Western Equine Encephalitis

Etiology

Alphavirus causes Western Equine encephalitis. It is from the Togaviridae family, which includes several viruses that cause other equine encephalitis infections.  The virus most closely resembles the Eastern Equine encephalitis virus, which may be a genetic predecessor. The vectors for human transmission are the Culex tarsalis, Culiseta, and Aedes mosquito species. Outbreaks in mules, horses, pheasants, and other birds often accompany human epidemics. Birds serve as amplifying hosts, but no cases of transmission through contact with birds have been reported making them a reservoir but not a vector for infection. There is no aerosolized transmission, but the virus may cross the placenta and be transmitted from mother to fetus. Transmission via infected blood transfusion is unlikely due to low viral loads in most hosts, but possible.

Epidemiology

Western Equine encephalitis has been reported in the western United States and Canada. There is a sub-type that has been reported in Argentina with an endemic reservoir in South America. 

Most cases have occurred west of the Mississippi River, west of the Rocky Mountains, and in California. The annual incidence of reported infections is highly variable due to periods of inactivity punctuated by outbreaks. Warm weather and heavy rainfall tend to increase vector populations leading to epidemics. Transmission is most common in rural areas. The most significant outbreak occurred in 1941, with over 3000 confirmed human cases. Since 1964 there have been fewer than 700 confirmed cases in the United States. Cases are more commonly reported in males, about twice the rate as females, possibly due to an increased likelihood of outdoor occupations and activities. Transmission is most likely between April and September, with peaks in July and August. During epidemics, a large portion of the population seroconverts but infectivity rates vary with age. Infants are most commonly infected as they have the greatest likelihood of contracting the virus after a mosquito bite. Adults are more commonly targeted by the vector but have lower infectivity rates. However, when they are infected, older adults are more likely to develop more severe, neuroinvasive disease or to die. Infants and very young children are also more likely to develop neurologic manifestations of the disease and seizures. They are more likely than adults to develop permanent disability after infection. Reported infectivity rates are 1:1000 for adults, 1:58 for children aged 1-4, and 1:1 in infants.[6][7][8][9]

Pathophysiology

The virus is transmitted into the subcutaneous tissue of the host via the bite of an infected mosquito. The virus then begins replication and synthesis of RNA and protein, usually in the local lymph nodes.  Viremia ensues, and if the viral load is high enough, the virus may translocate into the central nervous system across the blood-brain barrier resulting in cerebral and meningeal inflammation and necrosis.

History and Physical

Most cases are associated with epidemics in birds or horses. Patients may provide a history of mosquito exposure. The majority of cases are subclinical. There is no associated rash. When symptomatic, infected individuals present with nonspecific, prodromal symptoms of fever, chills, malaise, weakness, and myalgias, typical of many viral and mosquito-borne infections. Most symptomatic cases will still resolve spontaneously within a few days, without any sequelae. Patients may also complain of a headache, neck stiffness, nausea, and vomiting. Progression to neuroinvasive disease is most common in the extremes of age and presents with vertigo, photophobia, confusion, agitation, somnolence, coma, spasticity, and seizures. Neurologic symptoms may develop more quickly in children than in adults. Young children are most likely to have a permanent neurologic disability, and the elderly are most likely to die from complications. Patients who do recover from the acute neurologic disease may complain of fatigue, headaches, and irritability for years.

Evaluation

Because of the similar presentation to multiple other infections, diagnosis is often delayed or difficult. Patients with neurologic symptoms are evaluated with neuroimaging studies such as computed tomography (CT) or magnetic resonance imaging (MRI). Inflammatory changes may be seen in the thalamus or basal ganglia but are nonspecific and may be found with encephalitis due to many causes. A lumbar puncture may show elevated opening pressure, protein, and cell count with a lymphocytic predominance. These findings are also non-specific and common in many other forms of viral or inflammatory meningitis and encephalitis. 

Isolation of the virus from serum or CSF is difficult. In infected patients, IgG antibody is generally detectable within 1 to 3 weeks after infection and peaks at 1 to 2 months. IgG indicates exposure to the virus and, depending on the titer, suggests recent infection. The presence of IgM antibody correlates with acute infection and can be detected within 1 to 3 weeks from the onset of symptoms. The test for Western equine encephalitis cross-reacts with St. Louis encephalitis virus, making distinguishing between the two infections difficult.

Treatment / Management

There is currently no vaccine to prevent Western Equine encephalitis, but there are clinical trials underway by the United States (US) Army Medical Research and Material Command. Nor is there any effective antiviral therapy, so care is largely supportive and centered around the management of complications. Patients with encephalitis may require mechanical ventilation and management of increased intracranial pressure. Seizures are common with neuroinvasive disease and may require anticonvulsants. Patients with seizures are more likely to develop a lifetime seizure disorder.[10](B3)

Since there is no effective treatment or vaccine, prevention is critical.  This is best accomplished by avoiding mosquito bites entirely. Even very short periods of outdoor exposure can result in bites, so proper protective clothing should be worn. These protective measures include long sleeves, long pants, socks, and closed-toe shoes. Pant legs can be tucked into socks to prevent bites to exposed ankles. Transmission is common during the warmer months, and mosquitoes may bite through very thin clothing, so treating clothing with repellents containing permethrin, DEET, oil of lemon eucalyptus, or other EPA-registered insect repellants will reduce this risk.  Permethrin should not be applied directly to the skin but, when applied to clothing, provides protection even after the clothing is washed. Transmission is most frequent when mosquitoes feed, between dawn and dusk, so outdoor activities during this period should be avoided. Travelers should sleep in air-conditioned spaces or use mosquito nets or screens to prevent bites during sleep. Standing water is a breeding ground for mosquitoes, so flower pots, buckets, and other containers should be drained. Children’s wading pools should be emptied and stored on their sides, and tire swings should have holes drilled into the bottom to allow trapped water to drain.

Differential Diagnosis

The differential diagnosis of Western Equine encephalitis is broad and makes a careful travel history important. It includes:

• Murray Valley encephalitis
• Powassan Virus encephalitis
• West Nile virus encephalitis
• Japanese encephalitis
• Herpes simplex encephalitis
• Eastern equine encephalitis
• Venezuelan Equine encephalitis
• Creutzfeldt-Jacob disease
• Ehrlichiosis
• Enterovirus meningitis
• Mycoplasma meningitis
• Cytomegalovirus infection in the immunocompromised host
• Typhoid fever
• Dengue fever
• Malaria
• Brain abscess
• Tuberculous meningitis
• Nipah virus infection
• Rocky Mountain spotted fever
• Fungal meningitis
• Leptospirosis
• Neurocysticercosis
• Amebic meningoencephalitis
• Lupus with central nervous system involvement
• CNS tumor
• Cerebrovascular accident
• Overdose

Prognosis

Patients who contract the virus but do not develop neurologic symptoms will fully recover, as do most adults with the only mild neurologic disease. Children who develop neurologic disease have a 30% chance of having a permanent disability such as seizures, spasticity, and cognitive or behavioral disorders. As compared with Eastern equine encephalitis for which mortality approaches 70%, mortality is low, only around 4%. Most fatalities occur in elderly patients.