Clinical Evaluation and Disease

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Tick-borne encephalitis (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.

Clinical 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 disease 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.

Differential Diagnosis

The differential diagnoses will vary depending on the travel and exposure history of the patient, remembering 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.

Outcomes

The case fatality rate and frequency of neurologic sequelae vary by viral subtype. With the European subtype, the case fatality rate is about 1–2%, with the Siberian subtype about 6–8%, and with the Far Eastern subtype, the case fatality rate is about 20%. Sequelae rates 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.