What Is California Encephalitis?

California Encephalitis (CE) is a childhood central nervous system (CNS) disorder that is prevalent, reportable, and spreads through mosquito bites. Among the viral infections spread by mosquitoes in the United States, it is ranked second after West Nile virus (WNV) encephalitis.
Contrary to popular perception, the name “California Encephalitis” didn’t originate in California but derives from the California serogroup of viruses. Despite having the word “California” in its name, the disease is not exclusive to the state; it can exist in any part of North America. The Centres for Disease Control and Prevention (CDC) reports that 31 Americans contracted the La Crosse virus sickness in 2023.

Are you interested in learning more about the specifics of CE? There's much to explore, including the vital safety measures, different culprits and fascinating origins. For a thorough knowledge of this intriguing sickness spread by mosquitoes, continue reading.

Introduction

Since the first recorded human case of CE occurred in Kern County, California, in 1946, many cases in the United States are rarely from California or the West Coast. Following its first description, the La Crosse (LAC) virus, a virus closely related to the CE virus, has been linked to the majority of instances of CE. The 4-year-old kid who passed away in La Crosse County, Wisconsin, from encephalitis was the first person to have the LAC virus isolated from his brain. Most CE virus infections are asymptomatic, and most infected individuals who experience symptoms fully recover; 10% of patients develop recurring seizures or behavioural issues. In severe cases, the condition presents as encephalitis (brain inflammation), which can result in paralysis, coma, and seizures. 

Arboviral encephalitis varies by several epidemiologic factors, such as four main ones: season, geographic location, regional climate conditions (e.g. spring rainfall), and patient age. In the US, the midwestern states have the highest rate of CE. Most cases happen during late summer and early autumn, while some occur in the winter in subtropical endemic regions like the Gulf States. There is a higher risk of infection when engaging in outdoor activities, particularly in woodlands. Historically, reports of La Crosse encephalitis have come from 28 states, primarily from the northern Midwestern states. The mid-Atlantic, southeast, and northeastern states have reported a spike in cases recently. In terms of prevalence and severity, it may occasionally go undetected.¹

Types of CE

A class of viruses members of the family Bunyaviridae and genus Bunyavirus are responsible for CE. Around 350 identified strains from this family of RNA viruses split globally. The spherical, lipid membrane-enclosed bunyaviruses have a 90 to 110 nm diameter. They have a nucleocapsid that is enclosed and three segments of negative-sense RNA. The nucleocapsid protein appears to be immunogenic.

Figure 1 RNA virus structure (AI image by Leonardo.Ai).

The following table lists the main types of CE along with its geographic distribution, infections acquired, and modes of transmission.

Table 1 Main types of California Encephalitis. 

This illustration shows the LAC virus transmission cycle.

Figure 2 Created by Deepika Rana (created in Biorender).¹

Clinical presentation

CE takes three to seven days to incubate. A prodromal period lasting one to four days occurs before encephalitis manifests. The following characteristics describe this phase:¹

• Fever and chills
• Nausea and vomiting
• Headache
• Abdominal pain

Diagnosis

Figure 3 Created by Deepika Rana (created in Piktochart.com).

Since the virus does not appear in blood or secretions during a clinical case of CNS illness, immunology provides the basis for CE diagnosis. 

Antibody studies

More than 320 by haemagglutination inhibition (HI), >128 by complement fixation, > 256 by immunofluorescence (IF), and >160 by plaque reduction neutralisation test (PRNT) are considered significant antibody titers. For IgG and IgM antibodies against the La Crosse virus, a licenced indirect fluorescent antibody test (IFA) is available, which could be helpful for diagnosis.

Cerebrospinal fluid (CSF) examination

A CSF analysis could show usually slightly higher than normal pressure, normal blood sugar levels and moderately raised to regular protein levels. There is a neutrophil pleocytosis at first, followed by lymphocytic or monocytic leucocytosis.

Complete blood count (CBC)

CBC falls within the reference range and occasionally exhibits mild leukocytosis. Mostly, findings fall within the reference range. Nevertheless, in one case series, low serum sodium levels have been reported in up to 20% of the patients. 

Polymerase chain reaction (PCR)

Diagnostics for La Crosse encephalitis involve PCR and detection of several infections with a single test using the next-generation sequencing (NGS) of CSF.

Imaging studies

According to research by De los Reyes and associates, children with La Crosse encephalitis who have PLEDS on electroencephalograms (EEG) are more likely to experience problems.

Histologic findings

Pathologic analysis reveals diffuse foci of inflammatory necrosis involving grey and white matter, neuronophagia, and extensive degradation of individual nerve cells. The brain stem is intact. Patchy meningeal infiltration and perivascular cuffing with plasma cells and lymphocytes are apparent.¹

Treatment 

Since no particular antiviral therapy is currently approved, the cornerstone of disease management is supportive care. The medications used in supportive care include those that can treat neurologic issues. Anticonvulsant medications stop clinical and electrical seizure activity as well as prevent seizures from happening again.
Phenytoin may affect the motor cortex, where it may prevent seizure activity from spreading. Inhibition may also impact the activity of brain stem regions that control the tonic phase of grand mal seizures.
Diazepam depresses all levels of the central nervous system, including the limbic and reticular formation.
Antipyretics treats the disease's accompanying fever, malaise, and lethargy.
Through a direct effect on the hypothalamus heat-regulating centres, acetaminophen lowers fever. It boosts the body's ability to dissipate heat through sweating and vasodilation.
Control of seizures and adequate neurologic care are essential parts of therapy because neurologic consequences are the most severe and closely associated with disease mortality. There's no need to isolate a patient when they're sick. Resting in bed is always advised till you recover.¹

Prevention and control 

Most measures focus on mosquitoes, which were the target of early preventative programmes. Their rapid geographic spread, the significance of the viruses they grow, and the consequent risk to human life are the causes of this. The table provides a list of various control mechanisms.

Table 2 Control mechanisms of CE. 

FAQ's

What is the prognosis for CE?

Seizures are prevalent during acute illness, but less than 1% of cases are fatal, and most patients recover fully. On the other hand, reports of neurological consequences, such as anomalies in cognition and behaviour, exist.⁵

What are the complications of CE?

More severe diseases can be associated with complications, including

epilepsy (most serious), cognitive and memory deficits, lethargy, aphasia, incoordination, focal motor abnormalities, aseptic meningitis and paralysis.¹

Who is most vulnerable to CE?

Assigned males at birth have a higher chance than assigned females at birth to have CE, most likely due to greater outside exposure. Almost exclusively, children between the ages of 6 months and 16 years (peak, 4 to 10 years) experience clinical illness. The likelihood of a patient developing the condition decreases with age.¹

Is there a vaccination to prevent California encephalitis?

Presently, no vaccination or antiviral therapy is available for the California encephalitis group of viruses.²

Summary

• The viruses that cause CE are members of the California serogroup and spread via mosquito bites. These viruses cause inflammation in the brain, resulting in mild to severe neurological issues as symptoms.
• Frequent signs of CE include headache, nausea, vomiting, and fever.
• Specific treatment is not yet available, one can take preventive actions such as wearing protective clothing, clearing up mosquito breeding grounds near residences, and using insect repellent to lessen mosquito exposure.
• Public health education and community-based mosquito control programmes are also essential for preventative efforts.