LYME DISEASE: FROM THE HISTORY OF DISCOVERY TO MODERN CHALLENGES AND PROSPECTS FOR OVERCOMING
DOI:
https://doi.org/10.11603/1681-2727.2025.4.15758Keywords:
Lyme disease, Lyme borreliosis, Borrelia, biofilms, treatment, vaccinesAbstract
SUMMARY. The article highlights key historical facts about Lyme disease (LD, syn. Lyme borreliosis) – the most common infection worldwide, primarily transmitted by ticks of the genus Ixodes, and caused by spirochetes of the Borrelia burgdorferi sensu lato group. Information about it dates back thousands of years, but its official recognition as a distinct nosological form only occurred in the 1970s in the USA, following an investigation of arthritis cases in Lyme (USA) and the subsequent identification of the causative agent by Willy Burgdorfer. Although, clinical manifestations, in particular the characteristic rash – erythema migrans, were described by European physicians long before this. It is emphasized that in Europe and Asia, the disease is caused by different species of Borrelia, each having a tropism for specific organs or systems: B. burgdorferi s. s. – for joints, B. garinii – for the nervous system, B. afzelii – for the skin.
Lyme disease is a global issue. According to a meta-analysis, nearly 15% of the world’s population is infected, and its prevalence continues to rise, including in Ukraine, where over 55,000 cases have been registered since 2000. Diagnostics is limited by the capabilities of existing serological tests, so new rapid and highly accurate methods, such as the one-step AI-integrated test from the University of California, are considered promising.
A significant challenge is the therapy for chronic forms, specifically post-treatment Lyme disease syndrome (PTLDS), which develops in a significant part of patients and is associated with the ability of Borrelia bacteria to form antibiotic-resistant “persistent” cells in biofilms. In this regard, scientists are actively exploring new therapeutic approaches using antibiotics such as piperacillin and repurposed drugs (disulfiram), often in combinations. An important direction is also the development of vaccines, including the one currently in development (VLA15) and an innovative mRNA vaccine aimed not at the pathogen but at the proteins of the tick vector itself, which could potentially protect against a range of tick-borne infections. The article contains a number of recommendations regarding the necessity for the official recognition of LD as an occupational disease in Ukraine, increasing funding for scientific research, employing combined approaches to the treatment of chronic forms, and implementing the “One Health” principle.
References
Johns Hopkins Medicine Lyme Disease Research Center. (n.d.). Lyme disease. https://www.hopkinslyme.org/lyme-disease/
Skar, G. L., Blum, M. A., & Simonsen, K. A. (2025). Lyme disease. У StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK431066/
Андрейчин, М. А., Корда, М. М., Вишневська, Н. Ю., та ін. (2024). Кліщові інфекції: посібник (М. А. Андрейчин, ред.). ТНМУ.
Андрейчин, М. А., Корда, М. М., Шкільна, М. І., Івахів, О. Л., та ін. (2021). Лайм-бореліоз: монографія (М. А. Андрейчин & М. М. Корда, ред.). ТНМУ.
Bay Area Lyme Foundation. (n.d.). History of Lyme disease. Retrieved November 24, 2025, from https://www.bayarealyme.org/about-lyme/history-lyme-disease/
Insect Shield. (n.d.). The discovery of Lyme disease: How it was identified & studied. Retrieved November 24, 2025, from https://www.insectshield.com/blogs/blog/the-discovery-of-lyme-disease-how-it-was-identified-studied
Arvid Afzelius. (n.d.). Arvid Afzelius SPA3.jpg [Photograph]. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Arvid_Afzelius_SPA3.jpg
Quammen, D. (2012). Spillover: Animal infections and the next human pandemic. W. W. Norton & Co.
The Pharmacologist. (n.d.). Lyme disease. https://thepharmacologist.org/lyme-disease/
Steere, A. C. (2024). Lyme arthritis: A 50-year journey. The Journal of Infectious Diseases, 230(Supplement_1), S1–S10. https://doi.org/10.1093/infdis/jiae126 DOI: https://doi.org/10.1093/infdis/jiae126
Piller, C. (2016, October 12). The “Swiss Agent”: Long-forgotten research unearths new mystery about Lyme disease. STAT. https://www.statnews.com/2016/10/12/swiss-agent-lyme-disease-mystery/
Rosa, P. A., Tilly, K., & Stewart, P. E. (2005). The burgeoning molecular genetics of the Lyme disease spirochaete. Nature Reviews Microbiology, 3(2), 129–143. https://doi.org/10.1038/nrmicro1086 DOI: https://doi.org/10.1038/nrmicro1086
Cleveland, D. W., Anderson, C. C., & Brissette, C. A. (2023). Borrelia miyamotoi: A comprehensive review. Pathogens, 12(2), 267. https://doi.org/10.3390/pathogens12020267 DOI: https://doi.org/10.3390/pathogens12020267
Strnad, M., Rudenko, N., & Rego, R. O. M. (2023). Pathogenicity and virulence of Borrelia burgdorferi. Virulence, 14(1), 2265015. https://doi.org/10.1080/21505594.2023.2265015 DOI: https://doi.org/10.1080/21505594.2023.2265015
Trevisan, G., Cinco, M., Trevisini, S., di Meo, N., Ruscio, M., Forgione, P., & Bonin, S. (2021). Borreliae Part 2: Borrelia Relapsing Fever Group and Unclassified Borrelia. Biology, 10(11), 1117. https://doi.org/10.3390/biology10111117 DOI: https://doi.org/10.3390/biology10111117
Іnstitut Pasteur. (н.д.). Amédée Borrel, intuitif. https://www.pasteur.fr/fr/institut-pasteur/notre-histoire/amedee-borrel-intuitif
Андрейчин, М. А., Завіднюк, Н. Г., Ничик, Н. А., & Йосик, Я. І. (2021). Нові вірусні кліщові інфекції в XXI ст. та їх епідемічна потенція. Інфекційні хвороби, (4), 4–13. DOI: https://doi.org/10.11603/1681-2727.2021.4.12833
Dworkin, M. S., Schwan, T. G., Anderson, D. E., Jr, & Borchardt, S. M. (2008). Tick-borne relapsing fever. Infectious Disease Clinics of North America, 22(3), 449–viii. https://doi.org/10.1016/j.idc.2008.03.006 DOI: https://doi.org/10.1016/j.idc.2008.03.006
Stewart, P. (2023, 31 січня). Relapsing Fever: Modern Lessons from an Ancient Disease. ASM. https://asm.org/articles/2023/relapsing-fever-a-two-thousand-year-history
Oppler, Z. J., O’Keeffe, K. R., McCoy, K. D., & Brisson, D. (2021). Evolutionary genetics of Borrelia. Current Issues in Molecular Biology, 42, 97–112. https://doi.org/10.21775/cimb.042.097 DOI: https://doi.org/10.21775/cimb.042.097
Cirkovic, V., Veinovic, G., Stankovic, D., Mihaljica, D., Sukara, R., & Tomanovic, S. (2024). Evolutionary dynamics and geographical dispersal of Borrelia lusitaniae. Frontiers in Microbiology, 15, 1330914. https://doi.org/10.3389/fmicb.2024.1330914 DOI: https://doi.org/10.3389/fmicb.2024.1330914
Андрейчин, М. А., Юзьків, Т. І., Гук, М. Т., Шкільна, М. І., Івахів, О. Л., Ішук, І. С., & Завіднюк, Н. Г. (2024). Виявлення лайм-бореліозу, бартонельозу та Епштейна-Барр вірусної інфекції у пацієнтів із лімфаденопатією, жителів Тернопільщини. Інфекційні хвороби, (2), 30–39. DOI: https://doi.org/10.11603/1681-2727.2024.2.14610
Paster, B. J., Dewhirst, F. E., Weisburg, W. G., Tordoff, L. A., Fraser, G. J., Hespell, R. B., Stanton, T. B., Zablen, L., Mandelco, L., & Woese, C. R. (1991). Phylogenetic analysis of the spirochetes. Journal of Bacteriology, 173(19), 6101–6109. https://doi.org/10.1128/jb.173.19.6101-6109.1991 DOI: https://doi.org/10.1128/jb.173.19.6101-6109.1991
Bourgeois, J. S., & Hu, L. T. (2024). Hitchhiker’s Guide to Borrelia burgdorferi. Journal of Bacteriology, 206(9), e0011624. https://doi.org/10.1128/jb.00116-24 DOI: https://doi.org/10.1128/jb.00116-24
Steinbrink, A., Brugger, K., Margos, G., Kraiczy, P., & Klimpel, S. (2022). The evolving story of Borrelia burgdorferi sensu lato transmission in Europe. Parasitology Research, 121(3), 781–803. https://doi.org/10.1007/s00436-022-07445-3 DOI: https://doi.org/10.1007/s00436-022-07445-3
Čorak, N., Anniko, S., Daschkin-Steinborn, C., Krey, V., Koska, S.,
Futo, M., Široki, T., Woichansky, I., Opašić, L., Kifer, D., Tušar, A., Maxeiner, H.-G., Domazet-Lošo, M., Nicolaus, C., & Domazet-Lošo, T. (2023). Pleomorphic variants of Borreliella (syn. Borrelia) burgdorferi express evolutionary distinct transcriptomes. International Journal of Molecular Sciences, 24(6), 5594. https://doi.org/10.3390/ijms24065594 DOI: https://doi.org/10.3390/ijms24065594
Coburn, J., Garcia, B., Hu, L. T., Jewett, M. W., Kraiczy, P., Norris, S. J., & Skare, J. (2021). Lyme Disease Pathogenesis. Current Issues in Molecular Biology, 42, 473–518. https://doi.org/10.21775/cimb.042.473 DOI: https://doi.org/10.21775/cimb.042.473
Schwartz, I., Margos, G., Casjens, S. R., Qiu, W. G., & Eggers, C. H. (2021). Multipartite Genome of Lyme Disease Borrelia: Structure, Variation and Prophages. Current Issues in Molecular Biology, 42, 409–454. https://doi.org/10.21775/cimb.042.409 DOI: https://doi.org/10.21775/cimb.042.409
Brissette, C. A., & Gaultney, R. A. (2014). That’s my story, and I’m sticking to it–an update on B. burgdorferi adhesins. Frontiers in Cellular and Infection Microbiology, 4, 41. https://doi.org/10.3389/fcimb.2014.00041 DOI: https://doi.org/10.3389/fcimb.2014.00041
Cabello, F. C., Godfrey, H. P., Bugrysheva, J. V., & Newman, S. A. (2017). Sleeper cells: The stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle. Environmental Microbiology, 19(10), 3846–3862. https://doi.org/10.1111/1462-2920.13897 DOI: https://doi.org/10.1111/1462-2920.13897
Bernard, Q., Thakur, M., Smith, A. A., Kitsou, C., Yang, X., & Pal, U. (2019). Borrelia burgdorferi protein interactions critical for microbial persistence in mammals. Cellular Microbiology, 21(2), e12885. https://doi.org/10.1111/cmi.12885 DOI: https://doi.org/10.1111/cmi.12885
Burn, L., Pilz, A., Vyse, A., Gutiérrez Rabá, A. V., Angulo, F. J., Tran, T. M. P., Fletcher, M. A., Gessner, B. D., Moïsi, J. C., & Stark, J. H. (2023). Seroprevalence of Lyme Borreliosis in Europe: Results from a Systematic Literature Review (2005-2020). Vector Borne and Zoonotic Diseases (Larchmont, N.Y.), 23(4), 195–220. https://doi.org/10.1089/vbz.2022.0069 DOI: https://doi.org/10.1089/vbz.2022.0069
Ducharme, J. (2022, June 14). Nearly 15% of people worldwide have had Lyme disease, study says. TIME. https://time.com/6187215/lyme-disease-more-common/
Bay Area Lyme Foundation. (2024). Lyme disease facts and statistics. Retrieved from https://www.bayarealyme.org/about-lyme/lyme-disease-facts-statistics/
Shkilna, M. I., Shah, J. S., Andreychyn, M. A., Cruz, I. D., Ivakhiv, O. L., Korda, M. M., … Zaporozhan, S. Y. (2020). Лайм-бореліоз та кліщові поворотні гарячки у лісівників Тернопільщини. Інфекційні хвороби, (2), 22–30. https://doi.org/10.11603/1681-2727.2020.2.11283 DOI: https://doi.org/10.11603/1681-2727.2020.2.11283
Shkilna, M. I. (2018). Частота інфікування збудниками ХЛ лісників Закарпатської області та їх обізнаність щодо даної інфекційної хвороби. Південноукраїнський медичний науковий журнал, (19), 184–188.
Andreychyn, M., Pańczuk, A., Shkilna, M., Tokarska-Rodak, M., Korda, M., Kozioł-Montewka, M., & Klishch, I. (2017). Epidemiological situation of Lyme borreliosis and diagnosis standards in Poland and Ukraine. Health Problems of Civilization, 11(2), 190–194. https://www.termedia.pl/EPIDEMIOLOGICAL-SITUATION-OF-LYME-BORRELIOSIS-AND-DIAGNOSIS-STANDARDS-IN-POLAND-AND-UKRAINE,99,30333,1,1.html DOI: https://doi.org/10.5114/hpc.2017.69020
Shkilna, M. I., Shkilna, L. A., & Hrebeniuk, L. V. (2024). Lyme disease in Ukraine in 2000-2023. Wiadomości Lekarskie, 77(2), 401–405. https://pubmed.ncbi.nlm.nih.gov/40101003/
Kolomiiets, V. (2025, May 20). В Україні зафіксували понад 330 випадків захворювання на бореліоз за три місяці 2025 року [Over 330 cases of borreliosis recorded in Ukraine in three months of 2025]. Hromadske. https://hromadske.ua/zdorovya/245069-v-ukrayini-zafiksuvaly-ponad-330-vypadkiv-zakhvoriuvannia-na-borelioz-za-try-misiatsi-2025-roku
Центр громадського здоров’я МОЗ України. (2024, April 24). Обережно, кліщі: як захиститися та що робити, якщо помітили на собі кліща. https://phc.org.ua/news/oberezhno-klischi-yak-zakhistitisya-ta-scho-robiti-yakscho-pomitili-na-sobi-klischa
VoxUkraine. (2020, March 18). Public Health Fakes: Lyme disease is not treated in Poltava. Issue 108. https://voxukraine.org/en/public-health-fakes-lyme-disease-is-not-treated-in-poltava-issue-108
Centers for Disease Control and Prevention. (2024, May). Workshop summary: Prioritizing zoonotic diseases for multisectoral One Health collaboration in Ukraine. https://www.cdc.gov/one-health/media/pdfs/2024/05/Ukraine-508.pdf
Міністерство охорони здоров’я України. (2024). Клінічна настанова «Хвороба Лайма (Лайм-бореліоз)». Державний Експертний Центр МОЗ України. https://www.dec.gov.ua/wp-content/uploads/2024/09/kn_2024_hl.pdf
Державний експертний центр МОЗ України. (2024). Стандарт медичної допомоги «Хвороба Лайма (Лайм-бореліоз)» [SMD 1623 HL]. https://www.dec.gov.ua/wp-content/uploads/2024/09/smd_1623_hl.pdf
Penn Medicine. (н.д.). Lyme Disease – Symptoms and Causes. https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/lyme-disease
Centers for Disease Control and Prevention. (1980). Lyme disease–Connecticut. Morbidity and Mortality Weekly Report, 29(20), 241–242. https://www.cdc.gov/mmwr/preview/mmwrhtml/00001024.htm
Center for Infectious Disease Research and Policy. (2024, September 3). FDA clears new Lyme disease test. CIDRAP. https://www.cidrap.umn.edu/lyme-disease/fda-clears-new-lyme-disease-test
ID-FISH Technology, Inc. (2024, September 4). Lyme ImmunoBlot receives FDA clearance. IGeneX. https://igenex.com/press-release/lyme-immunoblot-receives-fda-clearance/
University of California, Los Angeles. (2024, August 26). Lyme disease early detection could get boost from simpler, faster testing technology. UCLA Newsroom. https://newsroom.ucla.edu/releases/lyme-disease-early-detection-simpler-faster-testing-technology
Andreychyn, M., Korda, M., Kopcha, V., Shkilna, M., Komorovsky, R. (2025). Thermographic Assessment of Lyme Borreliosis Without Erythema Migrans. Infection and Drug Resistance. 18, 4741-4748. DOI: https://doi.org/10.2147/IDR.S540248
Tufts University. (2025, April 7). Alternative approach to Lyme disease vaccine development shows promise in pre-clinical models. Tufts Now. https://now.tufts.edu/2025/04/07/alternative-approach-lyme-disease-vaccine-development-shows-promise-pre-clinical-models
Vax-Before-Travel. (н.д.). Lyme Disease Vaccine (VLA15). https://www.vax-before-travel.com/vaccines/lyme-disease-vaccine-vla15
Yale University. (2025, March 26). Yale researchers advance work in diagnosing and preventing tick-borne diseases. Yale School of Medicine. https://medicine.yale.edu/news-article/yale-researchers-advance-work-in-diagnosing-and-preventing-tickborne-diseases/
Yale School of Medicine. (н.д.). Lyme Disease. https://medicine.yale.edu/internal-medicine/raci/rheumatology/research/lyme/
Skar, G. L., Blum, M. A., & Simonsen, K. A. (2025). Lyme disease. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK431066/
Center for Infectious Disease Research and Policy. (2025, May 13). New recommendations seek treatments for post-Lyme disease condition. CIDRAP. https://www.cidrap.umn.edu/lyme-disease/new-recommendations-seek-treatments-post-lyme-disease-condition
Johns Hopkins University. (2019, April 23). Three-antibiotic cocktail clears “persister” Lyme bacteria in mouse study. Johns Hopkins Bloomberg School of Public Health. https://publichealth.jhu.edu/2019/three-antibiotic-cocktail-clears-persister-lyme-bacteria-in-mouse-study
Cairns, V. E. (2022, December 9). Lyme disease bacteria can form structures that confer resistance to antibiotics and protection against host defences [Letter to the editor]. British Journal of General Practice, 73(728), 133–134. https://bjgp.org/content/lyme-disease-bacteria-can-form-structures-confer-resistance-antibiotics-and-protection
Sharma, D., Misba, L., & Khan, A. U. (2019). Antibiotics against biofilm: An emerging battleground in microbial communities. Antimicrobial Resistance and Infection Control, 8(76). https://doi.org/10.1186/s13756-019-0533-3 DOI: https://doi.org/10.1186/s13756-019-0533-3
Parkinson, J. (2025, April 29). Pneumonia antibiotic cures Lyme disease at doses 100 times lower than standard treatment. Contagion Live. https://www.contagionlive.com/view/pneumonia-antibiotic-cures-lyme-disease-at-doses-100-times-lower-than-standard-treatment
Reynolds, W. (2025, April 25). Taking the bite out of Lyme disease. Northwestern Now. https://news.northwestern.edu/stories/2025/04/taking-the-bite-out-of-lyme-disease/
The British Deer Society. (2025, May 7). Lyme disease: New treatments and prevention. https://bds.org/2025/05/07/lyme-disease-new-treatments-and-prevention/
Lyme Wellness Initiative. (н.д.). Managing symptoms. Harvard Health Publishing. https://lyme.health.harvard.edu/managing-symptoms/
Sandoiu, A. (2018, May 7). Lyme disease treatment: 2 herbal compounds may beat antibiotics. Medical News Today. https://www.medicalnewstoday.com/articles/lyme-disease-treatment-2-herbal-compounds-may-beat-antibiotics
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