Clinical Signs and Symptoms of Tick-borne Encephalitis

Key points

  • Tick-borne encephalitis (TBE) can present as an acute febrile illness or neuroinvasive disease, with varying degrees of severity depending on viral subtype and patient risk factors.
  • TBE can present as a biphasic illness, particularly with the European subtype of the virus.
  • The percentage of cases resulting in death (1–20%) and neurologic sequelae (10–50%) vary by viral subtype.
brain imaging


TBE virus is an RNA virus in the genus Flavivirus (family Flaviviridae). It was discovered in the former Soviet Union in 1937. The three main subtypes are the European, Far Eastern, and Siberian subtypes. TBE virus is closely related to Powassan virus, a domestic arbovirus also transmitted by ticks.

Signs and symptoms

Most human infections with TBE virus are asymptomatic. For those who become ill, the incubation period is usually between 7 and 14 days (range: 4–28 days).

Acute neuroinvasive disease (i.e., aseptic meningitis, encephalitis, or meningoencephalomyelitis) is the most commonly recognized clinical manifestation of TBE virus infection. Milder forms of the disease (e.g., febrile illness) also occur.

TBE can present as a biphasic illness, particularly with the European subtype of the virus, as follows:

  • First phase: a nonspecific febrile illness that might be accompanied by symptoms such as headache, malaise, myalgia, anorexia, nausea, and/or vomiting. This phase usually lasts for several days and is followed by an afebrile and relatively asymptomatic period, typically of about one week's duration.
  • Second phase: a clinical illness with central nervous system involvement. Depending on specific presentation, findings can include meningeal signs, altered mental status, cognitive dysfunction, ataxia, rigidity, seizures, tremors, cranial nerve palsies, and limb paresis.

Infections with the Far Eastern TBE virus subtype are generally more severe than infections with the other two subtypes. Children typically have a milder illness than adults, more frequently presenting with meningitis. Disease severity is highest in older persons.

Clinical assessment

The differential diagnoses will vary depending on the travel and exposure history of the patient, considering that for some travelers, infection could have been acquired locally before or after travel. For patients presenting with neurologic disease, the differential diagnosis might include a wide range of infectious and non-infectious etiologies. Other arboviruses transmitted in some areas where TBE occurs include West Nile, Usutu, and Japanese encephalitis viruses. In patients with known exposure to ticks, other tickborne diseases might be considered, including Lyme borreliosis.


The case fatality and frequency of neurologic sequelae vary by viral subtype. With the European subtype, the case fatality is about 1–2%, with the Siberian subtype about 6–8%, and with the Far Eastern subtype about 20%. Frequencies of sequelae ranging from 10–50% have been reported from different areas. Chronic and progressive forms of disease have been reported, particularly after infection with the Siberian subtype.