a. Clinical Syndrome.
(1) Characteristics. Eight serologically distinct viruses belonging to the Venezuelan equine encephalitis (VEE) complex have been associated with human disease; the most important of these pathogens are designated subtype 1, variants A, B and C. These agents also cause severe disease in horses, mules, and donkeys (Equidae). Natural infections are acquired by the bites of a wide variety of mosquitoes; Equidae serve as the viremic hosts and source of mosquito infection. In natural human epidemics, severe and often fatal encephalitis in Equidae always precedes that in humans. A BW attack with virus disseminated as an aerosol would cause human disease as a primary event. If Equidae were present, disease in these animals would occur simultaneously with human disease. Secondary spread by person-to-person\contact occurs at a negligible rate. However, a BW attack in a region populated by Equidae and appropriate mosquito vectors could initiate an epizootic/epidemic.
(2) Clinical Features. Nearly 100% of those infected suffer an overt illness. After an incubation period of 1-5 days, onset of illness is extremely sudden, with generalized malaise, spiking fever, rigors, severe headache, photophobia, myalgia in the legs and lumbosacral area. Nausea, vomiting, cough, sore throat, and diarrhea may follow. This acute phase lasts 24-72 hours. A prolonged period of aesthenia and lethargy may follow, with full health and activity regained only after 1-2 weeks. Approximately 4% of patients during natural epidemics develop signs of central nervous system infection, with meningismus, convulsions, coma, and paralysis. These necrologic cases are seen almost exclusively in children. The overall case-fatality rate is <1%, but in children with encephalitis, it may reach 20%. Permanent neurological sequelae are reported in survivors. Aerosol infection does not appear to increase the likelihood of CNS disease. A VEE infection during pregnancy may cause encephalitis in the fetus, placental damage, abortion, or severe congenital neuroanatomical anomalies.
(1) Routine Laboratory Findings. The white blood cell count shows a striking leukopenia and lymphopenia. In cases with encephalitis, the cerebrospinal fluid may be under increased pressure and contain up to 1000 white cells/mm 3 (predominantly mononuclear cells) and mildly elevated protein concentration.
(2) Differential Diagnosis. An outbreak of VEE may be difficult to distinguish from influenza on clinical grounds. Clues to the diagnosis are the appearance of a small proportion of neurological cases or disease in Equidae, but these might be absent in a BW attack.
(3) Specific Laboratory Diagnosis. Viremia during the acute phase of illness is generally high enough to allow detection by antigen-capture enzyme immunoassay. Virus isolation may be made from serum, and in some cases throat swab specimens, by inoculation of cell cultures. A variety of serological tests are applicable, including the IgM ELISA, indirect fluorescent assay (FA), hemagglutination inhibition, complement-fixation, and neutralization. For persons without prior exposure to VEE complex viruses in tropical areas, a presumptive diagnosis may be made by finding antibodies in a single serum sample taken 5-7 days after onset of illness.
c. Therapy. There is no specific therapy. Patients with uncomplicated VEE infection may be treated with analgesics to relieve headache and myalgia. Patients who develop encephalitis may require anticonvulsant and intensive supportive care to maintain fluid and electrolyte balance, adequate ventilation, and to avoid complicating secondary bacterial infections.
(a) An experimental vaccine, designated TC-83 is a live, attenuated cellculture-propagated vaccine which has been used in several thousand persons to prevent laboratory infections. The vaccine is given as a single 0.5 ml subcutaneous dose. Febrile reactions occur in up to 18% of persons vaccinated, and may be moderate-to-severe in 5%, with fever, myalgia, headache, and prostration. Approximately 10% of vaccinees fail to develop detectable neutralizing antibodies, but it is unknown whether they are susceptible to clinical infection if challenged. Nonresponders may be revaccinated with TC-83. Contraindications for use include an intercurrent viral infection or pregnancy. TC-83 is a licensed vaccine for Equidae.
(b) A second investigational product that has been tested in humans is the C-84 vaccine, prepared by formalin-inactivation of the TC-83 strain. The vaccine is presently not recommended for primary immunization, on the basis of animal studies indicating that it may not protect against aerosol infection. However, it may be useful for aerosol protection for persons not responding to TC-83 (0.5 ml subcutaneously at 2 to 4 week intervals for up to 3 inoculations or until an antibody response is measured.)
(2) Antiviral Drugs. In experimental animals, alpha-interferon and the interferon-inducer poly-ICLC (lysine-polyadenosine) have proven highly effective for post-exposure prophylaxis of VEE. There are no clinical data on which to assess efficacy in humans.