Tick-borne Encephalitis and Borrelial Antibodies in Serum

Antibiotic Therapy for Patients With Tick-borne Encephalitis and Borrelial Antibodies in Serum

In Slovenia, tick-borne encephalitis and Lyme borreliosis are both endemic diseases with high incidence rates and they are both transmitted by a bite of infected Ixodes ricinus tick. In clinical practice, tick-borne encephalitis is confirmed by demonstration of tick-borne encephalitis antibodies in serum of a patient with compatible clinical presentation and cerebrospinal pleocytosis. Patients with Lyme meningitis or meningoradiculitis also have cerebrospinal pleocytosis, however the presence of borrelial antibodies in serum does not attest Lyme neuroborreliosis. Patients with tick-borne encephalitis and positive borrelial antibodies in serum, but not fulfilling criteria for Lyme neuroborreliosis, are often being treated with antibiotics in several European countries due to the possibility of double infection. The investigators hypothesise that such patients do not benefit from antibiotics. Such an approach may appear safe regarding the possibility of borrelial infection, however it can also be associated with detrimental consequences such as antibiotic related adverse reactions, negative epidemiological impact on bacterial resistance, and intravenous catheter related complications.

Study Overview

• Status: Recruiting
• Conditions: Tick Borne Encephalitis
• Intervention / Treatment: Drug: Doxycycline; Drug: Symptomatic therapy; Other: Questionnaire

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maša Velušček, MD; Phone Number: +38631332904; Email: masa.veluscek@kclj.si
• Study Contact Backup: Name: Daša Stupica, MD PhD; Phone Number: +386 31 689324; Email: dasa.stupica@kclj.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia
    • Recruiting
    • University Medical Center Ljubljana
    • Contact: Daša Stupica, MD, PhD; Phone Number: +386 31 689 324; Email: dasa.stupica@kclj.si
    • Contact: Maša Velušček, MD; Phone Number: +386 1 522 21 10; Email: masa.veluscek@kclj.si

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 years or older
• clinical picture compatible with tick-borne encephalitis,
• clear cerebrospinal fluid,
• cerebrospinal pleocytosis (leucocytes in cerebrospinal fluid >5 x 106/)L,
• positive serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against tick-borne encephalitis virus,
• positive serum IgG antibodies against Lyme borreliae.

Exclusion Criteria:

• isolation of B.burgdorferi sensu lato from cerebrospinal fluid,
• positive intrathecal borrelial antibody production index,
• seroconversion of borrelial IgG antibodies,
• presence of erythema migrans and/or borrelial lymphocytoma in the last month,
• Bannwarth syndrome.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Doxycycline, Doxy®; Beside symptomatic therapy, patients will receive oral doxycycline 100 mg (Doxy®) twice daily. Patients will answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.	Drug: Doxycycline; Beside symptomatic therapy, patients will receive oral Doxycycline 100 mg, Doxy® twice daily.; Drug: Symptomatic therapy; Patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics, and parenteral hydration: metamizole, Analgin®, paracetamol, Lekadol®, thiethylperazine, Kytril®, saline. Questionnaire Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.; Other: Questionnaire; Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.
Other: No antibiotics; Patients will receive symptomatic therapy (paracetamol, Lekadol®, granisetron, Kytril®, metamizol, Analgin®, parenteral hydration with saline). Patients will answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.	Drug: Symptomatic therapy; Patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics, and parenteral hydration: metamizole, Analgin®, paracetamol, Lekadol®, thiethylperazine, Kytril®, saline. Questionnaire Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.; Other: Questionnaire; Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.
Other: Healthy controls; Patients will be asked to refer a spouse to serve as a control. If unmarried they will be asked to refer a family member or a friend of +/- 5 years to serve as a control. Control subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.	Other: Questionnaire; Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with objective manifestations of Lyme borreliosis	At each visit physical examination will be performed and clinical signs indicating objective manifestations of Lyme borreliosis, such as erythema migrans, will be searched for.	one year
Frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia		one year

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: University of Ljubljana School of Medicine, Slovenia
• Investigators: Principal Investigator: Daša Stupica, MD PhD, University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Tick-Borne Diseases; Neuroinflammatory Diseases; Encephalitis; Encephalitis, Tick-Borne; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: TBE-BB prospect

Drug and device information, study documents

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