Tick-Borne Encephalitis

◆

Subtypes

3

European Subtype (TBEV-Eu)

Transmitted primarily by Ixodes ricinus across Europe; typically produces a biphasic illness with a case fatality rate below 2%.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Ixodes ricinus is the main vector for the European subtype TBE virus and Ixodes persulcatus for the Siberian and Far Eastern subtype viruses"

Identifies Ixodes ricinus as the main vector for the European subtype TBE virus.

Siberian Subtype (TBEV-Sib)

Transmitted primarily by Ixodes persulcatus in Siberia, the Baltic region, and northern Europe; associated with a 2% to 3% case fatality rate and rare chronic or progressive neurological disease.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Ixodes ricinus is the main vector for the European subtype TBE virus and Ixodes persulcatus for the Siberian and Far Eastern subtype viruses"

Identifies Ixodes persulcatus as the primary vector for the Siberian subtype TBE virus.

Far Eastern Subtype (TBEV-FE)

Transmitted primarily by Ixodes persulcatus in eastern Russia, China, and Japan; causes the most severe clinical course with monophasic presentation and higher fatality rates.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Ixodes ricinus is the main vector for the European subtype TBE virus and Ixodes persulcatus for the Siberian and Far Eastern subtype viruses"

Identifies Ixodes persulcatus as the primary vector for the Far Eastern subtype TBE virus.

⚙

Pathophysiology

2

Cutaneous Inoculation, Peripheral Viral Replication, and Primary Viremia

Following inoculation of TBEV via tick bite into the skin (or across the gastrointestinal tract after dairy ingestion), the virus replicates locally in cutaneous dendritic cells, drains to regional lymph nodes, and establishes a primary viremia that causes the first febrile phase of biphasic illness with transient bone marrow suppression (leukopenia and thrombocytopenia) and mild hepatic injury.

dendritic cell CL:0000451

viral genome replication GO:0019079 ↑ INCREASED

zone of skin UBERON:0000014 lymph node UBERON:0000029 blood UBERON:0000178

Downstream

Neuroinvasion and Central Nervous System Inflammation In a subset of infected individuals, peripheral viremia breaches the blood-brain barrier to invade the meninges, brain parenchyma, and spinal cord.

Fever Systemic viremia and innate cytokine release trigger the initial febrile phase.

Headache Systemic viral replication and inflammatory cytokines produce headache during the initial viremic phase.

Leukopenia Transient viral bone marrow suppression during primary viremia causes leukopenia.

Thrombocytopenia Transient bone marrow suppression and peripheral platelet consumption during primary viremia cause thrombocytopenia.

Show evidence (2 references)

PMID:37943707 SUPPORT Human clinical

"When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting)."

Describes the initial viremic phase of biphasic TBE illness.

PMID:37943707 SUPPORT Human clinical

"In the initial phase of a biphasic illness, findings can include leukopenia, thrombocytopenia, or elevated hepatic enzymes"

Documents systemic hematologic and hepatic manifestations during the initial viremic phase.

Neuroinvasion and Central Nervous System Inflammation

During the second phase of illness, TBEV crosses the blood-brain barrier and infects neurons across the meninges, cerebral cortex, brainstem, cerebellum, and spinal cord anterior horns, provoking lymphocytic CSF pleocytosis and meningeal and parenchymal neuroinflammation that manifests clinically as meningitis, meningoencephalitis, or meningoencephalomyelitis.

neuron CL:0000540

inflammatory response GO:0006954 ↑ INCREASED

central nervous system UBERON:0001017 meninx UBERON:0002360 cerebrospinal fluid UBERON:0001359

Downstream

Meningitis Meningeal viral invasion and lymphocytic inflammation cause acute meningitis.

Infectious encephalitis Viral infection of brain parenchyma produces meningoencephalitis with cognitive dysfunction, ataxia, and tremor.

Headache Meningeal inflammation and elevated intracranial pressure cause severe headache in the neuroinvasive phase.

Ataxia Cerebellar and brainstem neuronal infection and neuroinflammation cause cerebellar ataxia.

Tremor Basal ganglia, brainstem, and cerebellar involvement during meningoencephalitis produces extremity and tongue tremors.

Show evidence (2 references)

PMID:37943707 SUPPORT Human clinical

"Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"

Quantifies the clinical spectrum of central nervous system involvement in TBE.

PMID:37943707 SUPPORT Human clinical

"Cerebrospinal fluid (CSF) testing usually indicates a pleocytosis, typically lymphocytic, with moderately elevated protein levels"

Confirms lymphocytic CSF pleocytosis as a hallmark of CNS inflammation in TBE.

⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

8

Blood 2

Leukopenia FREQUENT Decreased total leukocyte count HP:0001882

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"In the initial phase of a biphasic illness, findings can include leukopenia, thrombocytopenia, or elevated hepatic enzymes"

Identifies leukopenia as a laboratory finding in the first phase of biphasic TBE.

Thrombocytopenia FREQUENT HP:0001873

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"In the initial phase of a biphasic illness, findings can include leukopenia, thrombocytopenia, or elevated hepatic enzymes"

Identifies thrombocytopenia as a laboratory finding in the first phase of biphasic TBE.

Immune 2

Meningitis FREQUENT HP:0001287

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"

Reports meningitis in 35% to 45% of clinical TBE cases.

Infectious encephalitis FREQUENT HP:0002383

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"

Reports meningoencephalitis in 45% to 55% of patients with clinical TBE.

Metabolism 1

Fever VERY_FREQUENT HP:0001945

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting)."

Documents fever as a characteristic symptom of the initial viremic phase.

Nervous System 3

Headache VERY_FREQUENT HP:0002315

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting)."

Documents headache during TBE illness.

Ataxia OCCASIONAL HP:0001251

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Neurologic signs and symptoms of TBE vary but can include meningeal signs, altered mental status, cognitive dysfunction (e.g., decreased concentration and memory impairment), ataxia, rigidity, tremors, and cranial nerve and limb paresis or palsies."

Lists ataxia among characteristic neurologic signs of TBE.

Tremor OCCASIONAL HP:0001337

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Neurologic signs and symptoms of TBE vary but can include meningeal signs, altered mental status, cognitive dysfunction (e.g., decreased concentration and memory impairment), ataxia, rigidity, tremors, and cranial nerve and limb paresis or palsies."

Lists tremors among the neurologic manifestations of TBE.

💊

Medical Actions

2

Inactivated Tick-Borne Encephalitis Vaccination (FSME-IMMUN / TICOVAC)

Action: vaccination Ontology label: Vaccination NCIT:C15346

Platform: Vaccine

Three-dose primary immunization series with formaldehyde-inactivated, whole-virus European subtype TBE vaccine (TICOVAC / FSME-IMMUN) induces neutralizing antibodies in 99% of seronegative adults (GMT 259 at 21-28 days post-dose 3) and confers 91% to 99% vaccine effectiveness against clinical TBE and hospitalization. Older adults achieve lower post-vaccination neutralizing antibody titers and experience more rapid seroreversion over time.

Mechanism Target:

INHIBITS Cutaneous Inoculation, Peripheral Viral Replication, and Primary Viremia — Vaccine-induced E-glycoprotein neutralizing antibodies neutralize TBEV following tick inoculation and prevent systemic viremia and neuroinvasion.

Show evidence (1 reference)

PMID:37943707 SUPPORT INDIRECT Human clinical

"TBE virus neutralizing antibodies are believed to confer protection against disease on the basis of animal and human studies"

Establishes neutralizing antibody-mediated block of infection and disease progression.

Effect differs by subgroup:

age older adults vs younger adults — smaller effect on post-vaccination neutralizing antibody geometric mean titer and persistence

Older adults mount lower post-primary neutralizing antibody titers than younger adults and have higher rates of seroreversion over time after vaccination.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Overall, seropositivity rates immediately after completion of the 3-dose primary series are high among older persons but levels of neutralizing antibodies are lower than among younger adults. Over time postvaccination, lower neutralizing antibody levels continue to be observed among older adults..."

Demonstrates age-related reduction in neutralizing antibody levels and durability after TBE vaccination.

Show evidence (3 references)

PMID:37943707 SUPPORT Human clinical

"The vaccine is an inactivated, whole virus vaccine, prepared using a European subtype TBE virus."

Describes the composition of the licensed TBE vaccine.

PMID:37943707 SUPPORT Human clinical

"Overall, VE estimates for the European subtype virus TBE vaccines against disease caused by the European subtype virus after ≥3 doses of vaccine are 91%–99% for prevention of various outcomes (e.g., all TBE disease and hospitalization)"

Documents 91% to 99% real-world vaccine effectiveness after at least 3 doses.

PMID:37943707 SUPPORT Human clinical

"Among 416 adults seronegative at baseline, 411 (99%) were seropositive at 21–28 days after dose 3 of the primary series with a geometric mean titer (GMT) of 259 (95% CI = 235–285)."

Reports 99% seropositivity and neutralizing GMT of 259 after the 3-dose primary series in adults.

Supportive Care

Action: supportive care Ontology label: Supportive Care NCIT:C15747

No specific antiviral therapy is licensed for TBE; clinical management consists of supportive care, symptom control, and management of neurologic and secondary complications.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"No specific antiviral treatment for TBE is available. Patient management consists of supportive care, treatment of symptoms, and interventions to prevent secondary complications"

Confirms supportive care as the standard clinical management in the absence of specific antiviral therapy.

🔬

Diagnosis

1

TBE Virus-Specific IgM ELISA and Plaque Reduction Neutralization Test (PRNT)

Laboratory diagnosis of tick-borne encephalitis is established primarily by detection of TBEV-specific IgM and IgG antibodies in serum or cerebrospinal fluid by ELISA at the onset of neurologic symptoms, confirmed by plaque reduction neutralization testing (PRNT) to exclude flavivirus cross-reactivity or demonstrate a >=4-fold neutralizing titer rise between acute and convalescent sera.

laboratory examination NCIT:C25294

Show evidence (2 references)

PMID:37943707 SUPPORT Human clinical

"The laboratory diagnosis of TBE usually is based on detection of virus-specific immunoglobulin M (IgM) antibody in CSF or serum ( 180). An IgM enzyme-linked immunosorbent assay is routinely used for testing samples and usually is positive when neurologic symptoms are present."

Establishes CSF or serum TBEV-specific IgM ELISA as the routine diagnostic assay during the neurologic phase.

PMID:37943707 SUPPORT Human clinical

"Plaque reduction neutralization tests can be performed to discriminate between cross-reacting antibodies attributable to another primary flavivirus infection or to confirm recent TBE virus infection on the basis of a fourfold or higher increase in virus-specific neutralizing antibodies between..."

Establishes PRNT as the confirmatory serological test to distinguish TBEV from cross-reactive flavivirus antibodies.

📈

Progression

3

Incubation Phase

Duration: 7-14 days after tick bite (range 2-28 days)

Following an infected Ixodes tick bite, the typical incubation period is 7 to 14 days (shorter, 3 to 4 days, after alimentary dairy transmission).

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Among patients who develop clinical symptoms after a bite from an infected tick, the incubation period is typically 7–14 days (range = 2–28 days)"

Documents the typical 7- to 14-day incubation period after an infected tick bite.

First (Viremic Febrile) Phase and Asymptomatic Remission

Duration: Median 4 days febrile illness followed by ~7 days remission

In biphasic illness, an initial nonspecific febrile phase with headache, myalgia, leukopenia, and thrombocytopenia lasts a median of ~4 days, followed by an asymptomatic remission interval of ~7 days before onset of neurologic disease.

Show evidence (2 references)

PMID:37943707 SUPPORT Human clinical

"When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting). These symptoms usually last for a median of approximately 4 days (range = 1–10 days), followed by a period of remission of"

Quantifies the duration of the initial viremic febrile phase (median ~4 days, range 1-10 days) in biphasic TBE.

PMID:37943707 SUPPORT Human clinical

"approximately 7 days (range = 1–33 days), followed by the second (neurologic) phase"

Quantifies the duration of the asymptomatic remission period (~7 days, range 1-33 days) preceding the second neurologic phase.

Second (Neuroinvasive) Phase and Chronic Neurological Sequelae

Central nervous system invasion manifests as meningitis (35%-45%), meningoencephalitis (45%-55%), or meningoencephalomyelitis (10%), and can be followed by long-term neurological sequelae.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"

Characterizes the clinical spectrum of the second (neurologic) phase of TBE.

📊

Prevalence

1

Endemic regions of Europe and Asia

Annual incidence

Approximately 5,000 to 10,000 new cases of tick-borne encephalitis are reported annually across endemic regions of Europe and Asia.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"In areas where TBE is endemic, approximately 5,000–10,000 new cases are reported annually"

Reports annual incidence of 5,000 to 10,000 TBE cases across endemic areas.

🦠

Infectious Agent

1

Tick-borne encephalitis virus

Single-stranded, positive-sense RNA orthoflavivirus of the family Flaviviridae comprising three main antigenic subtypes (European, Siberian, and Far Eastern) that share closely related envelope (E) glycoprotein neutralizing epitopes.

Tick-borne encephalitis virus NCBITaxon:11084

Show evidence (1 reference)

PMID:37943707 SUPPORT Other

"TBE virus is a single-stranded RNA virus in the genus Flavivirus, family Flaviviridae (4). TBE virus is closely related to Powassan virus, a tickborne flavivirus transmitted in parts of the United States (5). The three main antigenic subtypes of TBE virus (i.e., European, Siberian, and Far..."

Establishes the viral classification and three main subtypes of tick-borne encephalitis virus.

↔️

Transmission

2

Ixodes tick bite transmission

Primary transmission occurs through the bite of an infected Ixodes ricinus or Ixodes persulcatus tick, with virus inoculated in tick saliva almost immediately upon attachment.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"TBE virus is primarily transmitted to humans by the bites of infected Ixodes sp. ticks but can also be acquired less frequently by alimentary transmission."

Documents tick bites from infected Ixodes species as the primary route of human transmission.

Alimentary transmission via unpasteurized dairy

Secondary foodborne transmission occurs after ingestion of unpasteurized milk or cheese from viremic goats, sheep, or cattle.

Show evidence (1 reference)

PMID:37943707 SUPPORT Human clinical

"Alimentary transmission is a less frequent means of acquisition of TBE virus and occurs after ingestion of unpasteurized dairy products (e.g., milk and cheese) from infected cattle, goats, or sheep; transmission from goats is most commonly reported"

Documents alimentary transmission via unpasteurized dairy products from infected domestic ruminants.

{ }

Source YAML

click to show

name: Tick-Borne Encephalitis
creation_date: '2026-10-25T20:00:00Z'
category: Infectious Disease
description: >-
  Tick-borne encephalitis (TBE) is a neuroinvasive flavivirus infection caused
  by tick-borne encephalitis virus (TBEV), transmitted primarily by the bite of
  infected Ixodes ticks (Ixodes ricinus in Europe and Ixodes persulcatus in
  Siberia and the Far East) and less frequently by ingestion of unpasteurized
  dairy products from infected ruminants. Symptomatic European-subtype infection
  characteristically follows a biphasic course, with an initial nonspecific
  viremic febrile phase accompanied by leukopenia and thrombocytopenia, followed
  after an asymptomatic interval by central nervous system invasion presenting
  as meningitis, meningoencephalitis, or meningoencephalomyelitis.
disease_term:
  preferred_term: tick-borne encephalitis
  term:
    id: MONDO:0017572
    label: tick-borne encephalitis
parents:
- Arbovirus Infection
- Viral Encephalitis
synonyms:
- TBE
- Central European encephalitis
- Russian spring-summer encephalitis
- Far Eastern tick-borne encephalitis
has_subtypes:
- name: European Subtype (TBEV-Eu)
  description: >-
    Transmitted primarily by Ixodes ricinus across Europe; typically produces a
    biphasic illness with a case fatality rate below 2%.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ixodes ricinus is the main vector for the European subtype TBE virus and Ixodes persulcatus for the Siberian and Far Eastern subtype viruses"
    explanation: Identifies Ixodes ricinus as the main vector for the European subtype TBE virus.
- name: Siberian Subtype (TBEV-Sib)
  description: >-
    Transmitted primarily by Ixodes persulcatus in Siberia, the Baltic region,
    and northern Europe; associated with a 2% to 3% case fatality rate and rare
    chronic or progressive neurological disease.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ixodes ricinus is the main vector for the European subtype TBE virus and Ixodes persulcatus for the Siberian and Far Eastern subtype viruses"
    explanation: Identifies Ixodes persulcatus as the primary vector for the Siberian subtype TBE virus.
- name: Far Eastern Subtype (TBEV-FE)
  description: >-
    Transmitted primarily by Ixodes persulcatus in eastern Russia, China, and
    Japan; causes the most severe clinical course with monophasic presentation
    and higher fatality rates.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ixodes ricinus is the main vector for the European subtype TBE virus and Ixodes persulcatus for the Siberian and Far Eastern subtype viruses"
    explanation: Identifies Ixodes persulcatus as the primary vector for the Far Eastern subtype TBE virus.
infectious_agent:
- name: Tick-borne encephalitis virus
  description: >-
    Single-stranded, positive-sense RNA orthoflavivirus of the family
    Flaviviridae comprising three main antigenic subtypes (European, Siberian,
    and Far Eastern) that share closely related envelope (E) glycoprotein
    neutralizing epitopes.
  infectious_agent_term:
    preferred_term: Tick-borne encephalitis virus
    term:
      id: NCBITaxon:11084
      label: Tick-borne encephalitis virus
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "TBE virus is a single-stranded RNA virus in the genus Flavivirus, family Flaviviridae (4). TBE virus is closely related to Powassan virus, a tickborne flavivirus transmitted in parts of the United States (5). The three main antigenic subtypes of TBE virus (i.e., European, Siberian, and Far Eastern) differ in the severity of disease they cause and geographic distribution"
    explanation: Establishes the viral classification and three main subtypes of tick-borne encephalitis virus.
agent_life_cycle:
  description: >-
    TBEV is maintained in natural foci between hard ticks (Ixodes ricinus and
    Ixodes persulcatus) and small woodland rodent reservoirs; domestic
    ruminants (goats, sheep, cattle) can become viremic and shed virus in milk,
    while humans are incidental dead-end hosts.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: incidental dead-end host
  - preferred_term: Ixodes ricinus
    term:
      id: NCBITaxon:34613
      label: Ixodes ricinus
    role: vector
  - preferred_term: Ixodes persulcatus
    term:
      id: NCBITaxon:34615
      label: Ixodes persulcatus
    role: vector
  - preferred_term: goat
    term:
      id: NCBITaxon:9925
      label: Capra hircus
    role: intermediate amplifying host for alimentary transmission
transmission:
- name: Ixodes tick bite transmission
  description: >-
    Primary transmission occurs through the bite of an infected Ixodes ricinus
    or Ixodes persulcatus tick, with virus inoculated in tick saliva almost
    immediately upon attachment.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "TBE virus is primarily transmitted to humans by the bites of infected Ixodes sp. ticks but can also be acquired less frequently by alimentary transmission."
    explanation: Documents tick bites from infected Ixodes species as the primary route of human transmission.
- name: Alimentary transmission via unpasteurized dairy
  description: >-
    Secondary foodborne transmission occurs after ingestion of unpasteurized
    milk or cheese from viremic goats, sheep, or cattle.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Alimentary transmission is a less frequent means of acquisition of TBE virus and occurs after ingestion of unpasteurized dairy products (e.g., milk and cheese) from infected cattle, goats, or sheep; transmission from goats is most commonly reported"
    explanation: Documents alimentary transmission via unpasteurized dairy products from infected domestic ruminants.
prevalence:
- population: Endemic regions of Europe and Asia
  measure_type: ANNUAL_INCIDENCE
  rate_denominator: POPULATION_PER_YEAR
  notes: >-
    Approximately 5,000 to 10,000 new cases of tick-borne encephalitis are
    reported annually across endemic regions of Europe and Asia.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In areas where TBE is endemic, approximately 5,000–10,000 new cases are reported annually"
    explanation: Reports annual incidence of 5,000 to 10,000 TBE cases across endemic areas.
progression:
- phase: Incubation Phase
  duration: 7-14 days after tick bite (range 2-28 days)
  notes: >-
    Following an infected Ixodes tick bite, the typical incubation period is 7
    to 14 days (shorter, 3 to 4 days, after alimentary dairy transmission).
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among patients who develop clinical symptoms after a bite from an infected tick, the incubation period is typically 7–14 days (range = 2–28 days)"
    explanation: Documents the typical 7- to 14-day incubation period after an infected tick bite.
- phase: First (Viremic Febrile) Phase and Asymptomatic Remission
  duration: Median 4 days febrile illness followed by ~7 days remission
  notes: >-
    In biphasic illness, an initial nonspecific febrile phase with headache,
    myalgia, leukopenia, and thrombocytopenia lasts a median of ~4 days,
    followed by an asymptomatic remission interval of ~7 days before onset of
    neurologic disease.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting). These symptoms usually last for a median of approximately 4 days (range = 1–10 days), followed by a period of remission of"
    explanation: Quantifies the duration of the initial viremic febrile phase (median ~4 days, range 1-10 days) in biphasic TBE.
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "approximately 7 days (range = 1–33 days), followed by the second (neurologic) phase"
    explanation: Quantifies the duration of the asymptomatic remission period (~7 days, range 1-33 days) preceding the second neurologic phase.
- phase: Second (Neuroinvasive) Phase and Chronic Neurological Sequelae
  notes: >-
    Central nervous system invasion manifests as meningitis (35%-45%),
    meningoencephalitis (45%-55%), or meningoencephalomyelitis (10%), and can
    be followed by long-term neurological sequelae.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"
    explanation: Characterizes the clinical spectrum of the second (neurologic) phase of TBE.
pathophysiology:
- name: Cutaneous Inoculation, Peripheral Viral Replication, and Primary Viremia
  description: >-
    Following inoculation of TBEV via tick bite into the skin (or across the
    gastrointestinal tract after dairy ingestion), the virus replicates locally
    in cutaneous dendritic cells, drains to regional lymph nodes, and
    establishes a primary viremia that causes the first febrile phase of
    biphasic illness with transient bone marrow suppression (leukopenia and
    thrombocytopenia) and mild hepatic injury.
  role: trigger
  biological_scale: ORGANISM
  locations:
  - preferred_term: zone of skin
    term:
      id: UBERON:0000014
      label: zone of skin
  - preferred_term: lymph node
    term:
      id: UBERON:0000029
      label: lymph node
  - preferred_term: blood
    term:
      id: UBERON:0000178
      label: blood
  cell_types:
  - preferred_term: dendritic cell
    term:
      id: CL:0000451
      label: dendritic cell
  biological_processes:
  - preferred_term: viral genome replication
    modifier: INCREASED
    term:
      id: GO:0019079
      label: viral genome replication
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting)."
    explanation: Describes the initial viremic phase of biphasic TBE illness.
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In the initial phase of a biphasic illness, findings can include leukopenia, thrombocytopenia, or elevated hepatic enzymes"
    explanation: Documents systemic hematologic and hepatic manifestations during the initial viremic phase.
  downstream:
  - target: Neuroinvasion and Central Nervous System Inflammation
    description: >-
      In a subset of infected individuals, peripheral viremia breaches the
      blood-brain barrier to invade the meninges, brain parenchyma, and spinal
      cord.
    causal_link_type: DIRECT
  - target: Fever
    description: Systemic viremia and innate cytokine release trigger the initial febrile phase.
  - target: Headache
    description: Systemic viral replication and inflammatory cytokines produce headache during the initial viremic phase.
  - target: Leukopenia
    description: Transient viral bone marrow suppression during primary viremia causes leukopenia.
  - target: Thrombocytopenia
    description: Transient bone marrow suppression and peripheral platelet consumption during primary viremia cause thrombocytopenia.
- name: Neuroinvasion and Central Nervous System Inflammation
  description: >-
    During the second phase of illness, TBEV crosses the blood-brain barrier and
    infects neurons across the meninges, cerebral cortex, brainstem, cerebellum,
    and spinal cord anterior horns, provoking lymphocytic CSF pleocytosis and
    meningeal and parenchymal neuroinflammation that manifests clinically as
    meningitis, meningoencephalitis, or meningoencephalomyelitis.
  role: central_effector
  biological_scale: TISSUE
  locations:
  - preferred_term: central nervous system
    term:
      id: UBERON:0001017
      label: central nervous system
  - preferred_term: meninx
    term:
      id: UBERON:0002360
      label: meninx
  - preferred_term: cerebrospinal fluid
    term:
      id: UBERON:0001359
      label: cerebrospinal fluid
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"
    explanation: Quantifies the clinical spectrum of central nervous system involvement in TBE.
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cerebrospinal fluid (CSF) testing usually indicates a pleocytosis, typically lymphocytic, with moderately elevated protein levels"
    explanation: Confirms lymphocytic CSF pleocytosis as a hallmark of CNS inflammation in TBE.
  downstream:
  - target: Meningitis
    description: Meningeal viral invasion and lymphocytic inflammation cause acute meningitis.
  - target: Infectious encephalitis
    description: Viral infection of brain parenchyma produces meningoencephalitis with cognitive dysfunction, ataxia, and tremor.
  - target: Headache
    description: Meningeal inflammation and elevated intracranial pressure cause severe headache in the neuroinvasive phase.
  - target: Ataxia
    description: Cerebellar and brainstem neuronal infection and neuroinflammation cause cerebellar ataxia.
  - target: Tremor
    description: Basal ganglia, brainstem, and cerebellar involvement during meningoencephalitis produces extremity and tongue tremors.
phenotypes:
- name: Fever
  category: Constitutional
  frequency: VERY_FREQUENT
  description: Fever occurs in both phases of biphasic TBE illness.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting)."
    explanation: Documents fever as a characteristic symptom of the initial viremic phase.
- name: Headache
  category: Neurological
  frequency: VERY_FREQUENT
  description: Headache is a prominent feature of both the initial febrile phase and the subsequent meningeal phase.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When biphasic illness occurs, the initial phase includes nonspecific symptoms (e.g., fever, headache, malaise, myalgia, nausea, and vomiting)."
    explanation: Documents headache during TBE illness.
- name: Meningitis
  category: Neurological
  frequency: FREQUENT
  description: Isolated aseptic meningitis occurs in approximately 35% to 45% of clinical TBE patients.
  phenotype_term:
    preferred_term: Meningitis
    term:
      id: HP:0001287
      label: Meningitis
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"
    explanation: Reports meningitis in 35% to 45% of clinical TBE cases.
- name: Infectious encephalitis
  category: Neurological
  frequency: FREQUENT
  description: Meningoencephalitis occurs in 45% to 55% of clinical TBE cases and meningoencephalomyelitis in 10%.
  phenotype_term:
    preferred_term: Infectious encephalitis
    term:
      id: HP:0002383
      label: Infectious encephalitis
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, meningitis is reported in approximately 35%–45% of patients, meningoencephalitis in 45%–55%, and meningoencephalomyelitis in 10%"
    explanation: Reports meningoencephalitis in 45% to 55% of patients with clinical TBE.
- name: Ataxia
  category: Neurological
  frequency: OCCASIONAL
  description: Cerebellar ataxia is a characteristic neurologic sign during the meningoencephalitic phase.
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurologic signs and symptoms of TBE vary but can include meningeal signs, altered mental status, cognitive dysfunction (e.g., decreased concentration and memory impairment), ataxia, rigidity, tremors, and cranial nerve and limb paresis or palsies."
    explanation: Lists ataxia among characteristic neurologic signs of TBE.
- name: Tremor
  category: Neurological
  frequency: OCCASIONAL
  description: Tremors of the extremities and tongue occur in patients with TBE meningoencephalitis.
  phenotype_term:
    preferred_term: Tremor
    term:
      id: HP:0001337
      label: Tremor
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurologic signs and symptoms of TBE vary but can include meningeal signs, altered mental status, cognitive dysfunction (e.g., decreased concentration and memory impairment), ataxia, rigidity, tremors, and cranial nerve and limb paresis or palsies."
    explanation: Lists tremors among the neurologic manifestations of TBE.
- name: Leukopenia
  category: Hematologic
  frequency: FREQUENT
  description: Transient leukopenia is a characteristic laboratory abnormality during the initial viremic phase.
  phenotype_term:
    preferred_term: Leukopenia
    term:
      id: HP:0001882
      label: Decreased total leukocyte count
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In the initial phase of a biphasic illness, findings can include leukopenia, thrombocytopenia, or elevated hepatic enzymes"
    explanation: Identifies leukopenia as a laboratory finding in the first phase of biphasic TBE.
- name: Thrombocytopenia
  category: Hematologic
  frequency: FREQUENT
  description: Transient thrombocytopenia frequently accompanies leukopenia in the initial viremic phase of TBE.
  phenotype_term:
    preferred_term: Thrombocytopenia
    term:
      id: HP:0001873
      label: Thrombocytopenia
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In the initial phase of a biphasic illness, findings can include leukopenia, thrombocytopenia, or elevated hepatic enzymes"
    explanation: Identifies thrombocytopenia as a laboratory finding in the first phase of biphasic TBE.
diagnosis:
- name: TBE Virus-Specific IgM ELISA and Plaque Reduction Neutralization Test (PRNT)
  description: >-
    Laboratory diagnosis of tick-borne encephalitis is established primarily by
    detection of TBEV-specific IgM and IgG antibodies in serum or cerebrospinal
    fluid by ELISA at the onset of neurologic symptoms, confirmed by plaque
    reduction neutralization testing (PRNT) to exclude flavivirus
    cross-reactivity or demonstrate a >=4-fold neutralizing titer rise between
    acute and convalescent sera.
  diagnosis_term:
    preferred_term: laboratory examination
    term:
      id: NCIT:C25294
      label: Laboratory Procedure
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The laboratory diagnosis of TBE usually is based on detection of virus-specific immunoglobulin M (IgM) antibody in CSF or serum ( 180). An IgM enzyme-linked immunosorbent assay is routinely used for testing samples and usually is positive when neurologic symptoms are present."
    explanation: Establishes CSF or serum TBEV-specific IgM ELISA as the routine diagnostic assay during the neurologic phase.
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Plaque reduction neutralization tests can be performed to discriminate between cross-reacting antibodies attributable to another primary flavivirus infection or to confirm recent TBE virus infection on the basis of a fourfold or higher increase in virus-specific neutralizing antibodies between acute- and convalescent-phase serum specimens."
    explanation: Establishes PRNT as the confirmatory serological test to distinguish TBEV from cross-reactive flavivirus antibodies.
treatments:
- name: Inactivated Tick-Borne Encephalitis Vaccination (FSME-IMMUN / TICOVAC)
  description: >-
    Three-dose primary immunization series with formaldehyde-inactivated,
    whole-virus European subtype TBE vaccine (TICOVAC / FSME-IMMUN) induces
    neutralizing antibodies in 99% of seronegative adults (GMT 259 at 21-28 days
    post-dose 3) and confers 91% to 99% vaccine effectiveness against clinical
    TBE and hospitalization. Older adults achieve lower post-vaccination
    neutralizing antibody titers and experience more rapid seroreversion over
    time.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  target_mechanisms:
  - target: Cutaneous Inoculation, Peripheral Viral Replication, and Primary Viremia
    treatment_effect: INHIBITS
    description: >-
      Vaccine-induced E-glycoprotein neutralizing antibodies neutralize TBEV
      following tick inoculation and prevent systemic viremia and neuroinvasion.
    evidence:
    - reference: PMID:37943707
      reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "TBE virus neutralizing antibodies are believed to confer protection against disease on the basis of animal and human studies"
      explanation: Establishes neutralizing antibody-mediated block of infection and disease progression.
  effect_modifiers:
  - effect_modifier_type: AGE
    stratum: older adults
    comparator_stratum: younger adults
    modified_outcome: post-vaccination neutralizing antibody geometric mean titer and persistence
    effect_in_stratum: SMALLER_EFFECT
    description: >-
      Older adults mount lower post-primary neutralizing antibody titers than
      younger adults and have higher rates of seroreversion over time after
      vaccination.
    evidence:
    - reference: PMID:37943707
      reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Overall, seropositivity rates immediately after completion of the 3-dose primary series are high among older persons but levels of neutralizing antibodies are lower than among younger adults. Over time postvaccination, lower neutralizing antibody levels continue to be observed among older adults and they are more likely to become seronegative."
      explanation: Demonstrates age-related reduction in neutralizing antibody levels and durability after TBE vaccination.
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The vaccine is an inactivated, whole virus vaccine, prepared using a European subtype TBE virus."
    explanation: Describes the composition of the licensed TBE vaccine.
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, VE estimates for the European subtype virus TBE vaccines against disease caused by the European subtype virus after ≥3 doses of vaccine are 91%–99% for prevention of various outcomes (e.g., all TBE disease and hospitalization)"
    explanation: Documents 91% to 99% real-world vaccine effectiveness after at least 3 doses.
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among 416 adults seronegative at baseline, 411 (99%) were seropositive at 21–28 days after dose 3 of the primary series with a geometric mean titer (GMT) of 259 (95% CI = 235–285)."
    explanation: Reports 99% seropositivity and neutralizing GMT of 259 after the 3-dose primary series in adults.
- name: Supportive Care
  description: >-
    No specific antiviral therapy is licensed for TBE; clinical management
    consists of supportive care, symptom control, and management of neurologic
    and secondary complications.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:37943707
    reference_title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No specific antiviral treatment for TBE is available. Patient management consists of supportive care, treatment of symptoms, and interventions to prevent secondary complications"
    explanation: Confirms supportive care as the standard clinical management in the absence of specific antiviral therapy.
references:
- reference: PMID:37943707
  title: "Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023."
  findings: []

📚

References & Deep Research

References

1

PMID:37943707

Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023.

No top-level findings curated for this source.

Tick-Borne Encephalitis

Ask OpenScientist

OpenScientist Report

Subtypes

Pathophysiology

Pathograph

Phenotypes

Medical Actions

Diagnosis

Progression

Prevalence

Infectious Agent

Transmission

Source YAML

References & Deep Research

References