Japanese encephalitis
Information about Japanese encephalitis disease, vaccines and recommendations for vaccination from the Australian Immunisation Handbook
Vaccination against this disease is not funded under the National Immunisation Program, nor by states and territories.
What's changed
No new updates available.
Summary
What
Japanese encephalitis (JE) is caused by infection with the mosquito-borne JE virus. The disease mainly affects the central nervous system.
Who
JE vaccines are recommended for:
- routine vaccination of laboratory workers who may be exposed to JE virus
- routine vaccination of travellers spending 1 month or more in endemic areas during the JE virus transmission season
- routine vaccination of people who live or work on the outer islands of Torres Strait
How
JE vaccination is recommended for all research laboratory workers who may be exposed to the virus. These people may need a booster dose if they have ongoing risk of exposure to the virus.
JE vaccination is recommended for travellers spending 1 month or more in endemic areas in Asia and Papua New Guinea during the JE virus transmission season.
JE vaccination is recommended for residents of the outer islands in Torres Strait and non-residents who will be living or working on the outer islands of Torres Strait for 30 days or more during the wet season.
People who are at ongoing risk of acquiring JE may need booster doses.
Why
JE is a significant public health problem in many parts of Asia, and occasional outbreaks have occurred in Torres Strait. JE has a high case-fatality rate of around 30%. Around 50% of people who survive the acute illness will have neurological sequelae.
Recommendations
Laboratory workers
Laboratory workers who may be exposed to JE virus are recommended to receive JE vaccine
Japanese encephalitis (JE) vaccination is recommended for all research laboratory workers who may be exposed to the virus.
People who are at ongoing risk of exposure to JE virus may need booster doses.
The need for a booster dose of JE vaccine depends on:
- the person’s age when they received their primary vaccination course
- the vaccine used for the primary course
See Table. Recommended doses of Japanese encephalitis vaccines.
Travellers
Travellers spending 1 month or more in endemic areas during the JE virus transmission season are recommended to receive JE vaccine
Japanese encephalitis (JE) vaccination is recommended for travellers spending 1 month or more in endemic areas in Asia and Papua New Guinea during the JE virus transmission season.1 This includes people who will be based in urban areas, but are likely to visit endemic rural or agricultural areas.1 The risk is probably negligible during short trips to urban areas.2
JE vaccination is not routinely recommended for travellers spending less than 1 month in endemic areas. However, travellers can acquire JE after less than 1 month of travel. Vaccination should be considered for shorter-term travellers, particularly if:3
- the travel is during the wet season
- there may be ongoing travel to at-risk areas
- there is considerable outdoor activity during the travel
- the traveller is staying in accommodation without air-conditioning, screens or bed nets
See Epidemiology.
Travellers should seek up-to-date information about JE virus activity and risk of JE in travel destinations from a reputable source, such as the Centers for Disease Control and Prevention (CDC) Yellow Book.4
People who are at ongoing risk of acquiring JE may need booster doses.
The need for a booster dose of JE vaccine depends on:
- the person’s age when they received their primary vaccination course
- the vaccine used for the primary course
See Table. Recommended doses of Japanese encephalitis vaccines.
Avoiding mosquitoes
All travellers to Asia and other tropical regions should understand the importance of avoiding mosquitoes. This is an important step to reducing the risk of JE and other mosquito-borne diseases.
Ways to avoid mosquitoes include:
- using insect repellents containing at least 30% DEET
- using mosquito nets (preferably insecticide-treated nets)
- minimising outdoor exposure at dusk and dawn
- wearing clothing that leaves a minimum of exposed skin
People who live or work on the outer islands of Torres Strait
People who live or work on the outer islands of Torres Strait are recommended to receive JE vaccine
Japanese encephalitis (JE) vaccination is recommended for:
- residents of the outer islands in Torres Strait
- non-residents who will be living or working on the outer islands of Torres Strait for a cumulative total of 30 days or more during the wet season (December to May)
JE virus transmission in Torres Strait usually peaks in February and March. Timing of vaccination in residents should consider age, time of year, vaccine schedule and recent epidemiology.
People who do not need to be vaccinated are those who are:
- arriving in the outer islands in May, because this is late in the wet season and after the risk period for transmission
- visiting the outer islands in the dry season (June to November)
- visiting only the inner islands, including Thursday Island
People who are at ongoing risk of acquiring JE may need booster doses.
The need for a booster dose of JE vaccine depends on:
- the person’s age when they received their primary vaccination course
- the vaccine used for the primary course
See Table. Recommended doses of Japanese encephalitis vaccines.
Vaccines, dosage and administration
Japanese encephalitis vaccines available in Australia
The Therapeutic Goods Administration website provides product information for each vaccine.
See also Vaccine information and Variations from product information for more details.
Japanese encephalitis vaccines
Imojev
Registered for use in people aged ≥9 months.
Live attenuated Japanese encephalitis vaccine
Lyophilised powder in a monodose vial with separate diluent.
Each 0.5 mL reconstituted dose contains:
- 4.0–5.8 log plaque-forming units of live attenuated recombinant Japanese encephalitis virus
- mannitol
- lactose
- glutamic acid
- potassium hydroxide
- histidine
- human serum albumin
No adjuvants or antibiotics are added.
JEspect
Registered for use in people aged ≥18 years.
Inactivated Japanese encephalitis vaccine
Each 0.5 mL monodose pre-filled syringe contains:
- 6 antigen units of purified inactivated Japanese encephalitis virus
- 0.25 mg aluminium as aluminium hydroxide
No preservatives or antibiotics are added.
Dose and route
Recommended doses and schedules are shown in Table. Recommended doses of Japanese encephalitis vaccines.
Imojev
People aged ≥9 months can receive Imojev. The dose is 0.5 mL given by subcutaneous injection.
JEspect
JEspect is given by intramuscular injection. The primary dose needed depends on the age of the person:
- infants and children aged ≥2 months to <3 years should receive 2 doses, each of 0.25 mL, 28 days apart
- children aged ≥3 years and adults should receive 2 doses, each of 0.5 mL, 28 days apart
| Age at vaccination | Vaccine | Number of doses | Booster | Notes |
|---|---|---|---|---|
| ≥2 months to <18 years | JEspect | 2 doses (28 days apart) | No recommendation |
Each dose of JEspect in infants and children aged ≥2 months to <3 years is 0.25 mL. There are no data to inform recommendations for booster doses in infants and children <18 years. Consider a booster if the child needs sustained protection. |
| ≥9 months to <18 years | Imojev | 1 dose | 1–2 years after primary dose if ongoing risk of JE virus exposure | None |
| ≥18 years | Imojev | 1 dose | Not required | Seroprotective antibody levels persist in most adults 5 years after a single dose of Imojev.5 |
| JEspect | 2 doses (28 days apart) | 1–2 years after primary dose if ongoing risk of JE virus exposure | Adults can receive an accelerated primary course of JEspect (2 × 0.5 mL doses, 7 days apart) if they are at imminent risk of exposure to JE virus. |
Co-administration with other vaccines
Imojev
People can receive Imojev at the same time as:
- yellow fever vaccine6
- MMR (measles-mumps-rubella) vaccine7
Use separate syringes and inject in separate limbs. If a person does not receive Imojev and yellow fever vaccine (or other live vaccines) at the same time, they should receive them at least 4 weeks apart.
No data on co-administration with other vaccines are available.
JEspect
People can receive JEspect at the same time as:
- hepatitis A vaccine8
- quadrivalent (ACWY) meningococcal conjugate vaccine9
- rabies vaccine9
Use separate syringes and inject in separate limbs.
Co-administration with other vaccines (including yellow fever vaccine) has not been assessed.
Interchangeability of JE vaccines
Try to use the same vaccine for the booster dose as was used for the primary course. No studies have looked at the immune response to an Imojev booster in people who received a primary course of JEspect, or vice versa.
However, both vaccines use the same virus strain, so a booster using the alternative vaccine should give a satisfactory immune response, based on first principles.
Some people would have been previously vaccinated with the mouse brain-derived Japanese encephalitis (JE) vaccine, JE-Vax. These people can receive either Imojev or JEspect if they have an ongoing risk of JE virus exposure. 10-12
Contraindications and precautions
Contraindications
Japanese encephalitis (JE) vaccines are contraindicated in people who have had:
- anaphylaxis after a previous dose of any JE vaccine
- anaphylaxis after any component of a JE vaccine
Imojev is contraindicated in people who are immunocompromised and in pregnant women because it is a live attenuated viral vaccine. Women should avoid pregnancy for 28 days after vaccination.
Breastfeeding women should not receive Imojev because it is not known whether the virus is excreted in breast milk.
See Table. Vaccines contraindicated in pregnancy: live attenuated vaccines in Vaccination for women who are planning pregnancy, pregnant or breastfeeding for more details.
Precautions
People with an acute febrile illness should not receive JE vaccines.
People who are immunocompromised
JEspect is an inactivated vaccine, so it is not expected to cause any safety concerns in people who are immunocompromised. However, there are few data on the safety and efficacy of JEspect in those who are immunocompromised. These people may not mount an adequate immune response to the vaccine.
Women who are pregnant or breastfeeding
JE vaccine is not routinely recommended for pregnant or breastfeeding women. However, pregnant women at risk of acquiring JE are recommended to receive JEspect. JE virus infection during the 1st and 2nd trimesters has been associated with miscarriage. No adverse outcomes of pregnancy have been attributed to vaccination with JEspect.
Breastfeeding women who are at increased risk of acquiring JE are recommended to receive JEspect. However, no specific data are available about using JEspect in breastfeeding women.
Vaccination after immunoglobulin or blood product administration
Do not give Imojev within 6 weeks after giving immunoglobulins or immunoglobulin-containing blood products. It is preferable to wait 3 months.
Adverse events
Injection site reactions and minor systemic reactions are common after Japanese encephalitis vaccination.
Adverse events following Imojev
In adults
In studies of adults, adverse events after receiving Imojev were similar to those in placebo recipients,5,13 but occurred less often than in recipients of JE-Vax.13 The most common adverse events in 2 key studies were:5,13
- injection site pain
- headache
- fatigue
- malaise
Most symptoms resolved within 3 days.13
In children
In studies of children aged 12 to 24 months, the frequency of adverse events after receiving Imojev was similar to that after the hepatitis A vaccine. About 40% of children reported injection site reactions, including:14
- pain (32%)
- redness (23%)
- swelling (9%)
About 50% reported at least 1 systemic reaction, including:14
- fever (21%)
- appetite loss (26%)
- irritability (28%)
- abnormal crying (23%)
In children aged 2–5 years who received Imojev after JE-Vax, the frequency of adverse events was similar to, or lower than, that in children aged 12–24 months who had not previously been vaccinated. All reactions were transient, and almost all were mild. Most systemic reactions were mild or moderate, appeared within 7 days of vaccination, and lasted for up to 3 days.14
Adverse events following JEspect
In a pooled analysis of more than 4000 healthy adults who received at least 1 dose of JEspect, 54% reported injection site reactions, most commonly: 15
- pain (33%)
- tenderness (33%)
- redness (9%)
Headache and myalgia were the most commonly reported systemic adverse events. 15-19
Another analysis compared adverse events after receiving JEspect vaccine and aluminium-containing placebo. The rate of adverse events was similar.18
Post-marketing surveillance reported adverse events after receiving JEspect at a rate of about 10 per 100,000 doses distributed. No serious allergic reactions were observed during the first 12 months after marketing approval.15
Frequencies of adverse events reported following a booster dose of JEspect were similar to those reported after a primary course.16,20
Nature of the disease
Japanese encephalitis (JE) is caused by a mosquito-borne RNA flavivirus called Japanese encephalitis virus.
Pathogenesis
After an infectious mosquito bite, the virus multiplies locally and in regional lymph nodes. The virus then spreads to secondary sites, particularly the central nervous system. 21
Transmission
JE is a zoonosis of pigs and wading birds. Culicine mosquitoes transmit the virus between these animals. 1
Pigs and wading birds are ‘amplifying hosts’ for JE virus. This means that the virus replicates in the animal and causes transient high-level viraemia. Other large vertebrates, such as horses and humans, are not amplifying hosts. Humans are an incidental host.
Clinical features
Asymptomatic infection
Most infections are asymptomatic. Estimates of the symptomatic to asymptomatic infection ratio vary in different populations from 1:25 to 1:1000. 1
Acute neurological illness
Japanese encephalitis (JE) is typically an acute neurological illness. It is characterised by: 22
- headache
- fever
- convulsions
- focal neurological signs
- depressed level of consciousness
JE has a high case-fatality rate of around 30%. There is no specific treatment. Around 50% of people who survive the acute illness will have neurological sequelae. 1
JE sometimes presents as acute flaccid paralysis.1 Milder forms of JE include febrile illness with headache, and aseptic meningitis.21
Epidemiology
JE in Torres Strait and mainland Australia
Occasional outbreaks of Japanese encephalitis (JE) have occurred in Torres Strait.23,24 The first outbreak of JE in Australia occurred in the remote outer islands of Torres Strait in 1995. There were 3 cases, including 2 deaths.25
A 2nd outbreak of JE occurred in 1998.26 To date, 5 cases of JE have been acquired in Australia, 1 of which was on the mainland.25
Torres Strait has not reported a case of JE since 1998. The risk of JE is much lower now than it was in the mid-1990s. Most communities have moved pigs well away from homes. Major drainage works on most islands have reduced breeding sites for mosquitoes.
Between 2001 and 2014, 9 cases of JE were notified in Australia. All were acquired overseas.27,28
JE in Asia
Japanese encephalitis (JE) is a significant public health problem in many parts of Asia, including: 1,21
- China
- the Indian subcontinent
- Southeast Asia
The disease is also present in eastern Indonesia (including Bali) and Papua New Guinea.
JE virus is maintained in an enzootic cycle. Areas that have established JE immunisation programs may not have many cases in humans, but susceptible people who visit these areas may still be at risk.
People are most commonly infected if they live close to amplifying hosts and mosquitoes. This usually occurs in rural areas where the mosquito vectors can breed in flooded rice fields.1 Incidence of JE has declined considerably in Japan, Taiwan, South Korea and some provinces of China. Singapore has eradicated the disease. These changes can be attributed to:1
- immunisation
- changes in pig husbandry
- less land used for rice farming
- improved socioeconomic circumstances
Up-to-date information about JE virus activity in specific locations is available from sources such as the Centers for Disease Control and Prevention (CDC) Yellow Book.4
Seasonal patterns of JE
In temperate or subtropical regions of Asia, JE mainly occurs in epidemics during the summer or wet season. This is usually April–May to September–October.
In tropical regions, the disease occurs throughout the year, but is more prominent during the wet season.1
Vaccine information
Two Japanese encephalitis (JE) vaccines are available for use in Australia: Imojev and JEspect. They have different:
- registered age groups
- vaccination schedules
- booster dose requirements
- contraindications for use
Consider these factors when deciding the most appropriate vaccine.
See Contraindications and precautions for more details.
Imojev is produced using recombinant technology using genes from the SA 14-14-2 JE virus strain. It is:
- Vero cell derived
- live attenuated
JEspect is based on the attenuated SA 14-14-2 JE virus strain. It is:
- Vero cell derived
- inactivated
- aluminium adjuvanted
The World Health Organization considers that a neutralising antibody titre of ≥1:10 correlates to immunity. Imojev and JEspect were registered based on this immunologic correlate rather than efficacy trials.
Imojev
1 dose of Imojev:
- causes seroconversion to a homologous JE virus strain in about 94% of healthy adults aged 18–84 years within 14 days13
- causes seroconversion to various wild-type, non-homologous JE virus strains in 70–100% of adults14,29
- generates protective levels of neutralising antibodies against the homologous vaccine virus strain in 99% of adults after 28 days5,13,14,30
- generates protective levels of neutralising antibodies against all 4 wild-type strains used for testing in 85% of adults5
Duration of immunity in adults
Protective antibodies against the vaccine strain were maintained in: 5
- 98% of adults at 1 year after vaccination
- 92% at 3 years after vaccination
- 87% at 5 years after vaccination
About 65% of adults maintain protective antibody levels to at least 3 wild-type virus strains 5 years after a single vaccine dose. 5 Studies also show immunological memory in vaccinated adults. 29
Immunogenicity in children
In vaccine-naive children aged 12–24 months, 1 dose of Imojev induces protective levels of neutralising antibodies against the homologous vaccine virus strain in:
- 96% at 28 days14
- 87% at 7 months14
- 75% at 3 years31
70–97% of children aged 12–24 months seroconverted to various wild-type, non-homologous, JE virus strains.14-29
In children aged 2–5 years who previously received JE-Vax, 86% were seropositive against the vaccine strain at baseline, and 72–81% were seropositive against 4 wild-type strains at baseline. A dose of Imojev produced seroprotective antibody levels against the vaccine strain in 100% of the children, and against all wild-type strains in 99%. Of these children:
- 93% seroconverted to the vaccine strain
- 90% seroconverted to all wild-type strains14
No immunogenicity data are available for Imojev in children aged 6–17 years. Immunogenicity in this age group is assumed based on studies in younger children and adults.
Duration of immunity in children
In children aged 9–18 months, protective levels of neutralising antibodies were present 12 months after a single dose of Imojev.32 After a booster dose in these children, 100% demonstrated seroprotection after 28 days and 98% remained seroprotected after 5 years.33
In children aged 2–5 years who previously received JE-Vax, 98% maintained protective antibody levels for 3 years after a dose of Imojev.31
JEspect
Immunogenicity in adults
A randomised controlled trial conducted among more than 860 adults using neutralising antibody responses 1 month after the last vaccine dose showed that 98% of people had seroconverted.34
A small study looked at travellers who had received at least 2 doses of JE-Vax 1–21 years before a dose of JEspect. 4–8 weeks after 1 dose of JEspect, 98% of people had protective antibody levels against homologous strains and 95% against heterologous strains.11
Accelerated JEspect schedule in adults
A phase III study in healthy adults compared an accelerated (days 0 and 7) and conventional (days 0 and 28) JEspect schedule. The results suggested a non-inferior immune response for the accelerated schedule of JEspect compared with the conventional schedule. This was at 28 days and 1 year after the 2nd dose. 35,36
Duration of immunity in adults
| Region | 6 months after vaccination | 12 months after vaccination | 24 months after vaccination |
|---|---|---|---|
| Central Europe37,38 | 95% | 83% | 48% |
| Western and northern Europe16 | 83% | 58% | 48% |
The 2 studies show a discrepancy, especially in the first 12 months. This may be because of previous vaccination with the tick-borne encephalitis (TBE) vaccine in a large proportion of people in the central European study.16,37
Another study looked at JEspect-vaccinated people after 5 years.39 The seroprotection rates were:
- 64% for TBE-naive people
- 92% for those who received TBE vaccine before or during the study
The western and northern European study also reviewed JE booster doses. People who did not have a seroprotective antibody level at the 6- or 12-month follow-up received a booster dose at 11 and/or 23 months after 1st vaccination. 100% of these people became seropositive.16
Immunogenicity in children
The key paediatric clinical trial of JEspect was a phase III study in children aged 2 months to 17 years in the Philippines.40,41
Children received age-appropriate doses of JEspect, and the proportions with protective antibody titres were:41
- 99–100% after 56 days
- 85–100% after 7 months
There was no obvious pattern by age.
A phase III immunogenicity study involved 64 children from non-JE-endemic countries aged 2 months to <18 years (mean 11.6 years; range 11 months to 17.9 years). All children seroconverted to protective levels. The proportion seroprotected at 6 months after the 2nd dose was:42
- 100% in the <3 years age group (n = 2)
- 90.6% in the ≥3 years age group (n = 32)
Transporting, storing and handling vaccines
Transport according to National Vaccine Storage Guidelines: Strive for 5.43 Store at +2°C to +8°C. Do not freeze. Protect from light.
Imojev vaccine must be reconstituted. Add the entire contents of the diluent container to the vial and shake until the powder completely dissolves. Use the reconstituted vaccine within 1 hour.
Public health management
Japanese encephalitis virus infection is a notifiable disease in all states and territories in Australia.
State and territory public health authorities can provide advice about the public health management of Japanese encephalitis, including management of cases.
Variations from product information
The product information for JEspect states that this vaccine is for use in people aged ≥18 years.
The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that children and adolescents aged ≥2 months to <18 years can receive JEspect if an alternative is not available or is contraindicated. ATAGI also recommends that children aged ≥2 months to <3 years receive 0.25 mL doses of JEspect.
The product information for JEspect states that it can be given with inactivated hepatitis A vaccine.
ATAGI recommends that JEspect can also be given with quadrivalent (ACWY) meningococcal conjugate vaccine and rabies vaccine (see Vaccines, dosage and administration).
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- Dubischar-Kastner K, Ayad A, Cramer JP, et al. Safety and immunogenicity data for inactivated Japanese encephalitis vaccine (JE-VC), IC51, in children from JE non-endemic countries [poster 2.7]. Presented at: 5th Northern European Conference on Travel Medicine; June 2014; Bergen, Norway.
- National vaccine storage guidelines: Strive for 5. 2nd ed. Canberra: Australian Government Department of Health and Ageing; 2013.
Page history
Changes to multiple sections 4.8.3 Epidemiology, 4.8.4 Vaccines, 4.8.6 Dosage and administration, 4.8.7 Recommendations, 4.8.10 Precautions and 4.8.13 Variations from product information
Definitions
- JE
- Japanese encephalitis
- MMR
- measles-mumps-rubella
- RNA
- ribonucleic acid
- ATAGI
- Australian Technical Advisory Group on Immunisation
- WA
- Western Australia
This document was printed on: 22/10/2018. Printed content may be out of date. For up to date information, always refer to the digital version: https://immunisationhandbook.health.gov.au/vaccine-preventable-diseases/japanese-encephalitis.