. "Appendix D-6: The Prospects for Immunizing Against Japanese Encephalitis Virus." New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press, 1986.
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
Only a small fraction of persons infected with the virus develop acute encephalitis; the majority of infections are asymptomatic. Estimates of the ratio of apparent to inapparent infections range from 1:63 among American military personnel (Benenson et al., 1975; Halstead and Grosz, 1962) to 1:1,000 among Asian children (Grossman et al., 1974; Southam, 1956). Undifferentiated fever or aseptic meningitis also may result from infection with JEV.
Existing Vaccines and Limitations
An estimated 0.5 billion doses of various Japanese encephalitis vaccine preparations have been manufactured and administered to humans in Asia over the past 20 years, principally in the People’s Republic of China, Japan, and Korea. This enormous, sustained effort reflects the importance placed on JE control in countries stricken by the epidemic disease. However, none of the vaccines in use is ideal by current standards (see below), and none is licensed for use outside Asia.
Japanese encephalitis virus is a 45-nm enveloped, single (+) stranded RNA virus composed of three structural proteins (envelope, membrane, and core). The genome is 12,000 nucleotides in length and codes for seven to nine poorly characterized nonstructural proteins, as well as the three structural proteins (Shapiro et al., 1971; Westaway, 1973). The virus is antigenically related to a large number of other arthropod-borne viruses recently placed in their own family, the Flaviviridae. The family includes yellow fever and dengue, as well as several viruses closely related to JEV that produce epidemic encephalitis in other parts of the globe (St. Louis encephalitis virus in the Americas, West Nile encephalitis virus in Southwest Asia and Africa, and Murray Valley encephalitis virus in Australia). Preliminary analysis of the nucleotide sequence of JEV (Fournier, personal communication, 1986) shows a genome organization similar to that of the more completely characterized yellow fever virus (Rice et al., 1985).
JEV exists in nature as a mosquito-borne zoonosis, with birds and domestic mammals (principally pigs) serving as the vertebrate hosts (Buescher and Scherer, 1959). Infections in these vertebrate hosts are essentially asymptomatic, and the viremia is relatively short-lived but of high titer. Man is a nontransmitting host; the viremia in humans is probably too low to provide an efficient inoculum to biting mosquitoes. Principal vectors of JE are rice-field-breeding mosquitoes of the Culex vishnui group. Female mosquitoes usually become infected by feeding on a viremic animal and, after a temperature-dependent extrinsic incubation period of 3 days to 3 weeks, can transmit the virus during subsequent blood meals. Infected adult female mosquitoes can transmit JEV to their progeny through transovarial transmission (Rosen et al., 1978), but the epidemiologic significance of this mechanism is unknown.