# A rare case of breakthrough tick-borne encephalitis in early adolescence after vaccination with four doses of TBE vaccine

## TL;DR

A teenager who was fully vaccinated against tick-borne encephalitis (TBE) still developed a severe case, highlighting the challenges of diagnosing and treating breakthrough infections.

## Contribution

This case highlights the delayed IgM response and early IgG response to NS1 in cerebrospinal fluid as diagnostic markers for breakthrough TBE.

## Key findings

- Breakthrough TBE can occur despite full vaccination, with delayed TBEV IgM and early IgG NS1 response in cerebrospinal fluid.
- Immunomodulatory treatment was used due to suspected autoimmune encephalitis, but the cause of severe outcome remains unclear.
- MRI showed persistent brain changes years after the initial infection.

## Abstract

Tick-borne encephalitis (TBE) is an emerging infectious disease with effective vaccines available. However, breakthrough TBE occurs in previously vaccinated patients, a condition that is difficult to diagnose. We report a case of a previously healthy teenager who fell severely ill and was hospitalized for three months despite full TBE vaccination. Initial fever and headache progressed during the first week to encephalitis and, since autoimmune encephalitis was suspected, treatment with immunoglobulins and methylprednisolone was given. This case demonstrates the delayed response of TBEV IgM, typical for breakthrough infection, and the diagnostic value of an early IgG response to the non-structural protein 1 (NS1) in the cerebrospinal fluid. It also discusses the diagnostic challenges, the phenomenon of serological cross reactions with other flaviviruses, and the potential effect of immunomodulatory treatment in TBE. Serial MRI examinations of the brain were performed and confirmed persistent changes years after onset. The reasons for the severe outcome are discussed, but remain unclear.