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Japanese encephalitis (JE), a mosquito-borne arboviral Flavivirus infection, is the leading cause of viral encephalitis in Asia.

Infection leads to overt encephalitis in 1 of 20 to 1000 cases. Encephalitis, usually is severe, resulting in a fatal outcome in 25% of cases and residual neuropsychiatric sequelae in 50% of cases. JE acquired during the first or second trimesters of pregnancy may cause intrauterine infection and miscarriage. Infections that occur during the third trimester of pregnancy have not been associated with adverse outcomes in newborns.1

The virus is transmitted in an enzootic cycle among mosquitoes and vertebrate amplifying hosts, chiefly domestic pigs and, in some areas, wild Ardeid (wading) birds. Viral infection rates in mosquitoes range from < 1% to 3%. These species are prolific in rural areas where their larvae breed in ground pools and flooded rice fields. Thus all elements of the transmission cycle are prevalent in rural areas of Asia and human infections occur principally in this setting. Because vertebrate amplifying hosts and agricultural activities may be situated within and at the periphery of cities, human cases occasionally are reported from urban locations.1

JE virus is transmitted seasonally in most areas of Asia. The seasonal patterns of viral transmission are correlated with the abundance of vector mosquitoes and of vertebrate amplifying hosts. Although the abundance of vector mosquitoes fluctuates with the amount of rainfall, and with the impact of the rainy season, in some tropical locations, irrigation associated with agricultural practices is a more important factor affecting vector abundance, and transmission may occur year-round. Thus the periods of greatest risk for JE viral transmission vary regionally and within countries, and from year to year.1

In areas where JE is endemic, annual incidence ranges from 1 to 10 per 10,000 people. Cases occur primarily in children under 10 years of age. Seroprevalence studies in these endemic areas indicate nearly universal exposure by adulthood (calculating from a ratio of asymptomatic to symptomatic infections of 200 to 1, approximately 10% of the susceptible population is infected per year). In addition to children < 10 years, an increase in JE incidence has been observed in the elderly.1

Challenge experiments in passively protected mice have defined the levels of neutralizing antibody that may be protective for humans.2 Mice passively immunized to achieve a neutralizing antibody titer of ≥ 1:10 were protected from a JE virus challenge of 105LD50, a viral dose thought to be transmitted by an infected mosquito2.

The efficacy of the BIKEN Nakayama-NIH strain Japanese Encephalitis Virus Vaccine Inactivated was demonstrated in a placebo-controlled, randomized clinical trial in Thai children, sponsored by the US Army.3 In this trial, children between 1 and 14 years of age received BIKEN monovalent Nakayama-NIH strain (n = 21,628) or a bivalent vaccine containing the Nakayama-NIH and Beijing JE virus strains (n = 22,080) or tetanus toxoid as a placebo (n = 21,516). Immunization consisted of two (2) subcutaneous 1.0 mL doses of vaccine, except in children under 3 years of age who received two 0.5 mL doses. One case (5 cases/100,000) of JE occurred in the monovalent vaccine group, one case (5 cases/100,000) in the bivalent vaccine group, and 11 cases (51 cases/100,000) in the placebo group. The observed efficacy of both monovalent and bivalent vaccines was 91% (95% confidence interval, 54% to 98%). Side effects of vaccination, including headache, sore arm, rash, and swelling were reported at rates similar to those in the placebo group, usually less than 1%. Symptoms did not increase after the second dose. It should be noted that a schedule of two doses, separated by seven days, as employed in this trial, may be appropriate for use in residents of endemic or epidemic areas, where pre-existing exposure to Flaviviruses may contribute to the immune response.3

A three-dose vaccination schedule is recommended for US travelers and military personnel, based on the Centers for Disease Control and Prevention (CDC) experience and on a controlled immunogenicity trial performed in US military personnel.4,5 The CDC experience demonstrated that neutralizing antibody was produced in fewer than 80% of vaccinees following two doses of vaccine in US travelers and antibody levels declined substantially in most vaccinees within six months. The US Army studied the immunogenicity of JE-VAX (japanese encephalitis virus vaccine inactivated) in 538 volunteers. Two three-dose regimens were evaluated (Day 0, 7, and 14 or Day 0, 7, and 30). All vaccine recipients demonstrated neutralizing antibodies at 2 months and 6 months after initiation of vaccination. The schedule of Day 0, 7, and 30 produced higher antibody responses than the Day 0, 7, and 14 schedule. Two hundred and seventy-three of the original study participants were tested at 12 months post-vaccination and there was no longer a statistical difference in antibody titers between the two vaccination regimens.5

The full duration of protection is unknown. Of US Army volunteers completing a three-dose regimen, 252 agreed to receive a booster dose of vaccine one year after the primary series. All boosted participants still had antibody 12 months after the booster. Protective levels of neutralizing antibody persisted for 24 months (2 years) in all 21 persons who had not received a booster.5 Definitive recommendations cannot be given on the timing of booster doses at this time.


1. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Inactivated Japanese Encephalitis Virus Vaccine. MMWR 42: 1-15, 1993

2. Oya A. Japanese Encephalitis Vaccine. Acta Paediatr Jpn 30: 175-184, 1988

3. Hoke CH, et al. Protection Against Japanese Encephalitis by Inactivated Vaccines. N Eng J Med 319: 608-614,1988

4. Poland JD, et al. Evaluation of the Potency and Safety of Inactivated Japanese Encephalitis Vaccine in US Inhabitants. J Infect Dis 161: 878-882, 1990

5. DeFraites RF. Immunogenicity and Safety of Japanese Encephalitis Vaccine (Inactivated: Nakayama/BIKEN) in U.S. Army Soldiers: Evaluation of Three Consecutively Manufactured Lots of Vaccine Administered in Two Dosing Regimens. April 30, 1991, and November 12, 1992. Unpublished Data, on file with BIKEN and with Walter Reed Army Institute of Research, Washington, DC

Last reviewed on RxList: 11/4/2008
This monograph has been modified to include the generic and brand name in many instances.

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