Fatal European subtype tick-borne encephalitis in a fully vaccinated immunocompetent child: a case report with viral sequencing

BACKGROUND: Tick-borne encephalitis (TBE) is considered to have a more favourable outcome in children compared to adults, and death from TBE in children is infrequent. Severe cases are primarily seen in immunocompromised or unvaccinated individuals. We report a case of TBE with a fatal outcome in a previously healthy child. The case is unique in several aspects: an atypical clinical presentation without fever or biphasic illness, and a fulminant course despite full vaccination and absence of known predisposing risk factors for severe disease. In addition, sequencing revealed the TBE virus (TBEV) as a previously identified European subtype covered by the vaccine. CASE PRESENTATION: The 9-year-old child had an acute onset of headache but no fever. On the fourth day, the child was lethargic but responded adequately to questions and was sent home after assessment at the Emergency Department (ED). The next day, the child returned to the ED, where four generalised tonic-clonic seizures were observed. Analysis of cerebrospinal fluid showed lymphocytic pleocytosis consistent with viral encephalitis. A computed tomography scan showed general oedema of the brain, hydrocephalus, and incipient herniation. Intracranial pressure remained extremely high despite hyperventilation with mechanical ventilation, mannitol, thiopental, bilateral ventricular drainage, and methylprednisolone. Four-vessel angiography on day 10 showed a picture consistent with brain death. No immunodeficiency was identified by whole-genome sequencing. The aetiology of the encephalitis was determined by detection of IgG antibodies against the TBEV non-structural protein 1 (NS1) antigen (which is not present in existing vaccines) and by post-mortem PCR of brain tissue. A previously unpublished tiled amplicon method was used to recover the TBEV genome, which was assigned to the European subtype (TBEV-Eur). CONCLUSIONS: This case report highlights the risk of delayed diagnosis when atypical symptoms are present. TBE should be considered when investigating causes of headaches in highly endemic areas, even if the patient lacks fever or is vaccinated. Further, since children may also develop very severe disease, it is important to vaccinate children against TBE. Finally, analysis of antibodies to TBE NS1 antigen is a valuable tool to diagnose TBE in vaccinated individuals.