Clinical Management of Lyme Disease and Borreliosis

Lyme disease and related borrelioses are multisystem tickborne infections caused by Borrelia burgdorferi sensu lato species. Early recognition of hallmark signs, such as erythema migrans rash and nonspecific flu-like symptoms, is central to prompt therapy. Standard outpatient regimens—typically doxycycline, amoxicillin or cefuroxime axetil—are highly effective in early disease. In disseminated infection, manifestations may include neuroborreliosis, carditis or large-joint arthritis, warranting intravenous ceftriaxone or extended oral therapy. Laboratory diagnosis relies primarily on serological assays, employing a two-tiered approach to balance sensitivity and specificity; however, antibody responses may lag during the initial “window period.” Management of late or chronic presentations often requires multidisciplinary care, combining antimicrobial treatment with rehabilitation and symptom-directed therapies. A subset of patients experience persistent fatigue, musculoskeletal pain or cognitive difficulties despite adequate antibiotic courses, a condition termed post-treatment Lyme disease syndrome. Global variations in Borrelia genospecies and vector ecology contribute to regional differences in clinical presentation, diagnostic performance and treatment protocols. Integration of clinical assessment with improved diagnostics, patient education and surveillance underpins public health strategies to reduce disease burden and optimise outcomes.

Research from Nature Portfolio

Recent studies have introduced a rapid, single-tier serodiagnostic assay compatible with point-of-care settings. This paper-based test employs a multiplexed panel of synthetic peptide epitopes conserved across Borrelia genospecies and integrates a machine learning model to interpret combined IgG and IgM signals. Validation against reference sample sets demonstrated sensitivity and specificity comparable to conventional two-tier testing, offering streamlined workflows, reduced turnaround time and potential for decentralised screening and early initiation of treatment.

Clinical Management of Lyme Disease and Borreliosis publication trend

The graph below shows the total number of articles in clinical management of lyme disease and borreliosis across all publications each year (not limited to Nature Index journals).

Technical terms

Erythema migrans: Expanding annular skin lesion at the tick-bite site, pathognomonic for early Lyme infection.

Two-tiered serologic testing: Sequential use of an initial enzyme immunoassay or immunofluorescence assay followed by confirmatory immunoblotting to detect Borrelia antibodies.

Post-Treatment Lyme Disease Syndrome (PTLDS): Persistence of fatigue, pain and cognitive symptoms for months after completion of recommended antibiotic therapy.

Serological antibody index: Ratio assessing intrathecal production of Borrelia-specific antibodies in cerebrospinal fluid to support neuroborreliosis diagnosis.

Epitope spreading: Diversification of immune responses from microbial determinants to host tissue antigens, contributing to autoimmune pathology.

References

1. Rapid single-tier serodiagnosis of Lyme disease. Nature Communications (2024).
2. Autoimmunity to synovial extracellular matrix proteins in patients with post-infectious lyme arthritis. Journal of Clinical Investigation (2023).
3. Comparison of Lyme Disease in the United States and Europe - Volume 27, Number 8—August 2021 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases (2021).
4. Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States - Volume 22, Number 7—July 2016 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases (2016).