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TBE is the most important tick-borne viral disease in the Northern Hemisphere (Europe and Asia), is endemic in 27 European countries, and represents a considerable disease burden. It is predominantly transmitted to humans by the bite of the Ixodes ricinus and Ixodes persulcatus ticks, or in some cases, by alimentary infection through the milk of infected animals. TBEV is generally restricted to endemic areas where the virus circulates among ticks and reservoir hosts. Over the past two decades, the incidence of TBE has risen across Europe, including at higher altitudes, and in regions previously considered virus-free. The highest incidence rates are reported from the Baltic states and Central Europe (>10/100,000 inhabitants per year). There are wide fluctuations in registered annual cases. Infection rates are elevated in the 45-64 years age group, with a male preponderance.

Clinical presentation partly (but not solely) depends on the TBEV subtype. In the majority of patients infected with the European subtype of TBEV, CNS inflammation is preceded by a febrile illness, resulting in a biphasic course of the disease. The first phase (which corresponds to viremia) presents with fever, fatigue, malaise, headache, and muscle and joint pain which occur in the absence of CNS inflammation. It usually lasts <1 week and is followed by an asymptomatic period lasting several days. The hallmark of the second phase of TBE is CNS involvement. Meningitis is the predominant manifestation in children (70%), whereas approximately 50% of adult patients develop meningitis, 40% meningoencephalitis, and 5-10% meningoencephalomyelitis. The disease is on average milder in children than in adults and has the highest severity in the elderly. The fatality rate in patients infected with the European TBEV subtype is up to 1%. Moreover, 5% of patients have permanent paresis and >30% suffer from postencephalitic syndrome. The Siberian subtype is associated with similar TBE course, but may persist as chronic viral infection. The Far Eastern subtype is associated with a usually more severe disease with monophasic course and higher fatality and neurological sequelae rates.

TBE is caused by three main subtypes of TBEV (a member of the genus Flavivirus in the family Flaviviridae): European, Siberian and Far Eastern; recently, Baikal and Himalayan TBEV subtypes have also been reported.

TBE is suspected on clinical signs and symptoms associated with a living or travel history of the patient in endemic zones. Diagnosis is confirmed by: i) clinical presentation of meningitis or meningoencephalitis; ii) elevated cerebrospinal fluid leukocyte counts (>5×106 cells/L); iii) demonstration of a recent infection with TBEV indicated by the presence of specific serum IgM and IgG antibodies or IgG seroconversion in paired serum samples.

Differential diagnosis depends on the travel history of the patient and includes other arboviral and tick-borne diseases, as well as meningitis, meningoencephalitis or meningoencephalomyelitis of other etiology.

Treatment is symptomatic. Vaccination of individuals living in or visiting to TBE endemic regions is recommended.

The fatality rate is up to 1% for the European subtype; 5% of patients have permanent paresis and >30% suffer from postencephalitic syndrome. Various nonspecific symptoms and cognitive and neuropsychiatric sequelae (i.e. apathy, irritability, memory and concentration disorders, altered sleep pattern, headache, hearing defects, visual disturbances, ataxia, and flaccid paresis or paralysis) may affect the patient's quality of life, and sometime require lifestyle changes.