Introduction

Venezuelan equine encephalitis (VEE) is a mosquito-borne viral pathogen infection that infects horses and humans that can cause the brain to become inflamed.¹ VEE is endemic to Central America, South America, Mexico and southern parts of the United States¹ where there are outbreaks of VEE.¹ VEE can infect humans and equines, including:²

• Horses
• Donkey
• Mules 
• And zebras

Previous outbreaks of VEE infection have infected up to 750,000 individuals during a single epidemic.² Different subtypes of VEE virus can cause disease in both humans and equines and can affect individuals regardless of sex or age.² However, VEE infection in children are more likely to develop longer-lasting neurological disorders compared to VEE infection in adults. Pregnant mothers infected with VEE are also at risk for stillbirths, early delivery and congenital disabilities for their children.²

Symptoms of VEE include:³

• Fever
• Headache
• Dehydration
• Weakness
• Nausea and vomiting
• Difficulty in swallowing and sore throat
• Rashes
• Chills
• Inflammation of the brain (encephalomyelitis)
• Paralysis, seizures and other neurological signs¹

Understanding the transmission of VEE virus is important in preventing and controlling VEE outbreaks. VEE is transmitted by mosquitoes and VEE infection does possess a significant threat to both humans and equine health. Understanding the modes of transmission, we can then develop intervention and control measurements that can be implemented to reduce VEE outbreaks and save lives. 

Virology of VEE

VEE virus belongs to the Togaviridae family³ and is a single-stranded RNA alphavirus.² Alphavirus are pathogens that are transmitted by mosquitoes and transmission can occur between different species and between individual humans via mosquitoes.² VEE was first isolated in 1938 from a horse and the first human viral isolation was in 1950 during an outbreak in Espinal, Colombia.³

Variants and strains:

There are six subtypes of VEE virus (I- VI) and many variants within each subtypes.² Subtype I, variant A, B and C are the only variants and strains that cause epidemic outbreak in both humans and equine and they are called epizootic.³ Epizootic strains are pathogenic, and can transmit quickly and in equine populations.²

Other strains and subtypes (ID, IE, subtypes II-VI) are known as enzootic strains³ and they are found in rodents.² Enzootic strains are avirulent in horses and cause mild or no illness but they can cause epidemic outbreaks in humans and can cause significant harm.²

Epizootic strains are responsible for disease outbreaks in humans and in the equine population. Horses are susceptible to the VEE virus and fatality rate for horses is between 20% to 80%.⁴ This is due to horses having a higher body area exposed to mosquitos compared to humans.⁴ As described earlier, symptoms of VEE is neurological disorder and this is because VEE virus is neuroinvasive as it can replicate inside the lymphoid tissues and in the brain.⁴

Up to 14% of infection in humans lead to neurological symptoms and there is 1% infection that has resulted in encephalitis (inflammation in the brain) which is lethal.⁴ However, in most individuals, the virus infection is resolved by the immune system.⁴

Modes of transmission

VEE is transmitted by mosquito vectors, through zoonotic transmission or by vertical transmission.²

Mosquito vectors:

There are several species of mosquito that can transmit VEE virus. Ochlerotatus taeniorhynchus is the mosquito species responsible for transmitting epizootic strains of VEE and Culex mosquito species transmit the enzootic species.² VEE is transmitted when the mosquito bites and feeds on infected natural hosts like equines or rodents which then makes the mosquito infected.²

When the mosquito goes to feed again, the virus, which is present in the mosquito‘s salivary glands, will be passed on again, infecting humans and animals.⁴ The virus will mature inside the host and will replicate itself, producing high levels of viral amplification and this makes the infected humans and animals a source of further mosquito infection.² This means that the infected humans and animals can pass on the virus to uninfected mosquitoes during blood-feeding, which will make the mosquito infectious before infecting another host.

Using mosquitoes, the VEE virus is able to replicate itself and can infect more humans and animals, which would then infect more mosquitoes. This continuing cycle transmits more VEE virus, leading to an outbreak of VEE in the area. 

Zoonotic transmission:

VEE virus can be transmitted through natural hosts like equines, rodents and birds. Equines are the primary reservoir for the epizootic strains of VEE and rodents and small birds are main hosts for enzootic strains.² The main reservoir for enzootic strains are sigmodontines rodents where they become infected naturally and they pass on the virus through mosquitoes during blood-feeding.⁴

Incidental hosts like humans can also spread VEE virus and this usually occurs when infected horses release the VEE virus through bodily fluids and humans become infected through direct contact or through aerosolised fluids.²

Vertical transmission:

Vertical transmission is when infection is passed on to the fetus through the mother during pregnancy. As described earlier, pregnant mothers are at risk for developing birth defects, early births or even stillbirths.² Virus tires have been obtained from the brain and uterus and these have shown that VEE virus is able to replicate in the fetus⁴, showing a vertical transmission of VEE is possible.

Environmental factors influencing transmission

Climate and weather patterns:

Climate and weather patterns can have an impact on mosquito population and the seasonal variation in transmission. Epizootic epidemics depend on where the animal hosts are and are usually restricted to where the animals are.⁴ On the other hand, enzootic transmission are found in specific regions and at tropical climates with rainy seasons.⁴

However, climate change and changes in weather patterns can influence the mode of transmission.³ Due to changes in weather patterns and global warming, there has been an increase in northward distribution of mosquitoes, especially the Culex species which carry enzootic strains of VEE virus and could infect humans and animals as far north into the South-east of the US.³

Rodents which act as the primary reservoir for enzootic strains of VEE virus have also been moving up north, leading to outbreaks in the southern USA.³ Another important note is that enzootic infection cycles during the rainy season³, but with the disruption in weather patterns and changes to the seasons due to climate change, there could be seasonal variation in transmission, leading to a series of outbreak depending on the weather. This is due to mosquitoes being in high numbers during heavy rainfall during the rainy season.³

Ecological factors:

Urban transmission is an important environmental factor that is influencing transmission. Due to deforestation of forests where enzootic vectors like the mice and birds live, to make space for equine and human population to live, increases exposure to the VEE virus.³

The forests were the preferred habitat for the mosquito vectors but now they are in more contact with us and with horses, leading to an increase in VEE virus infection. With more of the rural landscapes becoming more urbanised, an increase in VEE virus infection is expected as we are in more contact with the natural reservoir of the virus.

Human factors contributing to transmission

Occupational exposures like farmers and veterinarians can spread the VEE infection as infected horses release the viruses through bodily fluids, causing humans to become infected.² Due to an increase in travel, there can be an increase in travel-related transmission when an infected mosquito feeds on an individual, which causes them to become infected. Prevention and control measures:

Vector control strategies:

Controlling mosquito vectors (for both epizootic and enzootic strains) is an important strategy to reduce the transmission of VEE virus. Vector control strategies are important as it prevents the transmission of the virus by preventing it from interacting with humans.⁴ 

There are several steps available that are used to control mosquito vectors:³

• Larval source reduction 
• Insecticide spraying

Larval source reduction: is a process known as removing the breeding sites of mosquitoes. This is done by draining the water present in swamps or collecting water. Destroying the larvals means that the mosquito vectors will not develop into an adult and will not transmit the VEE virus to both animals and humans.⁴ Insecticide spraying is used to target adult mosquito vectors and destroying the mosquito means that the mosquito cannot feed on animals and humans, and will then not spread the VEE virus. 

Other techniques being developed to control the mosquito vectors are:

• Genetically modifying the mosquitoes to not carry the VEE virus by interbreeding it with other mosquitoes that don't carry the virus⁴
• Using repellents that prevent the mosquitoes from interacting with humans, therefore preventing the spread of the virus

Vaccination programs:

Vaccination of equids is the best method to reduce transmission of the VEE virus and has been used since 1930.³ TC-83 live attenuated vaccine is made from the VEE virus type 1 strain AB to be used for horses and has been successful in epidemics.³ However, there are no vaccines for humans but the TC-83 vaccine has been used to provide immunity for those who work in laboratory research.⁴

Emerging challenges and future directions:

Climate change is an emerging anticipated challenge that can impact VEE transmission as it can affect how the vectors behave, which will then infect transmission. Like all viruses, there is a chance that the virus can mutate and become more virulent or spread more in other vectors.³

This is quite worrying as the new vector could survive in more temperate environments, which could mean that the virus can spread to more regions and infect more individuals. To deal with the emerging challenges of VEE virus, more research is needed to understand the transmission dynamics of the virus.

Summary

Venezuelan equine encephalitis (VEE) is a virus that is spread through mosquito vectors that infect equine population and humans. It is currently endemic to South American countries but due to many factors like climate change, air travel, and human and ecological factors, it is possible for the virus to be present in more regions.

To understand the transmission of the virus, more monitoring of the virus will be required to prevent large outbreaks from occurring. This is important as the VEE infection can lead to neurological symptoms like encephalomyelitis which can be fatal.