Eastern, Western and Venezuelan equine encephalitis viruses (EEEV, WEEV and VEEV)

The equine encephalitis viruses are "Group A" arboviruses (Alphaviruses in the Togavirus family) that cause encephalitis and/or febrile disease in both horses and humans. Mosquitoes are obligatory biological vectors for transmission of these viruses.

EEEV and WEEV

The reservoir hosts for these equine encephalitis viruses are primarily wild birds (also rodents AND HORSES for VEEV). In the reservoir hosts, the virus replicates to high enough titer to be infectious for mosquitoes and, therefore, to perpetuate the virus in nature. Horses and humans, in contrast, are "dead-end" hosts for EEEV and WEEV.

• For EEEV, Culiseta spp. mosquitoes are the vectors involved in the enzootic reservoir cycle among birds, whereas Aedes spp. mosquitoes transmit the virus to horses, humans and other clinically-affected hosts.
• For WEEV, Culex spp. are the primary mosquito vectors for both transmission among wild birds enzootically and transmission to humans.

Geographically, both viruses exist throughout Central America and northern portions of South America. In the U.S., EEEV and WEEV exist in the eastern and western 2/3 of the country, respectively.

EEEV and WEEV clinical disease:

Clinical disease occurs in the summer during the mosquito season. Following the bite of an infected mosquito, the virus replicates locally at the site of the bite in the skin, then enters the blood stream and spreads to the CNS.

In horses:

• Infections with EEEV or WEEV begin with fever, inappetence and lethargy, progressing to various degrees of excitability and then drowsiness, ultimately ending in paresis, seizures and coma in fatal cases. (5-10 day course)
  • Mortality is much higher with EEEV infections (up to 90%) than with WEEV infections (<20-40%).

In humans:

• Fever, headache, depression and nausea progress to altered mentation, paralysis and coma.
  • The mortality rate can be as high as 65% with EEEV infections.
  • Infections with EEEV are most severe in children, and they often have residual sequelae such as paralysis, mental retardation and persistent seizure disorders.
  • Virtually all people infected with EEEV will develop clinical disease. WEEV infection is much less threatening, with a clinical disease-to-infection ratio of ~1:1000.

Cases of equine encephalitis virus infections in humans in a given locality generally appear about 2 weeks after cases in horses. Thus, the first appearance of disease in horses should set off intensive efforts to control mosquitoes and to conduct virus surveillance by local health departments. Veterinarians can, therefore, play a very important role in protecting the community by prompt recognition and reporting of suspected equine encephalitis cases in horses.

Ratites (emus, ostriches) and swine:

• These animals can also be infected with EEEV/WEEV and develop clinical disease. However, the infections in these species may present as hepatitis and/or GI tract disease, rather than encephalitis.

VEEV

For VEEV, the enzootic and epizootic cycles are quite independent:

• The enzootic (Culex spp.) versus epizootic (Psorophora spp., Aedes spp. and others) cycles of transmission utilize different species of mosquitoes.
• The strains of enzootic VEEV that circulate among rodent reservoirs are distinct from the epizootic strains of VEEV that infect and cause disease in horses and humans.
  • Experimental infection of horses with enzootic strains of VEEV produces only mild fever and leukopenia. Likewise, human disease with the enzootic strains appears to be limited, although people living in endemic regions are often sero (+).
• It remains unclear how the epizootic strains develop and are maintained. Do they simply circulate among horses or some other unknown reservoir, or do they arise de novo in each epizootic by mutation from an enzootic strain? Results of recent sequence analyses suggest the later, i.e., that the epizootic strains arise by mutation from particular enzootic strains. In particular, mutations that introduce positively-charged amino acids in the E2 protein may be associated with transformation from an enzootic to a pathogenic epizootic strain biotype for horses.

HORSES ARE NOT DEAD-END HOSTS FOR VEEV LIKE THEY ARE FOR EEEV AND WEEV! HORSES ARE, IN FACT, THE KEY RESERVOIR SPECIES FOR THE EPIZOOTIC STRAINS OF VEEV THAT CAUSE CLINICAL DISEASE IN BOTH HORSES AND HUMANS.

• People replicate virus to high enough titer to infect mosquitoes as well, but they have never been implicated as being epidemiologically important to the spread of the virus in nature.

VEEV clinical disease:

Infections with VEEV may present, in both humans and horses, as either encephalitic disease or as simply a febrile disease without profound neurologic signs. Horses may die after a very acute course, even without any neurologic signs, but mortality in humans is generally low.

VEE in South America, 1995:

• 55,000 human cases (and countless cases in horses) occurred in Venezuela and Colombia in 1995. This outbreak was attributed to low rates of vaccination of horses against VEEV, thus allowing epizootic strains to replicate widely in horses and subsequently spill-over into the human population.

Prevention of equine encephalitis virus transmission:

• drainage of standing water to reduce mosquito replication
• use of insecticides during times of high mosquito populations
• sentinel pheasants (pheasants are susceptible to infection with EEEV) or light traps (and subsequent virus isolation from mosquitoes that are caught) to alert public health officials to the presence of virus in a given geographic area
• vaccination of horses
  • This is particularly critical from a public health point-of-view for VEEV because of the role of horses as reservoir hosts for the virus.
  • For EEEV and WEEV, vaccination is conducted to prevent clinical disease in horses themselves. Vaccination should be conducted in the spring, prior to the mosquito season, to optimize protection. In most parts of the U.S., horses are vaccinated only against EEEV and WEEV, but in the southern U.S., horses may also be vaccinated against VEEV to protect against transmission via mosquitos from Central America.

References:

Acha, P.N. and B. Szyfres (Eds.). 1989. Zoonoses and Communicable Diseases Common to Man and Animals. Pan American Health Organization; Washington, D.C.

Ayers, J.R., T. L. Lester and A.B. Angulo. 1994. An epizootic attributable to western equine encephalitis virus infection in emus in Texas. J. Am. Vet. Med. Assoc. 205:600-601.

Benenson, A.S. (Ed.). 1995. Control of Communicable Diseases Manual. American Public Health Assoc.; Washington, D.C.

Brault, A.C. et al. 2002. Positively charged amino acid substitutions in the E2 envelope glycoprotein are associated with the emergence of Venezuelan equine encephalitis virus. J. Virol. 76:1718-1730.

Deresiewicz, R.L. et al. 1997. Clinical and neuroradiographic manifestations of eastern equine encephalitis. N. Eng. J. Med. 336:1867-1874.

Elvinger, F. et al. 1994. Eastern equine encephalomyelitis virus infection in swine. J.A.V.M.A. 205:1014-1016.

Markoff, L. 1995. Alphaviruses, in: Principles and Practice of Infectious Diseases (Eds. G.L. Mandel, J.E. Bennett and R. Dolin), pp. 1455-1459. Churchill Livingston, Inc.; New York, NY.

Powers, A.M. et al. 1997. Repeated emergence of epidemic/epizootic Venezuelan equine encephalitis from a single genotype of enzootic subtype ID virus. J. Virol. 71:6697-6705.

Tully, T.N. et al. 1992. Eastern equine encephalitis in a flock of emus (Dromaius novaehollandiae). Avian Dis. 36:808-812.