Tick-borne encephalitis overview

# Overview
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.

# Historical Perspective
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.

# Classification
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.

# Pahtophysiology
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.

# Causes
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. 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.

# Differentiating tick-borne encephalitis from other diseases
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.

# Epidemiology and Demographics
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.

# Risk factors
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.

# Natural history, complications, and prognosis
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.

# History and symptoms
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.

# Physical examination
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.

# Laboratory findings
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.

# Medical therapy
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.

# Future or investigational new therapies
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.

# Prevention
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.