Tick-borne encephalitis virus: Infectious substances pathogen safety data sheet

Section I: Infectious agent


Tick-borne encephalitis virus

Agent type








Tick-borne encephalitis virus

Synonym or cross reference

Tick-borne encephalitis virus (TBEV) causes disease formerly known as: Central European encephalitis, Russian spring-summer encephalitis, West Siberian virus, and biphasic milk feverFootnote 1,Footnote 2. There are three TBEV subtypes: Siberian (TBEV-Sib), Far Eastern (TBEV-FE), and European (TBEV-Eu), also known as Western TBEVFootnote 2. Baikalian (TBEV-Bkl) and Himalayan (TBEV-Him) subtypes have been proposedFootnote 3.


Brief description

TBEV is a single stranded, positive-sense RNA virus, whose genome is approximately 11 kb in lengthFootnote 2. TBEV has icosahedral symmetry, measuring approximately 50 nm in diameter and is surrounded by a lipid envelopeFootnote 2.


Virulence varies among TBEV subtypes. Although mild and severe infection can occur from any subtype, TBEV-Eu infections tend to be mild, while TBEV-FE tend to cause more severe infectionsFootnote 1,Footnote 4.

Section II: Hazard identification

Pathogenicity and toxicity

Approximately 2 out of 3 TBEV infections are subclinical in humansFootnote 2,Footnote 3,Footnote 5. Disease is biphasic in 46%-75% of symptomatic casesFootnote 1,Footnote 5. In the first phase of disease, TBEV replicates in dermal cells, Langerhans cells, neutrophils of skin, and others, such as monocytes and macrophages, that enable transport to lymph nodes and dissemination to other parts of the bodyFootnote 3,Footnote 5. In the second phase of disease, TBEV invades the central nervous system (CNS), crossing the blood-brain barrier and infecting large neuronal cells in the brainFootnote 2,Footnote 3.

Initial symptoms of tick-borne encephalitis (TBE) include fever, malaise, headache, vomiting and myalgia, which persist for about 5 days (range 2-10 days)Footnote 6. Some individuals are symptom-free for 2-8 days (range 1-20 days), and then symptoms resumeFootnote 1,Footnote 2,Footnote 6. This second phase may manifest as a meningeal form (main form in children), meningoencephalitis form, meningoencephalomyelitis or poliomyelitic form (poliomyelitic-like flaccid paralysis), polyradiculoneuritic form (Guillain-Barré-like paralysis), or hemorrhagic formFootnote 2,Footnote 3. All of these forms of acute illness usually resolve, but some patients develop chronic sequelae of TBEV infectionFootnote 3,Footnote 4. Infection tends to be milder in children, although long-term cognitive effects have been observed in children post-infectionFootnote 7.

Sequelae occur in 26-46% of cases, mostly in adults, and include hearing loss, asthenia, memory loss, ataxia, tremor, hemiparesis, cranial or spinal muscular paralysis, and Kozhevnikov's epilepsyFootnote 2,Footnote 3,Footnote 7,Footnote 8. TBEV infection complications associated with prolonged hospitalization include pneumonia and heart failureFootnote 2.

TBEV-FE tends to cause more severe disease; the mortality rate is estimated to be 5-40%Footnote 9,Footnote 10 and up to 60% of recovered patients have neurologic sequelaeFootnote 2. Mortality rates are estimated to be 6-8% for TBEV-Sib, and 1-2% for TBEV-EuFootnote 2,Footnote 5. Fatalities are rare in childrenFootnote 5,Footnote 7.

TBEV infection in livestock and wild animals is usually subclinicalFootnote 11. Neurological symptoms (ataxia, paralysis of neck and shoulder muscles) of TBEV infection have infrequently been reported in cattle, horses, sheep, goats and dogsFootnote 2,Footnote 11,Footnote 12,Footnote 13,Footnote 14. The mortality rate for animals that present with neurological symptoms is significant. Non-human primates can develop asymptomatic infection or neurological symptoms of disease similar to those observed in humansFootnote 15,Footnote 16.

Predisposing factors

Adults have higher risk of neurologic sequelae compared to childrenFootnote 7. A short or no asymptomatic period between initial symptoms (first phase) and CNS involvement (second phase) has been associated with severe TBEV infectionFootnote 3. The disease also tends to be more severe for individuals with dual-infection and those who are immunocompromised (e.g., organ transplant recipients)Footnote 2,Footnote 3,Footnote 6,Footnote 17.


TBEV is often transmitted to animals and humans via bites from infected ticksFootnote 2. TBEV is also transmitted to humans via unpasteurized milk or milk products from infected goats, sheep, and cowsFootnote 18,Footnote 19,Footnote 20. Indirect human-to-human transmission via blood transfusion and organ transplantation has been reportedFootnote 3,Footnote 6,Footnote 17. Intranasal infection route has been demonstrated experimentally in non-human primates, but the extent of aerosol-mediated transmission occurring in nature is unknownFootnote 16.


TBEV is endemic in Europe, Russia, Japan, and ChinaFootnote 2. TBEV-FE is prevalent in eastern Russia, Korea, China, Japan, Baltic states; TBEV-Eu in Europe; and TBEV-Sib in RussiaFootnote 2. TBEV vaccines have been commercially available since the 1970s in Europe and 1980s in RussiaFootnote 3,Footnote 4. Incidence of TBE has been drastically reduced in areas with high vaccine coverage, such as AustriaFootnote 21. Incidence of TBE varies geographically and year-to-yearFootnote 6. In 2016, TBE incidence in European countries varied from <0.1 to 21.9 cases per 100,000 people per yearFootnote 3,Footnote 4. Infections mostly occur between April and November, likely due to increased tick activity for vector based infection, and animal milk production for ingestion related infectionsFootnote 2.

TBEV endemic areas have been characterized according to habitat of ixodid tick vectors (e.g., meadows, forests with high humidity)Footnote 1,Footnote 2. The geographic distribution of ixodid ticks appears to be expanding; this may be due in part to changing climatic factorsFootnote 2,Footnote 22. TBEV is emerging in areas that were previously non-endemicFootnote 9,Footnote 23,Footnote 24.

Outbreaks of TBE have been associated with consumption of unpasteurized milk or milk products containing TBEVFootnote 18,Footnote 19.

Host range

Natural host(s)

Humans, non-human primates, horses, dogs, cows, sheep, goats, field mice, voles, foxes, wild boars, deer, moose, bison, hedgehogs, squirrels, birds, and mosquitos (Aedes vexans)Footnote 9,Footnote 15,Footnote 25,Footnote 26,Footnote 27,Footnote 28,Footnote 29,Footnote 30,Footnote 31,Footnote 32.

Other host(s)


Infectious dose


Incubation period

Usually 8 days but can range from 4 to 28 daysFootnote 2. Goats shed TBEV in milk from 6 to more than 23 days after infectionFootnote 33.

Section III: Dissemination


Small-to-medium sized mammals including rodents (voles), hedgehogs, and molesFootnote 34.

Zoonosis/Reverse zoonosis

TBEV can be transmitted to humans from infected livestock via consumption of unpasteurized milk and milk productsFootnote 18,Footnote 19.


TBEV are transmitted to animal and human hosts via tick bites. TBEV has been found in 22 hard-tick species of the Ixodidae familyFootnote 32. The primary tick vector is Ixodes ricinus in Europe and Ixodes persulcatus in Baltic regions, Russia, China and JapanFootnote 32,Footnote 35. Other vector species include Ixodes hexagonus, Ixodes ovatus, Haemaphysalis spp., and Dermacentor spp.Footnote 32,Footnote 35. Uninfected ticks can acquire TBEV during a blood meal from a TBEV-infected vertebrate host in viremic phase, or via co-feeding with a TBEV-infected tickFootnote 34,Footnote 36. Vertical transmission also occurs infrequentlyFootnote 35. The ticks remain infected through all stages of their life cycleFootnote 2.

Section IV: Stability and viability

Drug susceptibility

Nucleoside analogue 7-deaza-2'-C-methyladenosine (7-deaza-2'-CMA) and perylenyltriazoles inhibited TBEV replication and showed low cytotoxicity in vitroFootnote 37,Footnote 38,Footnote 39. Arbidol (Umifenovir), a broad-spectrum antiviral drug approved in China and Russia for influenza treatment, showed antiviral activity against TBEV in vitroFootnote 40. An aglycon analogue of the antibiotic teicoplanin (LCTA-949) showed antiviral activity in vitroFootnote 41.

Drug resistance


Susceptibility to disinfectants

TBEV is susceptible to alcohol and iodine-based (1%) disinfectantsFootnote 1,Footnote 2. Other members of the Flavivirus genus are inactivated by hypochlorite (1%), paraformaldehyde, and glutaraldehyde (2%)Footnote 42.

Physical inactivation

TBEV is sensitive to heat and UV irradiationFootnote 1,Footnote 2,Footnote 43. Pasteurization processes that involve heating milk to 72 °C for 15 seconds are sufficient to inactivate TBEV in milkFootnote 43.

Survival outside host

Other tick-borne flaviviruses are stable in milk for 72 hours at refrigeration temperature but are not detectable after 48 hours at room temperatureFootnote 43.

Section V: First aid/medical


Diagnosis is accomplished through the monitoring of clinical symptoms. In the first phase of disease, TBEV can be detected in blood using viral isolation, reverse transcriptase PCR, or ELISAFootnote 4,Footnote 6,Footnote 44. Many commercial ELISA tests are available, but cross-reactivity with other flaviviruses previously encountered through infection or vaccination can be problematicFootnote 4,Footnote 6,Footnote 44. In the second phase of disease, TBEV can be detected in cerebrospinal fluid using reverse transcriptase PCRFootnote 4.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

There is no available antiviral treatment for TBE; treatment is supportiveFootnote 3,Footnote 4.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which should be developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.


There are two vaccines available in Europe, three in Russia, and one in ChinaFootnote 2,Footnote 3,Footnote 45. FSME-Immun (Baxter, Austria) and Encepur (Novartis Vaccines, Germany) are available in Europe and are approved by the European Medicines AgencyFootnote 3. In Russia, EnceVir (Scientific Production Association Microgen, Russia), TBEV vaccine Moscow and Tick-E-Vac (Federal State Enterprise of Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Russia) are in useFootnote 3. In China, a primary hamster kidney (PHK) cell line TBEV vaccine (SenTaiBao, Changchun Institute of Biological Products Co., Ltd., China) is usedFootnote 45. A vaccine against TBEV is not available in Canada.

No veterinary vaccines are available to date, although a human TBEV vaccine has been used experimentally to immunize goats to prevent alimentary TBEV transmissionFootnote 33. Veterinary vaccine candidates are under developmentFootnote 46.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.


An anti-TBEV immunoglobulin is used as a post-exposure prophylaxis in Russia and Kazakhstan, but is not recommended in EuropeFootnote 3,Footnote 47.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI: Laboratory hazards

Laboratory-acquired infections

Two cases of fatal TBEV infection were acquired while preparing vaccines in Russia in 1938Footnote 3. In 1992, one microbiologist was infected with TBEV; the probable exposure route was via inhalation of infectious aerosols generated during sample centrifugationFootnote 48.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements and guidelines for reporting exposure incidents.


Blood/serum, cerebrospinal fluid, biopsy specimens (e.g., brain, lung, liver, spleen, kidney), milk from infected livestock, and urine can be sources of TBEVFootnote 2.

Primary hazards

Autoinoculation with infectious material and exposure to aerosolized infectious material are the primary hazards associated with TBEV exposure.

Special hazards


Section VII: Exposure controls/personal protection

Risk group classification

TBEV is a Risk Group 4 Human Pathogen and Risk Group 4 Animal PathogenFootnote 49,Footnote 50. TBEV is also a Security Sensitive Biological Agent (SSBA)Footnote 50.

Containment requirements

Containment Level 4 facilities, equipment, and operational practices outlined in the CBS are required for work involving infectious or potentially infectious materials, animals, or cultures.

Note: There are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving TBEV, since it is an SSBA.

Protective clothing

The applicable Containment Level 4 requirements for personal protective equipment (PPE) and clothing outlined in the CBS must be followed. The use of a positive-pressure suit is required for all work with RG4 pathogens unless infectious material is handled exclusively in a Class III biological safety cabinet (BSC).

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of infectious material are to be performed in a certified BSC or other appropriate primary containment device. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a BSC. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects is to be strictly limited. Open wounds, cuts, scratches, and grazes are to be covered with waterproof dressings. Additional precautions are to be considered with work involving animal activities.

Additional information

For diagnostic laboratories handling primary specimens that may contain TBEV, the following resources may be consulted:

Section VIII: Handling and storage


The spill area must be evacuated and secured. Aerosols must be allowed to settle for a minimum of 30 minutes. Spills of potentially contaminated material must be covered with absorbent paper-based material (e.g., paper towels), liberally covered with an effective disinfectant (e.g., 1% sodium hypochlorite), and left to soak for an appropriate amount of time (e.g., 10 minutes) before being wiped up. Following the removal of the initial material, the disinfection process must be repeated. Individuals performing this task must wear PPE, including particulate respirators (e.g., N95 or higher). Disposable gloves, impermeable gowns and protective eye wear are to be removed immediately after completion of the process, placed in an autoclave bag, and decontaminated prior to disposal (CBH).


All materials/substances that have come in contact with the infectious agent must be completely decontaminated before they are removed from the containment zone. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).


The applicable Containment Level 4 requirements for storage outlined in the CBS must be followed. Infectious material must be stored within the containment zone.

SSBA inventory consideration:

Inventory of Risk Group 4 (RG4) pathogens and security sensitive biological agent (SSBA) toxins in long-term storage to be maintained and to include:

Section IX: Regulatory and other information

Canadian regulatory context

Controlled activities with TBEV require a Human Pathogens and Toxins Licence, issued by the Public Health Agency of Canada. TBEV is a non-indigenous animal pathogen in Canada; therefore, importation of TBEV requires an import permit, issued by the Canadian Food Inspection AgencyFootnote 51.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:


November 2022

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.


The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright © Public Health Agency of Canada, 2023, Canada

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