Author’s Note: My grandfather and his neighbors in southern Idaho lost several work horses to “brain fever” in the 1930s. My grandfather’s family managed to save one mare; they tied her in the barn, supported her with a sling, and secured ice packs to her head during her fever and delirium. She survived, but was never normal. My father, whose chores as a young boy included driving the work teams, didn’t enjoy working with her; she had a tendency to travel crookedly, and it was difficult for her to turn to the left. Today the mare probably would have been diagnosed with encephalitis.
Eastern, Western, and Venezuelan equine encephalitis (EEE, WEE, and VEE) are arboviruses–meaning they are transmitted by blood-feeding insects or ticks–and these pathogens can cause fatal neurologic disease in horses. EEE, WEE, and VEE are all alphaviruses that are a part of the Togavirus family (Togaviridae), and collectively they are termed the equine viral encephalomyelitides. West Nile virus is also an arbovirus, but it is a member of the Flaviridae family, which is named after yellow fever virus. We will confine our in-depth discussion to the Togaviruses in this article.
All of these viruses have public health implications because they are zoonotic, meaning they can be communicable from animals to humans under natural conditions. EEE, WEE, and WNV can be spread from birds to humans via mosquitoes. Infected horses cannot pass these diseases to other horses, animals, or humans, however, so equine infection is generally indicative of a virus being active in a geographic area. EEE is a reportable disease in most states for this reason. VEE, however, is even more serious, as it can be transmitted from horses to mosquitoes to humans.
“Listed in order of importance, those of greatest significance would be VEE, WNV, and EEE, because of seriousness of clinical outcome of infection in humans,” says Peter J. Timoney, MVB, PhD, FRCVS, of the Gluck Equine Research Center at the University of Kentucky. Timoney is a leading authority on infectious diseases of horses. “People who become infected with EEE (for example) frequently die or are left severely brain damaged.”
These viruses are truly neurotropic (they localize selectively in the nerve tissue). “They have a predilection for infecting nervous tissue; not merely causing lesions in the central nervous system (which can result in neurologic deficits), but actually infecting various nerve cell elements,” says Timoney.
There are two variants of EEE. The one in North America is more pathogenic to horses than the one in South and Central America. EEE in North America occurs primarily in eastern parts of the United States and Canada, but it has been seen as far west as South Dakota and Texas. “The first case was identified in 1937 in Connecticut,” says Kathy Seino, DVM, PhD, an assistant professor of equine medicine at Washington State University. As mentioned before, “Horses don’t transmit EEE, but serve as a marker (sentinel) to show it’s (present) in a certain area. Last year 185 cases of EEE were reported in horses, with 89 of those in Florida, and a number of human cases as well.”
Dennis Seymore, DVM, a private practitioner in Daingerfield, Texas, agrees that EEE is fairly prevalent. “I had a horse tested early this spring; the diagnostic lab in Texas said they haven’t had any cases of WEE in a long time (although they know it’s still here). We are mainly seeing EEE.”
The fatality rate for EEE in horses is higher (75-95%, compared with a 20-40% fatality rate for WEE). The course of EEE can be swift, with death occurring two to three days after onset of clinical signs, despite intensive care. Horses that survive might have long-lasting impairments and neurologic problems.
Most of the cases Seymore has seen were in unvaccinated horses, or horses that had not been vaccinated recently. “The majority that actually showed clinical signs became so advanced that most of the time we ended up putting them down,” says Seymore. “One horse was actually climbing the walls, totally delirious. By the time we see clinical aspects of the disease (clinically affected animals with neurologic signs), we seldom can turn them around.”
Veterinarians say WEE is generally seen west of the Mississippi. “When first identified in outbreaks in the 1930s and 1940s–primarily in California and surrounding states–there were huge numbers of horses affected,” says Seino. “We haven’t seen cases recently, probably due to the fact there is an effective vaccine for horses.”
Debra Sellon, DVM, PhD, Dipl. ACVIM, professor of equine medicine at Washington State University, says even though WEE has not been diagnosed in a U.S. horse since the 1980s, there is still evidence the virus is circulating in wild birds in the western United States.
Veterinarians see VEE predominantly in South and Central America. The first VEE outbreak was identified in 1935. “VEE is an important public health problem in those regions because it can (also) cause disease in humans,” says Seino. “It usually causes influenzalike symptoms in adults, but in children and horses it can cause severe encephalitis (inflammation of the brain).”
The case-fatality rate for VEE in horses is 40-90%.
Practitioners must report any suspected cases of VEE in the United States to their state veterinarians so a quarantine can be put into effect. “There was a huge outbreak in 1969 in South America that spread northward to Texas by 1971, resulting in deaths of an estimated 200,000 horses and several thousand human infections,” says Seino. “By using an attenuated vaccine (virus has reduced virulence), health officials were able to shut it down.”
Veterinarians established a buffer zone around the areas with reported infections, and they vaccinated the populations within these areas, she says. Since then, the United States has carefully monitored for VEE, and officials recommend that owners with horses living in states bordering Mexico vaccinate their horses.
VEE: A Possible Emerging Problem
“The infected horse is a very effective amplifier of VEE virus,” says Timoney. “A wide range of mosquito species can become infected very readily when biting an infected horse, and, in turn, infect other naïve horses (those that have never been exposed to the disease) or transmit the virus to humans.”
The two most important of the six VEE subtypes are 1-AB and 1-C. “These are epizootic; they have the propensity to spread very rapidly and multiply in both humans and horses and give rise to epidemics,” says Timoney. Fortunately, they emerge infrequently.
The VEE viruses are endemic to a particular area in northeastern Venezuela, where it is believed the epidemic subtypes emerge. “Historically, years in which epidemics of VEE have occurred, the disease usually started in Venezuela and spread rapidly westward into Colombia, and on occasion to adjacent countries,” says Timoney.
Epidemic variants of VEE have also been known to pass from Venezuela to the island of Trinidad.
There is potential for subtypes 1-AB and 1-C to amplify very quickly once infection becomes established in an equid population that is unvaccinated. “Equids in these areas are not valuable animals, just farm animals, and not routinely vaccinated,” explains Timoney. “During an interepidemic period (between outbreaks), the immune status of such a population declines in the absence of vaccination or prior to natural exposure. When the virus emerges it moves very quickly, like a forest fire, because the population is very susceptible.”
Sellon adds, “For a long time we didn’t see VEE, and people were starting to think we don’t have epizootic VEE anymore. Then in the mid-1990s it popped up again and has been causing problems in Central and South America and Mexico.”
An outbreak in southern Mexico in 1993 prompted recommendations to vaccinate all horses in Mexico and those in the United States within 40 miles of the border.
Horse to Human Transmission
EEE and WEE cycle normally in bird populations through mosquito transmission. Neither of these viruses can survive outside the host. There is a possibility these viruses might overwinter in reptiles. As mentioned previously, horses, humans, and other mammals are considered accidental or dead-end hosts that are infected by “bridge vectors” or mosquitoes that feed on both birds and mammals, and they cannot serve as sources of infection.
The enzootic (endemic animal disease) subtypes of VEE virus usually cycle between mosquitoes and rodents and sometimes birds. Horses and humans are dead-end hosts for these subtypes. However, the epizootic subtypes are a different story. As noted before, horses with VEE can develop a high enough level of the virus in their blood (viremia) to serve as a reservoir for spreading the disease. “Most mosquitoes, after biting a horse infected with VEE, can transmit it to people or to other horses,” says Seino.
Horses are the main “amplifiers” for epizootic VEE during an outbreak. A horse infected with subtype 1-AB or 1-C can develop significant viremia for up to five days. “Titers frequently exceed one million infectious virus particles per mL of blood,” says Timoney. “This huge virus load in the acutely infected horse is well above levels needed to establish infection in mosquitoes.”
Sellon notes, “VEE also has the potential to pass from horse to horse because we think it can be spread in nasal secretions. It also has some potential for aerosol spread (via airborne droplets from infected horses’ nasal passages).”
Clinical Signs and Treatment
Once a mammal is bitten by an infected mosquito, the incubation period can vary from two to three days up to two weeks. “Most horses develop inapparent infections,” says Seino. “Young and immunocompromised horses are most likely to develop clinical signs. These include moderate to high fever, depression, lack of appetite, cranial nerve deficits (facial paralysis, tongue weakness, difficulty swallowing), behavioral changes (aggression, self-mutilation, or drowsiness), gait abnormalities, or severe central nervous system signs, such as head-pressing, circling, blindness, and seizures.
“Treatment relies on intensive care, making sure the horse is well-hydrated and has adequate nutrition, control of seizures, use of anti-inflammatories, such as NSAIDs (non-steroidal anti-inflammatory drugs) and DMSO (dimethyl sulfoxide), and providing good bedding to prevent bed sores,” says Seino.
An accurate diagnosis is important since other infectious agents (including rabies, equine herpesvirus-1, WNV, and equine protozoal myeloencephalitis, or EPM) could be a potential cause of symptoms.
“A variety of diagnostic tests can be performed,” says Seino. “These involve testing blood and CSF (cerebrospinal fluid) samples. A positive IgM antibody titer greater than 1:400 against EEE/WEE/WNV on a MAC-ELISA (enzyme-linked immunosorbent assay test) is considered diagnostic (confirms the horse is infected). In horses with a history of vaccination, a fourfold rise in neutralizing antibody titer from acute and convalescent blood samples (taken two to four weeks apart) is diagnostic. PCR (polymerase chain reaction test, which detects virus DNA) tests for EHV-1/WNV/EEE are also available.”
There are effective equine vaccines for every one of these viruses. “EEE, WEE, and WNV are three of the five core vaccines for horses recommended by the American Association of Equine Practitioners (AAEP, www.aaep.org/vaccination_guidelines.htm),” says Seino. “After the primary series, you need to annually revaccinate one month before mosquito season starts in your area. In regions with a long mosquito season you may need to revaccinate once or twice. In Florida, many horsemen vaccinate every four months.”
Vaccines for EEE and WEE are available as inactivated (also known as “killed”) products, often combined with protection against other diseases, such as WNV, tetanus, or influenza. “Your veterinarian can help you determine which vaccines are best suited for your horse and an appropriate vaccination schedule,” says Seino.
There are two VEE vaccines: a modified-live vaccine (TC-83) and an inactivated adjuvant vaccine, both of which have been used under field conditions. When the VEE outbreak occurred in Mexico and Texas in 1971, horses were vaccinated with TC-83 for humans because there wasn’t an equine vaccine available. TC-83 is still being used for humans who work with the virus.
“The live virus vaccine generates immunity more rapidly than the killed (inactivated adjuvant) vaccine,” says Sellon. “There is current research for new types of vaccines, but they are geared more toward humans than horses.”
The inactivated VEE vaccine is generally included in vaccines designed to protect against other viral encephalomyelitis problems. Sellon says the most recent vaccination recommendations from AAEP (in 2008) suggest that vaccination of horses with killed VEE vaccine should only be performed in very high-risk areas of the United States under the guidance of state agriculture officials.
The viral diseases EEE and WEE, like WNV, have become endemic in some areas of the United States. Veterinarians have detected VEE in the United States in the past, and some researchers predict the disease will become a problem in the future. Protecting horses with vaccination, where appropriate, and mosquito management can go a long way in preventing these diseases in your horses.