Clinicaly Manifested Reinfections with Borrelia Burgdorferi Sensu Lato

Data on reinfections with B. burgdorferi sensu lato in humans are scarce; they are limited to case reports and a few small groups of patients, mostly from the USA and less frequently from Europe. In these reports, the clinical manifestation of reinfection was usually erythema migrans and was most often documented after successful treatment of a previous infection (almost always erythema migrans). The clinical manifestations of Lyme disease in reinfection appear to be similar to those of primary infection, but there are no studies on possible differences in serological or immunological responses.

The current study has 3 primary objectives:

• To determine the frequency of clinically detectable reinfections and to identify the circumstances under which they occur;
• To determine possible differences between primary and reinfection in clinical presentation, disease course and outcome, and specific serum antibody response;
• To determine the aetiology of clinically detectable reinfections by comparing Borrelia isolates recovered from the skin of the same patient at primary and reinfection.

Study Overview

• Status: Active, not recruiting
• Conditions: Lyme Borreliosis

Detailed Description

The current study will encompass all patients aged ≥18 years who were treated at the Department of Infectious Diseases, UMC Ljubljana for proven, clinically well-defined Lyme borreliosis in the period 1989 - 2023. Organised data collection in patients with Lyme borreliosis started in 1986 when we established an Outpatient Lyme borreliosis Clinic and introduced uniform approaches to diagnosis, treatment and follow-up of the disease course, thus obtaining a database of high quality clinical and laboratory data in a large number of patients.

The aims:

1. To determine the frequency of clinically detectable reinfections and to identify the circumstances under which they occur (in a cohort of ~15000 European patients with erythema migrans and ~1500 patients with early extradermal or late Lyme disease).
2. To determine possible differences between primary and reinfection in clinical presentation, disease course and outcome, and specific serum antibody response (by comparing clinical findings and serological test results in ~1500 patients who were diagnosed with erythema migrans more than 1 time).
3. To determine the aetiology of clinically detectable reinfections by comparing Borrelia isolates recovered from the skin of the same patient at primary and reinfection (~100 patients and 200 isolates, respectively).

• Study Type: Observational
• Enrollment (Actual): 15000

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1525
    • Department of Infectious Diseases, University Medical Centre Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients diagnosed with definitive Lyme borreliosis at LBOC in the period 35 years (1989 to 2023).

Description

Inclusion Criteria:

• Diagnosis of definitive Lyme borreliosis

Exclusion Criteria:

• /

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The frequency of clinically detectable reinfections and identification of the circumstances under which they occur		At diagnosis
Comparison of the aetiology of clinically detectable reinfections by comparing Borrelia isolates recovered from the skin of the same patient at primary infection and reinfection	We will compare the proportion of positive cultures in patients with a primary cutaneous lesion of EM versus patients with EM due to reinfection.; In the subgroup of patients in whom Borrelia were isolated from skin of primary as well as from EM as a result of reinfection, we will compare Borrelia pairs according to species (determined by PCR) and according to sequencing findings.	The time frame between primary EM and EM as a result of reinfection ranges from 1 month to 35 years.
Differences between primary erythema migrans and erythema migrans as a result of reinfection according to clinical findings, the presence of borrelial antibodies, and Borrelia skin culture results	The objectives of the current study were to assess and compare findings in patients with primary erythema migrans (EM) skin lesion versus those with EM due to reinfection, including: i) clinical findings: age (years), sex, tick bite at the site of EM, duration of EM till diagnosis (days), largest diameter of EM at diagnosis (cm), ring-like EM, number of EM, local symptoms (present or absent), systemic symptoms, underlying chronic illness, abnormalities on physical examination; ii) Borrelia antibody responses (IgM ang IgG determined with chemi-luminescence immunoassay, LIAISON, Diasorin, Saluggia, Italy); iii) Borrelia skin culture positivity rate.	The time frame between primary EM and EM as a result of reinfection ranges from 1 month to 35 years.

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 31, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Reinfection; Lyme borreliosis; Borrelia burgdorferi sensu lato
• Additional Relevant MeSH Terms: Vector Borne Diseases; Pathologic Processes; Disease Attributes; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Tick-Borne Diseases; Recurrence; Reinfection; Lyme Disease; Borrelia Infections
• Other Study ID Numbers: 0120-551/2023/3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Personal, highly confidential data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No