Borrelia infection after tick bite Lyme disease
Conditions
Interventions
None listed
Sponsors
RIVM
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria are partly dependent on the patient group and the route of inclusion. Patients included through Tekenradar.nl: - are 5 yrs and older. (there are no age restrictions for patients included through clinical Lyme centers) EM patients included through Tekenradar.nl: - report an EM at Tekenradar.nl with a diameter larger than 5 cm and that has been present for less than 3 months; - have a confirmed (typical or atypical) EM diagnosed by their GP; - have not yet started treatment for the EM or started maximum 4 days earlier at the moment of inclusion; Confirmed Lyme patients: - have a confirmed diagnosis of early or late Lyme borreliosis; - have not yet started treatment at the moment of inclusion, or, if included via Tekenradar.nl at most 4 days before inclusion, or, if included via Clinical Lyme Centers, at most 1 week before inclusion. Unconfirmed Lyme patients included through the Clinical Lyme Centers: - symptoms that are present at the time of inclusion and have persisted for more than 6 months, such as myalgia and arthralgia, neuralgia, concentration disorders and cognitive disturbances, with or without fatigue. - have a history of an unconfirmed suspicion for Lyme disease based on a positive result of a non-recommended diagnostic test OR onset of disease symptoms (as described above) that have started within one month after a documented tick bite; -have a negative serological test for Borrelia spp.
Exclusion criteria
Exclusion criteria: Exclusion criteria are partly dependent on patient group and route of inclusion. All patients (and/or their parents/guardians): - are unable to give informed consent or do not have a thorough command of the Dutch language. Confirmed Lyme patients included through Tekenradar.nl: -started treatment more than 4 days before inclusion. Confirmed Lyme patients included through the Clinical Lyme Centers: - started treatment more than one week before inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main study endpoint is whom of the confirmed Lyme patients develop persisting symptoms, based upon the validated symptom and disability questionnaires. The main study parameters are all microbiological, immunological, genetic, clinical, cognitive-behavioral, and epidemiological parameters measured during follow-up of these confirmed Lyme patients, that possibly predict development of such persisting symptoms, i.e.: -Quantitative PCRs for Borrelia on skin and blood samples -typed Borrelia cultures from skin samples, and minimal inhibitory concentrations (MICs) for relevant antibiotics, as well as molecular typing of cultivated Borrelia burgdorferi subspecies -PCRs for other tick-borne pathogens on skin and blood samples -Antibiotic trough levels in blood samples collected during standard antibiotic treatment in all clinical Lyme center patients -Borrelia C6 ELISA (IgM/IgG; Immunetics) and both a IgM and IgG immunoblot (Mikrogen) and serology for other tick-borne pathogens in blood samples. -Cellular immune responses: ex-vivo stimulation of whole blood and (fresh) PBMCs - collected before and after antibiotic treatment with Borrelia and other stimuli. - Four cellular tests (Spirofind® (Oxford Immunotec), QuantiFERON Lyme® (QIAGEN), the EliSpot assay developed by AID (Autoimmun Diagnostika GmbH) in Strassberg, Germany) and the LTT-MELISA (developed by Invitalabs in Neuss, Germany) before and after antibiotic treatment. The tests are based on the ex vivo stimulation of blood (whole blood or PBMCs) with Borrelia according to the manufacturers protocol to examine the specific cellular immune reactivity to B. burgdorferi s.l and to assess whether test results are related to clinical outcome. -Gene expression arrays: we will perform micro-arrays (Illumina) using RNA from frozen peripheral blood mononuclear cells (PBMCs) * collected before and after antibiotic treatment * that are ex-vivo stimulated with Borrelia and other stimuli. -Humoral | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study parameters are all microbiological, immunological, genetic, clinical, cognitive-behavioral, and epidemiological parameters as described above * but now in the unconfirmed Lyme patients with existing persisting symptoms * that are possibly similar to the determinants of such persisting symptoms that were identified in the confirmed Lyme patients. | — |
Countries
Netherlands
Outcome results
None listed