Tick-borne encephalitis

The number of reported cases has been increasing in most countries. TBE is posing a concerning health challenge to Europe, as the number of reported human cases of TBE in all endemic regions of Europe has increased by almost 400% within the last three decades. Historically, TBE virus has been thought to be absent in the UK, but in 2020 Public Health England declared the first two TBE cases contracted within the country.

The tick-borne encephalitis virus is known to infect a range of hosts including ruminants, birds, rodents, carnivores, horses, and humans. The disease can also be spread from animals to humans, with ruminants and dogs providing the principal source of infection for humans.

Signs and symptoms

TBE virus infections are often asymptomatic, which means that the infected individual show no symptoms of disease. In clinical cases, 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 occur. These symptoms are fever, malaise, headache, nausea, vomiting, and myalgias that persist for about 5 days. 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. Tongue tremor has also been described as a characteristic neurological manifestation of TBE, occurring in more than 30% of patients during the neurological phase.

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

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.

In dogs, the disease also manifests as a neurological disorder with signs varying from tremors to seizures and death.

In ruminants, neurological disease is also present, and animals may refuse to eat, appear lethargic, and also develop respiratory signs.

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Cause

TBE is caused by tick-borne encephalitis virus, a member of the genus Flavivirus in the family Flaviviridae. It was first isolated in 1937 in the USSR by a team led by Lev A. Zilber.

Three TBEV subtypes have traditionally been recognized: European (TBEV-Eu), Siberian (TBEV-Sib), and Far Eastern (TBEV-FE). The European subtype is mainly associated with Ixodes ricinus, whereas the Siberian and Far Eastern subtypes are mainly associated with Ixodes persulcatus. Two additional subtypes, Baikalian (TBEV-Bkl) and Himalayan (TBEV-Him), have also been described.

Transmission

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

Milk

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

From 1980 to 2021, 384 confirmed cases of TBE in Europe were acquired through the consumption of raw milk or cheese. Countries that reported food-borne tick-borne encephalitis (FB-TBE) cases during this period included Slovakia, the Czech Republic, Poland, Hungary, Estonia, Germany, Croatia, Austria, Russia and Slovenia. Proven neuroinvasive disease was reported in 53 patients, with the described CNS syndromes including meningoencephalitis, meningitis, and meningoencephalomyelitis.

Diagnosis

Detection of specific IgM and IgG antibodies in patients' sera, combined with typical clinical signs, is the principal method for diagnosis. The antibodies usually appear within six days after the onset of symptoms and are generally detectable once neurological signs appear. IgM antibodies may remain detectable for up to 10 months in both vaccinated individuals and those infected naturally. In more complicated situations, e.g., after vaccination, testing for the presence of antibodies in cerebrospinal fluid may be necessary. It has been stated that lumbar puncture should always be performed when diagnosing TBE and that pleocytosis in cerebrospinal fluid (CSF) should be added to the diagnostic criteria. The severity of TBE could be assessed using CSF calcium levels, according to recent studies of diagnostic markers for tick-borne encephalitis virus (TBEV).

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.

Prevention

Prevention includes non-specific (tick-bite prevention) and specific prophylaxis in the form of a vaccination. According to the CDC, non-specific tick-bite prevention for TBEV includes using insect repellent, wearing long-sleeved shirts and pants in high-risk areas, and treating clothing and gear with 0.5% permethrin. Tick checks, while useful for preventing some other tick-borne diseases such as Lyme disease, would not be expected to be effective in the prevention of tick-borne encephalitis, as the virus is transmitted within minutes of attachment by the tick.

Tick-borne encephalitis vaccines are very effective and available in many disease-endemic areas and in travel clinics. Trade names are Encepur N and FSME-Immun CC. The vaccines are administered in two injections, given at least two weeks apart.

Treatment

There is no specific antiviral treatment for TBE. Symptomatic brain damage requires hospitalization and supportive care based on syndrome severity. Anti-inflammatory drugs, such as corticosteroids, may be considered under specific circumstances for symptomatic relief although their long term effectiveness is debated. Tracheal intubation and respiratory support may be necessary.

Epidemiology

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. 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%.

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 in women. Most cases were acquired in Bavaria (46%) and Baden-Württemberg (37%), much less in Saxony, Hesse, Lower Saxony, and other states. Altogether 164 Landkreise are designated TBE-risk areas, including all of Baden-Württemberg except for the city of Heilbronn.

In Czech Republic, a reported 10 year record was reached in 2025, with a low average vaccination rate estimated at 40% of the population having received at least a dose (a 3 doses protocol is normally considered necessary for effectiveness).

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. 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. In some regions of Russia and Slovenia, the prevalence of cases can be as high as 70 cases per 100,000 people per year. Travelers to endemic regions do not often become cases, with only 8 cases reported among U.S. travelers returning from Eurasia between 2000 and 2017, a rate so low that as of 2020 the U.S. Centers for Disease Control and Prevention recommended vaccination only for those who will be extensively exposed in high risk areas.

Influence of climate change

Warming temperatures caused by climate change increase the expansion of tick populations and lengthen their active seasons which in turn increase the prevalence and geographical range of tick-borne diseases. In Europe, expansion of tick-borne diseases to the north due to climate change has already been observed, especially for Lyme disease and tick-borne encephalitis. Ixodes ricinus is predicted to become 5–7% more prevalent on livestock farms in Great Britain, depending on the extent of future climate change.