AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

The St. Louis encephalitis virus (SLEV) belongs to the family Flaviviridae (group B arborviruses). Its principal reservoirs are wild birds and domestic fowl, and it is transmitted to humans by mosquitos (Culex tarsalis, Culex quinquefasciatus, Culex pipiens). The clinical manifestations of SLEV infection range from mild, flulike syndromes to fatal encephalitis.

Pathophysiology

A primary viremia follows reproduction of the SLEV at the site of inoculation. In the case of subclinical disease, the pathogen is cleared by the reticuloendothelial system (the liver, spleen, and lymph nodes) before invasion of the CNS can take place.

Continued viral replication gives rise to a secondary viremia. Saturation of the filtering capacity of the reticuloendothelial system enables invasion of the CNS. The probability of CNS infection depends on the efficiency of viral replication at the extraneural sites and the degree of viremia. The virus enters the CNS either through the cerebral capillary endothelial cell/astrocyte complex (the blood-brain barrier) or across fenestrated endothelium in areas of the CNS that do not have the usual blood-brain barrier capacity (ie, choroid plexus). Rarely, SLEV may tract retrograde from a peripheral site (the olfactory nerve) that was infected during the viremia.

Many of the flaviviruses exhibit various types of neurotropism. The specific neurotropic mechanisms in the case of SLEV have not been established.

Focal neuronal degeneration with necrosis occurs. This leads to the development of glial nodules. Upon healing, spongiform changes take place. The perivascular inflammatory infiltrates are made up of activated T cells and macrophages.

Frequency

United States

The virus is widely distributed in the United States, and infections occur as periodic focal outbreaks of encephalitis in the midwestern, western, and southwestern United States, followed by years of sporadic cases. It has caused large urban epidemics of encephalitis. Outbreaks occur from August through October. During the last 5 decades, 10,000 cases were reported. St. Louis encephalitis is mostly sporadic. Annual incidence is 0.003-0.752 cases per 100,000 population. Median occurrence is 35 cases per year. In the United States, the virus exhibits an endemic pattern primarily along the western coast and sporadic infections occur in the east.

International

Outbreaks of SLEV have occurred in Canada and Mexico. Sporadic cases have occurred in South America and the Caribbean.

Mortality/Morbidity

The mortality rate ranges from 2-20% (higher among older patients). Of patients with clinical illness, 20% develop sequelae, including irritability, memory loss, various types of movement disorders, and motor deficits. Seizures and coma are unusual. Focal deficits are uncommon, except for cranial nerve palsies.

Sex

Incidence is higher in males compared to females, probably due to more outdoor exposure.

Age

Severity of the symptoms increases with age. Older patients have a greater risk of developing a clinical picture (especially those >60 y). The literature has reported that up to 90% of elderly individuals develop the clinical illness.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

After an incubation period of 4-21 days, the virus can cause mild febrile illness, aseptic meningitis, or encephalitis. A prodrome of malaise and fever accompanied by cough and sore throat characterizes the onset of encephalitis. Headache, nausea, vomiting, confusion, disorientation, irritability, tremors, and, occasionally, convulsions follow.

• Several days after the onset, the patient will defervesce, with gradual neurological improvement over several days.
• Chronic infection does not occur. Relapsing infection has not been reported.
• Risks factors for clinical disease include the following:
• • Individuals older than 70 years have a 10-fold increased risk of clinical illness.
  • Exposure to endemic areas or outdoor activities increases risk.
  • Male sex is a risk factor.
  • Most outbreaks occur in people of low socioeconomic status, which probably is due to less access to heath care and poor environmental control of mosquitos.
  • Comorbidity with atherosclerosis, heart disease, and hypertension is associated with increased fatality with encephalitis.

Physical

• Most cases of SLEV infection demonstrate a significant elevation in temperature.
• Meningismus may or not be present.
• Photophobia seldom is present.
• The neurological examination usually is normal.
• • Five percent of patients present with deep coma, and 25% develop cranial nerve palsies. Fewer exhibit ataxia.
  • Seizures are unusual and occur more frequently in children.

Causes

St. Louis encephalitis is caused by an enveloped, single-stranded, positive-sense RNA virus of the Flaviviridae subgroup.

• It has a relatively conserved nucleotide sequence.
• It is an arbovirus transmitted via a mosquito vector from wild birds to humans. Birds, primarily passerine birds such as finches and sparrows, are the principal virus hosts. The vector is the mosquito C pipiens, C tarsalis, or C quinquefasciatus.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Other arbovirus encephalitis
Herpes simplex encephalitis
Bacterial (including listerial), tuberculous, or fungal meningitis
Brain abscess
Carcinomatous meningitis
CNS vasculitis
Cerebrovascular disease

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• According to the US Centers for Disease Control and Prevention, guidelines for the diagnosis of arbovirus encephalitis include febrile illness or mild aseptic meningitis or encephalitis (onset during a period when transmission of the virus is likely to occur) and one of the following:
• • A 4-fold increase in the antivirus antibody titer between the acute and the convalescent periods
  • Virus isolation from tissue, blood, or cerebrospinal fluid (CSF).
  • Specific immunoglobulin M antibody to the virus
• Antibody titers are considered to be significant if higher than 1/320 by hemoagglutination inhibition, higher than 1/128 by complement fixation, higher than 1/256 by immunofluorescence, or higher than 1/160 by the plaque reduction neutralization test.
• The white blood cell count usually is not elevated. Pyuria or proteinuria may occur. More than one third of patients develop hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
• CSF examination reveals pressure that ranges from normal to mildly elevated, glucose at normal levels, and protein that ranges from normal to mildly elevated. Initially, polymorphonuclear leukocytic pleocytosis occurs, followed by lymphocytic or monocytic leukocytosis. Usually, the CSF white blood cell count is less than 200 per mm³.

Imaging Studies

• Neuroimaging using conventional CT scan and MRI is not helpful in establishing the diagnosis.

Histologic Findings

Microscopically, as in all viral encephalitis diseases, widespread degeneration of single nerve cells occurs with neuronophagia and scattered foci of inflammatory necrosis involving the gray and white matter. The brainstem is relatively spared. Perivascular cuffing with lymphocytes and plasma cells occurs. Patchy infiltration of the meninges with microglial nodules also develops. Notably, no axonal or demyelinating lesions occur.

Pathological features are evident only in the CNS, although the virus has been isolated from vitreous humor, lung, liver, spleen, and kidney.

Grossly, the brain and the meninges appear swollen, with widely distributed changes in the brain, mostly in the substantia nigra, thalamus, hypothalamus, cerebellum, cerebral cortex, basal ganglia, and cervical spinal cord, with more involvement of gray matter than white matter.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

• No antiviral agent is available.
• Supportive care is the mainstay of treatment.
• Manage seizures or any neurological symptoms.
• No vaccine is available for preexposure protection.

Activity

Bedrest is advised.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention

• Mosquito control with insecticides
• Increased public health awareness in the endemic areas
• Avoidance of outdoor exposure
• Increased environmental drainage to decrease mosquito habitat
• Application of mosquito repellent
• Questionable role of passive immunity using antibodies

Complications

• Of survivors, 20% develop sequelae, including irritability, memory loss, seizures, or motor deficits.
• The medical literature contains isolated reports of hyponatremia due to SIADH with St. Louis encephalitis.

Prognosis

• Of survivors, 20% develop sequelae, including irritability, memory loss, seizures, or motor deficits.
• The mortality rate is 2-20% within 1-2 weeks. Older patients have a higher mortality rate.

Patient Education

• Increase public health awareness in endemic areas.
• Educate patients to avoid outdoor exposure, to wear long sleeves outdoors, and to apply mosquito repellent.
• For excellent patient education resources, visit eMedicine’s Brain and Nervous System Center. Also, see eMedicine’s patient education article Encephalitis.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize and diagnosis the disease
• Failure to provide adequate supportive care
• Failure to properly manage seizures or any neurological symptoms
• Failure to educate patients to avoid outdoor exposure, to wear long sleeves outdoors, and to apply mosquito repellent

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Centers for Disease Control and Prevention. From the Centers for Disease Control and Prevention. Arboviral disease-- United States, 1994. JAMA. Oct 11 1995;274(14):1110-2. [Medline].
• Centers for Disease Control and Prevention. Arboviral disease--United States, 1994. MMWR Morb Mortal Wkly Rep. Sep 8 1995;44(35):641-4. [Medline].
• Cerna F, Mehrad B, Luby JP. St. Louis encephalitis and the substantia nigra: MR imaging evaluation. AJNR Am J Neuroradiol. Aug 1999;20(7):1281-3. [Medline].
• Chandler LJ, Nordoff NG. Identification of genetic variation among St. Louis encephalitis virus isolates, using single-strand conformation polymorphism analysis. J Virol Methods. Jul 1999;80(2):169-78. [Medline].
• Chiles RE, Reisen WK. A new enzyme immunoassay to detect antibodies to arboviruses in the blood of wild birds. J Vector Ecol. Dec 1998;23(2):123-35. [Medline].
• Chu CT, Howell DN, Morgenlander JC. Electron microscopic diagnosis of human flavivirus encephalitis: use of confocal microscopy as an aid. Am J Surg Pathol. Oct 1999;23(10):1217-26. [Medline].
• Day JF. Predicting St. Louis encephalitis virus epidemics: lessons from recent, and not so recent, outbreaks. Annu Rev Entomol. 2001;46:111-38. [Medline].
• Day JF, Stark LM. Frequency of Saint Louis encephalitis virus in humans from Florida, USA: 1990-1999. J Med Entomol. Jul 2000;37(4):626-33. [Medline].
• Day JF, Stark LM. Transmission patterns of St. Louis encephalitis and eastern equine encephalitis viruses in Florida: 1978-1993. J Med Entomol. Jan 1996;33(1):132-9. [Medline].
• Day JF, Stark LM. Avian serology in a St. Louis encephalitis epicenter before, during, and after a widespread epidemic in south Florida, USA. J Med Entomol. Sep 1999;36(5):614-24. [Medline].
• Glaser C, Lewis P, Wong S. Pet-, animal-, and vector-borne infections. Pediatr Rev. Jul 2000;21(7):219-32. [Medline].
• Kramer LD, Presser SB, Hardy JL. Genotypic and phenotypic variation of selected Saint Louis encephalitis viral strains isolated in California. Am J Trop Med Hyg. Aug 1997;57(2):222-9. [Medline].
• Naidech A, Elliott D. St. Louis encephalitis with focal neurological signs. Clin Infect Dis. Nov 1999;29(5):1334-5. [Medline].
• Pelegrino JL, Suarez M, Guzman MG. [Surveillance of St. Louis encephalitis, Eastern equine and Western equine in the province of Ciego de Avila]. Rev Cubana Med Trop. 1996;48(2):109-13. [Medline].
• Reisen WK, Lundstrom JO, Scott TW. Patterns of avian seroprevalence to western equine encephalomyelitis and Saint Louis encephalitis viruses in California, USA. J Med Entomol. Jul 2000;37(4):507-27. [Medline].
• Rocco IM, Santos CL, Bisordi I. St. Louis encephalitis virus: first isolation from a human in São Paulo State, Brazil. Rev Inst Med Trop Sao Paulo. Sep-Oct 2005;47(5):281-5.
• Sejvar JJ, Bode AV, Curiel M. Post-infectious encephalomyelitis associated with St. Louis encephalitis virus infection. Neurology. Nov 9 2004;63(9):1719-21.
• Steele MT. Update on emerging infections from the Centers for Disease Control and Prevention. Arboviral infections of the central nervous system--United States, 1996-1997. Ann Emerg Med. Mar 1999;33(3):365-7. [Medline].
• Venugopal K, Jiang WR, Gould EA. Immunity to St. Louis encephalitis virus by sequential immunization with recombinant vaccinia and baculovirus derived PrM/E proteins. Vaccine. Aug 1995;13(11):1000-5. [Medline].
• Vodkin MH, Szymzcak L, Koll M. Mosquito productivity and surveillance for St. Louis encephalitis virus in Chicago during 1993. J Am Mosq Control Assoc. Sep 1995;11(3):302-6. [Medline].
• Wasay M, Diaz-Arrastia R, Suss RA. St. Louis encephalitis: a review of 11 cases in a 1995 Dallas, Tex, epidemic. Arch Neurol. Jan 2000;57(1):114-8. [Medline].
• Wegbreit J, Reisen WK. Relationships among weather, mosquito abundance, and encephalitis virus activity in California: Kern County 1990-98. J Am Mosq Control Assoc. Mar 2000;16(1):22-7. [Medline].
• Wootton SH, Kaplan SL, Perrotta DM. St. Louis encephalitis in early infancy. Pediatr Infect Dis J. Oct 2004;23(10):951-4.

Article Last Updated: Jun 26, 2006