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Tick-borne Encephalitis

Disease Details

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Description: Tick-borne encephalitis is a viral infectious disease that affects the central nervous system, causing symptoms ranging from mild flu-like illness to severe neurological complications.
Type: Tick-borne encephalitis (TBE) is a viral infectious disease. It is caused by the tick-borne encephalitis virus (TBEV) and is primarily transmitted to humans through the bite of infected ticks. The virus can also be transmitted via the consumption of unpasteurized dairy products from infected animals. TBE is not genetically transmitted from person to person.
Signs And Symptoms: The disease is most often biphasic. After an incubation period of approximately one week (range: 4–28 days) from exposure (tick bite) non-specific symptoms occurs. These symptoms are fever, malaise, headache, nausea, vomiting and myalgias that persist for about 5 days. Then, after approximately one week without symptoms, some of the infected develop neurological symptoms, i.e. meningitis, encephalitis or meningoencephalitis. Myelitis also occurs with or without encephalitis.Sequelae persist for a year or more in approximately one third of people who develop neurological disease. Most common long-term symptoms are headache, concentration difficulties, memory impairment and other symptoms of cognitive dysfunction.Mortality depends on the subtype of the virus. For the European subtype mortality rates are 0.5% to 2% for people who develop neurological disease.In dogs, the disease also manifests as a neurological disorder with signs varying from tremors to seizures and death.In ruminants, neurological disease is also present, and animals may refuse to eat, appear lethargic, and also develop respiratory signs.
Prognosis: Tick-borne encephalitis (TBE) is a viral infectious disease that can lead to serious neurological complications. The prognosis for TBE varies depending on factors such as the patient's age, general health, and the timeliness of medical intervention. Generally, the disease can result in one of three outcomes:

1. **Mild Cases:** In some individuals, especially younger and healthier people, TBE can present only mild symptoms that resolve without lasting effects.

2. **Moderate to Severe Cases:** In cases where the central nervous system is affected, symptoms can include severe headaches, high fever, meningitis, or encephalitis. Recovery may be prolonged, and there can be complications such as long-term neurological impairment.

3. **Severe Outcomes:** Particularly in older adults or those with compromised health, TBE can lead to lasting neurological damage or even be fatal.

It's essential to seek medical attention if TBE is suspected, as early diagnosis and supportive treatment can improve outcomes. Vaccination is available and is one of the best preventive measures against the disease.
Onset: Tick-borne encephalitis (TBE) typically has an onset characterized by a biphasic pattern. The initial phase usually occurs 7-14 days after a tick bite, presenting with nonspecific flu-like symptoms such as fever, headache, fatigue, and muscle aches. There may be an asymptomatic interval lasting about 1-20 days, followed by the second phase, which includes more severe neurological symptoms such as high fever, severe headache, neck stiffness, confusion, seizures, and in some cases, paralysis. The severity and range of symptoms can vary widely among individuals.
Prevalence: Tick-borne encephalitis (TBE) is most prevalent in parts of Europe and Asia, particularly in regions with high populations of ticks such as forested areas. The highest incidence rates are reported in Central and Eastern Europe as well as the Baltic states, Russia, and some parts of China and Japan. The prevalence varies seasonally and geographically, with increased risk during the warmer months when ticks are most active.
Epidemiology: As of 2011, the disease was most common in Central and Eastern Europe, and Northern Asia. About ten to twelve thousand cases are documented a year but the rates vary widely from one region to another. Most of the variation has been the result of variation in host population, particularly that of deer. In Austria, an extensive vaccination program since the 1970s reduced the incidence in 2013 by roughly 85%.In Germany, during the 2010s, there have been a minimum of 95 (2012) and a maximum of 584 cases (2018) of TBE (or FSME as it is known in German). More than half of the reported cases from 2019 had meningitis, encephalitis or myelitis. The risk of infection was noted to be increasing with age, especially in people older than 40 years and it was greater in men than women. Most cases were acquired in Bavaria (46%) and Baden-Württemberg (37%), much less in Saxony, Hesse, Lower Saxony and other states. Altogether 164 Landkreise are designated TBE-risk areas, including all of Baden-Württemberg except for the city of Heilbronn.In Sweden, most cases of TBE occur in a band running from Stockholm to the west, especially around lakes and the nearby region of the Baltic sea. It reflects the greater population involved in outdoor activities in these areas. Overall, for Europe, the estimated risk is roughly 1 case per 10,000 human-months of woodland activity. Although in some regions of Russia and Slovenia, the prevalence of cases can be as high as 70 cases per 100,000 people per year. Travelers to endemic regions do not often become cases, with only 8 cases reported among U.S. travelers returning from Eurasia between 2000 and 2017, a rate so low that as of 2020 the U.S. Centers for Disease Control and Prevention recommended vaccination only for those who will be extensively exposed in high risk areas.
Intractability: Tick-borne encephalitis (TBE) is not considered intractable but can be serious and challenging to manage. The disease, caused by the tick-borne encephalitis virus, often results in a range of symptoms from mild febrile illness to severe neurological complications. While there is no specific antiviral treatment for TBE, supportive care can mitigate symptoms. Vaccination is available and effective in preventing the disease, especially for people in endemic areas. Recovery varies; some patients experience long-term neurological deficits while others recover fully. Early detection and supportive care are crucial for better outcomes.
Disease Severity: Tick-borne encephalitis (TBE) can vary in severity. The disease typically progresses through two phases. The first phase may involve mild flu-like symptoms such as fever, fatigue, and muscle pain. After a short asymptomatic period, the second phase can occur, which affects the central nervous system. This phase can range from mild meningitis to severe encephalitis, leading to symptoms such as high fever, severe headache, confusion, seizures, and paralysis. In severe cases, TBE can result in long-term neurological complications or even be fatal. It is important to seek prompt medical attention if TBE is suspected.
Healthcare Professionals: Disease Ontology ID - DOID:0050175
Pathophysiology: Tick-borne encephalitis (TBE) is caused by the tick-borne encephalitis virus (TBEV), a member of the flavivirus family. The pathophysiology of TBE involves several key steps:

1. **Transmission**: TBEV is primarily transmitted through the bite of infected Ixodes ticks. It can also be transmitted through the consumption of unpasteurized dairy products from infected animals.

2. **Viral Entry and Initial Replication**: After entry through the skin, the virus initially replicates in local dendritic cells and macrophages.

3. **Viremia**: The virus then spreads through the bloodstream (viremia) to various organs, including the central nervous system (CNS).

4. **Crossing the Blood-Brain Barrier**: TBEV crosses the blood-brain barrier, likely facilitated by inflammation and changes in vascular permeability induced by the infection.

5. **CNS Infection**: Once in the CNS, TBEV infects neurons, glial cells, and endothelial cells, leading to neuronal damage and inflammation. This results in encephalitis, characterized by symptoms such as fever, headache, nausea, vomiting, and in severe cases, neurological deficits, seizures, or even coma.

6. **Immune Response**: The host immune response, including the activation of both innate and adaptive immune mechanisms, attempts to control and clear the infection. However, immune-mediated damage often contributes to the pathology observed in TBE.

Pathophysiological outcomes of TBE range from mild febrile illness to severe encephalitis with long-term neurological sequelae.
Carrier Status: Carrier status for tick-borne encephalitis: Ticks, primarily Ixodes ricinus and Ixodes persulcatus, are the primary carriers of the virus that causes tick-borne encephalitis.
Mechanism: Tick-borne encephalitis (TBE) is caused by the tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family. The mechanism of TBE involves transmission of the virus through the bite of an infected tick, primarily from the Ixodes species.

### Molecular Mechanisms:

1. **Virus Entry:**
- TBEV enters the human body through the bite of an infected tick.
- The virus initially infects dendritic cells and macrophages at the site of the tick bite.

2. **Replication:**
- After entry, TBEV replicates in the local lymphoid tissue.
- The viral RNA genome is translated into a single polyprotein, which is cleaved into structural (C, M, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5).
- The RNA-dependent RNA polymerase (NS5) and the protease (NS3) are critical for viral replication and polyprotein processing.

3. **Dissemination:**
- TBEV spreads through the bloodstream (viremia) to distant organs, including the central nervous system (CNS).
- The virus crosses the blood-brain barrier, though the exact mechanism remains unclear. Possible mechanisms include a Trojan horse model via infected immune cells, increased permeability of the blood-brain barrier, or direct infection of endothelial cells.

4. **Central Nervous System Infection:**
- Once in the CNS, TBEV targets neurons, particularly in the brainstem, cerebellum, and spinal cord.
- Neuronal infection leads to cell damage and death primarily through apoptosis mediated by viral proteins and host immune responses.
- The inflammatory response, involving cytokines and leukocytes, exacerbates neuronal damage.

5. **Immune Response:**
- The host immune response includes the production of specific antibodies (IgM and IgG) and activation of T cells.
- Interferons and other cytokines play a protective role but can also contribute to inflammation and tissue damage.

Understanding these molecular mechanisms helps in developing preventive measures such as vaccines and therapeutic approaches targeting specific viral processes.
Treatment: There is no specific antiviral treatment for TBE. Symptomatic brain damage requires hospitalization and supportive care based on syndrome severity. Anti-inflammatory drugs, such as corticosteroids, may be considered under specific circumstances for symptomatic relief. Tracheal intubation and respiratory support may be necessary.
Compassionate Use Treatment: Tick-borne encephalitis (TBE) is primarily addressed through supportive care, as there is no specific antiviral treatment approved. However, some experimental or off-label approaches include:

1. **Immunoglobulins**: Administration of hyperimmune globulins containing antibodies against the TBE virus has been explored, although its efficacy is not well-established.

2. **Interferons**: Interferon-alpha has been investigated due to its antiviral properties, but its use remains experimental and not widely adopted.

3. **Antivirals**: Some antiviral drugs, typically used for other viral infections, might be considered experimentally, though there is limited evidence supporting their effectiveness against TBE.

These treatments should only be considered in a controlled clinical setting or under compassionate use protocols when no other options are available.
Lifestyle Recommendations: To reduce the risk of tick-borne encephalitis (TBE):

1. **Avoid Tick-Prone Areas:** Stay away from wooded, bushy areas with high grass and leaf litter where ticks are common.

2. **Protective Clothing:** Wear long sleeves, long pants, and tuck your pants into your socks or boots. Light-colored clothing can help you spot ticks more easily.

3. **Use Tick Repellents:** Apply insect repellents containing DEET, picaridin, or permethrin to exposed skin and clothing.

4. **Regular Tick Checks:** Perform regular tick checks after spending time outdoors. Pay special attention to areas like the scalp, behind the ears, under the arms, and around the waist.

5. **Prompt Tick Removal:** If you find a tick attached to your skin, remove it promptly using fine-tipped tweezers. Grasp the tick as close to the skin's surface as possible and pull straight up with steady, even pressure.

6. **Vaccination:** If you live in or plan to travel to an area where TBE is common, consider getting vaccinated against TBE.

7. **Landscape Management:** Keep your yard and surroundings tick-free by clearing tall grass and brush, and keeping the lawn mowed and tidy.

Taking these precautions can significantly reduce the chances of contracting tick-borne encephalitis.
Medication: There is no specific antiviral medication for tick-borne encephalitis (TBE). Treatment primarily focuses on supportive care, which includes managing symptoms and complications. This can involve pain relief, hydration, and, in severe cases, respiratory support or intensive care. Vaccination is available and recommended for individuals in high-risk areas to prevent TBE.
Repurposable Drugs: There are currently no widely recognized repurposable drugs specifically for tick-borne encephalitis (TBE). Treatment primarily focuses on supportive care, addressing neurological symptoms, and managing complications. Research into antiviral therapies and repurposed drugs continues, but no definitive options have been established.
Metabolites: There isn't specific information available regarding metabolites for tick-borne encephalitis (TBE). TBE is primarily a viral infection affecting the central nervous system, caused by the tick-borne encephalitis virus. The diagnostic process usually involves detecting the virus or antibodies rather than focusing on specific metabolites. Treatment generally involves supportive care, as there is no specific antiviral therapy for TBE.
Nutraceuticals: Nutraceuticals have not been specifically proven to treat or prevent tick-borne encephalitis (TBE). The disease is typically managed through supportive care once contracted, and prevention methods include vaccination and protective measures against tick bites. The role of nutraceuticals in TBE is not established; always consult healthcare professionals for advice on disease prevention and treatment.
Peptides: Tick-borne encephalitis (TBE) is a viral infectious disease involving the central nervous system. There is no widely established treatment specifically involving peptides for TBE. Research on peptides could potentially contribute to antiviral strategies, but it's still an emerging field. Use of nanoparticles (nanomedicine) is also being explored in various viral infections for targeted drug delivery and improved treatment efficacy, but these are not standard treatments for TBE as of now.