BOrrelia BUrgdorferi IN Children and Adolescents

Lyme borreliosis is one of the most prevalent tick-borne zoonosis in the northern hemisphere. Children with Borrelia (B.) burgdorferi infection present with different clinical stages and related symptoms: an early localized stage is commonly associated with an erythema migrans or a borrelial lymphocytoma. Early disseminated disease include early neuroborreliosis, acute arthritis or carditis. Later disease stages include acrodermatitis chronica atrophicans, late neuroborreliosis or Lyme Arthritis. B. burgdorferi prevalence is highest in Europe and has been increasing in the last decade.

Only limited data about the seroprevalence in children is available. A recently published systematic review and meta-analysis estimated the overall global seroprevalence at 14.5% (95% confidence interval (CI) 12.8-16.3%), and at 7.1% (95% CI 5.1-9.5%) in those <40 years of age (based on 18 studies). Only a few studies included in this systematic review assessed paediatric cohorts in Europe: One study from Germany was published 10 years ago and estimated the seroprevalence at 4.5% (95% CI 4.3-5.4%) in the age group 1-17 years. The seroprevalence was higher in males and in the southern part of Germany, and it increased by 11% and 6% for every year of age in boys and girls, respectively. A study from Sweden looked at 5-year old children and estimated a seroprevalence of 3.2%. More data about the seroprevalence is available in adults with heterogenous findings: recent studies from southern Germany, eastern Slovakia, Jordan, Finland and Romania, reported seroprevalence values of 2.4%, 13%, 11.7%, 3.9% and 7.4% respectively.

More recent estimates of the seroprevalence stratified by age are needed in routine care to enable definition of pre-test probability for this serological test in the clinical evaluation of children with suspected Lyme disease. Since an age dependant relationship is plausible and has been shown in studies, seroprevalence estimates from adults should not be used in children. Knowledge of the seroprevalence of B. burgdorferi in children will help to better differentiate between active Lyme disease and seroprevalence due to previous Borrelia infection without signs of active disease. This is also important for avoiding overtreatment of children without active diseases. Only a small amount of plasma or serum is needed to determine the B. burgdorferi antibodies. Therefore, this study aims to evaluate the seroprevalence B. burgdorferi antibodies from left-over blood samples that were taken for other clinically relevant tests without an additional invasive procedure for the child.

Inclusion criteria

• signed informed general consent
• residence in cantons Basel city, Basel country, Aargau, Solothurn and neighboring areas of France and Germany (Germany postal codes 794x, 795x, 796x, 797x and France postal codes 68480, 68640, 68220, 68330, 68300, 68128, 68730, 68870, 68510, 68130, 68640, 68960, 56890, 68118, 68580, 68680, 68440, 68720)

Exclusion criteria

• case blood is taken repetitively from the same child, only the first sample will be used and the child will only be included in the study once.

Refugees seeking asylum will be excluded. These children will be identified by postal address of the Bundesasylzentrum.

• Children presenting for a diagnosis related to a B. burgdorferi infection will be excluded since including these children would result in an over-estimation of the pre-test prevalence of B. burgdorferi IgG due to a possible selection bias. Diagnosis related to a B. burgdorferi infection will include erythema migrans, borrelial lymphocytoma, early or late neuroborreliosis, acute arthritis or carditis, acrodermatitis chronica atrophicans.
• Children with underlying chronic disease, that potentially affects plasma antibodies will be excluded, these include for example the following conditions:

• known inborn or acquired immunodeficiency syndrome
• Systemic lupus erythematosus
• Children with history of intravenous immunoglobulin treatment in the past 12 months for any reason including Kawasaki Disease, Paediatric Inflammatory Multisystem Syndrome, Immunothrombocytopenia.
• Children after allogenic stem cell transplantation.
• Children with cancer or known chronic hematology disease.
• Children treated with immunosuppressive treatment in the last 6 months including systemic steroids >2 weeks duration (>2mg/kg or >20 mg prednisone equivalent) or immunosuppressive combination treatments (e.g. biological disease modifying antirheumatic drugs (DMARDs) + conventional DMARDs), Rituximab or leflunomide