General Characteristics and Epidemiology
Basic features of tick-borne encephalitis virus (TBEV)
- Family: Flaviviridae
- Genus: Flavivirus
- RNA virus
- Icosahedral symmetry
- Size: approximately 50 nm
Clinically relevant species
Tick-borne encephalitis (TBE) is caused by 3 subtypes:
- Far Eastern
TBE is the most common tick-borne CNS infection in Europe and Asia.
- Approximately 10,000–15,000 cases reported annually
- Infections are most common in parts of:
- Former Soviet Union
- Rare in Europe: 1%–2%
- Higher in Asia: 5%–20%
- Ixodes ticks act as both the vector and the reservoir.
- The main hosts are small rodents.
- Humans are accidental hosts.
- Ixodes tick bites in endemic areas:
- Ixodes ricinus (European subtype)
- I. persulcatus (Siberian and Far Eastern subtypes)
- Consumption of raw milk from infected
Host risk factors
Outdoor recreational and occupational activities in endemic regions can increase the risk of acquiring TBEV:
- Forest workers
Viral replication cycle
- Virion interacts with cell surface receptors → endocytosis
- ↓ pH in the endosome → fusion of viral and endosomal membranes → uncoating of the virus
- Viral protein synthesis occurs in the rough endoplasmic reticulum (ER).
- Genomic replication occurs in invaginations of the ER → virions are repackaged and assembled.
- Mature virions leave the cell.
- Tick bite → TBEV is transmitted from the saliva within minutes
- TBEV replication occurs locally in dendritic cells → transported to local lymph nodes
- Disseminates to extraneural tissues:
- Bone marrow
- Continued replication → viremia → initial phase of symptoms
- Eventual spread to the brain (process not understood) → inflammation → neuronal injury → 2nd phase of neurologic symptoms
Most patients are asymptomatic. Symptomatic individuals may have a biphasic course.
- Incubation period: 7–14 days after a tick bite
- Initial viremic phase:
- Asymptomatic interval
- 2nd neurologic phase:
- Acute flaccid paralysis
Diagnosis and Management
Blood or CSF samples can be used for diagnostic testing:
- Serology (ELISA) for IgM antibodies
- Appear 0–6 days after onset
- May be detected if neurologic symptoms are present
- PCR for viral RNA
- CSF studies:
- Neutrophil predominance (early in the disease)
- Lymphocyte predominance (later in the disease)
- Normal glucose
- Normal or slight ↑ protein
- Transaminitis (rare)
There is no specific drug therapy. Management is supportive.
- Use insect repellent.
- Wear protective clothing.
- Pasteurize milk.
- A vaccine is available in endemic areas (not in the United States).
Comparison of Similar Flavivirus Species
|Organism||Tick-borne encephalitis virus||Japanese encephalitis virus||St. Louis encephalitis virus||West Nile virus|
|Characteristics||The structural features are almost identical.|
|Prevention||Mosquito avoidance measures||Mosquito avoidance measures|
- Bacterial meningitis: acute infection of the meninges. Patients with bacterial meningitis present with headache, fever, nuchal rigidity, and rapid clinical deterioration. Lumbar puncture is performed to make the diagnosis. Unlike with viral meningitis, CSF studies will show a turbid fluid, low glucose, and high WBC count with neutrophil predominance. Gram stain and culture will determine the causative bacteria. Treatment includes antibiotics and corticosteroids.
- Lyme disease: tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. The presentation of Lyme disease can vary depending on the stage of the disease and may include the characteristic erythema migrans rash, which is not seen in TBE. Neurologic, cardiac, ocular, and joint manifestations are also common in later stages. The diagnosis relies on clinical findings and tick exposure and is supported by serologic testing. Antibiotics are used for treatment.
- Ehrlichiosis and anaplasmosis: tick-borne infections caused by Ehrlichia chaffeensis and Anaplasmosis phagocytophilum, respectively. Symptoms of ehrlichiosis and anaplasmosis include fever, headache, and malaise. Meningoencephalitis can also occur with severe disease. The diagnosis is made using PCR. Treatment of both diseases is with doxycycline.
- Babesiosis: tick-borne infection caused by Babesia. Patients with babesiosis can be asymptomatic or develop fever, fatigue, malaise, and arthralgias. Asplenic, immunocompromised, and elderly patients are at risk for severe disease, which causes neurologic symptoms, hemolytic anemia, thrombocytopenia, hepatosplenomegaly, renal failure, and death. Diagnosis is confirmed with a peripheral blood smear, serologic testing, and PCR. Management includes antimicrobials such as atovaquone plus azithromycin.
- Tularemia: infection caused by Francisella tularensis. The presentation of tularemia depends on the type of exposure and can include ulcerations, nonspecific systemic symptoms, ocular disease, lymphadenitis, pneumonia, mediastinitis, or meningitis. Diagnosis is made with cultures, serology, and PCR testing. Antibiotics are used for treatment.
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