Tick-borne encephalitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Tick-borne diseases are most often transmitted during a blood meal, either by a nymph of adult tick. Blood meals will occur with a higher rate of incidence from the late spring into the early fall, with the highest rate of tick-borne encephalitis viral (TBEV) infections during the early and late summer. The primary disease vector for TBEV is the Ixodidae tick family, found throughout most of Eurasia. The virus itself is a member of the flavivirus genus, with three distinct subtypes. The virus is a (+) ssRNA genome enclosed in a capsid protein. It begins by locating a host cell receptor. The virus is internalized through the process of endocytosis. During this time the virus hi-jacks the host cells replication machinery, in order to replicate many times within the host cell. Upon completion the cell releases many immature virions for further progression of the disease. Progression of the disease results in an infection of the central nervous system, with clinical manifestation such as meningitis and encephalitis.

Incidence of tick-borne encephalitis is documented as far back as 18th century Scandinavian church records. During the early years of this discovery, the Russian Ministry of Health launched expeditions to explore incidence within the Far East. These expeditions led to the development of a successful vaccine in the 1940’s. The European strain afflicted many Czechoslovakian patients until the late 1940’s when a vaccine had finally been administered. Incidence since has drastically decreased with minor spikes here and there in recent history. However recent outbreaks in Hungary and the Czech Republic have been tied to the consumption of unpasteurized dairy products versus an infected tick bite.^[1]

There are three distinct subtypes associated with the tick-borne encephalitis virus. They include a Siberian, a Far Eastern, and a European subtype. Each subtype infection will display with different clinical manifestations. Identifying the subtype responsible for infection may assist in predicting the overall severity of the disease.

Tick-borne diseases are most often transmitted during a blood meal, either by a nymph or adult tick. Blood meals will occur with a higher rate of incidence from the late spring into the early fall, with the highest rate of tick-borne encephalitis viral (TBEV) infections during the early and late summer. The primary disease vector for TBEV is the Ixodidae tick family, found throughout most of Eurasia. The virus itself is a member of the flavivirus genus, with three distinct subtypes; Siberian, European, and Far Eastern. Pathogenesis occurs as the virus binds to a host cell receptor. Through a series of reactions, the virus enters the cell, is translated, and hi-jacks the host cell’s replication machinery. After which immature virions are released within the cell, to ultimately spread infection. Viral replication will often occur within subcutaneous tissue. Replication also occurs within the lymph nodes, causing immense damage to the immune system. A later phase of the virus results in an infection of the CNS as the immune response increases the permeability of the blood-brain barrier.^[1]

Tick-borne encephalitis is caused by a (+) ssRNA virus of the Flavivirus genus. Three subtypes of the virus exist including the Far East, European, and Siberian subtypes. The Ixodidae family of ticks is the primary vector associated with transmission, with other modes of transmission including the consumption of unpasteurized, raw milk.^[2] The virus itself is a member of the flavivirus genus with a (+) ssRNA genome enclosed in a capsid protein. The pathogenic process begins with the location of a host cell receptor. The virus is internalized through the process of endocytosis. During this time the virus hi-jacks the host cells replication machinery, in order to replicate many times within the host cell. Upon completion, the cell releases many immature virions for further progression of the disease.^[1][3]

Tick-borne encephalitis must be differentiated form other tick-borne diseases as well as infections induced by the different subtypes of tick-borne encephalitis virus (TBEV). TBEV also shares a common disease vector with many other tick-borne diseases, therefore a healthcare provider must recognize the potential for multiple co-infections. Found below are tables outlining the clinical manifestations of TBEV subtypes as well as commonly transmitted tick-borne diseases.

Tick-borne encephalitis is endemic to regions within Europe and Asia. These areas include territories spanning from France to Northern Japan; and from Russia to Albania. Incidence is approximately 5,000 to 13,000 infections per year. Vaccination is a method of preventing the virus, however the virus will still persist at 1 case per 10,000 unvaccinated individuals. The majority of infections occur between April and November with the highest rates of infection in the early and late summer periods. There is a higher incidence of infection among individuals above the age of 50.

The primary risk factors associated with tick-borne encephalitis are exposure to endemic environments and the consumption of unpasteurized dairy products. More severe infections have been reported in individuals over the age of 50 years.^[4]

Tick-borne encephalitis commonly presents itself as a biphasic infection. Following an incubation period of 7 to 14 days, a patient will experience an early phase including non-specific flu like symptoms. Once early phase symptoms reside, a remission phase occurs in which a patient experiences lessened severity of symptoms or appears entirely asymptomatic. Infection will conclude at this point within nearly two-thirds of patients. However, a second phase will onset within the remaining one-third. This phase includes the infection of the central nervous system. Progression of the disease at this point will present itself as aseptic meningitis, encephalitis, or myelitis. Complications are commonly associated with this later phase, including the aforementioned meningitis and encephalitis as well as long term cognitive dysfunction and limb paresis. The prognosis is usually good for the majority of infected patients. Many patients will appear to be asymptomatic during the course of infection. For individuals displaying signs and symptoms, the clinical manifestations will typically reside after the first wave of non-specific flu like symptoms. However as mentioned earlier, a second phase can occur. The prognosis for patients undergoing this course of infection is still fairly good. Yet, patients experience an infection of the central nervous system are more prone to long term complications.^[3]

Tick-borne encephalitis infections will often present themselves with biphasic clinical manifestations. Following an incubation period of 7 to 14 days, a patient will experience early onset, non-specific flu like symptoms. A patient will then experience a remission period of lessened symptoms or will appear to be completely asymptomatic. A second phase will occur in which patients will experience an infection of the central nervous system resulting in a number of neurological, clinical manifestations.^[3]

Early onset signs include fever, lethargy, and overall weakness. As the infection progresses, further clinical manifestations will present themselves in the form of tachycardia, changes in blood pressure, sensitivity of the eye and skin, and the appearance of a rash. Signs may appear to be similar to other diseases within the umbrella of tick-borne fevers however a biphasic infection period (early onset symptoms, remission period, and second phase of symptoms) is a characteristic sign of tick-borne encephalitis.^[3]

An array of laboratory tests exist to assist with the diagnoses of tick-borne encephalitis. Polymerase chain reactions are most effective during the first week of infection. An early detection as a result of a successful PCR enables quicker medical treatment and ultimately a potentially higher survival rate. Other test useful during the later stages of infection include immunofluorescence assays, antibody titers, ELISA, and other serologic tests.^[1]

No specific treatment has been outlined for Tick-borne encephalitis. Progression of the illness may lead to stages and complications that require hospitalization and supportive treatment.^[5]

An investigational new therapy, Phosphrenyl treatment, similar to interferon treatment for Hepatitis C, is the mainstay investigational treatment in treating tick-borne encephalitis. Antibiotic therapies are useful as many disease vectors responsible for transmission of tick-borne encephalitis also carry many other tick-borne diseases. An antibiotic therapy may be helpful in anticipating any potential tick-borne co-infections.

Tick- borne encephalitis prevention strategies are based on avoiding potential, infected tick bites. Avoiding tick bites may be accomplished through limiting exposure to endemic areas. However if it is impossible or impractical to avoid these areas, several preventative strategies may be implemented. Other prevention strategies include a proper removal of the tick.^[6]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Incidence of tick-borne encephalitis is documented as far back as 18th century Scandinavian church records. During the early years of this discovery, the Russian Ministry of Health launched expeditions to explore incidence within the Far East. These expeditions led to the development of a successful vaccine in the 1940’s. The European strain afflicted many Czechoslovakian patients until the late 1940’s when a vaccine had finally been administered. Incidence since has drastically decreased with minor spikes here and there in recent history. However recent outbreaks in Hungary and the Czech Republic have been tied to the consumption of unpasteurized dairy products versus an infected tick bite.^[1]

• Historically documented disease with appearances in 18th century Scandinavian church records.
• In 1931 tick-borne encephalitis was officially discovered by the Austrian physician, H.Schneider.^[1]

• Far east expeditions for further discovery were organized by the Russian Ministry of Health in 1937, and continuing through 1939.
• Expeditions revealed the origin of the virus to be an I. persulcatus tick vector. At this point the virus was named Russian spring-summer encephalitis.
• Viral strains were first isolated by M.P. Chumakov and N.A. Zeitlenok in 1939.
• A vaccination had been developed by the year 1940.^[1]

• Identification of the virus occurred a mass infection within the Volkhov Front’s armies in 1942 to 1943.
• Research revealed that I.ricinus was the primary tick vector of the infection.
• Viral strains were first isolated by L. Zilber in 1946.
• Zilber noted that the virus shared many common characteristics with a common virus at the time, Louping ill virus.
• Discovery in Central Europe occurred as the virus was first isolated in central Europe from Czechoslovakia patients in 1948.
• Incidence of infection increased ten fold from 1945 to 1948 in Czechoslovakia.
• Following the isolation of the virus in Czechoslovakia, many other European countries began to isolate viral strains.
• Incidence in Europe has decreased dramatically post-development of an effective vaccination.
• Prior to vaccination, incidence rates were as high as 5,000 reported cases per year in the mid 1950’s.
• By the mid 1960’s to the 1970’s these rates dramatically decreased to an estimated 1,000 cases per year.
• Incidence peaks occurred throughout Europe in 1999 with nearly 10,000 cases that year.
• Two more peaks occurred in 1993 and 1996 with incidence escalating from 7,500 cases per year in 1993 to nearly 11,000 cases per year in 1996.^[1]

• Strains of the virus had been isolated in Northern China and Japan between the late 1940’s and early 1950’s.
• Recently strains have been isolated in parts of South Korea.^[1]

• An outbreak recently occurred in the Czech Republic, infecting 22 people. The outbreak was a result of infected sheep cheese consumption.
• In 2007 an outbreak occurred in Hungary, infecting 25 patients and exposing 154. The outbreak was a result of infected goat cheese consumption.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Tick-borne diseases are most often transmitted during a blood meal, either by a nymph or adult tick. Blood meals will occur with a higher rate of incidence from the late spring into the early fall, with the highest rate of tick-borne encephalitis viral (TBEV) infections during the early and late summer. The primary disease vector for TBEV is the Ixodidae tick family, found throughout most of Eurasia. The virus itself is a member of the flavivirus genus, with three distinct subtypes; Siberian, European, and Far Eastern. Pathogenesis occurs as the virus binds to a host cell receptor. Through a series of reactions, the virus enters the cell, is translated, and hi-jacks the host cell’s replication machinery. After which immature virions are released within the cell, to ultimately spread infection. Viral replication will often occur within subcutaneous tissue. Replication also occurs within the lymph nodes, causing immense damage to the immune system. A later phase of the virus results in an infection of the CNS as the immune response increases the permeability of the blood-brain barrier.^[1]

General Tick Life Cycle^[2]

• A tick’s life cycle is composed of four stages: hatching (egg), nymph (six legged), nymph (eight legged), and an adult.
• Ticks require blood meal to survive through their life cycle.
• Hosts for tick blood meals include mammals, birds, reptiles, and amphibians. Ticks will most likely transfer between different hosts during the different stages of their life cycle.
• Humans are most often targeted during the nymph and adult stages of the life cycle.
• Life cycle is also dependent on seasonal variation.
• Ticks will go from eggs to larva during the summer months, infecting bird or rodent host during the larval stage.
• Larva will infect the host from the summer until the following spring, at which point they will progress into the nymph stage.
• During the nymph stage, a tick will most likely seek a mammal host (including humans).
• A nymph will remain with the selected host until the following fall at which point it will progress into an adult.
• As an adult, a tick will feed on a mammalian host. However unlike previous stages, ticks will prefer larger mammals over rodents.
• The average tick life cycle requires three years for completion.
  • Different species will undergo certain variations within their individual life cycles.

• Ticks require blood meals in order to progress through their life cycles.
• The average tick requires 10 minutes to 2 hours when preparing a blood meal.
• Once feeding, releases anesthetic properties into its host, via its saliva.
• A feeding tube enters the host followed by an adhesive-like substance, attaching the tick to the host during the blood meal.
• A tick will feed for several days, feeding on the host blood and ingesting the host’s pathogens.
• Once feeding is completed, the tick will seek a new host and transfer any pathogens during the next feeding process.^[2]

• The Ixodidae family of hard ticks have been reported as the vector and reservoir of the Tick-borne encephalitis virus.
• Other modes of transmission include the consumption of raw milk as well as vertical transmission from mother to fetus.^[3]

• Member of the Falvivirus genus
• Flaviviridae family
• Three subtypes: Far East, European, and Siberian
• Viral strains are mostly homogeneous within infected European tick populations.
• Diversity exists within viral strains carried by Siberian and Far Eastern tick populations. Thus these populations host antigenic variations and a variety of subtypes.
• However the antigenic similarity within these populations allows for a generalized protection method among the different subtypes.^[1]

• (+)ssRNA genome enclosed in a capsid protein.
• Genome is protected by a lipid bilayer, provided by the host or target cell.
• Virus’s physical attributes include a spherical particle with an approximate diameter of 50-60nm.
• The genome lacks a 3′-poly(A) tail, yet provides a 5′ cap.
• In terms of length, the genome spans an average of 11kb.^[1]

• The process begins as the virus binds to a host cell receptor.
• A host cell will internalize the virus using endocytosis.
• Post-endocytosis, acidification of the viral envelope causes conformation changes of the E protein, resulting in the attachment of the viral envelope to a endosomal vesicle.
• Once properly mounted on the endosomal vesicle, the viral envelope will release the viral nucleocapsid into the surrounding cytoplasm.
• Translation of the virus yields a 3414 amino acid long polyprotein.
• The polyprotein is cleaved by both cellular and viral proteases.
• The cleaving process results in three structural proteins called C, prM, and E as well as seven non-structural proteins.^[1]
• The C protein forms a virion nucleocapsid through binding to viral DNA.
• The E protein is necessary as a ligand to cell receptors and as a fusion protein.
• The other non-structural proteins serve as proteases, polymerases, complement binding antigens, or function within the replication process.
• Finally the processes concludes as the positive-stranded genome is translated while the negative-strand of RNA provides grounds for the RNA replication process.
• Assembly of the virus occurs within the endoplasmic reticulum.
• Post-assembly immature virions are released within the cell.^[1]

• Virus replication commonly occurs within subcutaneous tissue.
• Dendritic cells transport the virus to the lymph nodes.
• The virus replicates at a high rate within the lymph nodes, further travelling into the bloodstream.
• Lymphocytes suffer great reductions due to infection with the regional lymph nodes.
• Further infection of external tissues occur within the viremic phase
• The later phase results in the infection of the CNS.
• Furthermore a host’s immune system will add to the severity of the infection, as resulting immune response includes inflammation CD8+ T-cells infiltrating the brain.
• Other immune responses such as the upregulation of proinflammatory cytokines increase the permeability of the blood-brain barrier.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Tick-borne encephalitis is caused by a (+) ssRNA virus of the Flavivirus genus. Three subtypes of the virus exist including the Far East, European, and Siberian subtypes. The Ixodidae family of ticks is the primary vector associated with transmission, with other modes of transmission including the consumption of unpasteurized, raw milk.^[1] The virus itself is a member of the flavivirus genus with a (+) ssRNA genome enclosed in a capsid protein. The pathogenic process begins with the location of a host cell receptor. The virus is internalized through the process of endocytosis. During this time the virus hi-jacks the host cells replication machinery, in order to replicate many times within the host cell. Upon completion, the cell releases many immature virions for further progression of the disease.

• Member of the Falvivirus genus
• Flaviviridae family
• Three subtypes: Far East, European, and Siberian
• Viral strains are mostly homogeneous within infected European tick populations.
• Diversity exists within viral strains carried by Siberian and Far Eastern tick populations. Thus these populations host antigenic variations and a variety of subtypes.
• However the antigenic similarity within these populations allows for a generalized protection method among the different subtypes.^[2]

• (+)ssRNA genome enclosed in a capsid protein.
• Genome is protected by a lipid bilayer, provided by the host or target cell.
• Virus’s physical attributes include a spherical particle with an approximate diameter of 50-60nm.
• The genome lacks a 3′-poly(A) tail, yet provides a 5′ cap.
• In terms of length, the genome spans an average of 11kb.^[2]

• The Ixodidae family of hard ticks have been reported as the vector and reservoir of the Tick-borne encephalitis virus.
• Other modes of transmission include the consumption of raw milk as well as vertical transmission from mother to fetus.^[1]

• Virus replication commonly occurs within subcutaneous tissue.
• Dendritic cells transport the virus to the lymph nodes.
• The virus replicates at a high rate within the lymph nodes, further travelling into the bloodstream.
• Lymphocytes suffer great reductions due to infection with the regional lymph nodes.
• Further infection of external tissues occur within the viremic phase
• The later phase results in the infection of the CNS.
• Furthermore a host’s immune system will add to the severity of the infection, as resulting immune response includes inflammation CD8+ T-cells infiltrating the brain.
• Other immune responses such as the upregulation of proinflammatory cytokines increase the permeability of the blood-brain barrier.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Tick-borne encephalitis must be differentiated form other tick-borne diseases as well as infections induced by the different subtypes of tick-borne encephalitis virus (TBEV). TBEV also shares a common disease vector with many other tick-borne diseases, therefore a healthcare provider must recognize the potential for multiple co-infections. Found below are tables outlining the clinical manifestations of TBEV subtypes as well as commonly transmitted tick-borne diseases.

• Three subtypes of tick-borne encephalitis are commonly responsible for infection. These subtypes and their specific clinical manifestations are outlined in the table below:

• Disease vectors responsible for the transmission of tick-borne encephalitis are commonly carriers of other tick-borne diseases. Therefore due to this common disease vector, a healthcare provider must recognize all potential co-infections. A healthcare provider must also be able to distinguish between the different tick-borne diseases and TBEV. Found below is a table of tick-borne diseases, including TBEV, and their typical clinical manifestations.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Tick-borne encephalitis is endemic to regions within Europe and Asia. These areas include territories spanning from France to Northern Japan; and from Russia to Albania. Incidence is approximately 5,000 to 13,000 infections per year. Vaccination is a method of preventing the virus, however the virus will still persist at 1 case per 10,000 unvaccinated individuals. The majority of infections occur between April and November with the highest rates of infection in the early and late summer periods. There is a higher incidence of infection among individuals above the age of 50.

• Located primarily in areas of Europe and Asia.
• From eastern France to Northern Japan, from northern Russia to Albania.
• European countries reporting tick-borne encephilitis infections include: Siberia, Baltic states, Albania, Austria, Belarus, Bosnia, Croatia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Norway, Poland, Romania ,Serbia, Slovakia, Slovenia, Sweden, Switzerland, and Ukraine.
• Asian countries reporting tick-borne encephilitis infections include: China, Japan, Kazakhstan, Mongolia, and South Korea.^[1]

• 5,000 to 13,000 tick-borne encephilitis infections are reported each year.
• Overall risk for an unvaccinated individuals living within endemic regions is approximately 1 case per 10,000 people. ^[1]
• Russia and Europe report between 10-12,000 human cases annually.^[2]

• Majority of cases occur between April and November.
• Peak activity rates have been reported during early and late summer.^[1]

• Peak levels of incidence, as well as severity, are reported within individuals over the age of 50 years.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

The primary risk factors associated with tick-borne encephalitis are exposure to endemic environments and the consumption of unpasteurized dairy products. More severe infections have been reported in individuals over the age of 50 years. Certain antibiotic treatment options have bee proven to activate the virus while others have caused its deactivation.

• Traveling or residing within endemic regions will increase chances of infection.
• Tick activity is generally heightened during certain the spring and summer months.
• Within endemic regions, tick may choose an animal host, including a domesticated animal such as a dog or cat.
• Although rare, cases of blood transfusion and organ transplantation have been recorded as methods of transmission.
• All together, individuals who spend time outdoors and/or have pets that go outdoors in endemic regions are at risk for tick-borne disease.^[1]

• Individuals with frequent exposure to dogs and who reside near wooded areas or areas with high grass may also be at increased risk of infection.

• Individuals who ingest unpasteurized milk and dairy products from infected livestock are at risk of infection.

• Individuals above the age of 50 years are at more of a risk of developing severe complications associated with tick-borne encephalitis infections.^[2]

• Although the TBE virus cannot be eradicated from the body, it can be inactivated. It can also be activated.^[3]
• Certain antibiotics activate the TBE virus while others have no effect.
• TBE virus may be a coinfection with a Borrelia Burgdorferi infection, Lyme disease, which needs treatment with antibiotics.
• The Russians studied this matter for years and their findings were as follows: gentamicin exerts no activating effect while streptomycin and ten other antibiotics activate the virus. ^[4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Tick-borne encephalitis commonly presents itself as a biphasic infection. Following an incubation period of 7 to 14 days, a patient will experience an early phase including non-specific flu like symptoms.^[1] Once early phase symptoms reside, a remission phase occurs in which a patient experiences lessened severity of symptoms or appears entirely asymptomatic. Infection will conclude at this point within nearly two-thirds of patients. However, a second phase will onset within the remaining one-third. This phase includes the infection of the central nervous system. Progression of the disease at this point will present itself as aseptic meningitis, encephalitis, or myelitis. Complications are commonly associated with this later phase, including the aforementioned meningitis and encephalitis as well as long term cognitive dysfunction and limb paresis. The prognosis is usually good for the majority of infected patients. Many patients will appear to be asymptomatic during the course of infection. For individuals displaying signs and symptoms, the clinical manifestations will typically reside after the first wave of non-specific flu like symptoms. However as mentioned earlier, a second phase can occur. The prognosis for patients undergoing this course of infection is still fairly good. Yet, patients experience an infection of the central nervous system are more prone to long term complications.^[2]

• Two thirds of infected individuals are asymptomatic and will not display any clinical manifestations.
• Incubation period will last an average of 8 days. However incubation periods have been shown to range from 4-28 days.
• Characteristic biphasic course:

• Disease will begin with the onset of nonspecific febrile illness accompanied by a headache, myalgia, and fatigue.
• The early phase of the biphasic course will commonly occur over the course of several days.
• Following common symptoms of the early infection phase, patient may display an afebrile and relatively asymptomatic period.
• Nearly two-thirds of patients have been reported to have recovered without any further illness, following the completion of the first phase.^[2]

• As the disease progresses the onset of a second phase may result in central nervous system involvement including aseptic meningitis, encephalitis, or myelitis.
• Further findings within the progression of tick borne-encephilitis include meningeal signs, altered mental status, cognitive dysfunction,ataxia, rigidity, seizures, tremors, cranial nerve palsies, and limb paresis.

The majority of complications associated with tick-borne encephilitis are commonly developed during the second phase. Complication may include:

• Aseptic meningitis
• Encephalitis
• Myelitis
• Meningeal signs
• Altered mental status
• Cognitive dysfunction
• Ataxia
• Rigidity
• Seizures
• Tremors
• Cranial nerve palsies
• Limb paresis^[2]

The TBE virus is a slow virus; it can take decades to become fulminant. This is termed Progressive Form of the TBE Virus (PFTBE). In 1983 in Russia a follow-up study was done of patients with acute TBE 2-22 years later. 68% developed PFTBE, the “overwhelming majority” of these developing ALS, Amyotrophic Lateral Sclerosis. The first isolation of a TBE virus connected with ALS was in 1975 when 70% of the ALS cases in Hamburg, Germany were found to have contact with this virus. In 1978, ALS was reproduced in laboratory animals by inoculation of the Schu virus, a TBE flavivirus, taken from the CSF of a patient with ALS. In regard to the sexual and vertical transmission of the TBE virus, it is thought provoking that conjugal and familial ALS have both been documented.^[2]

• The prognosis is usually good for two-thirds of individuals diagnosed with tick-borne encephilitis. These patient will remain asymptomatic for the duration of the infection.
• More severe cases have been associated with ages about 50 years as well as young children. Though severity in young children is less often reported than in elderly populations.
• Prognosis also depends on subtype. European subtypes are commonly associated with lesser to mild symptoms while Far Eastern subtypes are associated with more severe cases and a case fatality ratio of 20-40%.
• In humans, the disease is lethal in approximately 1.2% of cases and leaves 15-20% of its survivors with permanent neurological damage.^[2]