Fever After Tick Bite Study

NCT03932448 | Withdrawn

• 1 other identifier: FATB Study Group
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a collaboration between Microbiology, SU/Sahlgrenska and the Infectious Diseases clinic at SU/Östra as well as several Infectious Diseases clinics throughout Sweden aiming at improving microbiological diagnostic assays regarding the early identification of tick-borne microorganisms (including as of yet unidentified pathogens) capable of causing human disease using modern diagnostic tools. At the initial study visit (day 0) plasma, serum, urine, saliva, and PBMCs (and tick, if available) will be collected from patients developing fever within two weeks after a tick bite. Additional follow-up samples will be obtained after 9 and 30 days as well as after 6 months. The initial samples will be analyzed using (a) directed multiplex PCR analysis for Tick-Borne Encephalitis (TBE), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella, Tularemia, and Babesiosis in plasma, whole blood and urine, (b) conventional IgM and IgG serology for TBE, (c) "Next Generation Sequencing" (NGS) for the detection of bacterial 16s rRNA as well as unknown viruses, (d) potential biomarkers, and (e) host genetic factors. Among patients where initial sampling indicates the presence of a potential pathogen or in patients developing neurological symptoms, a lumbar puncture will be performed and CSF will be further analyzed. Samples will also be evaluated regarding potential microbiological factors predisposing for severity of infection. The primary objective of the study is to improve diagnostic tools in the initial early phase of infections caused by tick-borne pathogens, especially TBE prior to the affliction of the central nervous system, and to attempt to identify which factors impact the course of infection as it is believed that approximately 75% of infected individuals resolve their infection in this first phase whereas others develop meningoencephalitis with significant subsequent neurological sequelae. Secondary objectives of the study include investigating for the presence of and treating other tick-borne pathogens, setting the stage for coming clinical trials evaluating novel anti-viral therapies for TBE.

Conditions

Tick-Bite; Fever; Tick Fever; Tick-Borne Diseases; Encephalitis, Tick-Borne; Tick Bites

Outcome Measures

Primary Outcomes (3)

• Etiology of fever (≥38°C) developing within 2 weeks after a tick bite.

  Number of participants with detectable Tick-Borne Encephalitis Virus (TBEV), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella burnetii, Tularemia, and/or Babesia infections.

  Up to two weeks after the tick bite.

• Proportion of subjects developing neurological symptoms after a tick bite.

  The proportion of subjects developing neurological symptoms in each of the following etiological categories: Tick-Borne Encephalitis Virus (TBEV), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella burnetii, Tularemia, and/or Babesia.

  Up to six months after the tick bite.

• Proportion of subjects developing other serious, non-neurological symptoms or disease after a tick bite.

  The proportion of subjects developing other serious, non-neurological symptoms or disease in each of the following etiological categories: Tick-Borne Encephalitis Virus (TBEV), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella burnetii, Tularemia, and/or Babesia.

  Up to six months after the tick bite.

Secondary Outcomes (24)

• Impact of body mass index (BMI) of subjects on the risk of development of neurological symptoms.

  Up to six months after the tick bite.

• Impact of waist circumference of subjects on the risk of development of neurological symptoms.

  Up to six months after the tick bite.

• Impact of gender of subjects on the risk of development of neurological symptoms.

  Up to six months after the tick bite.

• Impact of age of subjects on the risk of development of neurological symptoms.

  Up to six months after the tick bite.

• Impact of body mass index of subjects developing other serious, non-neurological symptoms or disease.

  Up to six months after the tick bite.

Interventions

The proposed study is not interventional. OTHER

The proposed study is not interventional. However, if a treatable microorganism is detected, e.g. Borrelia or Anaplasma, suitable therapy, e.g. doxycycline, will be in initiated if appropriate.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Men and women ≥18 years old with documented or a medical history of fever (≥38°C) within 2 weeks after a tick bite.

You may qualify if:

• Written informed consent
• Male and female patients ≥18 years of age
• Medical history of tick bite within past 2 weeks
• Documented or medical history of fever (≥38°C) within past 2 weeks

You may not qualify if:

• Inability or unwillingness to provide informed consent or abide by the requirements of the study
• Presence of urinary tract symptoms
• Presence of non-tick related, infectious agent causing fever, e.g. a respiratory virus
• Presence of other medical, non-infectious cause of fever

Sponsors & Collaborators

• Göteborg University: lead
• Sahlgrenska University Hospital: collaborator
• Vastra Gotaland Region: collaborator

Study Sites (1)

Dept. of Infectious Diseases

Gothenburg, Sweden

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum, urine, saliva, and PBMCs will be sampled and stored.

MeSH Terms

Conditions

Tick Bites; Fever; Anaplasmosis; Tick-Borne Diseases; Encephalitis, Tick-Borne

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Anaplasmataceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vector Borne Diseases; Animal Diseases; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• Martin Lagging, MD, PhD

  Göteborg University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 30, 2019
• Study Start: May 15, 2019
• Primary Completion: April 4, 2025
• Study Completion: April 4, 2025
• Last Updated: April 9, 2025

Record last verified: 2025-04

Locations

SE (1)