St. Louis Encephalitis

St. Louis encephalitis virus (SLEV) belongs to the family Flaviviridae (group B arborviruses). The principal reservoirs of SLEV include wild birds and domestic fowl, and the virus is transmitted to humans by mosquitoes (Culex tarsalis, C quinquefasciatus, C pipiens). The clinical manifestations of SLEV infection range from mild flulike syndromes to fatal encephalitis.[1] (See Etiology and Pathophysiology.)

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 patient education information, see the Brain and Nervous System Center, as well as Encephalitis.

St. Louis encephalitis is caused by an enveloped, single-stranded, positive-sense ribonucleic acid (RNA) virus of the Flaviviridae subgroup. St. Louis encephalitis virus (SLEV) has a relatively conserved nucleotide sequence.

SLEV 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 hosts of the virus. Vectors include the mosquitoes C pipiens, C tarsalis, and C quinquefasciatus.

Risks factors for clinical SLEV infection 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 SLEV infection outbreaks occur in people of low socioeconomic status, which is probably due to less access to heath care and poor environmental control of mosquitoes

• Comorbidity with atherosclerosis, heart disease, and hypertension is associated with an increased mortality rate of St. Louis encephalitis

A primary viremia follows reproduction of the SLEV at the site of inoculation. In cases of subclinical SLEV infection, the pathogen is cleared by the reticuloendothelial system (the liver, spleen, and lymph nodes) before invasion of the central nervous system (CNS) can occur.

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).[2] Rarely, SLEV tracts 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 SLEV have not been established.

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

St. Louis encephalitis virus (SLEV) is widely distributed from Canada to Argentina. However, human cases have almost exclusively occurred in the United States, especially in eastern and central states. The infections occur as periodic focal outbreaks of encephalitis in the midwestern, western, and southwestern United States, followed by years of sporadic cases.[3] The annual incidence of 0.003-0.752 cases per 100,000 population. SLEV infections have caused large urban epidemics of encephalitis. Outbreaks occur from August through October; however, where the climate is milder, cases can occur year round. The annual reported SLEV neuroinvasive disease cases fluctuate with periodic epidemics. During the last 5 decades, 10,000 cases were reported, with an average of 102 cases reported annually (range 2-1,967).[4, 5, 6, 7, 8]

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

SLEV infection is reported more often in males than in females, probably due to more outdoor exposure.

The severity of symptoms of SLEV infection increases with age. Older patients are at greater risk of developing clinical illness (especially those >60 y). The literature has reported that up to 90% of elderly individuals who are infected with SLEV develop clinical illness.

Prognosis

The mortality rate of St. Louis encephalitis is 2-30%. This figure is higher in older patients.[9]

Of persons who survive St. Louis encephalitis, 20% develop sequelae, including irritability, memory loss, various types of movement disorders, or motor deficits. The medical literature also contains reports of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and hyponatremia in patients with St. Louis encephalitis.[10]

After an incubation period of 4-21 days, St. Louis encephalitis virus (SLEV) infection 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 St. Louis encephalitis. Headache, nausea, vomiting, confusion, disorientation, irritability, tremors, and, occasionally, convulsions follow.

Several days after the onset of infection, the patient will defervesce, with gradual neurologic improvement over several days. Chronic infection does not occur, and relapsing infection has not been reported.

Most patients with SLEV infection develop a significant fever. Meningismus may or not be present. Photophobia is seldom present.

The neurologic examination findings are usually normal. Five percent of patients with SLEV infection present with deep coma, and 25% develop cranial nerve palsies. Fewer exhibit ataxia. Seizures are unusual and occur more frequently in children.[11]

The diagnostic workup of St. Louis encephalitis virus (SLEV) infection is based on clinical features, history of exposure, and epidemiologic history. According to the US Centers for Disease Control and Prevention (CDC), guidelines for the diagnosis of arboviral encephalitis include febrile illness or mild aseptic meningitis or encephalitis and 1 of the following:

• A 4-fold increase in the antivirus antibody titer between the acute and the convalescent periods

• Isolation of SLEV via culture or detection via nucleic acid amplification from tissue, blood, or cerebrospinal fluid (CSF)[12]

• Specific immunoglobulin M (IgM) antibody to SLEV

The white blood cell (WBC) count is usually not elevated. Pyuria or proteinuria may occur. More than one third of patients develop hyponatremia due to SIADH.

Antibody evaluation

Antibody titers are considered to be significant if in excess of 1:320 by hemoagglutination inhibition, 1:128 by complement fixation, 1:256 by immunofluorescence, or 1:160 by the plaque reduction neutralization test.

CSF examination

CSF examination reveals pressure that ranges from normal to mildly elevated, normal glucose levels, and protein levels that range from normal to mildly elevated. Initially, polymorphonuclear leukocytic pleocytosis occurs, followed by lymphocytic or monocytic leukocytosis. In most cases, the CSF WBC count is less than 200 cells/µL.

Serologic testing

Initial serologic testing consists of IgM capture enzyme-linked immunoassay (ELISA), microsphere-based immunoassay (MIA), and IgG enzyme-linked immunoabsorbent assay (ELISA). If the initial results are positive, further confirmatory testing may delay the reporting of final results. It is also helpful to test CSF IgM antibody for the presence of CNS infection and local antibody production.

Evaluation of fatal cases

In fatal cases, diagnosis can be confirmed via nucleic acid amplification, histopathology with immunohistochemistry, and virus culture. The specimens require specialized laboratories, including those at the CDC and a few state laboratories.

CT scanning and MRI

Neuroimaging using conventional computed tomography (CT) scanning and magnetic resonance imaging (MRI) is not helpful in establishing a diagnosis of SLEV infection.

Microscopically, as in all viral encephalitides, widespread degeneration of single nerve cells occurs with neuronophagia and scattered foci of inflammatory necrosis involving the gray and white matter. The brain stem 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.

Pathologic features of St. Louis encephalitis are evident only in the CNS, although St. Louis encephalitis virus (SLEV) 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.

No antiviral agent is available for the treatment of St. Louis encephalitis virus (SLEV) infection, and no vaccine is available for preexposure protection. Supportive care is the mainstay of treatment. Manage seizures or any neurologic symptoms. Bedrest is advised.

A pilot study has shown that early use of interferon-alpha2b may decrease the severity of complications.[13]

Deterrence and prevention

Prevention measures include the following:

• Mosquito control with insecticides

• Increased public health awareness in endemic areas of St. Louis encephalitis virus (SLEV) infection

• Avoidance of outdoor exposure

• Increased environmental drainage to decrease mosquito habitat

• Application of mosquito repellent

• Questionable role of passive immunity using antibodies

Supportive care is the mainstay of treatment. The drugs in supportive care consist of agents capable of ameliorating neurologic complications. Antipyretics are used as needed.

A pilot study has shown that early use of interferon-alpha2b may decrease the severity of complications.[13] As previously stated, no antiviral agent is available for the treatment of St. Louis encephalitis virus (SLEV) infection, and no vaccine is available for preexposure protection.

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Phenytoin (Dilantin, Phenytek)

Phenytoin may act in the motor cortex, where it may inhibit the spread of seizure activity. The activity of brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited.

Individualize the dose. Administer a larger dose before retiring if the dose cannot be divided equally. The rate of infusion must not exceed 50 mg per minute to avoid hypotension and arrhythmia.

Diazepam (Valium)

Diazepam depresses all levels of the CNS (eg, limbic, reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). Alternatively, lorazepam can be used when indicated.

Class Summary

These agents are helpful in relieving the associated lethargy, malaise, and fever associated with the disease.

Acetaminophen (Acephen, Feverall, Tylenol)

Acetaminophen inhibits the action of endogenous pyrogens on heat-regulating centers. It reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increases the dissipation of body heat via sweating and vasodilation.