., 5, 1489–1498. doi: 10.1016/j.celrep.2013.11.041.
Nicholas John Bennett (2018). Pediatric Mononucleosis and Epstein-Barr Virus Infection. Retrieved from: https://emedicine.medscape.com/article/963894-overview.
Harley, J. B., Chen, X., Pujato, M., Miller, D., Maddox, A., Forney, C., et al. (2018). Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nat Genet, 50(5), 699–707.
Huang ,W., Lv, N., Ying, J., Qiu, T., Feng, X. (2014). Clinicopathological characteristics of four cases of EBV positive T-cell lymphoproliferative disorders of childhood in China. Int. J. Clin. Exp. Pathol, 7(8), 4991–4999.
Kessenich , C. R., Flanagan M. (2015). Diagnosis of infectious mononucleosis. Nurse Pract, 40(8), 13–14, 16.
Cunha, B. A., Petelin, A., George, S. (2013). Fever of unknown origin (FUO) in an elderly adult due to Epstein-Barr virus (EBV) presenting as "typhoidal mononucleosis", mimicking a lymphoma. Heart Lung, 42(1), 79–81.
Engelmann, I., Nasser, H., Belmiloudi, S., et al. (2013). Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid abnormalities in an immunocompetent adolescent: a case report. Diagn Microbiol Infect Dis, 76(2), 232–234.
Kuzembayeva, M., Hayes, M., Sugden, B. (2014). Multiple functions are mediated by the miRNAs of Epstein-Barr virus. Curr Opin Virol, 7, 61–65. doi: 10.1016/j.coviro.2014.04.003.
Langer-Gould, A., Wu, J., Lucas, R., Smith, J., Gonzales, E., Amezcua, L., et al. (2017). Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study. Neurology, 89(13), 1330–1337.
Rickinson, A.B., Fox, C.P. (2013). Epstein-barr virus and infectious mononucleosis: what students can teach us. Infect Dis, 207(1), 6–8.
Leskowitz, R., Fogg, M. H., Zhou, X. Y, Kau. r, A., Silveira, E. L., Villinger, F, Lieberman, P. M., et al. (2014). Adenovirus-based vaccines against rhesus lymphocryptovirus EBNA-1 induce expansion of specific CD8+ and CD4+ T cells in persistently infected rhesus macaques. Virol, 88, 4721–4735. doi: 10.1128/JVI.03744-13.
Michael, S. (2018). Mononucleosis in Emergency Medicine. Retrieved from: https://emedicine.medscape.com/article/784513-overview.
Styczynski, J., van der Velden, W, Fo. x, C. P, et al. (2016). Management of Epstein-Barr Virus. infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation. Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica, 101(7), 803–811.
Rostgaard, K., Wohlfahrt, J., Hjalgrim, H. (2014). A genetic basis for infectious mononucleosis: evidence from a family study of hospitalized cases in Denmark. Clin Infect Dis, 58(12), 1684–1689.
Zhou, C., Xie, Z., Gao, L., Liu, C., Ai, J., Zhang, L., et al. (2015). Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic Lymphohistiocytosis. Tohoku J Exp Med, 237, 117–126. doi: 10.1620/tjem.237.117.
Ali, A. S., Al-Shraim, M., Al-Hakami, A. M., Jones, I. M. (2015). Epstein-Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis. Open Virol J, 9, 7–28.
Okano, M., Gross, T. G. (2012). Acute or chronic life-threatening diseases associated with EpsteinBarr virus infection. Am J Med Sci, 343(6), 483-9.
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