Algorithm for monitoring patients after tick bite in the context of Lyme-borreliosis

Timely diagnosis of Lyme-borreliosis (LB) is the key to its successful treatment. Outpatient monitoring of patients after tick bite based on the algorithm is able to optimize the early diagnosis of LB, shorten the start of treatment and improve the disease surveillance.Purpose. Creation of an algorithm for monitoring patients after tick bite for use in outpatient settings by primary care physicians. Material and methods. A retrospective, non-randomized, single-center cohort study was conducted based on the analysis of data from 660 outpatient records of patients consulted by an infectious disease specialist in the Infectious clinical hospital No.1 in Moscow. Patients were divided by age and the presence or absence of a diagnosis of LB. Confirmation of the diagnosis was carried out according to clinical and/or laboratory criteria using methods of enzyme-linked immunoassay and immune blot. Results. The analysis of the results of enzyme immunoassay of antibodies to borrelia in patients with LB was carried out. The optimal sampling time was 7 or more weeks from the moment of tick bite and 4 or more weeks from the moment of onset of symptoms. The specificity of immunological diagnostics in patients with excluded LB was evaluated. The proportion of doubtful and false positive results in such patients was high — 28.1%. False positive results were more common in adults (37.6%) compared with children (9.8%), which is associated with more frequent false positive results of IgM determination (34.1% in adults, 4.9% in children). Based on the data of our study, an algorithm for monitoring patients after tick bite has been developed, focused on use in outpatient settings by primary care physicians.

1. The state of sanitary and epidemiological well-being of the population in the Russian Federation in 2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020, 2021: State report. Moscow: Federal Service for Supervision of Consumer Rights Protection and Human Welfare, 2013—2022. (In Russ)

2. Nelson CA, Saha S, Kugeler KJ, et al. Incidence of Clinician-Diagnosed Lyme Disease, United States, 2005—2010. Emerg Infect Dis. 2015;21(9):1625—1631. doi:10.3201/eid2109.150417

3. Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS, Hinckley AF. Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010—2018. Emerg Infect Dis. 2021;27(2):616—619. doi:10.3201/eid2702.202731

4. Enkelmann J, Böhmer M, Fingerle V, et al. Incidence of notified Lyme borreliosis in Germany, 2013—2017 [published correction appears in Sci Rep. 2021 Jun 21;11(1):13347]. Sci Rep. 2018; 8(1):14976. doi:10.1038/s41598-018-33136-0

5. Kullberg BJ, Vrijmoeth HD, van de Schoor F, Hovius JW. Lyme borreliosis: diagnosis and management. BMJ. 2020;369:m1041. doi:10.1136/bmj.m1041

6. Steere A.C. Lyme borreliosis / A.C. Steere, F. Strle, G.P. Wormser, L.T. Hu et.al. Nature Reviews. Disease Primers. 2016. 2:16090 .

7. Briciu VT, Flonta M, Ţăţulescu DF, et al. Clinical and serological one-year follow-up of patients after the bite of Ixodes ricinus ticks infected with Borrelia burgdorferi sensu lato. Infect Dis (Lond). 2017; 49(4):277—285. doi:10.1080/23744235.2016.1258488

8. Markowicz M, Schötta AM, Höss D, et al. Infections with Tickborne Pathogens after Tick Bite, Austria, 2015—2018. Emerg Infect Dis. 2021; 27(4):1048—1056. doi:10.3201/eid2704.203366

9. Wilhelmsson P, Fryland L, Lindblom P, et al. A prospective study on the incidence of Borrelia burgdorferi sensu lato infection after a tick bite in Sweden and on the Åland Islands, Finland (2008—2009). Ticks Tick Borne Dis. 2016; 7(1):71—79. doi:10.1016/j.ttbdis.2015.08.009

10. Warshafsky S, Lee DH, Francois LK, Nowakowski J, Nadelman RB, Wormser GP. Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis. J Antimicrob Chemother. 2010; 65(6):1137—1144. doi:10.1093/jac/dkq097

11. Figoni J, Chirouze C, Hansmann Y, et al. Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis. Med Mal Infect. 2019; 49(5):318—334. doi:10.1016/j.medmal.2019.04.381

12. SP 3.3686-21 «Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases» January 28, 2021. (In Russ)

13. Lobzin Y.V., Skripchenko N.V., Uskov A.N., Ivanova G.P. Ixodid tick-borne borreliosis in children and adults: Guidelines for doctors., St. Petersburg, Federal State Institution «NIIDI FMBA», 2010. (In Russ.)

14. Stanek G, Fingerle V, Hunfeld KP, et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. ClinMicrobiol Infect. 2011;1 7(1):69—79. doi:10.1111/j.1469-0691.2010.03175.x

15. Asbrink E, Hovmark A. Classification, geographic variations, and epidemiology of Lyme borreliosis. Clin Dermatol. 1993; 11(3):353—357. doi:10.1016/0738-081x(93)90089-u

16. Bennett J.E. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases 9-th edition. [Еd. by J.E. Bennett, R. Dolin, M.J. Blaser]. Philadelphia, 2020:2911-2922e.2.

17. Wilhelmsson P, Fryland L, Lindblom P, et al. A prospective study on the incidence of Borrelia burgdorferi sensu lato infection after a tick bite in Sweden and on the Åland Islands, Finland (2008—2009). Ticks Tick Borne Dis. 2016; 7(1):71—79. doi:10.1016/j.ttbdis.2015.08.009

18. Zákutná Ľ, Dorko E, Mattová E, Rimárová K. Sero-epidemiological study of Lyme disease among high-risk population groups in eastern Slovakia. Ann Agric Environ Med. 2015; 22(4):632—636. doi:10.5604/12321966.1185765

19. C. Eldin, A. Raffetin, K. Bouiller, Y. Hansmann, F. Roblot, D. Raoult, P. Parola, Review of European and American guidelines for the diagnosis of Lyme borreliosis. Médecine et Maladies Infectieuses, 2019. 49(2):121—132. https://doi.org/10.1016/j.medmal.2018.11.011.

20. Instruction for the medical use of the drug Human immunoglobulin against tick-borne encephalitis. URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routing-Guid=737b28fb-d8ea-4253-b741-b47ba588c7be (date of request: 14.06.2023)

21. Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001; 345(2):79—84. doi:10.1056/NEJM200107123450201

22. Sharkova V.A., Chernikova A.A., Savina O.G., Sil’vanovich K.I. Features of tick-borne borreliosis in children in Primorye. Natsional’niye prioriteti Rossii. 2016; 4(22):64—68. (In Russ.)

23. Bondarenko A.L., Utenkova E.O., Natural-focal diseases. Kirov state medical academy, 2009:65—109. (in Russ.)

24. Skogman B.H., J. Sjöwall, P.E. Lindgren. The NeBoP score — a clinical prediction test for evaluation of children with Lyme Neuroborreliosis in Europe. BMC Pediatrics. 2015. 15(214).