An Intervention in a Primary Healthcare Setting to Reduce Lyme Neuroborreliosis Treatment Delay (NBdelay)

This study evaluates the effect of written and oral information in a primary health care setting on 1) patients referred to specialised examination for Lyme neuroborreliosis, 2) delay from patient symptom debut to treatment for Lyme neuroborreliosis, and 3) number of Borrelia serology tests from primary health care.

Study Overview

• Status: Unknown
• Conditions: Lyme Neuroborreliosis
• Intervention / Treatment: Other: Oral and written information on tick-bites and Lyme disease

Detailed Description

Lyme neuroborreliosis is among the most common neuroinfections in northern Europe. Residual symptoms after treatment are a frequent problem in Lyme neuroborreliosis, and an association between the delay from symptom debut to antibiotic treatment has been established. In a previous study on Funen Island, Denmark, the delay from day of symptom debut to treatment for Lyme neuroborreliosis patients was 24 days. This considerable treatment delay did not change in the 20 years study period.

In the Danish health system, the general practitioners are the first medical professionals to see the majority of patients. They can refer patients to the hospital for further examination if indicated. Many general practitioners use Borrelia burgdorferi antibodies (igM/IgG) as a screening tool when they suspect Lyme disease or see patients with uncharacteristic symptoms. This is unfortunate, as the rash Erythema Migrans, the most common Borreliosis manifestation in Europe, is a clinical diagnosis. Only around 50% of patients have positive antibodies at time of Erythema Migrans diagnosis. Lyme neuroborreliosis is diagnosed based on symptoms and the results from the cerebrospinal fluid, and cannot be diagnosed based on serology, which only delays the time to diagnoses and treatment. The Danish guidelines on Lyme borreliosis therefore discourage general practitioners from using Borrelia serology.

In the before mentioned study from Funen Island, several patients described multiple contacts to their general practitioners, where the symptoms of Lyme neuroborreliosis were not recognized. The cardinal symptom of radicular pain was associated with a longer delay than many of the less common symptoms of Lyme neuroborreliosis.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fredrikke C Knudtzen, MD; Phone Number: 004529178083; Email: fredrikke.christie.knudtzen@rsyd.dk
• Study Contact Backup: Name: Sigurdur Skarphédinsson, MD, PhD; Phone Number: 004565414280; Email: s.skarphedinsson@rsyd.dk

Study Locations

• Denmark
  • Funen
    • Odense, Funen, Denmark, 5000
      • Clinical Center for Emerging and Vectorborne Infections
      • Contact: Sigurdur Skarphedinsson, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Primary care physicians with a postal code in an area of Funen Island with a Lyme neuroborreliosis incidens of > 4.6/100.000
• Patients with a postal address on Funen and a positive Borrelia intrathecal antibody test (diagnostic for lyme neuroborreliosis) performed at the Department of Clinical Microbiology, Odense University Hospital from January 1st 2017 - December 31st 2020
• A Borrelia IgM/IgG serology ordered from Primary Health Care and performed at the Department of Clinical Microbiology, Odense University Hospital from January 1st 2017 - December 31st 2020

Exclusion Criteria:

• Primary care physicians with a postal code in an area of Funen Island with a Lyme neuroborreliosis incidens of < 4.7/100.000

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teaching arm; The Primary Health Care physicians getting oral and written information on tick-bites and Lyme disease with focus on Lyme neuroborreliosis.	Other: Oral and written information on tick-bites and Lyme disease; See under study arm descriptions
No Intervention: Passive arm; The Primary Health Care physicians that does not get contacted with an offer to receive oral and written information.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days from symptom debut to beginning of antibiotic treatment for Lyme neuroborreliosis	Number of days from debut of neurological symptoms to beginning of antibiotic treatment for Lyme neuroborreliosis.	0-90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of yearly referred Lyme patients	Number of yearly referred patients in the two study arms in the two years before the intervention (2017+2018) and after the intervention (2019+2020).	Up to 4 years (1460 days).
Number of Borrelia antibody tests in peripheral blood ordered by primary care physicians	Number of Borrelia antibody tests in peripheral blood ordered by primary Health care physicians in the two study arms in the two years before (2017+2018) and after (2019 + 2020) the intervention.	Up to 4 years (1460 days).

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Principal Investigator: Fredrikke C Knudtzen, MD, Department of Infectious Diseases, Odense University Hospital

Publications and helpful links

General Publications

• Knudtzen FC, Andersen NS, Jensen TG, Skarphedinsson S. Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995-2014: A Retrospective Cohort Study in Denmark. Clin Infect Dis. 2017 Oct 16;65(9):1489-1495. doi: 10.1093/cid/cix568.
• Knudtzen FC, Jensen TG, Andersen NS, Johansen IS, Hovius JW, Skarphedinsson S. An intervention in general practice to improve the management of Lyme borreliosis in Denmark. Eur J Public Health. 2022 Jun 1;32(3):436-442. doi: 10.1093/eurpub/ckac013.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: primary health care; treatment delay
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Central Nervous System Bacterial Infections; Tick-Borne Diseases; Borrelia Infections; Spirochaetales Infections; Lyme Disease; Lyme Neuroborreliosis
• Other Study ID Numbers: FCKPhDProject4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to Denmark´s strict data-sharing Laws, data will not be shared after completion of study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No