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West Nile Encephalitis

Disease Details

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Description: West Nile encephalitis is a mosquito-borne viral infection that causes inflammation of the brain and can lead to severe neurological symptoms.
Type: West Nile encephalitis is a viral disease. It is not inherited genetically; instead, it is typically transmitted to humans through the bite of an infected mosquito.
Signs And Symptoms: About 80% of those infected with West Nile virus (WNV) show no symptoms and go unreported. About 20% of infected people develop symptoms. These vary in severity, and begin 3 to 14 days after being bitten. Most people with mild symptoms of WNV recover completely, though fatigue and weakness may last for weeks or months. Symptoms may range from mild, such as fever, to severe, such as paralysis and meningitis. A severe infection can last weeks and can, rarely, cause permanent brain damage. Death may ensue if the central nervous system is affected. Medical conditions such as cancer and diabetes, and age over 60 years, increase the risk of developing severe symptoms.Headache can be a prominent symptom of WNV fever, meningitis, encephalitis, meningoencephalitis, and it may or may not be present in poliomyelitis-like syndrome. Thus, headache is not a useful indicator of neuroinvasive disease.

West Nile fever (WNF), which occurs in 20 percent of cases, is a febrile syndrome that causes flu-like symptoms. Most characterizations of WNF describe it as a mild, acute syndrome lasting 3 to 6 days after symptom onset. Systematic follow-up studies of patients with WNF have not been done, so this information is largely anecdotal. Possible symptoms include high fever, headache, chills, excessive sweating, weakness, fatigue, swollen lymph nodes, drowsiness, pain in the joints and flu-like symptoms. There may be gastrointestinal symptoms including nausea, vomiting, loss of appetite, and diarrhea. Fewer than one-third of patients develop a rash.
West Nile neuroinvasive disease (WNND), which occurs in less than 1 percent of cases, is when the virus infects the central nervous system resulting in meningitis, encephalitis, meningoencephalitis or a poliomyelitis-like syndrome. Many patients with WNND have normal neuroimaging studies, although abnormalities may be present in various cerebral areas including the basal ganglia, thalamus, cerebellum, and brainstem.
West Nile virus encephalitis (WNE) is the most common neuroinvasive manifestation of WNND. WNE presents with similar symptoms to other viral encephalitis with fever, headaches, and altered mental status. A prominent finding in WNE is muscular weakness (30 to 50 percent of patients with encephalitis), often with lower motor neuron symptoms, flaccid paralysis, and hyporeflexia with no sensory abnormalities.
West Nile meningitis (WNM) usually involves fever, headache, stiff neck and pleocytosis, an increase of white blood cells in cerebrospinal fluid. Changes in consciousness are not usually seen and are mild when present.
West Nile meningoencephalitis is inflammation of both the brain (encephalitis) and meninges (meningitis).
West Nile poliomyelitis (WNP), an acute flaccid paralysis syndrome associated with WNV infection, is less common than WNM or WNE. This syndrome is generally characterized by the acute onset of asymmetric limb weakness or paralysis in the absence of sensory loss. Pain sometimes precedes the paralysis. The paralysis can occur in the absence of fever, headache, or other common symptoms associated with WNV infection. Involvement of respiratory muscles, leading to acute respiratory failure, sometimes occurs.
West-Nile reversible paralysis, Like WNP, the weakness or paralysis is asymmetric. Reported cases have been noted to have an initial preservation of deep tendon reflexes, which is not expected for a pure anterior horn involvement. Disconnect of upper motor neuron influences on the anterior horn cells possibly by myelitis or glutamate excitotoxicity have been suggested as mechanisms. The prognosis for recovery is excellent.
Nonneurologic complications of WNV infection that may rarely occur include fulminant hepatitis, pancreatitis, myocarditis, rhabdomyolysis, orchitis, nephritis, optic neuritis and cardiac dysrhythmias and hemorrhagic fever with coagulopathy. Chorioretinitis may also be more common than previously thought.
Skin manifestations, specifically rashes, are common; however, there are few detailed descriptions in case reports, and few images are available. Punctate erythematous, macular, and papular eruptions, most pronounced on the extremities have been observed in WNV cases and in some cases histopathologic findings have shown a sparse superficial perivascular lymphocytic infiltrate, a manifestation commonly seen in viral exanthems. A literature review provides support that this punctate rash is a common cutaneous presentation of WNV infection.
Prognosis: While the general prognosis is favorable, current studies indicate that West Nile Fever can often be more severe than previously recognized, with studies of various recent outbreaks indicating that it may take as long as 60 to 90 days to recover. Patients with milder WNF are just as likely as those with more severe manifestations of neuroinvasive disease to experience multiple somatic complaints such as tremor, and dysfunction in motor skills and executive functions for over a year. People with milder symptoms are just as likely as people with more severe symptoms to experience adverse outcomes. Recovery is marked by a long convalescence with fatigue. One study found that neuroinvasive WNV infection was associated with an increased risk for subsequent kidney disease.
Onset: West Nile encephalitis is an inflammation of the brain caused by the West Nile virus. The onset of symptoms typically occurs 2 to 14 days after the bite of an infected mosquito. Initial symptoms often include fever, headache, and sometimes gastrointestinal symptoms like nausea and vomiting. In severe cases, it can progress to encephalitis, characterized by high fever, neck stiffness, disorientation, tremors, convulsions, and, in some cases, coma or paralysis.
Prevalence: The prevalence of West Nile encephalitis varies significantly based on geographic region and year. It is most commonly reported in North America, Europe, Africa, and parts of Asia. The incidence can fluctuate with seasonal mosquito activity, typically increasing during the warmer months when mosquitoes are more active. It is important to monitor local health department reports for current prevalence data in a specific area.
Epidemiology: WNV was first isolated from a feverish 37-year-old woman at Omogo in the West Nile District of Uganda in 1937 during research on yellow fever virus. A series of serosurveys in 1939 in central Africa found anti-WNV positive results ranging from 1.4% (Congo) to 46.4% (White Nile region, Sudan). It was subsequently identified in Egypt (1942) and India (1953), a 1950 serosurvey in Egypt found 90% of those over 40 years in age had WNV antibodies. The ecology was characterized in 1953 with studies in Egypt and Israel. The virus became recognized as a cause of severe human meningoencephalitis in elderly patients during an outbreak in Israel in 1957. The disease was first noted in horses in Egypt and France in the early 1960s and found to be widespread in southern Europe, southwest Asia and Australia.The first appearance of WNV in the Western Hemisphere was in 1999 with encephalitis reported in humans, dogs, cats, and horses, and the subsequent spread in the United States may be an important milestone in the evolving history of this virus. The American outbreak began in College Point, Queens in New York City and was later spread to the neighboring states of New Jersey and Connecticut. The virus is believed to have entered in an infected bird or mosquito, although there is no clear evidence. West Nile virus is now endemic in Africa, Europe, the Middle East, west and central Asia, Oceania (subtype Kunjin), and most recently, North America and is spreading into Central and South America.Outbreaks of West Nile virus encephalitis in humans have occurred in Algeria (1994), Romania (1996 to 1997), the Czech Republic (1997), Congo (1998), Russia (1999), the United States (1999 to 2009), Canada (1999–2007), Israel (2000) and Greece (2010).Epizootics of disease in horses occurred in Morocco (1996), Italy (1998), the United States (1999 to 2001), and France (2000), Mexico (2003) and Sardinia (2011).Outdoor workers (including biological fieldworkers, construction workers, farmers, landscapers, and painters), healthcare personnel, and laboratory personnel who perform necropsies on animals are at risk of contracting WNV.In 2012, the US experienced one of its worst epidemics in which 286 people died, with the state of Texas being hard hit by this virus.
Intractability: West Nile encephalitis is not typically considered intractable. Most individuals infected with the West Nile virus do not develop severe symptoms, and those who do experience encephalitis often recover with supportive care and symptomatic treatment. However, recovery can be prolonged, and some individuals may have long-term neurological sequelae. In rare severe cases, the disease can be fatal. Prompt medical attention and supportive care are crucial for managing symptoms.
Disease Severity: West Nile encephalitis is a severe condition that affects the brain and can be life-threatening. The severity can range from mild symptoms to severe neurological complications. There is currently no specific antiviral treatment for West Nile virus infection.
Healthcare Professionals: Disease Ontology ID - DOID:2365
Pathophysiology: West Nile encephalitis is a neurological infection caused by the West Nile virus (WNV), which is primarily transmitted to humans through the bite of an infected mosquito. The pathophysiology of West Nile encephalitis involves:

1. **Viral Entry**: WNV enters the human body through the skin when an infected mosquito bites and releases the virus into the bloodstream.

2. **Initial Replication**: The virus initially replicates in local dendritic cells and spreads to the regional lymph nodes.

3. **Viremia**: After initial replication, WNV spreads to the bloodstream, leading to viremia, which is crucial for the virus to reach various organs, including the brain.

4. **Crossing the Blood-Brain Barrier (BBB)**: The exact mechanism is not fully understood, but WNV can cross the BBB, potentially through infected immune cells (the "Trojan horse" mechanism), direct infection of endothelial cells, or by increasing the permeability of the BBB due to inflammation.

5. **Neuronal Infection and Damage**: Once in the central nervous system, WNV infects neurons, leading to neuronal injury and death. This infection results in inflammation and encephalitis.

6. **Immune Response**: The immune system responds to the infection by activating microglia and recruiting leukocytes to the site of infection, which can contribute to neuronal damage through the release of pro-inflammatory cytokines and chemokines.

7. **Clinical Manifestations**: The neuronal damage and inflammation can lead to various neurological symptoms, including fever, headache, confusion, muscle weakness, and, in severe cases, seizures, paralysis, and coma.

The damage to neural tissue and the immune-mediated response in the central nervous system are the primary drivers of the symptoms associated with West Nile encephalitis.
Carrier Status: The primary carrier of West Nile encephalitis is the Culex species of mosquitoes. The virus is typically transmitted to humans and animals through the bite of an infected mosquito. Birds are the primary reservoir hosts for the West Nile virus, helping to amplify the virus in nature. Humans and horses are considered incidental or dead-end hosts because they do not develop high levels of the virus in their bloodstream and are unlikely to contribute to further transmission.
Mechanism: West Nile encephalitis is caused by the West Nile virus (WNV), a flavivirus transmitted primarily by mosquito bites. The key mechanisms and molecular mechanisms involved are as follows:

### Mechanism:
1. **Transmission**: WNV is transmitted to humans through the bite of an infected mosquito, typically of the Culex species.
2. **Initial Infection**: Once in the bloodstream, the virus targets host cells, particularly monocytes, macrophages, and dendritic cells.
3. **Dissemination**: The virus replicates and disseminates to various tissues, including the central nervous system (CNS).
4. **CNS Invasion**: WNV crosses the blood-brain barrier (BBB), leading to infection of neurons in the brain and spinal cord.
5. **Inflammation and Damage**: The immune response to the infection causes inflammation and neuronal damage, leading to encephalitis.

### Molecular Mechanisms:
1. **Viral Entry**: WNV enters host cells through endocytosis, facilitated by interactions between the viral envelope protein (E) and host cell receptors.
2. **Replication**: The viral RNA genome is released into the cytoplasm, where it is translated into a polyprotein. This polyprotein is processed into structural and non-structural proteins that form the viral replication complex.
3. **Viral Assembly**: New viral particles are assembled in the endoplasmic reticulum and transported to the Golgi apparatus for maturation.
4. **Egress**: Mature virions are released from the host cell via exocytosis, allowing the virus to spread to neighboring cells and tissues.
5. **Immune Evasion**: WNV evades the host immune response by various mechanisms, including inhibiting interferon signaling pathways and modulating the host's innate immune response to reduce antiviral activity.

Understanding these mechanisms is crucial for developing strategies to prevent and treat West Nile encephalitis.
Treatment: No specific treatment is available for WNV infection. Most people recover without treatment. In mild cases, over-the-counter pain relievers can help ease mild headaches and muscle aches in adults. In severe cases supportive care is provided, often in hospital, with intravenous fluids, pain medication, respiratory support, and prevention of secondary infections.
Compassionate Use Treatment: For West Nile encephalitis, there are no specific antiviral treatments that are broadly approved. However, several experimental and off-label treatments have been explored:

1. **Ribavirin**: This antiviral drug has shown some in vitro efficacy against West Nile virus, but clinical efficacy in humans remains uncertain.

2. **Interferon Alpha**: This immunomodulatory agent has been studied for potential use, with some indication of benefit, though it is not widely accepted or confirmed.

3. **IVIG (Intravenous Immunoglobulin)**: Use of high-dose intravenous immunoglobulin containing high titers of West Nile virus-specific antibodies has been tried experimentally.

4. **Monoclonal Antibodies**: Research is ongoing into monoclonal antibodies that target the West Nile virus, though these are still largely experimental.

5. **Steroids**: These have been used in other forms of viral encephalitis for their anti-inflammatory effects but lack specific efficacy data for West Nile encephalitis.

Compassionate use treatments are typically provided on a case-by-case basis through clinical trials or expanded access programs. Patients should discuss such options with their healthcare providers to gauge current availability and suitability.
Lifestyle Recommendations: For West Nile encephalitis, the following lifestyle recommendations can help reduce the risk of infection:

1. **Avoid Mosquito Bites:**
- Use insect repellent containing DEET, picaridin, or oil of lemon eucalyptus.
- Wear long-sleeved shirts, long pants, and socks, especially during dawn and dusk when mosquitoes are most active.
- Sleep under a mosquito net if you are in a high-risk area.

2. **Eliminate Mosquito Breeding Grounds:**
- Remove standing water around your home where mosquitoes can breed, such as in flowerpots, gutters, buckets, and birdbaths.
- Change the water in outdoor pet dishes and replace water in birdbaths regularly.

3. **Maintain Screens and Windows:**
- Ensure window and door screens are in good repair to prevent mosquitoes from entering your home.

By implementing these measures, you can significantly reduce the risk of West Nile virus infection, which can lead to West Nile encephalitis.
Medication: There is no specific antiviral medication for West Nile encephalitis. Treatment primarily focuses on supportive care, which may include hospitalization, intravenous fluids, respiratory support, and pain relief. In severe cases, patients may require intensive care management.
Repurposable Drugs: There are currently no specific antiviral drugs approved for treating West Nile encephalitis. However, some existing drugs have shown potential in preclinical studies and off-label use. These include:

1. **Ribavirin**: Though primarily an antiviral for hepatitis C, it has shown some efficacy in vitro against West Nile virus.
2. **Interferon-alpha**: Used in various viral infections and has demonstrated activity against West Nile virus in laboratory settings.
3. **Corticosteroids**: While mainly used to reduce inflammation, their use in West Nile encephalitis is controversial and generally not recommended due to potential side effects.

Research and clinical trials are ongoing to identify effective treatments. Adequate supportive care remains the primary approach for managing West Nile encephalitis in patients.
Metabolites: West Nile encephalitis is typically caused by the West Nile virus, which primarily affects the central nervous system. The virus does not produce unique metabolites that are used for diagnostic purposes in clinical settings. Instead, diagnosis is usually based on serologic tests, such as detecting West Nile virus-specific IgM antibodies in cerebrospinal fluid (CSF) or blood serum. Detection of viral RNA through PCR might also be used. The focus on managing West Nile encephalitis is on supportive care, as there are no specific antiviral treatments for the infection.
Nutraceuticals: For West Nile encephalitis, there are no specific nutraceuticals recognized for treatment. Nutraceuticals, which are foods or food products that provide health benefits, including the prevention and treatment of disease, have not been proven effective for this condition. Management typically involves supportive care and addressing symptoms. If you are exploring nutraceuticals, it is important to consult with a healthcare professional.
Peptides: For West Nile encephalitis, peptides are short chains of amino acids that can play a role in the body's immune response to the West Nile virus. Research on peptide vaccines involves identifying viral peptides that stimulate an immune response, aiming to develop effective preventive measures. "Nan" typically refers to nanotechnology, which can be used in designing advanced diagnostic tools or treatments. In the context of West Nile encephalitis, nanotechnology might be applied to create more sensitive diagnostic assays or to deliver antiviral drugs more effectively.