BRILLIANT: Borrelia B-cell Diagnostics
Study Details
Study Description
Brief Summary
We propose a single center, prospective observational study in children with Lyme disease (LD), the Borrelia B-cell diagnostics (BRILLIANT) study, to assess the immune response against Borrelia burgdorferi (Bb) with the following main objectives:
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Development of a new test method for diagnosis of early LD There is an urgent unmet clinical need for a better diagnostic tool for early LD, as the current standard two-tier testing has low sensitivity in recently infected patients and may show false positive results in recovered patients due to long-term persistence of antibodies against Bb.
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Extensive analysis of the immune response in LD The immune response in LD is not well understood. Large-scale studies assessing the detailed immune cell subsets/phenotypes present in blood, CSF, or synovial fluid of LD patients with respective manifestations are lacking.
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Isolation and characterization of causative Bb species Existing literature suggests that Bb genospecies and/or genotypes may determine virulence and manifestations, but large-scale studies assessing Bb genospecies/genotypes in different manifestation of LD are lacking.
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Collection of clinical data about symptoms, severity, routine laboratory and diagnostic test results, treatment, and outcome of LD This will allow us to include more patients into our (retrospective) analysis of clinical characteristics and serological profiles of LD.
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Biobanking samples for analysis in the future.
Project population
Inclusion criteria: Children, 0-17 years of age, at University Children's Hospital Zurich:
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LD differential diagnosis cohort: Patients presenting at the ED with differential diagnosis of LD according to the treating physician.
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Control cohort: Previously healthy patients (HC) with routine blood investigations presenting at the ED or PID outpatient department
Exclusion criteria: Primary or secondary immunodeficiency.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Background:
Lyme disease (LD) is the most common tick born disease in Europe. It is caused by an infection with several genospecies of the spirochaetal bacteria Borrelia burgdorferi (Bb).
Although classical disease manifestations are well-known, the clinical presentation in children is often variable and inconclusive, which results in delayed diagnosis and treatment.
Methods/design:
We are conducting an observational cohort study in children with LD. Study site is the University Children's Hospital Zurich. 502 patients will be enrolled. Children from 0-17 years of age presenting with signs and symptoms suspicious for LD are included in the study. Previously healthy children with routine blood investigation are enrolled as healthy controls. Patients will be excluded in cases of primary or secondary immunodeficiency.
Clinical and routine laboratory data regarding course and outcome, as well as venous blood samples are collected at first hospital contact and follow up visits (FUP). FUPs are scheduled at 28 days, 3 months and 6 months after hospital admission. Cerebrospinal fluid (CSF) and synovial fluid (SF) will be collected for the study only if sampling is indicated due to diagnostic or therapeutic reasons.
Primary objectives are to assess Bb-specific ASCs in blood using ELISpot assay, in order to develop new diagnostic tool for early LD. In addition, we will examine immune response in patients with various LD manifestations using flow cytometry, ELISA assay, and ELISpot assay. Finally, we will perform whole genome sequencing of causative Bb-species isolated from patients to investigate potential differences in virulence and associations with clinical presentations.
Discussion:
This single-centre, observational cohort study will improve our understanding of immunological response in LD in children. It will also provide new information about the virulence of distinct LD causing Bb-genospecies and will test a new approach in the diagnosis of early LD.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| LD_Diff_Diag LD differential diagnosis cohort: Patients presenting at the ED with differential diagnosis of LD according to the treating physician |
Procedure: venous blood puncture
Venous blood puncture performed at first hospital contact, and at 28 days, 3 month, and 6 months after hospital admission.
Lumbar puncture and joint puncture for the study will be performed if it is indicated due to diagnostic or therapeutic reasons.
Other Names:
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| Heathy_Control Previously healthy patients (HC) with routine blood investigations presenting at the ED or PID outpatient department |
Procedure: venous blood puncture
Venous blood puncture performed at first hospital contact, and at 28 days, 3 month, and 6 months after hospital admission.
Lumbar puncture and joint puncture for the study will be performed if it is indicated due to diagnostic or therapeutic reasons.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Development of a new test method for diagnosis of early LD [10/2023 - 10/2026]
Outcome: Bb-specific ASCs (IgM, IgG, IgA) in blood Method: ELISpot assay, flow cytometry Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
Secondary Outcome Measures
- High resolution analysis of the immune response in LD [10/2023 - 10/2028]
Outcome: Analysis of the immune response in LNB in blood, CSF, and SF innate and adaptive immune cell subsets IgM, IgG, and IgA antibodies (total and Bb-specific) Bb-specific INF-gamma response chemokines and cytokines Method: flow cytometry Enzyme-linked immunosorbant assay (ELISA) ELISpot assay ELISA, Bio-Plex 200 system (Bio-Rad) Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
- Isolation and characterization of causative Bb species [10/2023 - 10/2028]
Outcome: Bb species identified in blood, CSF, and SF Method: Culture, genotype- and genospecies-specific PCR, whole genome sequencing (WGS) of Bb Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients presenting at the ED with differential diagnosis of LD according to the treating physician
Exclusion Criteria:
- Patients will be excluded in cases of primary or secondary immunodeficiency
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chidren's Hospital Zurich | Zürich | Switzerland |
Sponsors and Collaborators
- University Children's Hospital, Zurich
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
Investigators
- Principal Investigator: Patrick Meyer, MD PhD, Division of infectious diseases Univesity Children's Hospital Zurich
- Study Director: Christoph Berger, PhD, Division of infectious diseases Univesity Children's Hospital Zurich
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2023-00528