Western Equine Encephalitis: How it Affects the Nervous System

Introduction

What is Western Equine Encephalitis (WEE)?

WEE is a rare mosquito-borne viral illness, commonly affecting horses and humans. Such organisms become infected as a result of the transmission of the virus from these mosquitoes. WEE causes a variety of symptoms, many of which result in permanent neurological deficits.¹

This article aims to explain the implications of WEE on the nervous system. The disease is highly transmissible so the importance of prevention measures to reduce the spread of WEE are discussed too. 

Understanding WEE

Causes and transmission

Mosquitoes are the primary vector (carrier) in WEE. This means that the virus is transmitted when organisms are bitten by infected mosquitoes. These organisms are termed ‘hosts’ since they are fed upon by mosquitoes. Birds are also known to act as a reservoir and amplify the spread of WEE from mosquitoes to horses and humans. Migration of birds, for example during seasonal changes, often causes a spike in WEE cases.²

Geographic distribution and global prevalence

As the name suggests, WEE is most prevalent in western areas. However, the virus is able to survive at cool temperatures, so cases can be seen in northern regions too and epidemics generally occur early in the summer season.³ From the 1930s until the 1950s widespread outbreaks were recorded in western North America, with areas as far north as Saskatchewan, Canada affected too. Case numbers began to decrease from the 1970s and, from 1998 to date, no human cases of WEE have been reported in the United States or Canada.²

Reports by the National Food Safety and Quality Service state that 1,258 animal cases were detected in Argentina from 25 November 2023 to 9 January 2024. The Pan American Health Organisation/World Health Organisation (PAHO/WHO) identified 21 confirmed cases in humans too, including one that was fatal. However, this number is likely to be much higher if suspected cases are also included, giving an overall total of more than 90 cases.⁴ These statistics act as a warning to us all about the risks of WEE outbreaks to human health and urge global health organisations to implement measures to combat the spread of the disease. 

Pathogenesis of WEE

It is important to understand the pathogenesis of a disease so that scientists can identify the root of the problem and suggest methods, such as vaccinations, to either prevent or reduce the severity of that disease.

In WEE, the infected mosquito first bites into its host, transferring the virus into the subcutaneous tissue of that host. Next, the virus replicates in order to increase its prevalence in other cells of the host’s body, thus causing widespread symptoms. It does this by inserting itself into the membrane of the target cell where it copies its genetic material and creates new proteins with the help of a cellular structure called the rough endoplasmic reticulum (RER). These new proteins then become infectious and are released from the cell to continue this process in cells elsewhere.⁵ Scientifically speaking, this is termed ‘viraemia’ and can result in the virus entering the central nervous system.⁶

Figure 1. Pathogenesis of WEE

Clinical manifestations of WEE

Initial symptoms

For humans, the incubation period ranges from anything between 2 to 15 days.⁷

In adults, WEE is generally a mild, asymptomatic illness. If symptoms are present, they appear quickly and can include fever, headache, nausea, vomiting, myalgia, and malaise. WEE is more severe in children, especially those under one year of age. 

Progression of neurological symptoms, complications and long-term effects

If the illness invades the central nervous system, more severe symptoms may present, such as drowsiness, neck stiffness, stupor, seizures and coma. These tend to develop more quickly in children and the elderly, and many will suffer permanent neurological deficits (e.g. epilepsy, paralysis) or die from complications. Of those patients who do recover, long-term problems, including fatigue and headaches, are often reported for many years, even after the infection has resolved.⁶ 

Diagnosis of WEE

Clinical evaluation and history

WEE symptoms closely resemble those of other conditions so accurately diagnosing the disease can be difficult. The PAHO defines a ‘suspected’ case of WEE using the following criteria:

• Patient presents with an acute onset fever, accompanied by a headache
• Patient is mentally confused, has other neurological symptoms (e.g. tremors, drowsiness) or is presenting with signs of meningitis or encephalitis⁸

Additional history, for example recent travel to an area where WEE is highly prevalent, provides strong evidence that WEE is the likely cause of the patient’s symptoms. 

Laboratory tests

Next, a selection of laboratory tests may be used to confirm the suspected case of WEE:

• Viral genetic material is detected through RT-PCR, a test that involves amplifying a virus (if present) to help detect it⁹
• Antibodies to WEE are detected through ELISA, a test that uses bodily samples, including blood and cerebrospinal fluid 

Differential diagnosis with other neurological conditions

As mentioned previously, WEE can be hard to diagnose due to its similarity with other neurological conditions. Clinicians must make a ‘differential diagnosis’, that is, individually considering similar diseases so that the correct final diagnosis can be made.¹⁰ Such diseases include typhoid fever, malaria, Creutzfeldt-Jakob disease and Venezuelan equine encephalitis.⁶

Treatment and management of WEE

Supportive care and symptom management

For mild cases of the disease, rest and sufficient hydration generally help to improve symptoms. Pain relief is recommended for symptoms like headaches. The antipyretic properties of paracetamol make it particularly effective for the treatment of fever.

Antiviral therapy

The use of antiviral therapy for WEE is generally poorly established. From the research available, it is suggested that these therapies work by inhibiting the WEE virus to halt its ability to damage neural cells and cause symptoms.¹¹ However, viruses constantly change through undergoing genetic mutations and this produces many strains of the virus, making effective treatments difficult to develop.

Treatment of complications

For patients who develop complications of WEE, measures such as mechanical ventilation may be necessary. Seizures can be treated with anti-epileptic drugs and can be continued in those who develop a chronic seizure disorder.⁶

Public health measures and prevention strategies

Vector control and surveillance data

The PAHO highlights the importance of vector control for WEE. They state that these measures should be implemented according to surveillance data that identifies which areas pose a particularly high risk of transmission of WEE.

Example measures include:

• using insecticides in areas where the mosquito population is high
• removing sources that accelerate mosquito breeding (e.g. overgrown grasses, areas of standing water)⁴

Vaccination efforts and efficacy

The availability of vaccines suitable for human use is limited, although an experimental vaccine known as ‘TSI-GSD 210’ has been used by the United States Army Medical Research Institute of Infectious Diseases since 1976. In 2020, an article was published by Frontiers in Immunology reaffirming the efficacy, safety and tolerability of this vaccine. Despite this, the vaccine’s usage is still limited, owing to manufacturing restrictions and a preference to develop alternative vaccines too.¹² 

Public awareness and community education

One of the most effective prevention strategies for WEE is ensuring local populations are educated on how to reduce transmission. Personal protective measures include:

• ensuring clothing covers arms and legs to reduce exposure to mosquitoes; spraying clothes with insect repellents containing ingredients such as permethrin can provide extra protection
• using mosquito nets on doors and windows
• avoiding outdoor activities during dawn and dusk periods when mosquito activity is particularly high^4,6

Directions for future research

Many disease outbreaks are unpredictable so there is a need to develop better treatment methods so that we can be prepared for such events and minimise the risk to human health. Drawbacks with current vaccines demonstrate that further research is needed in this area and greater emphasis needs to be placed on moving vaccine development from the research stage to human use. The WEE virus is capable of mutating to produce many strains, so it could be suggested that vaccines should be designed in a way that not only provide protection against current circulating strains but also offer broader immunity to reduce the threats that future strains might pose. 

Summary

• Host organisms such as horses and humans contract WEE following a bite from mosquitoes carrying the virus
• Most cases of the disease are mild but neurological symptoms including delirium, seizures and coma may develop if the disease progresses
• A diagnosis is made by considering the patient’s symptoms and using laboratory tests to confirm suspected cases
• In terms of treatment, antiviral therapies are generally limited, so the focus is on prevention strategies such as vector control and personal protective measures
• Future research should be centred on developing vaccines to provide effective protection against WEE