St. Louis Encephalitis Virus

The Saint Louis encephalitis virus (SLEV) is a member of the genus Flavivirus and is the cause of St. Louis encephalitis. This small, enveloped, positive-sense, single-stranded RNA virus is transmitted by Culex mosquito species and is prevalent in the United States. Most infections are asymptomatic. Symptomatic individuals may have varied presentations, with flu-like symptoms, aseptic meningitis, encephalitis, or meningoencephalitis. The diagnosis is confirmed with serology. There is no effective antiviral treatment, so management is supportive. Prevention is aimed at local mosquito control and personal protection with insect repellent and protective clothing.

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Classification

RNA Viruses Flowchart Classification

RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics and Epidemiology

Basic features of St. Louis encephalitis virus (SLEV)

  • Taxonomy:
    • Family: Flaviviridae
    • Genus: Flavivirus
  • RNA virus
    • Single-stranded
    • Positive-sense
    • Linear
  • Spherical
  • Icosahedral symmetry
  • Enveloped
  • Size: Approximately 50 nm
  • Positive-sense ssRNA core
St. Louis encephalitis virions Flaviviridae

Transmission electron microscopic image of numerous St. Louis encephalitis virions within an unidentified tissue sample:
This virus is a member of the genus Flavivirus.

Image: “Numerous St. Louis encephalitis (SLE) virions that were contained within an unidentified tissue sample” by CDC. License: Public Domain

Associated disease

St. Louis encephalitis virus causes St. Louis encephalitis (SLE).

Epidemiology

  • Incidence: 0.003–0.752 cases per 100,000 people in the United States
    • Approximately 100 cases per year
    • Incidence is declining
  • Most cases occur during the summer.
  • Mortality rate: 3%–30%
  • Geographic distribution:
    • United States (most common in the Mississippi River valley, along the Gulf Coast, and in the Southwest)
    • Canada
    • Caribbean
    • Central America
    • South America
St. Louis encephalitis map Flaviviridae

Cases of St. Louis encephalitis in the United States (1964–1998):
Note the distribution of the cases. The disease is most commonly found in the Mississippi River valley, along the Gulf Coast, and in the Southwest.

Image: “Human incidence of Saint Louis encephalitis in the United States, 1964-1998” by CDC. License: Public Domain

Pathogenesis

Reservoir

  • Primary hosts: birds
  • Accidental hosts: 
    • Humans
    • Other mammals

Transmission

  • Vector: Culex mosquitoes species
  • Solid organ transplantation (rare)
Culex mosquito St. Louis encephalitis virus Flaviviridae

Close-up photo of a Culex mosquito, the vector for St. Louis encephalitis virus.

Image: “Close-up photo of a Culex mosquito” by CDC. License: Public Domain

Host risk factors

Risk factors for developing SLEV infection:

  • Age > 70 years (most important)
  • Outdoor activities in endemic areas
  • Comorbidities:
    • Cardiovascular disease
    • Hypertension
    • Immunocompromised state

Pathophysiology

  • Mosquito inoculates SLEV into a human
  • Replication occurs in local tissues → spread to regional lymph nodes occurs
  • Spread of virus through lymphatics and bloodstream
  • Entry into the CNS (unclear mechanism) → predominantly affects gray matter
  • Inflammation and neuronal damage → neurologic symptoms

Clinical Presentation

The vast majority of infected individuals will be asymptomatic. The incubation period for symptomatic individuals is 4–21 days, and the disease varies in presentation and severity.

Prodrome

General:

  • Fever 
  • Headache
  • Malaise
  • Myalgias

Respiratory:

  • Cough
  • Sore throat

Urinary:

  • Dysuria
  • Urgency
  • Incontinence

Neurologic signs and symptoms

Patients may present with meningitis, encephalitis, or a combination of the 2 (meningoencephalitis).

Aseptic meningitis (most common):

  • Headache
  • Fever
  • Neck stiffness
  • Photophobia
  • Nausea and vomiting

Encephalitis:

  • Altered mental status
    • Disorientation
    • Agitation 
    • Coma
  • Tremors involving:
    • Eyelids
    • Tongue
    • Lips
    • Extremities
  • Cranial nerve dysfunction
  • Spastic paralysis
  • Ataxia
  • Seizure (rare)

Diagnosis and Management

Diagnosis

The diagnosis may be suspected from the history and physical examination. 

  • Definitive testing: serology (ELISA) of blood and CSF
  • Supporting evaluation:
    • Potential laboratory findings:
      • Normal or ↑ WBC
      • Hyponatremia → SIADH due to encephalitis
    • CSF analysis:
      • Normal or ↑ opening pressure
      • ↑ Protein
      • Normal glucose
      • Mild ↑ WBC (initial neutrophil predominance, followed by monocytic or lymphocyctic predominance)

Management

There are no effective antiviral treatments for SLEV, so management is supportive.

  • Monitoring fluid balance and electrolytes
  • Water restriction for SIADH
  • Symptomatic therapy
    • Antiemetics
    • Antipyretics
  • Ventilator support for respiratory failure or inability to protect airway

Prevention

  • Local mosquito control
  • Insect repellent 
  • Protective clothing 
  • Avoid standing water.
  • There are no vaccines for SLEV.

Comparison of Similar Flavivirus Species

Table: Features and diseases of several Flavivirus species
OrganismTick-borne encephalitis virusJapanese encephalitis virusSt. Louis encephalitis virusWest Nile virus
CharacteristicsThe structural features are almost identical.
Region
  • Europe
  • Siberia
  • Asia
  • Asia
  • Western Pacific
North America
  • Africa
  • Middle East
  • Europe
  • South Asia
  • Australia
  • North America
TransmissionTickMosquitoMosquitoMosquito
Clinical
  • Most are asymptomatic.
  • Initially nonspecific symptoms
  • Neurologic phase:
    • Meningitis
    • Encephalitis
    • Meningoencephalitis
  • Nonspecific febrile illness
  • Meningitis
  • Encephalitis
  • Acute flaccid paralysis
  • Guillain-Barré syndrome
  • Most are asymptomatic.
  • Nonspecific febrile illness
  • Meningitis
  • Encephalitis
  • Meningoencephalitis
  • Most are asymptomatic.
  • West Nile fever
  • Neuroinvasive disease:
    • Meningitis
    • Encephalitis
    • Acute flaccid paralysis
Diagnosis
  • Serology
  • PCR
SerologySerology
  • Serology
  • PCR
ManagementSupportiveSupportiveSupportiveSupportive
Prevention
  • Tick avoidance measures
  • Vaccination (in endemic areas)
  • Mosquito avoidance measures
  • Vaccination
Mosquito avoidance measuresMosquito avoidance measures

Differential Diagnosis

  • Lyme disease: tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. The presentation of Lyme disease can vary depending on the stage of the disease and may include the characteristic erythema migrans rash, which is not seen in TBE. Neurologic, cardiac, ocular, and joint manifestations are also common in later stages. The diagnosis relies on clinical findings and tick exposure and is supported by serologic testing. Antibiotics are used for treatment. 
  • Ehrlichiosis and anaplasmosis: tick-borne infections caused by Ehrlichia chaffeensis and Anaplasmosis phagocytophilum, respectively. Symptoms of ehrlichiosis and anaplasmosis include fever, headache, and malaise. Meningoencephalitis can also occur with severe disease. The diagnosis is made using PCR. Treatment of both diseases is with doxycycline.
  • Rocky Mountain spotted fever: disease caused by Rickettsia rickettsii that presents with fever, fatigue, headache, and a rash following a tick bite. Diagnosis is made based on the clinical features, biopsy of the rash, and serologic testing. Treatment involves antibiotics, including doxycycline.  
  • Herpes simplex encephalitis: severe CNS infection caused by herpes simplex viruses. Patients develop rapid onset of fever, headache, altered level of consciousness, focal neurologic deficits, and seizures. The diagnosis is confirmed with PCR testing of CSF. MRI may show hyperintense lesions in the temporal lobes. IV acyclovir is the treatment of choice.
  • Equine encephalitis viruses: mosquito-borne arboviruses of the Togaviridae family. Initial symptoms include fever, headache, and vomiting. A majority of patients recover, but the illness can progress to severe encephalitis. Diagnosis is by clinical findings and CSF analysis using serology or PCR. There is no specific treatment, and therapy is largely supportive. 
  • Bacterial meningitis: acute infection of the meninges. Patients with bacterial meningitis present with headache, fever, nuchal rigidity, and rapid clinical deterioration. Lumbar puncture is performed to make the diagnosis. Unlike with viral meningitis, CSF studies will show a turbid fluid, low glucose, and high WBC count with neutrophil predominance. Gram stain and culture will determine the causative bacteria. Treatment includes antibiotics and corticosteroids. 

References:

  1. Laurido-Soto O, Brier MR, Simon LE, McCullough A, Bucelli RC, Day GS. (2019). Patient characteristics and outcome associations in AMPA receptor encephalitis. J Neurol 266:450–460. https://www.ncbi.nlm.nih.gov/pubmed/30560455
  2. Auguste AJ, Pybus OG, Carrington CV. (2009). Evolution and dispersal of St. Louis encephalitis virus in the Americas. Infect Genet Evol 9:709–715. 
  3. Diaz A, Coffey LL, Burkett-Cadena N, Day JF. (2018). The reemergence of St. Louis encephalitis virus in the Americas. Emerg Infect Dis 24:2150–2147. https://www.ncbi.nlm.nih.gov/pubmed/30457961
  4. Curren EJ, Lindsey NP, Fischer M, Hills SL. (2018). St. Louis encephalitis virus disease in the United States, 2003-2017. Am J Trop Med Hyg 99:1074–1079. https://www.ncbi.nlm.nih.gov/pubmed/30182919
  5. Soung A, Klein RS. (2018). Viral encephalitis and neurologic diseases: focus on astrocytes. Trends Mol Med 24:950–962. https://www.ncbi.nlm.nih.gov/pubmed/30314877
  6. Centers for Disease Control and Prevention. (2009). Saint Louis encephalitis. https://www.cdc.gov/sle/technical/fact.html
  7. Monath, T.B. (2019). St. Louis encephalitis. In Mitty, J. (Ed.), UpToDate. Retrieved May 7, 2021, from https://www.uptodate.com/contents/st-louis-encephalitis
  8. Simon LV, Kong EL, Graham C. (2020). St. Louis encephalitis. StatPearls. Retrieved May 7, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK470426/
  9. Somboonwit C, Donovan FM, Katta JT. (2020). St. Louis encephalitis. In Bronze, M.S. (Ed.), Medscape. Retrieved May 7, 2021, from https://emedicine.medscape.com/article/233710-overview

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