The Topic of This Month Vol.24 No.7(No.281)

Japanese encephalitis, Japan, 1999-2002

(IASR 2003; 24:149-150)

Japanese encephalitis (JE) is a serious and acute form of encephalitis. It is transmitted by a mosquito, Culex tritaeniorhynchus , the vector of JE virus (JEV). JE is classified as a category IV notifiable infectious disease in the National Epidemiological Surveillance of Infectious Diseases (NESID) under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enacted in April 1999. In addition, the National Epidemiological Surveillance of Vaccine-Preventable Diseases has monitored herd immunity and JEV infection in pigs. In this article, the incidence of JE from 1999 to 2002 following the enforcement of the Infectious Diseases Control Law is discussed (see IASR Vol. 20, No. 8 for the incidence of JE in 1998 or before).

Incidence of JE: Several thousands JE cases were reported annually during the 1950s predominantly among children (Fig. 1). In 1966, more than 2,000 cases were reported predominantly among elderly people aged 55 years old or more (Ogata, Clinical Virology [in Japanese], Vol. 13, No. 2, pp. 150-155, 1985). Between 1967 and 1976, as a special program, children and adults, including the elderly, were actively vaccinated. As a result, the number of JE cases decreased rapidly to several dozen in the 1980s, and is keeping 10 or less per year since 1992.

Between 1999 and 2002, 25 JE cases were reported. The earliest date of onset was July 12 (2001, in Ehime Prefecture) and the latest was November 1 (2002, in Osaka Prefecture) (Fig. 2). All JE cases were observed west of central part Japan (Fig. 3); 8 cases in the Kyushu district, 5 in the Shikoku district, 9 in the Chugoku district, 2 in the Kinki district, and 1 in the Hokuriku district. Three JE cases each were observed in Hiroshima and Kochi Prefectures. In 2002, 6 JE cases were observed in the Chugoku district (3 in Hiroshima Prefecture, and 1 in each of Tottori, Okayama and Shimane Prefectures). The numbers of male and female cases were similar: 12 male and 13 female cases. More than 80% of cases were aged 55 years or more (20 cases). Two cases were in their 10s, 1 in their 30s, and 2 in their 40s (Fig. 4). Information on the vaccination history and prognosis of patients were not available because the individual case card reporting system for confirmation of patients notified in accordance with the old law (the Communicable Diseases Prevention Law) was abolished when the Infectious Diseases Control Law was enforced.

Antibody prevalence among general population: Approximately 2,000 people in 10 prefectures were surveyed in 2000 to determine antibody prevalence (Fig. 5). People with neutralizing antibody titer >=10 were approximately 40% in the 0 to 4 years group, and approximately 80% in the 5 to 29 years group. Although the prevalence of JEV antibodies was about 50% in the 30 to 59 years group, it exceeded 80% in the over 60 years group. In people under 60 years of age, the prevalence was 10-20% lower than the results in 1994 (see IASR Vol. 20, No. 8). Currently, the JE vaccine is given as a regular vaccination in a series of three stages. As a standard schedule, the first stage consists of 2 primary doses at 3 years of age, and a booster dose at 4 years of age. The second stage is a booster dose at 9-12 years of age. The third stage is a booster dose at 14-15 years of age. Although mass immunization used to be ruled, individual immunization has been applied since 1995 based on the amendment in the Preventive Vaccination Law. It was found that the JEV antibody prevalence was higher among vaccinees than among nonvaccinees (Fig. 5a) in children aged 14 or less. The geometric mean titer of JEV antibody positives was more than 32 in all age groups (Fig. 5b, solid line). Among children aged 14 or less, the geometric mean titer was higher in vaccinees than in nonvaccinees. In recent years, most JE cases have been elderly people. However, neither the JEV antibody prevalence nor the geometric mean titer of those aged over 60 years was significantly lower than those in other age groups.

JEV infection in pigs: Pigs are known to be an amplifier of JEV. Since 1965, prefectural public health institutes (PHIs) have been testing pigs (5-8 months old) that are brought to slaughterhouses in summer. Emergence of JEV HI antibody positive pigs (= rate of new infections in that year) is used as an indicator of the JEV activity (Fig. 6). Compared to the 1960s, the peak of seroconversion in pigs has become late. In recent years, new infections in pigs can be first observed around May in Okinawa Prefecture, and around July in other prefectures in western Japan. The area with JEV antibody-positive pigs extends to north as the season progress. Of the 32 prefectures in which the survey has been conducted in 2002, the JEV antibody prevalence in 22 prefectures was 50% or more in September. JE cases in 2002 were observed in the areas with high JEV antibody prevalence in pigs (see for the latest information on prevalence of pigs).

Virus isolation: JE viruses were isolated from 2 of the 3 cases reported in Hiroshima Prefecture in 2002. Of the 2 isolates, 1 strain was genotype III, which is the same as that used in the vaccine (see p. 152 of this issue). However, JE viruses isolated from pigs in 4 prefectures, namely, Kagawa, Mie, Shizuoka and Chiba, in 2002 were all genotype I and highly homologous (see p. 153 of this issue). A JE virus isolated from mosquitoes in Ishikawa Prefecture in 1998 was genotype III. It is considered that both genotype I and III currently exist in Japan. It is therefore important to isolate JE viruses from patients, pigs and mosquitoes for monitoring JE virus circulation (see p. 153 of this issue).

Conclusion: Although more than 100 JE cases occurred each year until the early 1970s, JE cases between 1992 and 1998 were 4 or less per year. There are three major reasons for this: (1) most children acquired protective immunity to JEV as a result of vaccination; (2) the population of C. tritaeniorhynchus has dropped due to a decrease of paddy fields where it propagates, and because of changes in the methods of rice production (Kamimura, Med. Entomol. Zool., Vol. 49, No. 3, pp. 181-185, 1998); and (3) the environment of pig farms has changed: pigs are being raised far from residential areas. Therefore, C. tritaeniorhynchus around pig farms are less likely to reach residential areas and to transmit JEV from pigs to people. However, it indicates a slightly upward trend that 5 to 8 JE cases were reported each year during the 1999-2002 period. Furthermore, JE occurred among children and middle-aged, as well as the elderly, who has been the majority in recent years. In addition, some cases occurred in prefectures where no JE case had been reported for years; in Wakayama for the first time in 11 years after 1990, in Hiroshima for the first time in 12 years after 1990 (see p. 152 of this issue), and in Ishikawa for the first time in 17 years after 1985 (see p. 151 of this issue). A survey in Toyama Prefecture revealed that the number of vector mosquitoes and the time of its increase vary each year (see p. 155 of this issue). It is inferred that JEV-infected mosquitoes appear every summer in all areas of Japan, except Hokkaido, because JEV antibody-positive pigs have even been observed in areas where no JE case has occurred. Thus, it is required to consider JE not as a disease of the past, but to be included in differential diagnoses when an encephalitis or encephalopathy case occurs in summer. In addition, it is necessary to consider the possibility of infection with West Nile Virus (WNV), which is closely related to JEV. The Department of Virology I, National Institute of Infectious Diseases conducted virological and serological examinations for WNV on the 7 JE patients in 2002 and confirmed all were WNV negative.

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