Aseptic Meningoencephalitis in Slovenia

Prospective Study of the Etiology, Pathogenesis, Clinical Picture and Outcome of Aseptic Meningitis in Slovenia

The main objective of this study is:

• to establish etiology of acute aseptic meningitis/meningoencephalitis in Slovenia
• to assess the clinical course and outcome of tick-borne encephalitis and Lyme neuroborreliosis
• to characterize the inflammatory proteins, gene polymorphisms, and transcriptome profiles in patients with tick-borne encephalitis and Lyme neuroborreliosis

Study Overview

• Status: Unknown
• Conditions: Aseptic Meningitis
• Intervention / Treatment: Drug: symptomatic therapy; Other: questionnaire; Drug: Ceftriaxone or Doxycycline; Drug: Acyclovir

• Study Type: Observational
• Enrollment (Anticipated): 800

Contacts and Locations

• Study Contact: Name: Franc Strle, MD, PhD; Phone Number: +386 1 5222610; Email: franc.strle@kclj.si
• Study Contact Backup: Name: Daša Stupica, MD, PhD; Phone Number: +386 1 5222110; Email: dasa.stupica@kclj.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1525
    • Recruiting
    • UMC Ljubljana, Department of Infectious Diseases
    • Contact: Daša Stupica, MD, PhD; Phone Number: +386 1 522 2110; Email: dasa.stupica@kclj.si
    • Contact: Franc Strle, MD, PhD; Phone Number: +386 1 522 2610; Email: franc.strle@kclj.si
  • Ljubljana, Slovenia, 1525
    • Recruiting
    • Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
    • Contact: Daša Stupica, MD; Phone Number: +386 1 522 2110; Email: dasa.stupica@kclj.si
    • Principal Investigator: Daša Stupica, MD
    • Sub-Investigator: Franc Strle, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

adult patients with acute aseptic meningitis/meningoencephalitis

Description

Inclusion Criteria:

• clinical picture compatible with aseptic meningitis/meningoencephalitis
• age 18 years or older
• clear cerebrospinal fluid on macroscopic examination
• cerebrospinal pleocytosis (> 5 x 106 white blood cells per liter)

Exclusion Criteria:

• younger than 18 years
• pregnant women

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
unidentified aseptic meningitis; Patients with etiologically unidentified aseptic meningitis will be treated with symptomatic therapy and will be asked to complete a questionnaire.	Drug: symptomatic therapy; patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics and parenteral hydration: metamizole, paracetamol, thiethylperazine, saline; Other: questionnaire; Control subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms.
tick-borne encephalitis; Patient with aseptic meningitis in whom serological diagnosis of tick-borne encephalitis will be established. Patients will be treated with symptomatic therapy and will be asked to complete a questionnaire.	Drug: symptomatic therapy; patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics and parenteral hydration: metamizole, paracetamol, thiethylperazine, saline; Other: questionnaire; Control subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms.
Lyme neuroborreliosis; Patients with acute aseptic meningitis in whom Lyme neuroborreliosis will be proven or suspected according to microbiological criteria. Patients will be treated with antibiotic therapy (ceftriaxone or doxycycline) and will be asked to complete a questionnaire.	Drug: symptomatic therapy; patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics and parenteral hydration: metamizole, paracetamol, thiethylperazine, saline; Other: questionnaire; Control subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms.; Drug: Ceftriaxone or Doxycycline; beside symptomatic therapy (metamizole, paracetamol, thiethylperazine, saline), patients with proven or probable Lyme neuroborreliosis will be treated with ceftriaxone 2 g intravenously once daily for 14 days OR doxycycline 100 mg orally twice daily for 14 days
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.	Drug: symptomatic therapy; patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics and parenteral hydration: metamizole, paracetamol, thiethylperazine, saline; Other: questionnaire; Control subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms.
identified aseptic meningitis; Patients with microbiologically identified cause of acute aseptic meningitis/meningoencephalitis will receive symptomatic therapy. If the identified causative agent will be Herpes Simplex Virus or Varicella Zoster Virus, patients will be treated with acyclovir and will be asked to complete a questionnaire.	Drug: symptomatic therapy; patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics and parenteral hydration: metamizole, paracetamol, thiethylperazine, saline; Other: questionnaire; Control subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms.; Drug: Acyclovir; Patients will be treated with intravenous acyclovir 10 mg per kg three times daily for 14 to 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in selected clinical parameters in patients with acute aseptic meningitis/meningoencephalitis	Selected clinical parameters (presence or absence of headache, nausea, vomiting, neurologic symptoms, maximal temperature, etc) in aseptic meningitis/meningoencephalitis patients at enrollment (at admission to hospital) and at follow-up visits: on day 7 or on day of discharge from hospital, on day 14, at 2, 6, and 12 months.	at enrollment and during 12 months follow-up
Changes in selected laboratory parameters in patients with acute aseptic meningitis/meningoencephalitis	Selected laboratory parameters (complete blood count, biochemistry test results) in aseptic meningitis/meningoencephalitis patients at enrollment (at admission to hospital) and at follow-up visits: on day 7 or on day of discharge from hospital, on day 14, at 2, 6, and 12 months.	at enrollment and during 12 months follow-up
Changes in selected microbiologic parameters in patients with acute aseptic meningitis/meningoencephalitis	Selected microbiologic parameters (anti Borrelia burgdorferi immunoglobulin M and G in serum and cerebrospinal fluid results, polymerase chain reaction for enteroviruses, herpes simplex virus type 1 and 2 in cerebrospinal fluid results) in aseptic meningitis/meningoencephalitis patients at enrollment (at admission to hospital) and anti Borrelia burgdorferi immunoglobulin M and G in serum at follow-up visits: at 2, 6, and 12 months.	at enrollment and during 12 months follow-up

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: Harvard University; University of Ljubljana School of Medicine, Slovenia; Slovenian Research Agency
• Investigators: Study Chair: Franc Strle, MD, PhD, UMC Ljubljana; Principal Investigator: Dasa Stupica, MD, PhD, UMC Ljubljana

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: May 27, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Actual): May 4, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: outcome; inflammation; Lyme neuroborreliosis; aseptic meningitis; tick-borne encephalitis
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Meningitis; Meningitis, Aseptic; Anti-Infective Agents; Antiviral Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Ceftriaxone; Doxycycline; Acyclovir
• Other Study ID Numbers: mgt-0614