PhD Project: LYME Neuroborreliosis IN Children: From Understanding Pathogenesis To Precise Diag

PhD Project: LYME NEUROBORRELIOSIS IN CHILDREN: from understanding pathogenesis to precise diagnosis and treatment

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The Pediatric Infectious Disease Research Zurich (PIDRZ) group at the University Children's Hospital is a small but growing international research group in one of Europe's leading centers for pediatric medicine. Our group is interested in understanding the epidemiology, microbiology, and immunology of pediatric infectious diseases, like Lyme disease (LD) and community‑acquired pneumonia (CAP), as well as developing novel diagnostic tools for clinical care.

Our group has strong links with clinics and is actively involved in clinical trials and epidemiological studies. Our work contributes towards the global goal of preventing the emergence of antimicrobial resistance and developing novel treatments and diagnostic tools for infectious diseases.

Lyme disease (LD) is caused by several genospecies of the spirochete Borrelia burgdorferi (Bb) and is increasing worldwide. The clinical presentation of LD in children varies, but mainly includes skin manifestations, Lyme neuroborreliosis (LNB), and Lyme arthritis. LNB accounts for 3–15% of LD cases and is the second most common presentation of LD in children. Overall, identifying LNB in children can be very challenging, which often results in delayed or missed diagnosis and treatment.

Antibiotic treatment is essential to prevent progression to the late stages of LNB, which can result in serious, persistent sequelae.

To investigate the pathogenesis of LNB in children, we initiated the prospective BRILLIANT study (Borrelia B‑cell diagnostics) of LD in children aged 0–17 years. Since 1 April 2024, we have enrolled 102 children presenting with a differential diagnosis of LD (cases), as well as 22 previously healthy patients (controls). In close collaboration with the Institute of Medical Microbiology (IMM UZH), we have established several advanced laboratory protocols for Bb detection, including Bb microscopy, Bb culture out of clinical samples, and a multiplex quantitative PCR (qPCR) assay for Bb DNA detection in clinical samples and cultures.

This project aims to improve the diagnosis of LNB in children by identifying new microbiological and immunological markers of Bb infection. Current diagnostic procedures fail to detect a significant proportion of LNB cases. We hypothesize that additional laboratory tests can confirm Bb infection in patients who are otherwise misdiagnosed. Our objectives are threefold, spanning clinical, microbiological, and immunological research:

• 1) Clinical: Define clinical features of LNB and evaluate the current diagnostic approach
• 2) Diagnostic: Identify further microbiological and immunological approaches for LNB diagnosis
• 3) Exploratory:
  Explore Bb genotypes and virulence factors in relation to disease phenotype

Your main task will be to manage the prospective clinical study of LD in children (BRILLIANT study) in order to draw conclusions on patho‑mechanisms of LD and identify new microbiological and immunological markers of Bb infection.

• Management of the BRILLIANT study: overseeing patient recruitment, scheduling follow‑ups, sample processing and storage, extracting data from hospital record, managing study database (REDCap).
• Establishment of Bb cultures from clinical isolates:
  Further protocol optimization by improving qPCR screening procedure and culture conditions. Evaluation of usefulness of culture and qPCR for clinical diagnosis.
• Phenotype the immune response in LD and LNB:
  Analyze preliminary data, design experiments to further investigate relevant immune cell subsets using flow cytometry, bead‑based cytokine/chemokine assay or scRNA‑seq approaches.
• Identify genotypes of Bb clinical isolates:
  Perform WGS on new Bb clinical isolates and identify genotypes and virulence factors associated with LD and LNB clinical subgroups.

• Writing scientific manuscripts (in English)
• Presentation of results at internal meetings and training events
• Participation in national and international conferences…