Tick-borne encephalitis

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Tick-borne encephalitis
Other names: TBE
Tick-borne encephalitis virus (crop).png
Virus which causes tick-borne encephalitis
SpecialtyInfectious disease
SymptomsInitial: None, fever, tiredness, headache, nausea[1]
Later: Meningitis, encephalitis, myelitis[2]
ComplicationsCognitive dysfunction[2]
Usual onset7 days[1]
TypesEuropean, Far Eastern, Siberian[3]
CausesTick-borne encephalitis virus spread by tick bites[1]
Risk factorsSpending time outdoors near forests[4]
Diagnostic methodDetection of specific antibodies[1]
Differential diagnosisWest Nile, Usutu, Japanese encephalitis, Lyme[3]
PreventionTick-borne encephalitis vaccine, insect repellent, protective clothing[1]
TreatmentSupportive care[1]
Frequency>10,000 cases/year[2]
Deaths1% to 20% depending on subtype[1][3]

Tick-borne encephalitis (TBE) is a viral infectious disease.[1] Many people have no symptoms while others develop fever, tiredness, headache, and nausea.[1] These initial symptoms last about 5 days and after a period without symptoms, may be followed by meningitis, encephalitis, or myelitis.[1][2] Onset is generally about 7 days after infection.[1] About a third of cases develop long term side effects, predominantly cognitive dysfunction.[2] Tick-borne encephalitis virus typically spreads to people through the bite of an infected tick and less commonly via eating unpasteurized dairy products from infected animals.[4] Risk factors include spending time outdoors near forests.[4] It does not spread between people.[1] Diagnosis is confirmed based on finding specific antibodies in the cerebrospinal fluid or blood.[1]

Prevention involves vaccination against the disease, using insect repellent, and wearing clothing to cover the skin.[1] If infected, management involves supportive care.[1] This may vary from rest and simple pain medication to hospitalization with breathing support.[5] The risk of deaths varies from about 1% with the European subtype to 20% with the Far Eastern subtype.[1][3]

Tick-borne encephalitis affects more than 10,000 people a year.[2] It primarily occurs in western and northern Europe and northern and eastern Asia.[4] In Europe, rates of disease have increased nearly 4 fold over the last three decades.[1] Infections most commonly occur in April through November.[4] The virus was first described in 1937.[3] Though descriptions of possible cases occur at least as far back as the 18th century.[2] A number of other animals including cows, goats, dogs, and bats may also be infected.[1]

Signs and symptoms

Symptoms over time along with changes in diagnostic markers

The disease is most often biphasic. After an incubation period of approximately one week (range: 4–28 days) from exposure (tick bite) non-specific symptoms occurs. These symptoms are fever, malaise, headache, nausea, vomiting and myalgias that persist for about 5 days.[2][1][6] Then, after approximately one week without symptoms, some of the infected develop neurological symptoms, i.e. meningitis, encephalitis or meningoencephalitis. Myelitis also occurs with or without encephalitis.[2][1][6][7]

Sequelae persists for a year or more in approximately one third of people who develop neurological disease. Most common long-term symptoms are headache, concentration difficulties, memory impairment and other symptoms of cognitive dysfunction.[2]

Mortality depends on the subtype of the virus. For the European subtype mortality rates are 0.5% to 2% for people who develop neurological disease.[1]

In dogs, the disease also manifests as a neurological disorder with signs varying from tremors to seizures and death.[8] In ruminants, neurological disease is also present, and animals may refuse to eat, appear lethargic, and also develop respiratory signs.[8]


TBE is caused by tick-borne encephalitis virus, a member of the genus Flavivirus in the family Flaviviridae. It was first isolated in 1937. Three virus sub-types also exist: European or Western tick-borne encephalitis virus (transmitted by Ixodes ricinus), Siberian tick-borne encephalitis virus (transmitted by I. persulcatus), and Far-Eastern tick-borne encephalitis virus, formerly known as Russian spring summer encephalitis virus (transmitted by I. persulcatus).[1][9]


It is transmitted by the bite of several species of infected woodland ticks, including Ixodes scapularis, I. ricinus and I. persulcatus,[10] or (rarely) through the non-pasteurized milk of infected cows.[11]

Infection acquired through goat milk consumed as raw milk or raw cheese (Frischkäse) has been documented in 2016 and 2017 in the German state of Baden-Württemberg. None of the infected had neurological disease.[12]


TBEV is a positive-sense single-stranded RNA virus, contained in a 40 to 60 nm spherical, enveloped capsid.[13] The TBEV genome is approximately 11kb in size, which contains a 5' cap, a single open reading frame with 3' and 5' UTRs, and is without polyadenylation.[13] Like other flaviviruses,[14] the TBEV genome codes for ten viral proteins, three structural, and seven nonstructural.[15][13]


With the exception of food-borne cases, infection begins in the skin at the site of the tick bite. Skin dendritic cells (DCs) are preferentially targeted.[15] Initially, the virus replicates locally and immune response is triggered when viral components are recognized by cytosolic pattern recognition receptors , such as Toll-like receptors.[16]

Recognition causes the release of cytokines including interferons (IFN) α, β , and γ and chemokines, attracting migratory immune cells to the site of the bite.[15] The infection may be halted at this stage and cleared, before the onset of noticeable symptoms. Tick saliva enhances infection by modulating host immune response, dampening apoptotic signals.[16] If the infection continues, migratory DCs and macrophages become infected and travel to the local draining lymph node where activation of polymorphonuclear leukocytes, monocytes and the complement system are activated.[16]


Detection of specific IgM and IgG antibodies in patients sera combined with typical clinical signs, is the principal method for diagnosis. In more complicated situations, e.g. after vaccination, testing for presence of antibodies in cerebrospinal fluid may be necessary.[1] It has been stated that lumbar puncture always should be performed when diagnosing TBE and that pleocytosis in cerebrospinal fluid should be added to the diagnostic criteria.[17]

PCR (Polymerase Chain Reaction) method is rarely used, since TBE virus RNA is most often not present in patient sera or cerebrospinal fluid at the time of neurological symptoms.[17]


TBE vaccine

Prevention includes non-specific (tick-bite prevention, tick checks) and specific prophylaxis in the form of a vaccination. Tick-borne encephalitis vaccines are very effective and available in many disease endemic areas and in travel clinics.[18]

Trade names are Encepur N[19] and FSME-Immun CC.[20]


There is no specific antiviral treatment for TBE. Symptomatic brain damage requires hospitalization and supportive care based on syndrome severity. [21]

Anti-inflammatory drugs, such as corticosteroids, may be considered under specific circumstances for symptomatic relief. Intubation and respiratory support may be necessary.[22][23]


Infected countries/areas in Eurasia

As of 2011, the disease was most common in Central and Eastern Europe, and Northern Asia. About ten to twelve thousand cases are documented a year but the rates vary widely from one region to another.[24] Most of the variation has been the result of variation in host population, particularly that of deer. In Austria, an extensive vaccination program since the 1970s reduced the incidence in 2013 by roughly 85%.[25]

In Germany, during the 2010s, there have been a minimum of 95 (2012) and a maximum of 584 cases (2018) of TBE (or FSME as it is known in German). More than half of the reported cases from 2019 had meningitis, encephalitis or myelitis. The risk of infection was noted to be increasing with age, especially in people older than 40 years and it was greater in men than women. Most cases were acquired in Bavaria (46%) and Baden-Württemberg (37%), much less in Saxonia, Hesse, Niedersachsen and other states. Altogether 164 Landkreise are designated TBE-risk areas, including all of Baden-Württemberg except for the city of Heilbronn.[12]

In Sweden, most cases of TBE occur in a band running from Stockholm to the west, especially around lakes and the nearby region of the Baltic sea.[26][27] It reflects the greater population involved in outdoor activities in these areas. Overall, for Europe, the estimated risk is roughly 1 case per 10,000 human-months of woodland activity. Although in some regions of Russia and Slovenia, the prevalence of cases can be as high as 70 cases per 100,000 people per year.[25][28] Travelers to endemic regions do not often become cases, with only 5 cases reported among U.S. travelers returning from Eurasia between 2000 and 2011, a rate so low that as of 2016 the U.S. Centers for Disease Control and Prevention recommended vaccination only for those who will be extensively exposed in high risk areas.[29]


Though the first description of what may have been TBE appears in records in the 1700s in Scandinavia,[30] identification of the TBEV virus occurred in the Soviet Union in the 1930s.[31]

The investigation began due to an outbreak of what was believed to be Japanese encephalitis, the expedition was led by virologist Lev A. Zilber, who assembled a team of twenty young scientists in a number of related fields such as acarology, microbiology, neurology, and epidemiology.[32][2][31]

Inside the month of May, the expedition had identified ticks as the likely vector, collected I. persucatus ticks by exposure of bare skin by entomologist Alexander V. Gutsevich and virologist Mikhail P. Chumakov had isolated the virus from ticks feeding on intentionally infected mice.[2]

During the summer, five expeditions members became infected with TBEV, and while there were no fatalities, three of the five suffered damaging sequelae.[2]


The first European Tick-borne encephalitis vaccine became available to the public in 1976.[33]


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