What is tick‑borne encephalitis in humans?

What is Tick-Borne Encephalitis?

Definition of TBE

Tick‑borne encephalitis (TBE) is an acute viral infection of the central nervous system transmitted to humans by the bite of infected Ixodes ticks. The disease is caused by the tick‑borne encephalitis virus (TBEV), a member of the Flaviviridae family, and occurs predominantly in temperate regions of Europe and Asia where the vector thrives.

Key characteristics of the definition include:

Etiology: TBEV, an RNA virus with three recognized subtypes (European, Siberian, Far‑Eastern) that differ in geographic distribution and clinical severity.
Transmission: Primary vector is the hard tick Ixodes ricinus (Europe) or Ixodes persulcatus (Asia); occasional infection through consumption of unpasteurized dairy products from infected livestock.
Pathogenesis: After inoculation, the virus replicates locally, spreads to regional lymph nodes, and subsequently invades the bloodstream, crossing the blood‑brain barrier to cause encephalitis, meningitis, or meningoencephalitis.
Clinical presentation: Biphasic course; first phase mimics a nonspecific febrile illness, followed by a neurologic phase with headache, fever, neck stiffness, and possible focal neurological deficits.
Epidemiology: Endemic in forested areas with high tick density; incidence peaks in late spring and early summer, correlating with tick activity.

In summary, TBE is a vector‑borne flaviviral disease that leads to inflammation of the brain and surrounding membranes in humans, characterized by a distinct viral etiology, tick transmission, and a biphasic clinical pattern.

Causative Agent

Tick‑borne encephalitis in humans is caused by the tick‑borne encephalitis virus (TBEV), a member of the Flaviviridae family. The virus is an enveloped, single‑stranded RNA pathogen with three recognized subtypes that differ in geographic distribution and clinical severity:

European (Western) subtype: prevalent in Central and Western Europe, generally associated with milder disease.
Siberian subtype: found in Siberia and parts of Eastern Europe, linked to more frequent neurological complications.
Far‑Eastern subtype: occurs in the Russian Far East, Japan, and the Korean Peninsula, often producing severe encephalitic forms.

Transmission occurs when infected Ixodes ticks, primarily Ixodes ricinus in Europe and Ixodes persulcatus in Asia, attach to a human host and feed for several hours. The virus resides in the tick’s salivary glands and is introduced into the skin during blood meal. Small mammals, especially rodents such as Myodes and Apodemus species, serve as natural reservoirs, maintaining viral circulation in endemic areas. Co‑feeding among ticks on the same host can amplify transmission without systemic infection of the vertebrate host.

Laboratory identification of TBEV relies on reverse‑transcription polymerase chain reaction (RT‑PCR) for viral RNA, serological detection of specific IgM and IgG antibodies, and virus isolation in cell culture. The virus exhibits a high degree of genetic stability within each subtype, enabling reliable molecular typing for epidemiological surveillance.

Transmission Mechanism

Tick‑borne encephalitis (TBE) spreads to humans primarily through the bite of infected hard ticks, most often Ixodes ricinus in Europe and Ixodes persulcatus in Asia. The virus persists in natural foci by cycling between ticks and small vertebrate hosts such as rodents, birds, and hares. Adult female ticks acquire the virus while feeding on infected hosts during their larval or nymphal stages; transstadial transmission carries the pathogen through molting to the next life stage. In addition, co‑feeding of infected and uninfected ticks on the same host enables virus transfer without systemic host infection.

Key elements of the transmission mechanism:

Acquisition: Larvae or nymphs ingest the virus from a viremic reservoir animal during blood feeding.
Maintenance: The virus survives through the tick’s developmental stages (larva → nymph → adult) via transstadial passage.
Co‑feeding: Simultaneous feeding of infected and naive ticks on a host facilitates direct virus exchange, amplifying local infection risk.
Human exposure: Humans become incidental hosts when an infected nymph or adult tick attaches and feeds for several hours, delivering the virus into the skin and subsequently into the bloodstream.
Seasonality: Peak human cases correspond with periods of high nymph activity (late spring to early summer) and adult activity (autumn), reflecting tick life‑cycle dynamics.

Effective prevention focuses on minimizing tick bites during these high‑risk periods and promptly removing attached ticks to interrupt the transmission chain.

Geographical Distribution and Risk Factors

Endemic Regions

Tick‑borne encephalitis (TBE) occurs primarily in temperate and boreal zones where Ixodes ticks thrive. The disease is endemic in distinct geographic clusters that reflect the distribution of the two main vectors, Ixodes ricinus (Western Europe) and Ixodes persulcatus (Eastern Europe and Asia).

Central and Northern Europe: Austria, Czech Republic, Germany, Hungary, Poland, Slovakia, Switzerland, and the Baltic states (Estonia, Latvia, Lithuania). The Scandinavian Peninsula (Finland, Sweden, Norway) also shows high incidence, especially in forested and coastal regions.
Eastern Europe and Russia: Russia (European part, Siberia, Far East), Belarus, Ukraine, and the western regions of Kazakhstan. Areas along the Volga River and the Ural Mountains report frequent cases.
Asian territories: Northeastern China (Heilongjiang, Jilin), the Russian Far East, Mongolia, and the northern islands of Japan (Hokkaido). These locations host I. persulcatus populations that transmit the virus.

Endemicity correlates with tick habitats characterized by mixed woodlands, humid meadows, and high rodent density, which sustain the natural virus cycle. Seasonal peaks align with tick activity, typically from late spring through early autumn. Public health measures, including vaccination campaigns, concentrate on these high‑risk zones to reduce human infection rates.

High-Risk Activities

Tick‑borne encephalitis (TBE) is a viral infection transmitted primarily through the bite of infected Ixodes ticks. Certain human behaviors markedly increase the chance of exposure to infected ticks.

Walking, hiking, or camping in forested or mountainous regions where ticks are abundant.
Collecting firewood, mushrooms, berries, or other forest products, which often involves close contact with low vegetation.
Working outdoors in agriculture, forestry, or landscaping, especially during spring and early summer when nymphal ticks are most active.
Participating in outdoor sports such as mountain biking, trail running, or hunting in endemic areas.
Spending extended periods in grasslands, meadows, or shrubbery without protective clothing or tick repellents.

Additional factors that elevate risk include:

Lack of regular body checks for attached ticks after outdoor activities.
Use of clothing that does not cover the limbs (short sleeves, shorts, sandals).
Absence of personal protective measures such as permethrin‑treated garments or DEET‑based repellents.

Mitigating these activities or applying preventive measures reduces the likelihood of acquiring TBE.

Seasonal Incidence

Tick‑borne encephalitis (TBE) displays a distinct seasonal pattern that mirrors the activity cycles of its vector, Ixodes ticks. Human cases rise sharply when nymphs, which are most likely to transmit the virus, become active. In most temperate regions, this period spans late spring to early summer, typically May and June. A secondary peak occurs in late summer to early autumn, often August and September, when adult ticks are feeding.

Northern and Central Europe: primary peak May–June; secondary peak August–September.
Baltic states and Russia: extended activity from April through July, with a smaller increase in September.
Eastern Asia (e.g., Russia’s Far East, China): peak May–July, occasional cases in October.

Winter months (November–February) show minimal incidence because tick questing ceases as temperatures drop below 5 °C. Year‑to‑year variations depend on climate anomalies; warmer springs advance nymph emergence, while humid summers sustain higher tick densities and increase case numbers.

The seasonal distribution informs public‑health measures: vaccination campaigns target the pre‑seasonal period, and public‑awareness messages emphasize protective clothing and repellents during the identified high‑risk months.

Symptoms and Disease Progression

Incubation Period

The incubation period of tick‑borne encephalitis (TBE) refers to the interval between a contagious bite and the appearance of the first clinical sign. In most cases it lasts 7–14 days, but the range can extend from 4 days up to 28 days depending on viral subtype and host factors.

Factors that modify the duration include:

Virus subtype – European strains usually produce a shorter incubation (5–10 days); Siberian and Far‑Eastern strains often require 10–14 days.
Inoculum size – larger quantities of virus introduced by the tick increase the likelihood of a brief interval.
Host age and immune status – children and immunocompromised individuals tend to develop symptoms earlier.
Co‑infection with other pathogens – simultaneous transmission of additional agents may alter the timeline.

The incubation period precedes a biphasic clinical course. The first phase, occurring after the incubation interval, presents with nonspecific flu‑like symptoms such as fever, headache, and malaise. After a brief remission, the second phase emerges, characterized by neurological involvement (meningitis, encephalitis, or meningoencephalitis). Recognizing the typical 7–14‑day window enables timely laboratory testing and early initiation of supportive care.

Initial Symptoms («Pre-encephalitic Stage»)

Tick‑borne encephalitis (TBE) begins with a short incubation period of 7‑14 days after a bite from an infected Ixodes tick. The disease then enters the pre‑encephalitic phase, during which viral replication in the peripheral nervous system produces the first clinical manifestations.

Typical initial symptoms include:

Sudden fever (often > 38 °C)
Severe headache, frequently described as frontal or occipital
Muscle aches and joint pain (myalgia, arthralgia)
Generalized fatigue and malaise
Nausea, sometimes accompanied by vomiting
Photophobia and mild neck stiffness

These signs appear abruptly and last from 1 to 5 days. Their presence signals the need for immediate medical evaluation, because progression to the encephalitic phase can follow within a few days, especially in unvaccinated individuals. Early recognition enables timely supportive care and, when appropriate, antiviral or immunomodulatory interventions.

Neurological Symptoms («Encephalitic Stage»)

The encephalitic phase follows the initial febrile period of tick‑borne encephalitis and is marked by central nervous system involvement. Neurological manifestations appear abruptly, typically 1–2 weeks after the first symptoms, and may progress within days.

Patients commonly exhibit:

Severe headache, often described as throbbing or pressure‑like
Photophobia and phonophobia
Neck stiffness indicative of meningeal irritation
Altered mental status ranging from confusion to coma
Focal neurological deficits such as unilateral weakness, ataxia, or dysarthria
Seizures, which may be focal or generalized
Cranial nerve palsies, most frequently involving the facial nerve

Additional findings can include tremor, involuntary movements, and dysphagia. The severity of these signs varies; some individuals experience mild encephalopathy, while others develop life‑threatening cerebral edema and respiratory failure.

Laboratory evaluation typically shows pleocytosis with lymphocytic predominance in cerebrospinal fluid, elevated protein, and normal glucose. Magnetic resonance imaging may reveal hyperintense lesions in the thalamus, basal ganglia, or brainstem, supporting the clinical diagnosis.

Prompt antiviral therapy is unavailable; management relies on supportive care, seizure control, and measures to reduce intracranial pressure. Early recognition of the encephalitic stage improves prognosis, as timely intensive care can mitigate permanent neurological sequelae.

Potential Complications and Long-Term Effects

Tick‑borne encephalitis can progress from a mild febrile illness to severe neurological involvement. When the central nervous system is affected, patients risk a range of acute complications and may experience lasting deficits.

Acute complications include:

Meningitis or meningoencephalitis with rapid onset of headache, neck stiffness, and altered consciousness.
Cerebellar ataxia causing loss of coordination and gait instability.
Cranial nerve palsies, most frequently facial nerve dysfunction.
Seizures, which may be focal or generalized.
Respiratory failure secondary to brainstem involvement.

Long‑term effects arise in a subset of survivors, often persisting for months or years. Documented sequelae comprise:

Persistent motor deficits such as weakness, tremor, or chronic ataxia.
Cognitive impairment, including reduced attention, memory lapses, and slowed information processing.
Sensory disturbances, notably persistent paresthesia or dysesthesia in extremities.
Psychiatric manifestations, ranging from mood disorders to anxiety and post‑traumatic stress symptoms.
Chronic fatigue syndrome with reduced exercise tolerance and daily functioning.

The likelihood of lasting impairment correlates with the severity of the initial neurological phase, patient age, and promptness of antiviral or supportive therapy. Rehabilitation programs focusing on physiotherapy, occupational therapy, and neuropsychological support improve functional outcomes, yet some deficits remain irreversible. Early recognition of neurological signs and aggressive management reduce the risk of severe sequelae.

Diagnosis of TBE

Clinical Evaluation

Tick‑borne encephalitis (TBE) requires systematic clinical evaluation to confirm diagnosis, determine disease severity, and guide management.

A thorough patient history should capture recent tick exposure, vaccination status, and the temporal pattern of symptoms. The illness typically progresses through three phases: an initial febrile stage lasting 2–7 days, a possible asymptomatic interval, and a second stage marked by neurological involvement such as meningitis, meningoencephalitis, or acute flaccid paralysis.

Physical examination focuses on neurological assessment. Clinicians must document fever, headache, neck stiffness, photophobia, altered mental status, focal motor deficits, ataxia, and cranial nerve abnormalities. Reflex asymmetry and gait disturbances provide clues to disease localization.

Laboratory investigations include:

Complete blood count and inflammatory markers (CRP, ESR).
Serum IgM and IgG antibodies against TBE virus; paired serology for seroconversion.
Cerebrospinal fluid (CSF) analysis: pleocytosis with lymphocytic predominance, elevated protein, normal to slightly reduced glucose.
Polymerase chain reaction (PCR) for viral RNA in CSF or blood when early presentation precludes seroconversion.

Neuroimaging assists in evaluating complications. Magnetic resonance imaging (MRI) with contrast reveals hyperintense lesions in the basal ganglia, thalamus, brainstem, or spinal cord. Computed tomography (CT) is reserved for acute intracranial hypertension or when MRI is unavailable.

Severity grading relies on clinical criteria such as level of consciousness, presence of seizures, respiratory failure, and extent of motor impairment. Prognostic indicators include age over 50 years, delayed treatment, and extensive MRI lesions.

Follow‑up includes repeat neurological examinations, serial CSF analysis if indicated, and functional outcome assessments (e.g., modified Rankin Scale) at 3 months and 12 months to identify persistent deficits and inform rehabilitation planning.

Laboratory Testing

Laboratory confirmation of tick‑borne encephalitis (TBE) in patients relies on detection of specific antibodies, viral nucleic acid, and characteristic changes in cerebrospinal fluid (CSF).

Serological testing is the primary method. Enzyme‑linked immunosorbent assay (ELISA) identifies IgM and IgG antibodies against TBE virus. IgM appears within 7–10 days of symptom onset and indicates recent infection; IgG persists for months to years and confirms exposure. A paired‑sample approach—testing acute‑phase serum and a convalescent sample 2–3 weeks later—distinguishes primary infection from past immunity.

Molecular techniques supplement serology when early diagnosis is required. Reverse‑transcription polymerase chain reaction (RT‑PCR) detects TBE viral RNA in blood, CSF, or brain tissue during the viremic phase, typically before antibody production. Sensitivity declines after the first week, limiting routine use.

CSF analysis provides supportive evidence. Typical findings include:

Elevated white‑cell count with lymphocytic predominance
Increased protein concentration
Normal or mildly reduced glucose

These results, together with clinical presentation, raise suspicion for TBE but are not disease‑specific.

Virus isolation, performed in cell culture or mouse inoculation, confirms infection but is rarely used because of biosafety constraints and low yield.

Neutralization tests (e.g., plaque reduction neutralization test) serve as the reference standard for confirming serological results, especially when cross‑reactivity with other flaviviruses is possible.

Specimen handling guidelines ensure assay reliability:

Collect serum and CSF in sterile tubes, keep at 2–8 °C, and process within 24 hours.
Freeze aliquots at –70 °C for later molecular or serological testing.
Use validated ELISA kits with defined cut‑off values and include internal controls.

Interpretation must consider timing of sample collection, vaccination status, and potential cross‑reactivity. A single positive IgM result without a corresponding rise in IgG may represent a false‑positive finding; confirmatory testing or repeat sampling is recommended.

Overall, accurate laboratory diagnosis integrates serology, molecular detection, and CSF analysis, guided by strict specimen management and awareness of assay limitations.

Differential Diagnosis

Tick‑borne encephalitis (TBE) presents with acute febrile illness, often followed by neurologic signs such as meningitis, encephalitis, or meningo‑encephalitis. The clinical picture overlaps with several infectious and non‑infectious conditions, requiring systematic differentiation.

Common disorders that mimic TBE include:

Viral meningitis/encephalitis (enteroviruses, herpes simplex virus, West Nile virus, Japanese encephalitis virus). Distinguish by cerebrospinal fluid (CSF) pleocytosis pattern, PCR results, and geographic exposure.
Bacterial meningitis (Neisseria meningitidis, Streptococcus pneumoniae). Identify through rapid CSF Gram stain, low glucose, high protein, and positive cultures.
Lyme neuroborreliosis. Recognize by history of erythema migrans, positive Borrelia serology, and CSF pleocytosis with elevated IgM/IgG index.
Other tick‑borne infections (Anaplasma phagocytophilum, Babesia spp.). Detect via peripheral blood smear, PCR, or specific serology.
Autoimmune encephalitis (anti‑NMDA receptor, anti‑LGI1). Confirm with neuronal antibody panels and absence of infectious agents.
Acute disseminated encephalomyelitis (ADEM). Separate by MRI showing multifocal demyelination and lack of infectious markers.
Metabolic encephalopathies (hepatic, uremic). Exclude by laboratory assessment of liver and renal function.

Key diagnostic steps for TBE differentiation:

Obtain detailed exposure history: recent tick bite, travel to endemic regions, seasonality.
Perform lumbar puncture; evaluate CSF for lymphocytic pleocytosis, normal to mildly reduced glucose, moderate protein rise.
Order serologic testing for TBE‑specific IgM and IgG; repeat after 2‑3 weeks to assess seroconversion.
Conduct PCR for alternative viral agents when early presentation suggests non‑specific viral meningitis.
Use MRI to identify characteristic brainstem or cerebellar involvement; compare with patterns typical for ADEM or herpes encephalitis.

Accurate differential diagnosis hinges on integrating epidemiologic data, laboratory findings, and imaging results. Prompt identification of the correct etiology directs appropriate therapy and improves patient outcomes.

Prevention and Treatment

Vaccination

Vaccination is the principal preventive measure against tick‑borne encephalitis (TBE) in humans. The vaccine contains inactivated virus strains derived from the European or Far‑Eastern subtypes, depending on the region of use. Immunogenicity is achieved through a three‑dose primary series followed by periodic boosters.

First dose: administered at any age, preferably before exposure season.
Second dose: given 1–3 months after the first.
Third dose: given 5–12 months after the second to establish long‑term protection.
Booster: recommended every 3–5 years, with the interval shortened for individuals at high risk or older adults.

Clinical trials report seroconversion rates above 95 % after the full primary series. Protective antibody levels persist for several years, justifying the booster schedule. Adverse events are generally mild, including injection‑site pain, transient fever, and headache. Severe reactions such as anaphylaxis occur rarely and are monitored through post‑marketing surveillance.

Vaccination is indicated for residents and travelers to endemic areas, outdoor workers, and persons with frequent exposure to tick habitats. Contraindications include severe allergic reactions to vaccine components and immunosuppression that precludes adequate antibody response. Pregnant or lactating individuals may receive the vaccine after risk assessment, as no teratogenic effects have been documented.

Serological testing can confirm adequate immunity, especially in immunocompromised patients. Failure to complete the primary series or maintain booster intervals markedly reduces protection, leading to increased incidence of severe neurological disease. Consequently, adherence to the recommended schedule remains essential for individual and public health protection against TBE.

Tick Bite Prevention Strategies

Tick‑borne encephalitis (TBE) is a viral infection transmitted by the bite of infected Ixodes ticks. Prevention of tick bites therefore reduces the risk of acquiring the disease. Effective measures focus on personal protection, environmental management, and awareness of high‑risk periods.

Wear long sleeves and trousers; tuck shirts into pants and use light-colored clothing to spot ticks easily.
Apply repellents containing 20‑30 % DEET, picaridin, or IR3535 to exposed skin and permethrin (0.5 %) to clothing and gear.
Perform thorough body checks every 2‑3 hours while in tick‑infested habitats; remove attached ticks with fine‑pointed tweezers, grasping the head close to the skin and pulling straight upward.
Avoid dense underbrush, tall grass, and leaf litter where ticks quest for hosts; stay on cleared paths.
Treat pets with veterinarian‑recommended acaricides and regularly inspect them for ticks after outdoor exposure.
Maintain yard hygiene by mowing grass weekly, removing leaf litter, and creating a 1‑meter barrier of wood chips or gravel between lawn and wooded areas.

Awareness of peak activity—typically April through October in temperate regions—guides timing of preventive actions. Vaccination against TBE is available for individuals with frequent exposure; it complements, but does not replace, bite‑avoidance strategies.

Post-Exposure Prophylaxis

Post‑exposure prophylaxis (PEP) for tick‑borne encephalitis (TBE) focuses on immediate actions after a potentially infectious tick bite and on preventing disease progression in the short term.

Vaccination is the primary preventive measure. If a person has not completed the standard TBE immunisation schedule, a rapid‑response regimen can be initiated within 24 hours of the bite. The accelerated schedule consists of three doses of inactivated vaccine administered on days 0, 7, and 14, followed by the regular booster series. This protocol induces protective antibody titres more quickly than the conventional schedule and is recommended for travelers, outdoor workers, and anyone exposed in high‑incidence regions.

Passive immunisation with TBE‑specific immunoglobulin is not routinely available; however, in countries where hyperimmune globulin is produced, a single intramuscular dose may be considered for individuals with severe immunodeficiency who cannot mount an adequate vaccine response. Administration should occur as soon as possible after exposure, ideally within 48 hours.

Supportive care complements immunisation. Immediate removal of the attached tick, thorough disinfection of the bite site, and observation for early neurologic symptoms (headache, fever, malaise) are essential. If symptoms develop, hospital admission for antiviral therapy, intracranial pressure monitoring, and intensive supportive measures is indicated.

Key steps in TBE PEP:

Verify vaccination status; initiate accelerated vaccine series if incomplete.
Administer hyperimmune immunoglobulin only when vaccine response is unlikely and product is available.
Perform prompt tick extraction and wound cleansing.
Monitor for prodromal signs for at least 14 days; seek medical evaluation at first indication of fever or neurological change.

Timely execution of these interventions reduces the risk of severe encephalitic disease following a tick bite.

Symptomatic Treatment and Supportive Care

Tick‑borne encephalitis is a viral infection of the central nervous system transmitted by Ixodes ticks. The disease lacks a specific antiviral cure; management focuses on relieving symptoms and preventing complications.

Symptomatic measures include:

Antipyretics such as acetaminophen to control fever.
Analgesics for headache and myalgia.
Anticonvulsants (e.g., levetiracetam) when seizures occur.
Corticosteroids may be considered for severe cerebral edema, although evidence is limited.

Supportive care addresses organ‑system dysfunction:

Intravenous fluids maintain adequate hydration and electrolyte balance.
Continuous monitoring of neurological status, blood pressure, and respiratory function.
Mechanical ventilation for patients with respiratory failure or impaired airway protection.
Nutritional support, preferably enteral, to meet caloric needs.
Prevention of secondary infections through aseptic techniques and prophylactic antibiotics when indicated.

Rehabilitation begins after acute stabilization, focusing on physical therapy, speech therapy, and neurocognitive exercises to restore functional capacity. Regular follow‑up evaluates long‑term sequelae such as persistent motor deficits or cognitive impairment.