Ratios of subclinical to clinical Japanese encephalitis (JE) virus infections in vaccinated populations: evaluation of an inactivated JE vaccine by comparing the ratios with those in unvaccinated populations.

Japanese encephalitis (JE) virus is characterized as a virus that produces a large number of subclinical infections. In this report, we estimated a ratio of subclinical to clinical infections in vaccinated human populations who acquired natural infection with JE virus, and evaluated protective capacity of the currently approved inactivated JE vaccine by comparing the ratio with those reported for unvaccinated populations. We developed a sensitive immunostaining method for detecting nonstructural 1 (NS1) antibody to demonstrate JE virus infection in vaccinated individuals. Serum samples collected from human populations in western Japan showed NS1 antibody prevalences of approximately 10% in an urban area in 1981 and 1995 and 20% in a rural area from 1982 through 1983. Analysis of annual change in NS1 antibody titer using paired samples provided a mean duration of NS1 antibody responses of approximately 2 years, indicating that 5% of the urban population or 10% of the rural population acquired natural JE virus infection in 1 year. Based on the number of JE cases from 1982 through 1991 and the number of people acquiring natural infection, and on the assumption that annual infection rates obtained in the present study areas are representative of the infection rate in entire Japan except for non-endemic northern areas, the ratio of subclinical to clinical infections in vaccinated populations was estimated to be 2000000:1, which was 2000-80000 times higher than the ratio previously reported for unvaccinated populations.