Continuing Education Activity

Saint Louis encephalitis virus is transmitted to humans from the bite of an infected Culex species mosquito. It is a flavivirus, a single-stranded RNA virus, which is closely related to the Japanese encephalitis, Powassan and West Nile virus. Most cases occur in the eastern and central United States during the summer and early fall. Most cases are asymptomatic or present with flu-like symptoms such as fatigue, headaches, nausea, vomiting and body aches. Most patients will spontaneously recover without progression to encephalitis. Severe, invasive disease resulting in encephalitis is unusual and is more common in older adults. Encephalitis or inflammation of the brain and meninges presents as dizziness, agitation, confusion, tremors, or coma following the flu-like prodrome. For patients with encephalitis, the overall case fatality rate is 5% to 15%. This activity reviews the cause, pathophysiology and presentation of St louis encephalitis and highlights the role of the interprofessional team in its management.

Objectives:

• Describe the workup of a patient with St Louis encephalitis.
• Recall the presentation of St Louis encephalitis.
• Summarize the treatment of St Louis encephalitis.
• Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by St. Louis encephalitis.

Introduction

Saint Louis encephalitis virus is transmitted to humans from the bite of an infected Culex species mosquito. It is a flavivirus, a single-stranded positive-sense RNA virus, which is closely related to the Japanese encephalitis, Powassan, and West Nile virus. Most cases occur in the eastern and central United States during the summer and early fall. Most cases are asymptomatic or present with flu-like symptoms such as fatigue, headaches, nausea, vomiting, and body aches. Most patients will spontaneously recover without progression to encephalitis. Severe, invasive disease resulting in encephalitis is unusual and is more common in older adults. Encephalitis or inflammation of the brain and meninges presents as dizziness, agitation, confusion, tremors, or coma following the flu-like prodrome. For patients with encephalitis, the overall case fatality rate is 5% to 15%. There is no specific treatment for St. Louis encephalitis beyond supportive care. Antivirals have not been shown to alter symptoms. There is no vaccine available, so the focus is on the prevention of mosquito bites.[1][2][3]

Etiology

Saint Louis encephalitis virus is a Flavivirus, a single-stranded RNA virus transmitted by the Culex species mosquitoes. The most common mosquito vectors are Culex pipiens, Culex quinquefasciatus, Culex tarsalis, and Culex nigripalpus. Wild birds serve as amplifying hosts in that they develop significant viremia to infect other mosquitoes but do not develop clinical symptoms themselves. The birds involved are present in both urban and rural environments and include pigeons, blue jays, robins, and house sparrows. Humans and domestic animals are dead-end hosts in that the contract the virus and may develop symptoms, but do not develop significant viremia to transmit the virus to other biting mosquitoes. There is no person-to-person transmission of Saint Louis encephalitis. Transmission for aerosolized laboratory samples is possible but rare. Transmission may be possible by blood transfusion.[4][5][6]

Epidemiology

Although the virus may be found in a wide geographic area ranging from Canada to Argentina, most cases occur in the United States. Periodic outbreaks and epidemics have occurred in the Mississippi River valley and along the Gulf Coast, but sporadic cases are reported throughout the United States in the Caribbean, Canada, Mexico, and Central America. In temperate areas, transmission occurs primarily during the late summer and early fall, but in warmer climates, transmission occurs year-round. The biggest epidemic of St. Louis encephalitis occurred in 1975 with nearly 2000 cases reported, primarily in the central states within the Ohio-Mississippi River basin. The annual number of annual reported cases fluctuates dramatically due to periodic epidemics. Since most cases are asymptomatic and testing is not widely available, reporting data is limited.

Pathophysiology

Viremia from Saint Louis encephalitis virus infection occurs after replication in the region of the mosquito bite and local lymph nodes. In most cases, the virus will clear within 7 days.  In cases where the virus crosses the blood-brain barrier, it causes lymphocytic meningitis, predominantly affecting gray matter. The most severely affected areas include the hypothalamus, cerebral and cerebellar cortex, basal ganglia, brainstem, and spinal cord. The virus may rarely involve white matter causing acute demyelinating encephalomyelitis.

History and Physical

Most infected individuals will provide a history of mosquito exposure in an endemic area. The incubation period is from 5 to 15 days. There is often a prodromal period of nonspecific symptoms of fever, headache, nausea, vomiting, diarrhea, and myalgias, which may last for several days. Rarely, symptoms then progress to meningitis, which is the most common neurologic manifestation, and even more rarely to encephalitis.  Symptoms may include altered mental status, agitation, confusion, and coma. About 40% of children and young adults develop only fever, headache, or aseptic meningitis but almost 90% of elderly patients develop encephalitis. Transplant and immunocompromised patients also have a greater risk of neuroinvasive disease. There is no associated rash.

Evaluation

Patients with symptoms consistent with encephalitis are initially evaluated with neuroimaging and lumbar puncture. MRI or CT scans are usually normal. A lumbar puncture may be significant for elevated opening pressure, normal or slightly decreased glucose, and cerebrospinal fluid (CSF) lymphocytic pleocytosis. Cerebrospinal fluid (CSF) cell counts rarely exceed 500 cells/mm3, and CSF protein is elevated in half to two-thirds of cases. Blood work may reveal leukocytosis but is often unremarkable. These findings are common in many forms of encephalitis or viral meningitis. In patients who develop neurologic disease about 30% will also develop hyponatremia and fluid overload due to inappropriate secretion of antidiuretic hormone (SIADH).[7][8][9]

Electroencephalography (EEG) may show diffuse slowing and delta-wave activity with isolated spikes. EEG abnormalities have not been shown to correlate well with clinical findings.

The diagnosis of Saint Louis encephalitis is usually made by detecting the presence of IgM antibodies to the virus in serum using the enzyme-linked immunosorbent assay (ELISA) test. The ELISA test may also be performed on CSF. Polymerase chain reaction (PCR) analysis of CSF is often performed to exclude enterovirus or herpes virus infection, as the presentations are similar. Virus culture from infected patients is usually unsuccessful.

Treatment / Management

There is no effective antiviral therapy for St. Louis encephalitis. Management is limited to supportive care with intravenous (IV) fluids and antipyretics. SIADH, if present is usually mild and most patients will respond to fluid restriction alone. There are no effective antiviral drugs, and there is currently no vaccine available to prevent infection. Since there is no adequate treatment or vaccine, prevention is critical. Prevention is best accomplished by avoiding mosquito bites entirely. Even very short periods of outdoor exposure can result in bites; therefore, proper protective clothing like long sleeves, long pants, socks, and closed-toe shoes should be worn. 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 to the skin directly, but when applied to clothes, it 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. Wading pools should be drained and stored, and tire swings should have holes drilled into the bottom to allow trapped water to drain.[10]

Differential Diagnosis

The differential diagnosis of St. Louis 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
• Western and Eastern equine encephalitis
• Venezuelan Equine encephalitis
• Zika virus
• 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

Most patients who contract the Saint Louis Encephalitis Virus (SLEV) are relatively asymptomatic or have mild flu-like symptoms from which they will fully recover. The overall case-fatality rate for Saint Louis encephalitis is 5% to 15%. The risk of fatal disease increases with age and is about 20% in patients over 60 versus 3% to 6% in children and young adults. During the first two weeks of infection, death is often due to the encephalitis, whereas deaths that occur after two weeks are more often attributable to complications of hospitalization, such as pneumonia.[11] Contraction of the virus is thought to confer life-long immunity to infection.

Complications

Although most patients recover from the disease, one’s recovery can be complicated by gastrointestinal hemorrhage, pulmonary embolism, and pneumonia. In some cases, it is thought that pneumonitis and respiratory decompensation might result from aspiration during periods of acute encephalopathy from viral meningoencephalitis.[11] Approximately one-third of patients who develop neurologic disease from the infection will also develop hyponatremia from SIADH,[12] and therefore, its related complications including cerebral edema and central pontine myelinolysis  (from overly rapid correction of hyponatremia.).

Adult survivors of St. Louis encephalitis may have a prolonged period of convalescence, usually with symptoms of asthenia, anxiety, irritability, emotional lability, depression, tremor, dizziness, attention deficits, memory deficits, and gait unsteadiness that can persist for months.[13][14]

In pediatric patients, younger age tends to be associated with a higher incidence of neurologic sequelae, particularly in patients younger than ten years of age. These include convulsions, pyramidal signs, extrapyramidal signs, and intellectual disability.[15]

There have also been case reports of post-infectious encephalomyelitis and subacute thyroiditis associated with SLEV infection.[16][17]

Deterrence and Patient Education

As there is no specific treatment St. Louis Encephalitis, and because the disease can cause significant morbidity, prevention of the disease is extremely important. Prevention is best accomplished by avoiding mosquito bites entirely. Even very short periods of outdoor exposure can result in bites; therefore, proper protective clothing like long sleeves, long pants, socks, and closed-toe shoes should be worn. 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. Wading pools should be drained and stored, and tire swings should have holes drilled into the bottom to allow trapped water to drain.

Enhancing Healthcare Team Outcomes

The diagnosis and management of St Louis encephalitis are best in the presence of an interprofessional team that includes a neurologist, internist, infectious disease expert, emergency department physician, nurse practitioner, and an intensivist. There is no effective antiviral therapy for St. Louis encephalitis. Management is limited to supportive care with intravenous (IV) fluids and antipyretics.

Patient education in preventing the transmission of the disease via mosquito avoidance is an important intervention to avoid the morbidity associated with SLEV infection.

In terms of mortality, the overall outlook for most patients with St Louis Encephalitis is good. However, residual neurological sequelae have been reported.[13][14][15] (Level 4)