Vaccine, TC-83 Venezuelan Equine Encephalitis in Pregnancy and Breastfeeding
Fetal Risk Summary
A live, attenuated strain of Venezuelan equine encephalitis (VEE) virus, TC-83, is used as a vaccine (1). VEE, transmitted by mosquitos, is primarily found in South America and Central America, but cases have occurred in Texas (1). Although many human cases of VEE are asymptomatic, some patients may have severe symptoms, including confusion, seizures, and nuchal rigidity (1).
VEE was embryo- and fetotoxic and teratogenic in rats inoculated with the virulent Guajira strain during the first 2 weeks of pregnancy (2). All embryos died within 34 days with evidence of necrosis and hemorrhage. Inoculation later in pregnancy resulted in similar outcomes, including infarcts of the placenta.
Fetal rhesus monkeys were administered TC-83 Venezuelan equine encephalitis virus vaccine via the intracerebral route at 100 days' gestation and then were allowed to proceed to term (159161 days' gestation) (3). All of the infected fetuses were born alive. Some of the newborns were killed and examined within 24 hours of birth, others at 1 month, and the remainder at 3 months. Malformations evident in all of the offspring were micrencephaly, hydrocephaly, and cataracts, and two-thirds had porencephaly.
A 1977 brief accounting of the 1962 outbreak of Venezuelan equine encephalitis in Venezuela cited the frequent abortion of women who were infected during the 1st trimester (4). In addition, the infection of seven pregnant women, between the 13th and 36th weeks of gestation, and the subsequent fatal fetal and newborn outcomes were discussed (4). All of the fetuses and newborns had destruction of the fetal cerebral cortex, the degree of which was determined by the interval between infection and delivery. In one of the cases, the mother had severe encephalitis at 13 weeks and eventually gave birth at 33 weeks' gestation. Microcephaly, microphthalmia, luxation of the hips, severe medulla hypoplasia, and the near absence of neural tissue in the cranium were evident in the stillborn fetus (4).
The fatal outcome of a case in which a 21-year-old laboratory worker became pregnant (against medical advice) after receiving the TC-83 vaccine was described in a 1987 report (1). The mother's VEE virus titers were 1:20 at 17 weeks' gestation and 1:10, 3 months later. Maternal serum a-fetoprotein and an ultrasound examination were normal at 17 weeks, but a lack of fetal movement was noted at 26 weeks. One week later, a stillborn, hydropic female fetus was delivered. Generalized edema, ascites, hydrothorax, and a large multilobulated cystic hygroma were noted on examination. Mononuclear infiltrate was found in the myocardium and pulmonary arterioles and an inflammatory cell infiltrate was noted in the trachea, intestinal adventitia, brain, uterus, and fallopian tubes (1). Marked autolysis of the brain had occurred. Abnormalities in the placenta included calcifications, infarcts, petechiae, and thrombosis in the decidua (1).
In summary, only a single case of human pregnancy exposure to TC-83 Venezuelan equine encephalitis vaccine has been reported, but the adverse fetal outcome combined with the animal data indicates that the vaccine should not be given to pregnant women. In the United States, routine immunization is not practiced, but some laboratory workers may require the vaccine because of potential exposure to the virus in their work (1). Based on the available data, pregnancy should be excluded before administration of the vaccine, and the woman warned against conception in the immediate future (in the case above, the woman was advised not to become pregnant for 1 month after vaccination, but References confirming this as a safe interval for this vaccine have not been located).
Breast Feeding Summary
No data are available.
- Casamassima AC, Hess LW, Marty A. TC-83 Venezuelan equine encephalitis vaccine exposure during pregnancy. Teratology 1987;36:2879.
- Garcia-Tamayo J, Esparza J, Martinez AJ. Placental and fetal alterations due to Venezuelan equine encephalitis virus in rats. Infect Immun 1981;32:81321.
- London WT, Levitt NH, Kent SG, Wong VG, Sever JL. Congenital cerebral and ocular malformations induced in rhesus monkeys by Venezuelan equine encephalitis virus. Teratology 1977;16:28596.
Wenger F. Venezuelan equine encephalitis. Teratology 1977;16:35962.