Japanese Encephalitis Viral Infection Remains Common in Japan

Abstract

To the Editor: Japanese encephalitis (JE) virus is a flavivirus that causes about 15,000 deaths in Asia every year. Mosquitoes and swine play important roles in the spread of JE virus in the paradomestic environment, the former as a vector and the latter as an amplifier. In the 1950s, approximately 5000 cases, about 20% fatal, were reported yearly in Japan, but recently fewer than 10 cases are reported each year. Reasons for the marked decrease in JE in Japan include decreases in the number of rice fields which are habitats of vector mosquitoes (mostly Culex tritaeniorhynchus), subsequent decreases in the mosquito population, and increased distance between the habitats of people and swine. However, urban residents are still bitten by mosquitoes during the summer, with the exception of northern Japan. Furthermore, 50–100% of Japanese pigs younger than 8 months have antibodies against the JE virus in summer and autumn, indicating that most Japanese pigs can still be JE virus producers. The extremely low reported incidence of JE in human patients in Japan, despite the high prevalence of antibodies against the JE virus in swine and continued mosquito bites in humans, constitutes a paradoxical situation. To explain this paradox, we proposed a hypothesis that human JE viral infections still occur, but produce only mild symptoms. To test this hypothesis, we measured titers of the nonstructural protein-1 (NS1) antibody,1 which increases only with natural JE viral infection, and titers of the HI antibody, which increases with both vaccination and JE viral natural infection, in blood samples obtained from 50 volunteers and patients, aged 1–88 years, at Eijudo Clinic, located in an urban area of eastern Tokyo. Blood samples were collected for 2–3 years from each subject. Results are shown in Figure 1. The black bars indicate changes in NS1 antibody titers in each serum series, and the gray bars show changes in HI antibody concentration. The adjacent bars are results for a single person. The bars are arranged horizontally by subject age. The NS1 titers indicate that the incidence of JE viral infection has increased with subject age, whereas HI titers, which reflect vaccination, have slowly fallen with subject age. Two of 50 subjects showed rapid and marked increases in the NS1 titer. One was a 57-year-old woman who took a 3-day trip from June 30 through July 2, 2002, to Okinawa, a southern Japanese island where 3 American soldiers contracted JE with severe sequelae several years ago.2 The NS1 titer on June 21 was <1:10 but by July 21 had increased to 1:20 and remained high for 1 year. During this time the subject exhibited no symptoms. Another subject was a 85-year-old woman who had remained at home for several years. The NS1 titer was <1:10 on July 8, 2002, but the titers on July 15 and September 8, 2002, were 1:80. From July 8 through 15 she had a low-grade fever, but no infectious focus was identified.FIGURE 1.: Range of NS1 and HI antibody titers against Japanese encephalitis. The black bars indicate changes in NS1 antibody titers in each serum series, and the grey bars show changes in HI antibody concentrations. The adjacent bars are results for a single person. Sera collected from each person for 2–3 years.We have shown rising NS1 antibody titers with subject age in a series of blood samples obtained at a clinic in eastern Tokyo and described 2 subjects with rapidly increasing NS1 titers. These results and a previous report3,4 suggest that human JE viral infection remains prevalent in Japan, although symptoms can be mild or absent. Therefore, vaccination against JE remains extremely important, although the Japanese Government halted strong recommendation of routine JE vaccination in 2005.5 Teiichi Matsunaga, MD, PhD Eijudo ClinicKatsushika-ku, Tokyo, Japan Mizue Shoda, MSc Eiji Konishi, PhD Department of International Health Kobe Univ. Graduate Sch. of Health Sciences Kobe, Japan