Venezuelan Equine Encephalitis: Epidemiology and Biological Insights

Introduction 

The arboviruses that comprise the Venezuelan equine encephalitis virus (VEEV) complex are members of the Togaviridae family's Alphavirus genus – originally discovered in horses in the 1930s. In the family Togaviridae: Alphavirus, the most significant disease for humans and horses is the Venezuelan equine encephalitis virus. The alphaviruses that make up the Venezuelan equine encephalitis (VEE) antigenic complex are related genetically and can be classified as a subgroup of the Alphaviridae due to their wide cross-reactivity against common antigens.¹ These nine species of alphaviruses are divided into six subtypes, I to VI, of which subtype I contains the veterinary and medically significant VEE virus. 

Over the past 100 years, VEEV has been responsible for recurrent epidemics of neurological and febrile illnesses, mostly in Latin America. Multiple epidemics have spanned broad geographic regions, including tens to hundreds of thousands of human and equine cases, and persisted for several years. The VEEV-associated human illness, known to be transmitted from animals, was not discovered until 1943, although epidemiological data suggests that outbreaks may have occurred as early as the 1920s. Recent epidemics in South America and Mexico have shown that VEE is a reemerging illness. Additionally, VEEV is a highly advanced biological weapon that can be used in terrorism or conflict.² 

The viruses linked to human disease, VEEV can cause acute, frequently severe feverish sickness that can proceed to encephalitis, causing severe human morbidity and mortality, even though many VEE complex viruses have not been linked to human disease.³ VEEV subtype II of the Everglades virus (EVEV), which is exclusive to Florida, can also cause neurologic illness in people and horses,⁴ in addition to VEEV (subtype I), which accounts for the bulk of encephalitis cases within the VEE subtype. The Mucambo virus, subtype IIIA, also causes fever in people.⁵

Geographical spread

The VEEV antigenic complex has been limited to tropical and subtropical areas of the Western Hemisphere. Reports of isolates from this complex have been traced back to Argentina and the southern United States. Most human cases of VEEV infection have happened during sizable epidemics in northern South America and Central America, mainly in Colombia and Venezuela.⁶

The majority of the encephalitic viruses of the genus Alphavirus of the Togaviridae family are zoonotic diseases that are spread by hematophagous arthropods. These infections are widely distributed throughout North, Central, and South America.⁷ Some have been created as biological weapons in the US and the former USSR, and some are highly contagious via the aerosol route, which has led to multiple laboratory accidents.²

Determining the quantity of virus spread is necessary to create pathogenesis studies for arboviruses that faithfully replicate natural infection. Arboviruses can spread by vectors or possibly through infectious aerosols, which can result in encephalitis in both animal and human populations. The importance of the Venezuelan equine encephalitis virus (VEEV) to veterinary medicine and public health is highlighted by its recent resurgence in South America.⁸

Essentially, there are two known transmission cycles: the enzootic cycle – sustained in rodent reservoirs in forest environments, and the epizootic cycle, which results in high horse mortality rates and outbreaks in human populations.⁹ Notably, for VEEV to develop from enzootic progenitors, the range of the mosquito-vector host must change. For instance, the Culex (Melanoconion) subgenus of mosquitoes includes all seven of the vector species found in enzootic VEEV cycles. 

Additionally, all seven of these mosquitoes belong to the Spissipes section of this subgenus, which includes 23 species.¹⁰ Having been investigated throughout numerous outbreaks, the epizootic transmission cycle of VEEV is quite well understood. The function of horses as extremely effective amplification hosts is a characteristic shared by all significant outbreaks.

Even though epizootics near large cities frequently occur, substantial epidemics in the absence of horse cases have never happened, although the vertebrates host a vast range of epizootic VEEV strains including people, sheep, dogs, bats, rats, and some birds.¹¹ These mosquitoes live near constant water sources, thus it is possible that some of their physiological and ecological traits, such as relative population stability, help them transmit enzootic VEEV efficiently.

However, the primary vectors of epizootic VEEV transmission during outbreaks are floodwater mosquitoes of genera like Ochlerotatus (previously termed Aedes) and Psorophora, which exhibit significant seasonal variations in population density. The amount of virus that is delivered to vertebrates during blood feeding can be estimated using assays on mosquito saliva. The quantity of virus obtained in vitro, however, might not precisely represent mosquito transmission.

The molecular causes of the emergence of VEEV strains that are enzootic and epizootic utilize distinct vertebrate hosts and mosquito vectors. Therefore, knowledge of the host-range alterations and their genetic foundation is necessary to understand the processes of VEE emergence by antigenic shifts and the acquisition of the equine viraemia phenotype.¹²

During the two to ten-day incubation period of VEEV infection, general flu-like symptoms are experienced. Compared to EEEV and WEEV infection, severe encephalitis is a less frequent result of VEEV infection; however, VEEV-associated encephalitis is more common in children.⁸

In enzoonotic cycles, the mosquito vector and rodent host exchange VEEV. The most frequent rodent host is thought to be the cotton Spiney rat.¹³

It's unclear, though, how important these hosts are ecologically. Similarly, VEEV mosquito vectors have been found in many locations. In general, mosquitoes classified as Aedes and Culex are thought to be the main vectors.^14,7

Epidemic and epizootic outbreaks happen when the virus is spread by infected mosquitoes to humans and horses.¹⁵

In contrast, humans have typically been considered dead-end hosts, capable of contracting infection and developing disease, but unable to transmit the virus further.¹⁶

More recent data points to the possibility that during acute infections, human populations could have high enough titer viremia to sustain epidemic transmission cycles in more urban settings.¹⁷

Periodically, severe outbreaks of sickness in human and equine populations have been caused by Venezuelan equine encephalomyelitis viruses, which have impacted numerous American countries. The origins of epidemic viruses have just lately been identified; they arise from clinically silent enzootic cycles that persist in several nations. The processes that give rise to these extremely contagious viruses seem to entail ongoing, spontaneous mutation and the selection of variations that can infect the susceptible equine population that exists in a given area.¹⁸

Role of enzootic vectors in VEEV emergence and disappearance

It will be possible to evaluate the role played by these mosquitoes in the generation of mutations that mediate VEE emergence by enhancing equine viremia and infection of epizootic mosquito vectors like Aedes taeniorhynchus, provided that the principal enzootic vectors (Cx. vomerifer and Cx. pedroi) of subtype ID VEEV strains are identified. These strains are thought to be closely related to epizootic progenitors.⁶

FAQs

How many people die from Venezuelan equine encephalitis?

Certain strains of the VEE virus infect horses, however, they do not cause significant illness. Other subtypes have mortality rates as high as 90% and can cause serious sickness and death.

What is the incubation period for the Venezuelan equine?

Numerous lab animals are susceptible to VEE infection. WEE or EEE require five to fourteen days to incubate. Usually occurring one to five days post-infection, VEE manifests as clinical symptoms. 

What are the symptoms of Venezuelan equine encephalitis?

The symptoms of Venezuelan equine encephalitis, an acute illness spread by mosquitoes, include fever, chills, headache, nausea, vomiting, lumbosacral discomfort, and myalgia. Encephalitis may develop in severe cases. It is primarily seen in the tropical Americas and is brought on by the Venezuelan equine encephalitis virus.