Etiological Structure, Clinical and Epidemiological Characteristics of Infections Transmitted by Ixodic Ticks in the Sverdlovsk Region at the Present Stage

Relevance. The Sverdlovsk region is a highly endemic territory for infections transmitted by ixodic ticks. The possibilities of laboratory diagnostics of tick–borne infections in the routine practice of a clinician in the region today are limited mainly by testing blood serum for antibodies to the tick-borne encephalitis virus (TBE virus) and Lyme disease (LD) pathogens – Borrelia burgdorferi sensu lato complex, therefore, among tick-borne infections in the region currently mainly TBE and LD are registered. In case of negative results for antibodies to the pathogens of the above infections, the diagnosis may remain unknown. Aims. To study the etiological structure of infections transmitted by ixodic ticks in the Sverdlovsk region at the present stage, as well as to characterize the epidemiological and clinical features of the course of tick-borne infections detected in conditions of a combination of natural foci. Materials and methods. The study included 227 patients undergoing inpatient or outpatient treatment during the epidemic season of tick activity in 2021 (June-August) at LLS MO "New Hospital" (Urban Center of Natural Focal Infections). The case histories (epidemiological, clinical and laboratory indicators) were studied from each patient, as well as the material (blood) was examined prospectively and retrospectively using molecular biological (PCR) and serological (ELISA, planar protein biochip) methods. Results and discussion. During the study, six diseases were identified among the examined patients: TBE, LD (erythematous and nonerythematous forms), Borrelia miyamotoi disease (BMD), human granulocytic anaplasmosis (HGA), human monocytic ehrlichiosis (HME), as well as "Viral fever transmitted by arthropods" (VFTA). Among the examined patients, the proportion of patients with monoinfection was 49,5%, with mixed infection – 50,5%. Additional studies conducted by us using specific PCR for the presence DNA rickettsia and the causative agent of Q-fever in the blood of patients gave negative results. The general epidemiological characteristics for the above identified infections were the vector-borne mechanism, the prevalence of diseases in groups of middle-aged and elderly people, the largest number of cases of infection with pathogens of any tick-borne infection occurred in Yekaterinburg and its surroundings, for all infections, the duration of tick bite in most cases did not exceed one day; there were differences by sex, incubation period. Clinical symptoms were similar, except for the erythematous form of LD (the presence of erythema migrans at the byte site of tick), because the vast majority of patients had a general infectious syndrome; general laboratory indicators varied. Confirmation of the diagnosis was based on the results of the complex application of molecular biological and serological research methods. Conclusions. The modern etiological structure of infections transmitted by ixodic ticks in the Sverdlovsk region is represented not only by TBE and LD, but also by new disease to our country, such as BMD, HGA, HME, while a high proportion of mixed infections in various combinations has been revealed.

1. Platonov AE, Karan LS, Garanina SB, et al. Natural focal infections in the XXI century in Russia. Epidemiology and infectious diseases. 2009;2:38–44 (In Russ).

2. Moore A, Nelson C, Molins C, et al. Current guidelines, common clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease, United States. Emerging Infectious Diseases.2016;22(7):1169–77. doi: 10.3201/eid2207.151694

3. Stanek G, Fingerle V, Hunfeld KP, et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clinical Microbiological and Infection. 2011;17(1):69–79. doi: 10.1111/j.1469-0691.2010.03175.x

4. Krause PJ, Fish D, Narasimhan S, et al. Borrelia miyamotoi infection in nature and in humans. Clinical Microbiological and Infection. 2015;21(7):631–9. doi: 10.1016/j.cmi.2015.02.006

5. Wagemakers A, Staarink PJ, Sprang H, et al. Borrelia miyamotoi: a widespread tick-borne relapsing fever spirochete. Trends in Parasitology. 2015;31(6):260–9. doi: 10.1016/j.pt.2015.03.008

6. Wagemakers A, Koetsveld J, Narasimhan S, et al. Variable major proteins as targets for specific antibodies against Borrelia miyamotoi. Journal of Immunology. 2016;196(10):4185–95. doi: 10.4049/jimmunol.1600014

7. Hoornstra D, Stukolova OA, Karan LS, et al. Development and validation of a protein array for detection of antibodies against the tick-borne pathogen Borrelia miyamotoi. Microbiology Spectrum. 2022;10(6):e0203622. doi: 10.1128/spectrum.02036-22

8. Karan LS, Kolyasnikova NM, Makhneva NA, et al. Usage of real time polymerase chain reaction for diagnostics of different tick-borne infections. Journal of Microbiology, Epidemiology and Immunology. 2010;3:72–77. (In Russ).

9. Platonov AE, Karan LS, Kolyasnikova NM, et al. Humans infected with relapsing fever spirochete Borrelia miyamotoi, Russia. Emerging Infectious Diseases. 2011;17(10):1816– 23. doi: 10.3201/eid1710.101474

10. Khasnatinov MA. The role of the genetic diversity of tick-borne encephalitis virus and other tick-borne pathogens in ensuring the sustainable existence of their epidemiologically significant natural foci in Eastern Siberia and Mongolia [abstract of the dissertation]. Moscow; 2019. Available at: https://www.dissercat.com/content/rol-geneticheskogo-raznoobraziya-virusa-kleshchevogo-entsefalita-i-drugikh-kleshchevykh-pato/read. Accessed: 5 Oct 2022. (In Russ).

11. Kumar S, Stecher G, Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Dataset. Molecular Biology and Evolution 2016;33(7):1870–74. doi: 10.1093/molbev/msw054

12. Altschul SF, Gish W, Miller W, et al. Basic local alignment search tool. Journal of Molecular Biology. 1990;215:403–10. doi: 10.1016/S0022-2836(05)80360-2

13. Platonov A.E. Statistical analysis in medicine and biology: problems, terminology, logic, computer methods. Moscow: Izdatel’stvo RAMN; 2000. (In Russ.)

14. Nasledov A. SPSS 19: professional statistical analysis of data. St. Petersburg: Mir knig; 2011. (In Russ.).

15. Lyubeznova ON, Bondarenko AL. Clinical and epidemiological aspects of tick-borne encephalitis in the endemic region of the European part of Russia. Journal of Infectology. 2016;8(2): 32–39. (In Russ).

16. Volkova LI. Kleschevoy encephalit na Srednem Urale: kliniko-epidemiologicheskiy analis ostrych I chronicheskich form, puti optimizatsii okazaniya spetsializirovannoy meditsinskoy pomoschi v endemichnom ochage. [abstract of the dissertation]. Yekaterinburg; 2009. Available at: https://medical-diss.com/docreader/287496/a#?page=1. Accessed: 5 Oct 2022. (In Russ).

17. Provorova VV. Znachenie epidemiologicheskich i klinicheskich dannych v rannem prognoze pri kleschevom encephalite. [abstract of the dissertation]. Novosibirsk; 2010. Available at: https://medical-diss.com/docreader/327484/a#?page=1. Accessed: 5 Oct 2022. (In Russ).

18. Ponfick M, Hacker S, Gdynia HJ, et al. Meningoencephaloradiculomyelitis after tick-borne encephalitis virus infection: a case series. European Journal of Neurology. 2012;19(5):776–82. doi: 10.1111/j.1468-1331.2011.03651.x

19. Platonov AE, Toporkova MG, Kolyasnikova NM, et al. Clinical manifestations of ixodic tick-borne borreliosis caused by Borrelia miyamotoi in the context of the immune response to the pathogen. Therapeutic Archive. 2017;89(11):35–43. doi:10.17116/terarkh2017891135-43

20. Sarksyan DS. Ixodovyi kleschevoy borreliosis vyzvannyi Borrelia miyamotoi – kliniko-epidemiologicheskaya charactetristica, diagnostika, lechenie. [abstract of the dissertation]. Moscow; 2016. Available at: https://www.dissercat.com/content/iksodovyi-kleshchevoi-borrelioz-vyzvannyi-borrelia-miyamotoi-kliniko-epidemiologicheskaya/read. Accessed: 5 Oct 2022. (In Russ).

21. Saveleva MV. Kliniko-laboratornaya characteristika kleschevych bacterial’nych infetsii u vzroslych v Novosibirskoy oblasti. [abstract of the dissertation]. Novosibirsk; 2019. Available at: https://www.dissercat.com/content/kliniko-laboratornaya-kharakteristika-kleshchevykh-bakterialnykh-infektsii-u-vzroslykh-v-nov/read. Accessed: 5 Oct 2022. (In Russ).

22. Kuleshov KV, Koetsveld J, Goptar IA, et al. Whole-Genome Sequencing of Six Borrelia miyamotoi Clinical Strains Isolated in Russia. Genome Announcements. 2018;6(1):e01424-17. doi: 10.1128/genomeA.01424-17

23. Pogodina VV, Levina LS, Skrynnik SM, et al. Tick-borne encephalitis with fulminant course and lethal outcome in a repeatedly vaccinated patient. Problems of Virology. 2013;58(2):33–7. (In Russ).

24. Pogodina VV, Luchinina SV, Stepanova ON, et al. An unusual case of lethal tick-borne encephalitis in a patient vaccinated with vaccines of different genotypes (Chelyabinsk region). Epidemiology and infectious diseases. 2015;20(1):56–64. (In Russ).

25. Teterin VYu, Korenberg EI, Nefedova VV, et al. Enzyme immunoassay and polymerase color reaction in laboratory diagnostics of human granulocytic anaplasmosis. Journal of Infectology. 2012;4(2):33–9. (In Russ).

26. Teterin VYu, Korenberg EI, Nefedova VV, et al. Features of human monocytic ehrlichiosis laboratory diagnostics. Perm Medical Journal. 2022:XXXX(3):73–82. (In Russ). doi: 10.17816/pmj39373-82

27. Rar V, Tkachev S, Tikunova N. Genetic diversity of Anaplasma bacteria: Twenty years later. Infection, Genetics and Evolution. 2021;91:104833. doi: 10.1016/j.meegid.2021.104833