Central Nervous System Infections in Denmark (DASGIB)

Danish Study Group of Infections of the Brain: A Nationwide Prospective Observational Cohort Study of All Central Nervous System Infections in Adults at Departments of Infectious Diseases in Denmark

The Danish Study Group of Infections of the Brain is a collaboration between all departments of infectious diseases in Denmark. The investigators aim to monitor epidemiological trends in central nervous system (CNS) infections by a prospective registration of clinical characteristics and outcome of all adult (>17 years of age) patients with community-acquired CNS infections diagnosed and/or treated at departments of infectious diseases in Denmark since 1st of January 2015.

Study Overview

• Status: Recruiting
• Conditions: Encephalitis; Central Nervous System Infections; Meningitis; Bacterial Meningitis; Lyme Disease; Brain Abscess; Aseptic Meningitis; Neurosyphilis; Viral Meningitis; Neuroborreliosis; Tertiary Syphilis; Cerebral Abscess
• Intervention / Treatment: Other: Community-acquired CNS infections

Detailed Description

The investigators include data on diagnosis at admission, symptoms and signs on admission, character and timing of diagnostic work-up and treatment and outcome assessed by the Glasgow Outcome Score (GOS).

Diagnostic work-up and treatment is left at the discretion of the local physician and therefore not standardised

In general any symptoms/deficits should only be listed if they are 'new' to the patient, e.g. a known palsy of the facial nerve should not be listed as a new relevant finding at admission. On the other hand, worsening of a known neurological deficit should be listed under signs in the given instrument (bacterial meningitis, encephalitis, neuroborreliosis etc). Likewise, for outcome only changes in pre-morbid conditions should be listed including place of residence, functional status, neurological deficits etc.

Time of admission is obtained in prioritized order from the ambulance charts or notifications of arrival by secretaries or nurses in the emergency departments. Timing of lumbar puncture and cranial imaging is extracted from the electronic records at the departments of biochemistry or radiology while timing of antibiotic therapy for meningitis is identified in electronic medication systems. Time to lumbar puncture, cranial imaging and antibiotic therapy is calculated as time from arrival at hospital to each of the above events.

Quality control of case enrollment is ensured by ad hoc case-to-case discussions and at study group meetings 2-3 times a year

To ensure completeness of reported CNS infections annual searches of selected International Classification of Diseases version 10 (ICD-10) codes are performed in local administrative databases at each department:

A17 A32.1 A32.7 A39.0 A52.1-52.3 A69.2 (neuroborreliosis) A83 A84 A85 A87 A89 B00.3-00.4 B01.0-01.1 B02.0-02.0 B582 B451 B375 G00 G01 G02 G03 G04 G05 G06 G07

• Study Type: Observational
• Enrollment (Anticipated): 1900

Contacts and Locations

• Study Contact: Name: Jacob Bodilsen, MD; Phone Number: +45 99663920; Email: jacob.bodilsen@rn.dk
• Study Contact Backup: Name: Henrik Nielsen, Professor; Phone Number: +45 99663920; Email: henrik.nielsen@rn.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Recruiting
    • Department of Infectious Diseases, Aalborg University Hospital
    • Contact: Jacob Bodilsen, MD; Phone Number: +45 99663920; Email: jacob.bodilsen@rn.dk
    • Contact: Henrik Nielsen, Professor; Phone Number: +45 99663920; Email: henrik.nielsen@rn.dk
  • Aarhus, Denmark, 8000
    • Recruiting
    • Department of Infectious Diseases, Aarhus University Hospital Skejby
    • Contact: Merete Storgaard, MD; Email: merestor@rm.dk
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Infectious Diseases, Rigshospitalet
    • Contact: Jannik Helweg-Larsen, MD; Email: Jannik.Helweg-Larsen@regionh.dk
  • Copenhagen, Denmark
    • Recruiting
    • Herlev-Gentofte Hospital
    • Contact: Hans Rudolf Lüttichau, MD
  • Hillerød, Denmark, 3400
    • Recruiting
    • Department of Pulmonary and Infectious Diseases, Nordsjællands Hospital Hillerød
    • Contact: Christian T Brandt, MD; Email: christian.thomas.brandt01@regionh.dk
  • Hvidovre, Denmark, 2650
    • Recruiting
    • Department of Infectious Diseases, Hvidovre Hospital
    • Contact: Birgitte R Hansen, MD; Email: birgitte.roende.hansen@regionh.dk
    • Contact: Hanse
  • Odense, Denmark, 5100
    • Recruiting
    • Department of Infectious Diseases, Odense University Hospital
    • Contact: Lykke Larsen, MD; Email: lykke.larsen@rsyd.dk
  • Roskilde, Denmark, 4000
    • Recruiting
    • Department of Pulmonary and Infectious Diseases, Sjællands University Hospital Roskilde
    • Contact: Lothar Wiese, MD; Email: low@regionsjaelland.dk

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

All patients above 17 years of age are prospectively included in the DASGIB cohort by the principal investigator at each site if they have a clinical presentation suggestive of CNS infection (e.g. any combination of neck stiffness, fever, headache or altered mental status) and either (i) Positive CSF culture or positive bacterial/viral DNA-based analysis for (community-acquired) pathogens in the CSF or (ii) a positive blood culture and CSF leukocytes >10/mL or (iii) CSF leukocytes > 10/mL without any alternative diagnoses more likely to explain the patients' conditions. Exceptions apply for brain abscess, neurosyphilis and neuroborreliosis and exact definitions of included CNS infections are provided below.

We exclude patients with hospital-acquired CNS infections as defined by the Centers for Disease Control and Prevention (Garner et al, Am J Infect Control, 1988), or an implanted neurosurgical device.

Description

Definitions of central nervous system infections:

For all cases with unproven aetiologies no alternative diagnosis than CNS infection is thought more likely after completed multidisciplinary diagnostic work-up.

Viral meningitis inclusion criteria

- All patients have to have a clinical presentation consistent with non-bacterial meningitis (e.g. headache, neck stiffness, photo- or phonophobia, fever)

and

Cerebrospinal fluid leukocytes>10 cells/ml

Patients with viral meningitis with undetermined pathogen have to have:

• CSF leukocytes> 10/mL and no other more probable diagnosis assessed by the local investigator.

In case of doubt, patients are discussed with the DASGIB secretary and chair or at meetings.

Bacterial meningitis inclusion criteria - All patients have to have a clinical presentation consistent with bacterial meningitis (e.g. headache, neck stiffness, fever, altered mental status)

and

Proven bacterial aetiology (CSF or blood culture/DNA based technology or antigen tests)

Patients with bacterial meningitis in whom the bacteria cannot not be cultured or identified by DNA-based technologies have to have:

- CSF leukocytes> 10/mL and no other more probable diagnosis assessed by the local investigator.

In case of doubt, patients are discussed with the DASGIB secretary and chair or at meetings.

Encephalitis inclusion criteria - All patients have to have a clinical presentation consistent with encephalitis (e.g. headache, fever, focal neurological deficit, altered mental status >24 hours) as defined by the International Encephalitis Consortium (Venkatesan A et al., Clin Infect Dis 2013; doi:10.1093/cid/cit458.).

Encephalitis exclusion criteria

- We exclude cases of proven or suspected autoimmune encephalitis.

Primary brain abscess inclusion criteria

- All patient have a clinical presentation consistent with brain abscess (e.g. headache, focal neurological deficit, mass lesion on cranial imaging)

and

- Proven microbiological aetiology by culture/DNA-based technology from pus from brain abscess or blood or CSF

or

- Aspiration of pus from the brain abscess

or

- Response to antimicrobial treatment

or

- Tumour ruled out

or

- Tumour thought less probable than abscess on MRI using diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences.

Lyme neuroborreliosis inclusion criteria

- A clinical presentation consistent with neuroborreliosis (e.g. radiculopathy)

and

- CSF pleocytosis>10 leukocytes/mL

and

- Positive intrathecal B.burgdorferi antibody production index.

Neurosyphilis inclusion criteria - A clinical presentation consistent with neurosyphilis (e.g. 'encephalitis-like symptoms', dementia, ocular or otogenic syphilis)

and either

- Positive syphilis serology in serum combined with CSF leukocytes>10/mL

or

- CSF syphilis antibodies.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence	Incidence of CNS infections in the adult population (>17 years of age) in Denmark.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow Outcome Scale score	A five tier assessment of functional status, 1=Death, 2=vegetative state, 3=dependency on others for daily activities, 4=some sequelae but able to live independently, 5= No or only minor sequelae	One month after end of treatment
Glasgow Outcome Scale score for viral meningitis	A five tier assessment of functional status, 1=Death, 2=vegetative state, 3=dependency on others for daily activities, 4=some sequelae but able to live independently, 5= No or only minor sequelae	30 days
Glasgow Outcome Scale score for bacterial meningitis	A five tier assessment of functional status, 1=Death, 2=vegetative state, 3=dependency on others for daily activities, 4=some sequelae but able to live independently, 5= No or only minor sequelae	30 days
Glasgow Outcome Scale score for encephalitis	A five tier assessment of functional status, 1=Death, 2=vegetative state, 3=dependency on others for daily activities, 4=some sequelae but able to live independently, 5= No or only minor sequelae	30 days
Glasgow Outcome Scale score for neurosyphilis	A five tier assessment of functional status, 1=Death, 2=vegetative state, 3=dependency on others for daily activities, 4=some sequelae but able to live independently, 5= No or only minor sequelae	2 weeks
Glasgow Outcome Scale score for neuroborreliosis	A five tier assessment of functional status, 1=Death, 2=vegetative state, 3=dependency on others for daily activities, 4=some sequelae but able to live independently, 5= No or only minor sequelae	2 weeks
Glasgow Outcome Scale score for brain abscess	A five tier assessment of functional status, 1=Death, 2=vegetative state, 3=dependency on others for daily activities, 4=some sequelae but able to live independently, 5= No or only minor sequelae	8 weeks

Collaborators and Investigators

• Sponsor: Aalborg University Hospital
• Collaborators: Danish Study Group of Infections of the Brain
• Investigators: Study Chair: Henrik Nielsen, Professor, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: January 25, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Meningitis; Epidemiology; Encephalitis; Lyme disease; Central Nervous System Infections; Neurosyphilis; Nationwide prospective observational cohort study; Brain abscess; Neuroborreliosis; Tertiary syphilis
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Sexually Transmitted Diseases; Inflammation; Disease Attributes; Central Nervous System Viral Diseases; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Suppuration; Central Nervous System Bacterial Infections; Sexually Transmitted Diseases, Bacterial; Tick-Borne Diseases; Borrelia Infections; Spirochaetales Infections; Treponemal Infections; Encephalitis; Infections; Communicable Diseases; Abscess; Meningitis; Lyme Disease; Syphilis; Central Nervous System Infections; Meningitis, Bacterial; Meningitis, Viral; Meningitis, Aseptic; Brain Abscess; Neurosyphilis
• Other Study ID Numbers: DASGIB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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