Discovery and Virion Morphology
TBEV was discovered in 1937 in the Far East by an expedition led by L.A. Zilber. The pathogen was isolated from the brains of deceased patients, patient blood, as well as from ticks and wild vertebrates. Taxonomically, the pathogen belongs to the family Flaviviridae (genus Flavivirus) and is a typical representative of the tick-borne encephalitis complex. The virion possesses a lipoprotein envelope enclosing a single-stranded positive-sense RNA. Among structural proteins, the surface glycoprotein E (dimer) is key. It determines cell tropism, carries viscerotropism and neurovirulence determinants, and acts as the main immunogen (inducing virus-neutralizing antibodies). Non-structural proteins (NS1–NS5) and viral RNA polymerase are responsible for replication.
Variability and Resistance
The virus exhibits high geographical and intrapopulation variability. Three main antigenically distinct genotypes are distinguished:
- Far Eastern.
- European.
- Ural-Siberian.
Despite these differences, structural protein E induces cross-protection common to all viral variants.
In the external environment, TBEV has low stability against physical and chemical factors. However, within the vector organism, it survives a vast temperature range (from –150 to +30 °C). An important clinical feature is its resistance to acidic environments, allowing the virus to overcome the gastric barrier during alimentary transmission.
Epidemiology: Reservoirs and Transmission Routes
The main reservoirs and vectors are hard ticks — Ixodes persulcatus (taiga tick) and Ixodes ricinis (castor bean tick). Within their bodies (gastrointestinal tract and salivary glands), the virus actively replicates and persists for life. Ticks transmit the pathogen transstadially (through molting from larva to nymph and adult) and transovarially (via eggs to progeny). Maintenance of the viral population requires vertebrate and avian hosts.
Humans (dead-end hosts for the virus) are infected through three routes:
- Transmissively: via the bite or crawling of an infected tick.
- Contact: through skin microtraumas, for example, when crushing a tick with bare hands.
- Alimentarily: by consuming raw goat and sheep milk, leading to two-wave meningoencephalitis ("milk fever").
Pathogenesis and Clinical Forms
The incubation period lasts from 8 to 28 days. Pathogenesis includes visceral and neural stages. Following primary replication at the portal of entry, the virus enters the bloodstream (viremia), settling in lymph nodes, the spleen, and vascular endothelium. Secondary viremia lasts about 5 days and coincides with the onset of fever and intoxication.
CNS invasion occurs via hematogenous and likely perineuronal pathways. The pathogen selectively attacks large motor neurons of the anterior horns of the spinal cord and cranial nerve nuclei in the brainstem. Viral accumulation causes necrosis of these motor neurons, clinically manifesting as flaccid paresis and paralysis.
Acute clinical forms include:
- Febrile (mild) — favorable outcome.
- Meningeal — favorable outcome.
- Focal (paralytic) — includes meningoencephalitic, poliomyelitic, and polyradiculoneuritic subtypes. Mortality reaches 15–20%, and sequelae include persistent paralysis and contractures.
Chronic Infection and Slow Viral Infection
In 2–12% of cases, the disease takes a progressive course. TBEV acts as an optional agent of slow infections. Chronicity develops despite active antibody synthesis, which fails to protect the organism.
The persistence mechanism relies on the virus remaining strictly intracellular: it does not express its antigens on the cell membrane and causes no cytopathic effect (CPE). Thus, the infected cell escapes immune surveillance. The course may be primary progressive (without a distinct acute phase) or secondary progressive.
Diagnosis and Prophylaxis
Diagnosis is confirmed by isolating the agent (in cell cultures or via intracerebral mouse inoculation), serologically (rising titers in complement fixation, hemagglutination inhibition, and IgM detection via ELISA in the first week), and rapid methods (PCR of blood, CSF, or the tick itself).
Etiotropic therapy consists of administering human immunoglobulin or immune plasma strictly in the first days of illness (no later than the 3rd–4th day).
Prophylaxis:
- Emergency: administration of immunoglobulin within the first 96 hours after an infected tick bite. Important: after the 4th day, antibody administration is strictly contraindicated due to the risk of antibody-dependent enhancement (ADE) of infection, which worsens the disease.
- Scheduled (vaccination): administration of inactivated cell-culture vaccines to residents of endemic areas.
- Nonspecific: boiling milk to interrupt the alimentary transmission route.