MODERN VIEWS ON THE EPIDEMIOLOGY, ETIOLOGY, AND CLINICAL PRESENTATION OF LYME DISEASE
Abstract
Relevance. Lyme disease (LD) is the most prevalent tick-borne infectious disease and poses a significant health risk in countries in the northern hemisphere. Unlike other zoonoses, LD causes significant medical, social, and economic damage due to its high incidence and the severity of its clinical course. Complications can lead to disability and necessitate long-term dispensary observation and costly examinations.
Objective: To find out the current scientific views on the peculiarities of epidemiology, clinical course of Lyme disease, and mechanisms leading to multiorgan damage.
Materials and methods. We analyzed scientific articles and studies on Lyme disease, covered in the databases PubMed, Medline, Cochrane Library, Center for Public Health of the Ministry of Health of Ukraine, Karger, RKI, Onlinelibrary, CDC, Ecdc. Particular attention was paid to studies that investigated the etiology, prevalence, and clinical features of LD. The articles published from 2016 to 2025 were analyzed using the methods of systematic literature review, comparative analysis of clinical outcomes, and meta-analysis to ensure the relevance and accuracy of the conclusions.
Results. Surveillance of LD in Europe is carried out in only 25 out of 52 countries (48.1%) and is hampered by differences in national standards and reporting agreements.
The introduction of standardized case definitions in surveillance systems in Europe will be important to establish the true incidence of LD and to track its burden in relation to future interventions, including vaccination. To this end, a review of national surveillance strategies is urgently needed, with wider adoption of standardized case definitions to optimize their utility before a vaccine is available.
The development of new methods of disease risk control and prediction for better targeted control interventions requires an understanding of pathogen and disease course, so it is desirable to create maps of the distribution of Ixodes ticks and the extent of their infection.
In order to confirm the diagnosis of LD in patients with peripheral or central nervous system disorders, it is recommended to detect antibodies in the blood serum rather than PCR, since PCR should be performed using cerebrospinal fluid.
When diagnosing heart rhythm disorders in endemic areas, patients should be examined to exclude or confirm the disease as a cause of carditis.
In patients with LD and high fever or characteristic laboratory abnormalities, the possibility of coinfection with A. phagocytophilum and/or B. microti in endemic areas should be excluded and other infectious agents should be considered.
Downloads
References
Bobe JR, Jutras BL, Horn EJ, Embers ME, Bailey A, Moritz RL, Zhang Y, Soloski MJ, Ostfeld RS, Marconi RT, Aucott J, Ma'ayan A, Keesing F, Lewis K, Ben Mamoun C, Rebman AW, McClune ME, Breitschwerdt EB, Reddy PJ, Maggi R, Yang F, Nemser B, Ozcan A, Garner O, Di Carlo D, Ballard Z, Joung HA, Garcia-Romeu A, Griffiths RR, Baumgarth N, Fallon BA. Recent progress in lyme disease and remaining challenges. Front Med [Internet]. 2021;8:666554. Available from: https://doi.org/10.3389/fmed.2021.666554
Madison-Antenucci S, Kramer LD, Gebhardt LL, Kauffman E. Emerging Tick-Borne Diseases. Clin Microbiol Rev [Internet]. 2020;33(2). Available from: https://doi.org/10.1128/cmr.00083-18
Boyer PH, Grillon A, Jaulhac B, Velay A, Schramm F, Talagrand-Reboul E. Other Ixodes-Borne Diseases. In: Hunfeld K, Gray J, editors. Lyme borreliosis [Internet]. [place unknown]: Springer, Cham; 2022. p. 193-234. Available from: https://doi.org/10.1007/978-3-030-93680-8_9
Rochlin I, Toledo A. Emerging tick-borne pathogens of public health importance: a mini-review. J Med Microbiol [Internet]. 2020;69(6):781-91. Available from: https://doi.org/10.1099/jmm.0.001206
Barbour AG, Benach JL. Discovery of the lyme disease agent. MBio [Internet]. 2019;10(5). Available from: https://doi.org/10.1128/mbio.02166-19
Coburn J, Garcia B, Hu LT, Jewett MW, Kraiczy P, Norris SJ, Skare J. Lyme disease pathogenesis. Curr Mol Biol [Internet]. 2022:473-518. Available from: https://doi.org/10.21775/cimb.042.473
Doskaliuk B, Zimba O. Borrelia burgdorferi and autoimmune mechanisms: implications for mimicry, misdiagnosis, and mismanagement in Lyme disease and autoimmune disorders. Rheumatol Int [Internet]. 2024. Available from: https://doi.org/10.1007/s00296-024-05580-x
Rebman AW, Aucott JN. Post-treatment lyme disease as a model for persistent symptoms in lyme disease. Front Med [Internet]. 2020;7. Available from: https://doi.org/10.3389/fmed.2020.00057
Lantos PM, Rumbaugh J, Bockenstedt LK, Falck‐Ytter YT, Aguero‐Rosenfeld ME, Auwaerter PG, Baldwin K, Bannuru RR, Belani KK, Bowie WR, Branda JA, Clifford DB, DiMario FJ, Halperin JJ, Krause PJ, Lavergne V, Liang MH, Meissner HC, Nigrovic LE, Nocton J, Osani MC, Pruitt AA, Rips J, Rosenfeld LE, Savoy ML, Sood SK, Steere AC, Strle F, Sundel R, Tsao J, Vaysbrot EE, Wormser GP, Zemel LS. Clinical practice guidelines by the Infectious Diseases Dociety of America (IDSA), American academy of neurology (AAN), and American college of rheumatology (ACR): 2020 guidelines for the prevention, diagnosis, and treatment of lyme disease. Arthritis Care Amp Res [Internet]. 2020;73(1):1-9. Available from: https://doi.org/10.1002/acr.24495
Pustijanac E, Buršić M, Millotti G, Paliaga P, Iveša N, Cvek M. Tick-Borne bacterial diseases in europe: threats to public health. Eur J Clin Microbiol Amp Infect Dis [Internet]. 2024 Apr. Available from: https://doi.org/10.1007/s10096-024-04836-5
Gorban VA, Bilova NA, Poleva JL, Huslystyi AO, Kotovych OV, Hunko SO. The influence of forest vegetation on the physical properties of chernozems in the steppe zone of Ukraine. Biosyst Divers [Internet]. 2024 Jan 31;32(1):3-11. Available from: https://doi.org/10.15421/012401
Eisen L. Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks. Ticks Tick Borne Dis [Internet]. 2018 Mar;9(3):535-42. Available from: https://doi.org/10.1016/j.ttbdis.2018.01.002
Kilpatrick AM, Dobson AD, Levi T, Salkeld DJ, Swei A, Ginsberg HS, Kjemtrup A, Padgett KA, Jensen PM, Fish D, Ogden NH, Diuk-Wasser MA. Lyme disease ecology in a changing world: consensus, uncertainty and critical gaps for improving control. Philos Trans R Soc B [Internet]. 2017 Apr;372(1722):20160117. Available from: https://doi.org/10.1098/rstb.2016.0117
Burn L, Tran TM, Pilz A, Vyse A, Fletcher MA, Angulo FJ, Gessner BD, Moïsi JC, Jodar L, Stark JH. Incidence of lyme borreliosis in europe from national surveillance systems (2005–2020). Borne Dis [Internet]. 2023 Apr;23(4):156-71. Available from: https://doi.org/10.1089/vbz.2022.0071
Andreichyn MA, Shkilna MI, Huk MT. Profilaktyka klishchovykh infektsii: suchasnyi stan i perspektyva / Prevention of tick-borne infections: current status and prospects Infekts khvoroby / Infectious Diseases [Internet]. 2023 Jan;(3):4-11. Available from: https://doi.org/10.11603/1681-2727.2022.3.13471
Panychev VO, Andreichyn MA, Kravchuk YuA, Dautov AH, Dubrovska AM. Zarazhenist klishchiv u lisovykh biotopakh Ternopilskoi oblasti / Infestation of ticks in forest biotopes of Ternopil region. Infekts. Khvoroby / Infectious Diseases [Internet]. 2021;(2):44-52. Available from: https://doi.org/10.11603/1681-2727.2021.2.12164
Strnad M, Vancová M, Rego RO. Borreliа (Borreliella) burgdorferi. Microbiolodgy [Internet]. 2024. Available from: https://doi.org/10.1016/j.tim.2024.09.002
Pritt BS, Mead PS, Hoang Johnson DK, Neitzel DF, Respicio-Kingry LB, Davis JP, Schiffman E, Sloan LM, Schriefer ME, Replogle AJ, Paskewitz SM, Ray JA, Bjork J, Steward CR, Deedon A, Lee X, Kingry LC, Miller TK, Feist MA, Petersen JM. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis [Internet]. 2016;16(5):556-64. Available from: https://doi.org/10.1016/S1473-3099(15)00464-8
Ostfeld RS, Brunner JL. Climate change and Ixodes tick-borne diseases of humans. Philos Trans R Soc B [Internet]. 2015;370(1665):20140051. Available from: https://doi.org/10.1098/RSTB.2014.0051
Marques AR, Strle F, Wormser GP. Comparison of Lyme disease in the United States and Europe. Emerg Infect Dis [Internet]. 2021;27(8):2017-24. Available from: https://doi.org/10.3201/eid2708.204763
Shkilna MI. Etiolohichna struktura hostroho laim-boreliozu za vydamy zbudnyka. / Etiological structure of acute lyme borreliosis by types of pathogen. . Infekts. Khvoroby / Infectious Diseases [Internet]. 2019;(1):43-9. Available from: https://doi.org/10.11603/1681-2727.2019.1.9942
Cerar T, Strle F, Stupica D, Ruzic-Sabljic E, McHugh G, Steere AC, Strle K. Differences in Genotype, Clinical Features, and Inflammatory Potential of Borrelia burgdorferi sensu stricto Strains from Europe and the United States. Emerg Infect Dis [Internet]. 2016;22(5):818-27. Available from: https://doi.org/10.3201/eid2205.151806
Gocko X, Lenormand C, Lemogne C, Bouiller K, Gehanno JF, Rabaud C, Perrot S, Eldin C, de Broucker T, Roblot F, Toubiana J, Sellal F, Vuillemet F, Sordet C, Fantin B, Lina G, Sobas C, Jaulhac B, Figoni J, Chirouze C, Hansmann Y, Hentgen V, Caumes E, Dieudonné M, Picone O, Bodaghi B, Gangneux JP, Degeilh B, Partouche H, Saunier A, Sotto A, Raffetin A, Monsuez JJ, Michel C, Boulanger N, Cathebras P, Tattevin P. Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies. Med Mal Infect [Internet]. 2019 Aug;49(5):296-317. Available from: https://doi.org/10.1016/j.medmal.2019.05.006
Yoshinari NH, Bonoldi VL, Bonin S, Falkingham E, Trevisan G. The current state of knowledge on baggio–yoshinari syndrome (brazilian lyme disease-like illness): chronological presentation of historical and scientific events observed over the last 30 years. Pathogens [Internet]. 2022;11(8):889. Available from: https://doi.org/10.3390/pathogens11080889
Abdelmaseih R, Ashraf B, Abdelmasih R, Dunn S, Nasser H. Southern Tick-Associated Rash Illness: Florida's Lyme disease variant. Cureus [Internet]. 2021 May 28. Available from: https://doi.org/10.7759/cureus.15306
Lin YP, Lin YP, Tan X, Caine JA, Castellanos M, Chaconas G, Coburn J, Leong JM. Strain-specific joint invasion and colonization by Lyme disease spirochetes is promoted by outer surface protein C. PLOS Pathog [Internet]. 2020;16(5). Available from: https://doi.org/10.1371/JOURNAL.PPAT.1008516
Stose LL. Lyme disease – borrelia burgdorferi. In: Samples OM, McCommon GW, Terrill TH, Stose LL, editors. The one health model as applied to zoonotic diseases [Internet]. [place unknown]: John Wiley & Sons, Inc.; 2025. Available from: https://doi.org/10.1002/9781119985853.ch3.20
Cardenas-de la Garza J, De la Cruz-Valadez E, Ocampo-Candiani JE. Clinical spectrum of Lyme disease. Eur J Clin Microbiol Infect Dis [Internet]. 2019;38:201-8. Available from: https://doi.org/10.1007/s10096-018-3417-1
García-Souto F, Coronel-Perez IM, Escudero-Ordoñez J. Erythema migrans. Med Clin (Engl Ed) [Internet]. 2021 Jan 22;156(2):103. Available from: https://doi.org/10.1016/j.medcli.2019.10.001
Schotthoefer A, Green C, Dempsey GE. The spectrum of erythema migrans in early lyme disease: can we improve its recognition? Cureus [Internet]. 2022 Oct 25;14(10):e30673. Available from: https://doi.org/10.7759/cureus.30673
Buettcher M. Borrelial lymphocytoma presentations of the ear. Arch Dis Child [Internet]. 2022;107:490. Available from: https://doi.org/10.1136/archdischild-2021-322652
Myszkowska-Torz A, Tomaszewski M, Kotowski M, Witczak C, Figlerowicz M, Mazur-Melewska K. Cutaneous manifestations of lyme borreliosis in children – a case series and review. Life [Internet]. 2023;13(1):72. Available from: https://doi.org/10.3390/life13010072
Chemych M, Lutai I. Khvoroba Laima. Suchasnyi stan problemy (ohliad literatury) / Lyme disease. Current status of the problem (literature review). Skhidnoukr. med. zhurn. / Eastern Ukrainian Medical Journal. [Internet]. 2020;8(2):230-41. Available from: https://doi.org/10.21272/eumj.2020;8(2):230-241
Bruinsma R, Zomer T, Skogman BE. Clinical manifestations of Lyme neuroborreliosis in children: a review. Eur J Pediatr [Internet]. 2023;182:1965-76. Available from: https://doi.org/10.1007/s00431-023-04811-w
Summer G, Rupprecht T. Neurologic manifestations of lyme borreliosis. Rev Neurol [Internet]. 2019;175(9-10):417-9. Available from: https://doi.org/10.1016/j.neurol.2019.07.012
Smith A, Oertle J, Warren D, Prato D. Chronic lyme disease complex and its commonly undiagnosed primary and secondary co-infections. Open J Med Microbiol [Internet]. 2015;5:143-58. Available from: https://doi.org/10.4236/ojmm.2015.53018
Gadila S, Rosoklija G, Dwork A, Fallon B, Embers M. Detecting borrelia spirochetes: a case study with validation among the autopsy specimens. Front Neurol [Internet]. 2021. Available from: https://doi.org/10.3389/fneur.2021.628045
Donta ST, States LJ, Adams WA, Bankhead T, Baumgarth N, Embers ME, Lochhead RB, Stevenson B. Report of the pathogenesis and pathophysiology of lyme disease subcommittee of the HHS tick borne disease working group. Front Med [Internet]. 2021 Jun. Available from: https://doi.org/10.3389/fmed.2021.643235
Arvikar SL, Steere AC. Diagnosis and treatment of Lyme arthritis. Infect Dis Clin N Am [Internet]. 2015;29(2):269-80. Available from: https://doi.org/10.1016/J.IDC.2015.02.004
Steere AC. Treatment of lyme arthritis. J Rheumatol [Internet]. 2019 Aug;46(8):871-3. Available from: https://doi.org/10.3899/jrheum.190320
Shen RV, McCarthy CA. Cardiac manifestations of lyme disease. Infect Dis Clin N Am [Internet]. 2022;36(3):553-61. Available from: https://doi.org/10.1016/j.idc.2022.03.001
Radesich C, Del Mestre E, Medo K, Vitrella G, Manca P, Chiatto M, Castrichini M, Sinagra G. Lyme carditis: from pathophysiology to clinical management. Pathogens [Internet]. 2022;11(5):582. Available from: https://doi.org/10.3390/pathogens11050582
Yeung C, Baranchuk A. Diagnosis and treatment of lyme carditis: JACC review topic of the week. J Am Coll Cardiol [Internet]. 2019;73(6):717-26. Available from: https://doi.org/10.1016/J.JACC.2018.11.035
Kostić TE. Manifestations of Lyme carditis. Int J Cardiol [Internet]. 2017;232:24-32. Available from: https://doi.org/10.1016/j.ijcard.2016.12.169
Esfandiari N, Beebe-Peat T, Quinlan A, Wagner B, Wark T, Lobel R. Lyme carditis complicated by polymorphic ventricular tachycardia and cardiac arrest: a case report. J Investig Med High Impact Case Rep [Internet]. 2022;10. Available from: https://doi.org/10.1177/23247096221098333
Fishe JN, Marchese RF, Callahan JM. Lyme myocarditis presenting as chest pain in an adolescent girl. Pediatr Emerg Care [Internet]. 2016 Jul;32(7):459-61. Available from: https://doi.org/10.1097/pec.0000000000000654
Eldin C, Raffetin A, Bouiller K, Hansmann Y, Roblot F, Raoult D, Parola P. Review of European and American guidelines for the diagnosis of Lyme borreliosis. Med Mal Infect [Internet]. 2019;49(2):121-32. Available from: https://doi.org/10.1016/J.MEDMAL.2018.11.011
Standart medychnoi dopomohy “Khvoroba Laima” / Medical Care Standard for Lyme Disease [Internet]; 2024. Available from: https://www.dec.gov.ua/wp-content/uploads/2024/09/smd_1623_hl.pdf
Khvoroba Laima. klinichna nastanova, zasnovana na dokazakh / Lyme disease. Clinical guidelines based on evidence. [Internet]; 2024. Available from: https://www.dec.gov.ua/wp-content/uploads/2024/09/kn_2024_hl.pdf
Nations U. Transforming our world: the 2030 agenda for sustainable development [Internet]; 2015. Available from: https://sdgs.un.org/2030agenda

This work is licensed under a Creative Commons Attribution 4.0 International License.

























