St. Louis Encephalitis


Article Author:
Leslie Simon


Article Editor:
Charles Graham


Editors In Chief:
Jessica Snowden
Asif Noor
H Davies


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
2/24/2019 2:15:28 PM

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 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 effective 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 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 pipiensCulex quinquefasciatusCulex 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 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. 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 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 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. Death usually occurs in the first 2 weeks from the onset of infection. Survivors of encephalitis may have a prolonged period of convalescence, usually with symptoms of headaches, anxiety, dizziness, tremor and memory deficits. Contraction of the virus is thought to confer life-long immunity to infection.

Enhancing Healthcare Team Outcomes

The diagnosis and management of St louis encephalitis is best done with a multidisciplinary 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.

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. 

The outlook for most patients with St Louis Encephalitis is good. Very few cases have residual neurological sequelae. [11](Level V)


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St. Louis Encephalitis - Questions

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Which type of encephalitis is endemic in the western United States?



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A 67-year-old woman with a history of liver transplant 6 years ago presents with altered mental status. Her husband describes a prodrome of fever, diarrhea, headache, and myalgia that started 10 days after returning from a boating trip along this Mississippi river. He that she had multiple mosquito bites. Which test is most likely to identify the causative agent?



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St. Louis Encephalitis - References

References

Laurido-Soto O,Brier MR,Simon LE,McCullough A,Bucelli RC,Day GS, Patient characteristics and outcome associations in AMPA receptor encephalitis. Journal of neurology. 2019 Feb;     [PubMed]
Diaz A,Coffey LL,Burkett-Cadena N,Day JF, Reemergence of St. Louis Encephalitis Virus in the Americas. Emerging infectious diseases. 2018 Dec;     [PubMed]
Curren EJ,Lindsey NP,Fischer M,Hills SL, St. Louis Encephalitis Virus Disease in the United States, 2003-2017. The American journal of tropical medicine and hygiene. 2018 Oct;     [PubMed]
Soung A,Klein RS, Viral Encephalitis and Neurologic Diseases: Focus on Astrocytes. Trends in molecular medicine. 2018 Nov;     [PubMed]
Staley EM,Jamy R,Phan AQ,Figge DA,Pham HP, N-Methyl-d-aspartate Receptor Antibody Encephalitis: A Concise Review of the Disorder, Diagnosis, and Management. ACS chemical neuroscience. 2018 Aug 31;     [PubMed]
Remy KE,Custer JW,Cappell J,Foster CB,Garber NA,Walker LK,Simon L,Bagdure D, Pediatric Anti-{i}N{/i}-Methyl-d-Aspartate Receptor Encephalitis: A Review with Pooled Analysis and Critical Care Emphasis. Frontiers in pediatrics. 2017;     [PubMed]
Agner SC,Klein RS, Viruses have multiple paths to central nervous system pathology. Current opinion in neurology. 2018 Jun;     [PubMed]
Ortiz-Martínez Y,Vega-Useche L,Villamil-Gómez WE,Rodriguez-Morales AJ, Saint Louis Encephalitis Virus, another re-emerging arbovirus: a literature review of worldwide research. Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive. 2017 Mar 1;     [PubMed]
Dorsett M,Liang SY, Diagnosis and Treatment of Central Nervous System Infections in the Emergency Department. Emergency medicine clinics of North America. 2016 Nov;     [PubMed]
Smith DR, Waiting in the wings: The potential of mosquito transmitted flaviviruses to emerge. Critical reviews in microbiology. 2017 Aug;     [PubMed]
Misra UK,Tan CT,Kalita J, Viral encephalitis and epilepsy. Epilepsia. 2008 Aug;     [PubMed]

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