japanese encephalitis travel

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• Disease Prevention Advice

Japanese Encephalitis

Introduction.

• Recommendations

Vaccination

Overview of the disease, the illness.

Japanese encephalitis is an infection spread through mosquito bites that can cause inflammation of the brain.

Recommendations for Travellers

Prevention is focused on avoiding mosquito bites, especially around dusk when this mosquito is most active. Use of insect repellents, appropriate clothing and mosquito nets is recommended for those at risk.

• Tips on how to avoid mosquito bites

The vaccine most commonly used in the UK is IXIARO; 2 doses of vaccine should be given before travel. The risk for most travellers will be very small. Individuals should consider being vaccinated:

• if travelling to a country where Japanese encephalitis is present and where the stay may be prolonged (e.g. more than four weeks)
• if at increased risk of exposure to the disease e.g. staying in or around rice growing areas
• if having prolonged periods outdoors in rural areas
• for shorter, but frequent trips to endemic areas
• if going to live in an endemic area.

View the Patient Information Leaflet (PIL) for IXIARO

Japanese encephalitis is caused by a virus transmitted through mosquito bites. The mosquito that spreads the infection favours breeding sites in and around rice paddies and bites mostly around dusk. It is found in South-East Asia and the Indian subcontinent. Transmission patterns are highly specific to locations and vary year to year; in some countries transmission is seasonal and in others, disease occurs all year round.

Japanese encephalitis causes headache, convulsions, encephalitis and meningitis. Most people will have a mild illness with no or few symptoms but for those with severe disease around 30% can develop permanent neurological problems and around 30% will die from the disease.

There is no specific treatment available for Japanese encephalitis.

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• General Travel Health Advice

Japanese encephalitis

Japanese encephalitis is a rare but serious infection you can get from mosquito bites in some parts of the world. If you're travelling to an area where there's a risk of catching it, you can get a vaccine to help prevent it.

Check if you're at risk of Japanese encephalitis

Japanese encephalitis is not found in the UK. It's mostly found in rural areas of Asia, but it's rare for travellers to get it.

It's caused by a virus which is spread through mosquito bites.

Places where Japanese encephalitis is found include parts of:

• South Korea
• Southeast Asia (such as Thailand, Malaysia and Vietnam)

Check your travel risk

You can get health advice for a country you're travelling to on the TravelHealthPro website .

How to lower your risk of Japanese encephalitis

There are some things you can do to avoid mosquito bites when travelling to areas with a risk of Japanese encephalitis.

Do use insect repellent on exposed skin, ideally containing at least 50% DEET sleep under a mosquito net treated with insecticide when possible, wear long-sleeved tops, trousers or long skirts, socks and shoes to protect your skin from mosquito bites get advice from a travel vaccination clinic before you travel Japanese encephalitis vaccine

A vaccine for Japanese encephalitis is recommended if you're travelling to a part of the world where the virus is found, especially if:

• you're staying for more than a month
• you're staying in a rural area
• you're staying near or visiting rice fields, wetlands, or places where pigs are kept

You'll have to pay for the Japanese encephalitis vaccine. You can get it from travel health clinics and pharmacies with travel health services.

Symptoms of Japanese encephalitis

Most people who get Japanese encephalitis have no symptoms.

Some people get flu-like symptoms such as:

• a high temperature
• feeling or being sick

The symptoms usually go away on their own, but in some people the infection spreads to the brain and causes more serious symptoms such as:

• a severe headache
• feeling confused
• not being able to feel or move parts of your body ( paralysis )
• seizures (fits)

Urgent advice: Ask for an urgent GP appointment or get help from NHS 111 if:

You've recently travelled to an area where Japanese encephalitis is found and you have flu-like symptoms such as:

Tell anyone you speak to about your recent travel, and if you were bitten by a mosquito or might have been.

You can call 111 or get help from 111 online .

Immediate action required: Call 999 if you or someone else has:

• a severe headache and a stiff neck
• sudden confusion (for example, not being sure of your name, age, or where you are)
• sudden weakness or suddenly not being able to feel or move part of your body (paralysis)
• a seizure (fit)
• loss of consciousness
• severe difficulty breathing

Do not drive to A&E. Ask someone to drive you or call 999 and ask for an ambulance.

Bring any medicines you take with you.

Get medical advice quickly if you have Japanese encephalitis symptoms while you're travelling.

Treatment for Japanese encephalitis

You'll need to be treated in hospital if you're seriously unwell because Japanese encephalitis can be life-threatening.

Treatments for Japanese encephalitis include medicines to help relieve the symptoms, such as painkillers and steroids .

Japanese encephalitis can sometimes cause long-term complications such as paralysis , seizures, and loss of speech.

Page last reviewed: 06 June 2023 Next review due: 06 June 2026

Travel-acquired Japanese encephalitis and vaccination considerations

Affiliation.

• 1 Hellenic Center for Disease Control and Prevention, Athens, Greece. [email protected].
• PMID: 26409731
• DOI: 10.3855/jidc.5108

Japanese encephalitis (JE) is a serious arboviral disease caused by a virus of the genus Flavivirus. Japanese encephalitis is the most common vaccine-preventable virus causing encephalitis in Asia, affecting more than 50,000 persons and leading to 15,000 fatalities per year in endemic countries. For most travelers to Asia, the risk of Japanese encephalitis infection is extremely low and depends on destination, duration of travel, season, and activities. This article reviews travel-acquired Japanese encephalitis with a focus on epidemiology and prevention in the light of the newly available options for active immunization against Japanese encephalitis which have become available, and of the increasing popularity of travels to Japanese encephalitis endemic countries.

Publication types

• Asia / epidemiology
• Encephalitis, Japanese / epidemiology*
• Encephalitis, Japanese / prevention & control*
• Endemic Diseases
• Japanese Encephalitis Vaccines / administration & dosage*
• Vaccination
• Japanese Encephalitis Vaccines

Japanese Encephalitis

What is japanese encephalitis.

Japanese encephalitis is a disease caused by flaviviruses and transmitted by Culex mosquitoes.  Most people who become infected develop no or very mild symptoms.  However, a small proportion (up to 1%) may develop encephalitis which presents with a rapid onset of headache, high fever, disorientation and convulsions. Up to 30% of symptomatic cases can be fatal.

Please note: We are currently unable to offer third vaccinations due to a vaccine shortage.

In which countries does Japanese encephalitis occur?

Japanese encephalitis occurs in rural areas in Southeast Asia. The distribution extends from Japan, eastern China and India to Indonesia and Papua New Guinea in the south.

When and how often should I be vaccinated against Japanese encephalitis?

Vaccination is only recommended for travelers who are going to Southeast Asia for an extended period of time and are staying in rural areas. The risk of infection increases when staying near rice fields or pig farms. If vaccination is recommended, at least 2 doses are needed before departure, ideally with an interval of 4 weeks. If there is a renewed risk, a booster vaccination can be given after one year.

Price: 131.20 CHF per dose plus consultation and injection fee

What else should I know about the Japanese encephalitis vaccine?

There are live but also inactivated vaccines against Japanese encephalitis. In Switzerland, only the inactivated vaccine (Ixiaro) is approved.

The virus that triggers Japanese encephalitis is closely related to tick-borne encephalitis (TBE), which is transmitted in Switzerland.

For more information on Japanese encephalitis, visit HealthyTravel .

Do you have a question or would you like to book an appointment?

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Japanese encephalitis vaccine: Canadian Immunization Guide

For health professionals

• Previous page
• Part 4 table of contents

Recommendations for use of Japanese Encephalitis (JE) vaccine have been updated based on the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement on Prevention of Japanese Encephalitis .

This information is captured in the table of updates .

On this page

• Key information

Epidemiology

• Preparations authorized for use in Canada

Immunogenicity, efficacy and effectiveness

Recommendations for use, vaccination of specific populations, serologic testing, administration practices.

• Storage requirements
• Safety and adverse events

Chapter revision process

Acknowledgements, selected references, key information.

• Japanese encephalitis (JE) is a disease caused by a mosquito-transmitted virus in parts of South Asia, Southeast Asia, East Asia and Oceania.
• JE is rare among Canadian travellers. However, it is a severe disease with a high case fatality rate (approximately 20% to 30%). Further, many JE survivors (approximately 30% to 50%) suffer permanent cognitive, behavioural and/or neurological sequelae.
• Travelling frequently and/or for an extended period to endemic regions, in particular if it involves significant exposure in rural areas, increases the likelihood of infection with the JE virus.
• Travellers can reduce risk of JE in a number of ways, including by preventing mosquito bites and through the use of JE vaccine.
• IXIARO ® is the only JE vaccine authorized for use in Canada. A high rate of seroconversion (greater than 95%) is achieved with a two-dose primary series.
• The most commonly reported adverse events following JE vaccination are injection site pain and tenderness, headache, myalgia and fatigue.
• JE vaccine should be considered for travellers who, by virtue of their itinerary, are believed to be at the highest risk for infection with the JE virus.
• JE vaccine is authorized for use in persons aged 2 months of age and older.
• Children aged 2 months to less than 3 years of age receive 0.25 mL per dose.
• Individuals 3 years of age and older receive 0.5 mL per dose.
• If time constraints preclude a 0 and 28-day schedule, an accelerated schedule (days 0 and 7) may be considered.
• Booster doses may be considered for persons who are at continued risk for JE.
• Because JE is a rare disease among Canadian travellers, the expected benefit of receiving the vaccine is usually small and might be outweighed by expected harms (e.g., cost, inconvenience and adverse effects).
• The absolute benefit of JE vaccine is likely higher for travellers who travel for a long period or take multiple trips to endemic areas and/or with extensive travel through rural areas.

Disease description

Infectious agent.

Japanese encephalitis (JE) is caused by a ribonucleic acid (RNA) virus from the family Flaviviridae . For additional information about the JE virus, refer to the Pathogen Safety Data Sheet .

The virus is primarily transmitted in an enzootic cycle that typically involves the Culex mosquito and wild birds. Spillover from this cycle, or from an epizootic cycle involving pigs as amplifying hosts can result in human infection.

Transmission

JE virus is transmitted to humans primarily through the bite of an infected mosquito. Mosquitoes acquire the virus from infected hosts (e.g., pigs and wild birds) and then transmit the virus to non-infected hosts (e.g., humans and horses). The principal vectors are Culex species mosquitoes that preferentially bite in the evening and night.

Larvae of Culex mosquitoes develop in standing water, such as rice fields. Thus, transmission of JE virus occurs primarily in rural agricultural areas where flooding irrigation is practiced; however, cases have been reported from urban areas.

Humans usually do not develop sufficient viremia to infect mosquitoes. Direct person-to-person spread of JE does not occur, except rarely, through intrauterine transmission. Blood transfusion and organ transplantation are possible modes of transmission based on experience with other Flaviviruses. The incubation period is 5 to 15 days.

Risk factors

A traveller's risk for developing JE is determined by multiple factors, including immunization status, use of protective measures against mosquito bites, location of travel, duration of exposure, season, and activities while travelling.  In general, the risk is extremely low for travellers, particularly for short-term visitors to major urban areas. Risk is thought to be relatively higher for those who:

• Visit rural agricultural areas, especially those associated with rice production and flooding irrigation
• Take multiple trips to and/or stay for extended periods in endemic regions
• Participate in outdoor activities in rural areas, especially during the evening or night (when the mosquitoes are more active)

Based on available case reports, the overall risk of JE among Canadians travelling to endemic regions has been estimated to be approximately 1/10,000,000 trips. However, by virtue of their itinerary, it is expected that some travellers will be subject to a significantly higher relative risk. Refer to the CDC Yellow Book for an overview of countries with JE virus transmission.

Seasonal and temporal patterns

In most temperate areas of Asia, JE virus transmission exhibits a seasonal pattern typically starting in April or May and lasting until September or October. In the subtropics and tropics, transmission patterns vary and cases can occur sporadically or year-round but often increase rapidly during the rainy season.

Spectrum of clinical illness

Most JE infections are asymptomatic, with less than 1% of people infected with JE virus developing clinical disease. Acute encephalitis is the most commonly identified clinical syndrome, which is associated with 20% to 30% mortality rates, and 30 to 50% permanent cognitive, behavioural and/or neurological problems among survivors. JE acquired during pregnancy carries the risk of intrauterine infection and miscarriage. There is no antiviral treatment for JE; management consists of supportive care and long term support for those who suffer permanent sequelae.

Disease distribution

Incidence and prevalence.

JE occurs in parts of South Asia, Southeast Asia, East Asia and Oceania. The World Health Organization (WHO) estimates that more than 68,000 cases and up to 20,000 deaths occur annually. Risk varies between and within countries, from year to year and by season. For residents of endemic areas without a vaccination program, the burden disproportionately falls upon children living in rural areas. Travellers of all ages are potentially at risk and because the disease is zoonotic, risk is present even if disease among local residents has been controlled through immunization.

To date, there has been one confirmed case (2010) and one possible case (1982) of JE reported among Canadians returning from Asia.

Preparation Authorized for Use in Canada

Japanese encephalitis vaccine.

• IXIARO ® : inactivated, Japanese encephalitis vaccine, Vero cell culture-derived, adsorbed. Valneva Austria GmbH, (JE)

For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database .

Refer to Table 1 in Contents of Immunizing Agents Authorized for Use in Canada in Part 1 for a list of all vaccines authorized for use in Canada and their contents.

Immunogenicity

A single dose of JE vaccine induces sufficient protective antibodies in 30% of vaccine recipients 10 days after vaccination and in 40% of vaccine recipients 28 days post-vaccination. A second dose of vaccine given 28 days after the first dose induces antibodies in more than 95% of vaccine recipients. The immunogenicity of the vaccine is lower in adults over 65 years of age, with seroconversion occurring in approximately 65% of vaccine recipients. The immunogenicity of the accelerated schedule (i.e., doses given at 0 and 7 days) has been demonstrated to be non-inferior to the regularly-dosed primary series. Vaccination with two doses of vaccine at the same time has been shown to increase the seroconversion rate to approximately 60% at 10 days post-vaccination.

Protective antibody concentrations decline over time with 80% to 95% of fully immunized vaccine recipients maintaining an adequate concentration at 6 months after the first dose and 58% to 83% maintaining adequate antibodies at 12 to 15 months after the first dose. A booster dose of vaccine following a recommended primary series induces an adequately protective boost to antibody concentration in those who have lost protective antibodies at 12 months after their first dose.

Efficacy and effectiveness

No efficacy or effectiveness data exist for the Vero cell culture-derived JE vaccine, IXIARO ® . IXIARO ® was authorized for use based on non-inferiority of serologic response compared to the previous mouse brain-derived JE vaccine and to the WHO threshold for protective antibody titre.

JE vaccine should only be considered for individuals 2 months and older who are at increased risk of disease. JE vaccine should not be routinely recommended for persons travelling to endemic areas without identified risks. Refer to Risk factors for more information.

For optimal protection, the immunization series should ideally be completed at least 7 days before an individual travels to an area where there is a potential for exposure to JE virus to develop an adequate antibody response. However, this advice should not discourage use where timelines are shorter and the vaccine is indicated/desired by the traveller.

All travellers to JE endemic areas should be advised to use measures to protect themselves against mosquito bites which will also provide protection against other mosquito-borne diseases such as dengue and malaria.

Refer to the CDC Yellow Book for an overview of countries with JE virus transmission.

For detailed information on vaccine recommendations and alternative preventive strategies for prevention of JE refer to the CATMAT Statement on Prevention of Japanese Encephalitis .

Recommended schedule

Infants and children (2 months to less than 18 years).

The primary series for children 2 months to less than 3 years of age consists of two separate 0.25 mL doses; for children 3 years of age to less than 18 years, two separate 0.5 mL doses. The doses should be provided on day 0 and day 28.

Adults (18 years of age and older)

The primary series for adults consists of two separate 0.5 mL doses on day 0 and day 28. An accelerated schedule (days 0 and 7) can be used for adults aged 18 to 65 years if there is insufficient time to provide the vaccine in accordance with the recommended primary schedule.

In situations where there is insufficient time to provide a recommended or an accelerated schedule, a single dose of JE vaccine can be considered. Alternatively, simultaneous administration of two doses of JE vaccine (provided at separate injection sites) may also be considered as this approach has been shown to lead to higher seroconversion rates in adults compared to a single dose. However, protection is probably less effective than the standard schedule. Refer to Immunogenicity for more information.

Booster doses and re-immunization

A single booster dose of JE vaccine can be administered 12 to 24 months after the primary series to individuals who remain at risk and desire vaccine-induced protection. For adults 65 years and older, a single booster dose should be considered earlier (before 12 months) following the primary series. A second booster can be considered for persons who remain at risk for JE if more than 10 years have elapsed since the first booster.

Pregnancy and breastfeeding

There are no data related to safety or efficacy of JE vaccine in pregnant or breastfeeding women. Pre-clinical studies of JE vaccine in pregnant rats did not indicate evidence of harm to the fetus or adverse effects with respect to fertility or pregnancy outcomes.

JE acquired during pregnancy carries the risk of intrauterine infection and miscarriage. Pregnant or breastfeeding women who must travel to areas where the risk of JE infection is high should be immunized as the risk of disease outweighs the unknown risk of vaccination.

Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional general information.

Immunocompromised persons

If travel must be undertaken, immunocompromised persons may be immunized with JE vaccine; however, the antibody response may be suboptimal and the person should be advised to be diligent about mosquito protection measures. Booster immunizations should be considered earlier, if needed, as the duration of protection may also be much shorter. When considering immunization of an immunocompromised person, consultation with the individual's attending physician may be of assistance. For complex cases, referral to a physician with expertise in immunization and/or immunodeficiency is advised.

Refer to Immunization of Immunocompromised Persons in Part 3 for additional general information.

Laboratory personnel who work with JE virus should receive JE vaccine. Laboratory workers at continuous risk for acquiring JE should receive a booster dose 12 months after primary immunization. Refer to Booster doses and re-immunization for more information.

As with other travellers, healthcare providers working abroad should be considered for JE vaccination if they, by virtue of their itinerary, are believed to be at high risk for infection. Refer to Risk factors for more information.

Refer to Immunization of Workers in Part 3 for additional general information.

Serologic testing is not recommended before or after receiving JE vaccine.

Dose and route of administration

Each dose of JE vaccine is 0.25 mL for infants and children aged 2 months to less than 3 years and 0.5 mL for individuals 3 years of age or older.

Route of administration

JE vaccine should be administered intramuscularly. Refer to Vaccine Administration Practices in Part 1 for general information on administration technique and infection prevention and control.

Interchangeability of vaccines

There are no data available regarding interchangeability of the currently available Vero cell culture-derived JE vaccine (IXIARO ® ) with the previous mouse brain-derived JE vaccine or other JE vaccines available internationally, either in primary series or in booster dosing. Refer to Principles of Vaccine Interchangeability in Part 1 for additional general information.

Concurrent administration with other vaccines

Data are limited regarding the safety and immunogenicity of JE vaccine when given concomitantly with other vaccines. In general, inactivated vaccines, such as JE vaccine, can be given concurrently with any other vaccine using different injection sites and separate needles and syringes. JE vaccine has been given concomitantly with hepatitis A vaccine without significant interference with safety and immunogenicity. Similarly, there was no interference with the immune response when JE vaccine was administered concomitantly with rabies vaccine. There are no data available regarding possible interference between JE vaccine and yellow fever vaccine.

Refer to Timing of Vaccine Administration in Part 1 for additional general information.

Storage Requirements

JE vaccine should be stored in a refrigerator at +2°C to +8°C. Do not freeze. Protect from light. Refer to Storage and Handling of Immunizing Agents in Part 1 for additional general information.

Safety and Adverse Events

Refer to Vaccine Safety and Pharmacovigilance in Part 2 for additional information on vaccine safety.

Common and very common adverse events

Common adverse events occur in 1% to less than 10% of vaccine recipients. Very common adverse events occur in 10% or more of vaccine recipients.

Infants and children 2 months to less than 3 years of age

Most commonly reported adverse reactions in infants and children 2 months to less than 3 years of age included fever (28.5%), diarrhea (11.9%), influenza like illness (10.9%), irritability (10.9%), decreased appetite (8.2%) and vomiting (7.3%). Injection site reactions such as tenderness (4.2%), swelling (3.6%) and hardening (1.2%) have also been reported.

Children and adolescents 3 years to less than 18 years of age

Most commonly reported adverse reactions in children and adolescents 3 to less than 18 years of age included injection site reactions such as tenderness (14.7%), fever (10.4%), myalgia (7.1%), headache (6.1%), and fatigue (3.5%).

Most commonly reported adverse reactions in adults included headache (20% of subjects) myalgia (13%), fatigue (12.9%), injection site pain (33%) and injection site tenderness (33%).

Uncommon, rare and very rare adverse events

Uncommon adverse events occur in 0.1% to less than 1% of vaccine recipients. Rare and very rare adverse events occur, respectively, in 0.01% to less than 0.1% and less than 0.01% of vaccine recipients.

Serious adverse events following immunization may occur in less than 0.01% vaccine recipients and, in most cases, data are insufficient to determine a causal association. Anaphylaxis following vaccination with JE vaccine may occur in less than 0.01% of vaccine recipients.

No pattern of serious hypersensitivity, neurologic or other adverse events considered to be related to JE vaccine has been identified in the U.S. post market surveillance data. In two analyses of AE reported to the US Vaccine Adverse Event Reporting System (VAERS) following administration of IXIARO ® with or without other vaccines; hypersensitivity events were reported at rates of 3.0 and 4.4 per 100,000 doses distributed, and 56% (20 of 36) occurred after concomitant administration of JE vaccine with other vaccines. Neurologic events were reported at rates of 2.2 and 1.2 events per 100,000 doses distributed. The neurologic adverse event reports included four reports of seizures which all occurred after administration of JE vaccine with other vaccines. VAERS data cannot generally be used to determine causality, especially with concomitant administration of vaccines.

Guidance on reporting Adverse Events Following Immunization (AEFI)

To ensure the ongoing safety of vaccines in Canada, reporting of AEFIs by vaccine providers and other clinicians is critical, and in some jurisdictions, reporting is mandatory under the law.

Vaccine providers are asked to report AEFIs through local public health officials and to check for specific AEFI reporting requirements in their province or territory. In general, any serious or unexpected adverse event felt to be temporally related to vaccination should be reported.

For additional information about AEFI reporting, please refer to Adverse Events Following Immunization in Part 2 and Reporting Adverse Events Following Immunization (AEFI) in Canada .

Contraindications and precautions

JE containing vaccines are contraindicated in persons with a history of anaphylaxis after previous administration of the vaccine and in persons with proven immediate or anaphylactic hypersensitivity to any component of the vaccine or its container. Refer to Table 1 in Contents of Immunizing Agents Authorized for Use in Canada in Part 1 for a list of immunizing agents authorized for use in Canada and their contents.

Administration of JE containing vaccine should be postponed in persons suffering from severe acute illness. Immunization should not be delayed because of minor or moderate acute illness, with or without fever. Refer to Contraindications and Precautions in Part 2 for additional general information.

This chapter was reviewed and updated based on the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement on Prevention of Japanese Encephalitis . CATMAT recommendations on the prevention of Japanese encephalitis were developed using the GRADE process or were informed by literature reviews and expert opinion.

The Public Health Agency of Canada (PHAC) would like to acknowledge the contributions of CATMAT members M Libman, P Lagacé-Wiens, J Pernica, K Plewes, SW Schofield, S Vaughan, and PHAC participants N Mohamed, L Coward, C Jensen, O Baclic, J Zafack and E Abrams.

• Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, et al. Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ 2011;89(10):766-774.
• Centers for Disease Control and Prevention (CDC). Japanese encephalitis: CDC Yellow Book 2024 [Internet]. 2023 May 1 [cited 2023 Jul 28]. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/japanese-encephalitis
• Centers for Disease Control and Prevention (CDC). Use of Japanese encephalitis vaccine in children: Recommendations of the advisory committee on immunization practices, 2013. MMWR Morb Mortal Wkly Rep 2013;62(45):898-900.
• Centers for Disease Control and Prevention (CDC). Japanese Encephalitis Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010;59(RR01):1-27.
• Centers for Disease Control and Prevention (CDC). Japanese Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2019; 68(2);1–33. 
• Centers for Disease Control and Prevention (CDC). Recommendations for use of a booster dose of inactivated vero cell culture-derived Japanese encephalitis vaccine: advisory committee on immunization practices, 2011. MMWR Morb Mortal Wkly Rep 2011;60(20):661-663.
• Centers for Disease Control and Prevention (CDC). Grading of recommendations, assessment, development, and evaluation (GRADE) for use of inactivated Vero cell culture-derived Japanese encephalitis vaccine in children; 2014. Accessed May 16, 2016 at:  https://www.cdc.gov/vaccines/acip/recs/grade/je-child.html.
• Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on Prevention of Japanese Encephalitis. 2019. Accessed January 2020 at: https://www.canada.ca/en/public-health/services/catmat/statement-prevention-japanese-encephalitis.html
• Fischer M, Lindsey N, Staples JE, Hills S, Centers for Disease Control and Prevention (CDC). Japanese encephalitis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity & Mortality Weekly Report. Recommendations & Reports 2010;59(RR-1):1-27.
• Halstead SB, Jacobson J, Dubischar-Kastner K. Japanese encephalitis vaccines. In: Plotkin S, Orenstein WA, Offit P, editors. Vaccines. 6th ed. China: Elsevier Saunders; 2013. p. 312-351.
• Valneva Austria GmbH. IXIARO ® Product Monograph. 2018.
• World Health Organization (WH). Japanese Encephalitis Vaccines: WHO position paper - February 2015. Weekly Epidemiological Record 2015;9(90):69-88.

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INTRODUCTION

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the most important cause of viral encephalitis in Asia based on its frequency and severity. Despite vaccination programs in many countries in Asia, JEV continues to cause substantial numbers of cases of childhood viral neurological infection and disability [ 1 ]. JEV is closely related to West Nile, St. Louis encephalitis, and Murray Valley encephalitis viruses [ 2 ].

About 68,000 cases of Japanese encephalitis (JE) are estimated to occur each year. JEV is endemic throughout most of Asia and parts of the western Pacific. For travelers to Asia, the risk of JE is very low but varies based on season, destination, duration, and activities [ 3 ]. The estimated incidence of JE among travelers to Asia from nonendemic countries is <1 case per 1 million travelers. Risk is likely to be higher for individuals with longer duration of travel or whose plans include extensive outdoor activities in rural areas [ 3 ]. Between 1973 and 2020, 88 cases of JE among individuals from nonendemic countries were reported [ 3 ]. Since a JE vaccine became available in the United States in 1993, only 15 cases of JE were reported among United States travelers through 2023 [ 4,5 ].

Most human JEV infections are asymptomatic or cause a nonspecific febrile illness. Fewer than 1 percent of JEV infections results in symptomatic neuroinvasive disease [ 6 ]. However, when neurologic disease does occur, it is usually very severe with a high case-fatality rate; among survivors, neurological sequelae are common. All travelers to JEV-endemic countries should be given advice on measures to prevent JE, and JE should be considered among the differential diagnoses for patients with suspected neurological infection who have returned from recent travel in a JEV-endemic country in Asia or the Western Pacific region.

EPIDEMIOLOGY

JE is endemic throughout most of Asia and parts of the Western Pacific region ( figure 1 ). The JEV transmission area has expanded with emergence of JE in new areas of Australia. During 2021 to 2022, an outbreak was reported that was focused in rural areas surrounding the Murray River in southeastern Australia, but cases were reported from widespread areas of the country [ 7 ].

Within the JE-endemic region, there are two typical patterns of transmission:

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Japanese encephalitis.

Leslie V. Simon ; Divyajot S. Sandhu ; Amandeep Goyal ; Brian Kruse .

Affiliations

Last Update: August 28, 2023 .

• Continuing Education Activity

Japanese encephalitis is the most common preventable cause of mosquito-borne encephalitis in Asia, Australia, and the western Pacific. The Culex species of mosquitoes transmit the virus with their bite. Transmission occurs most commonly in agricultural areas such as farms and rice paddies but may occur in urban areas under certain conditions. While the vast majority of infections are asymptomatic, those who do develop symptoms of encephalitis suffer significant morbidity and mortality. This activity describes the clinical evaluation of Japanese encephalitis and explains the role of the health professional team in coordinating the care of this condition.

• Review how Japanese encephalitis is acquired.
• Describe the history and physical exam of a patient with japanese encephalitis.
• Summarize the treatment of japanese encephalitis.
• Explain modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by Japanese encephalitis.
• Introduction

Japanese encephalitis is the most common preventable cause of mosquito-borne encephalitis in Asia, Australia, and the western Pacific.  The Culex species of mosquitoes transmit the virus with their bite. Transmission occurs most commonly in agricultural areas such as farms and rice paddies but may occur in urban areas under certain conditions. While the vast majority of infections are asymptomatic, those who do develop symptoms of encephalitis suffer significant morbidity and mortality. Symptomatic patients develop a high fever, headache, disorientation, coma, tremors and mental status changes due to cerebral inflammation. Movement disorders, neurologic deficits, and seizures are common, particularly in children. Approximately one in four symptomatic cases are fatal. Children are most commonly affected, and most people who reside in endemic areas will have immunity by adulthood. There is no specific therapy beyond supportive care, but there is an effective vaccine available to prevent infection. The vaccine is recommended for high-risk travelers to endemic areas. Many endemic areas have implemented childhood vaccination programs. The best protection is the prevention of mosquito bites. [1] [2] [3] [4]

Japanese encephalitis is a mosquito-borne illness caused by a single-stranded RNA virus, closely related to the West Nile flavivirus. Japanese encephalitis transmission is primarily due to the bite of Culex mosquito species, most commonly Culex tritaeniorhynchus. The virus is maintained and amplified in intermediate hosts, specifically pigs and wading birds. Humans are considered dead-end hosts in that they do not generally develop high enough levels of virus to transmit the infection to feeding mosquitoes. Because the amplifying hosts tend to be most abundant in agricultural areas such as farms and rice paddies where flooding irrigation attracts wading birds, most infections occur in rural areas. Recently, however, infections are being documented more commonly in suburban regions, particularly in South Korea, China, Singapore, and Taiwan. This suggests that the vaccine recommendations for travelers should be expanded to include some suburban regions. While mosquitoes transmit the vast majority of infections, there is some concern that exposure to infected pigs, which are amplifying hosts, may result in virus transmission from close contact without vector involvement. [5] [6]

• Epidemiology

There are between 30,000 and 50,000 global cases of Japanese encephalitis each year. Severe disease is estimated to occur in about one in 250 infections. Transmission is seasonal in temperate climates and peaks between May and October, but the risk persists year-round in more tropical climates. The time of greatest risk for infection is during the rainy season and the pre-harvest period in rice cultivating areas due to increased mosquito vector populations. Most mosquito bites occur between dawn and dusk. Twenty-four countries in South-East Asia and the Western Pacific have endemic Japanese encephalitis virus transmission placing more than three billion people at risk for infection. Major outbreaks occur every 2 to 15 years. Between 1965 and 1975 more than one million cases were reported in China alone. The introduction of routine childhood vaccination programs in Japan, Korea, and Taiwan has nearly eliminated the risk in vaccinated patients despite ongoing infection in endemic animals and birds. Most cases in these areas are now reported in unvaccinated visitors.

• Pathophysiology

The Japanese encephalitis virus attaches to host cell membranes, initially propagating at the site of the bite and nearby lymph nodes. Subsequent viremia develops but most cases are cleared before the virus enters the central nervous system, resulting in subclinical disease. If the virus is transmitted to the brain hematogenously with the invasion of the blood-brain barrier, neuroinvasive disease develops. Japanese encephalitis virus has both direct neurotoxic effects and the capacity to alter neuro stem cell development.

• History and Physical

Most infected individuals will provide a history of mosquito exposure in an endemic area. The incubation period averages 6 to 8 days but ranges from 4 to 15 days. There is often a prodromal period of nonspecific symptoms of fever, headache, nausea, vomiting, diarrhea, and myalgias which may last for several days. Symptoms then progress to encephalitis, which is the most common neurologic manifestation.  Symptoms may include altered mental status, agitation, confusion, and psychosis. A headache and meningismus are frequently reported in adults while children often develop seizures. More unusual presentations include mutism and flaccid paralysis. As the disease progresses, patients may develop dystonia, choreoathetoid movements that mimic extrapyramidal symptoms of Parkinson disease.

Patients with symptoms consistent with encephalitis are initially evaluated with neuroimaging and lumbar puncture. MRI or CT may show bilateral thalamic edema, lesions, or hemorrhage. A lumbar puncture may be significant for elevated opening pressure, elevated protein, and normal glucose. Blood work may reveal leukocytosis or hyponatremia. These findings are common in many forms of encephalitis or viral meningitis. If clinically suspected based on travel history, Japanese encephalitis virus immunoglobulin M (IgM) may be detected using an enzyme-linked immunoassay (ELISA) on serum or cerebrospinal fluid. Humans are dead-end hosts with low, transient viral loads making virus isolation difficult. [7] [8]

• Treatment / Management

There is no effective antiviral therapy for Japanese encephalitis. Management is limited to supportive care with intravenous (IV) fluids and antipyretics. Anticonvulsants may be required for seizure control. Survivors often have poor neurologic outcomes requiring long-term care due to neurologic devastation and ongoing psychiatric symptoms. Up to 30% will suffer permanent intellectual, behavioral or neurologic issues ranging from paralysis, recurrent seizures or inability to speak or perform independent activities of daily living. [9] [10]

Since there is no effective treatment prevention is critical. This is best accomplished by avoiding mosquito bites entirely. Even very short periods of outdoor exposure can result in bites, so proper protective clothing that includes long sleeves, long pants, socks, and closed-toe shoes should be worn.  Pant legs can be tucked into socks to prevent bites to exposed ankles. Transmission is common during the warmer months and mosquitoes may bite through very thin clothing so treating clothing with repellents containing permethrin, DEET or other EPA-registered insect repellants will reduce this risk. Transmission is most frequent when mosquitoes feed, between dawn and dusk, so outdoor activities during this period should be avoided. Travelers should sleep in air-conditioned spaces or use mosquito nets or screens to prevent bites during sleep.

A safe, effective vaccine exists and may be administered in a short-course regimen. The vaccine is quite underutilized. The current Center for Disease Control and Prevention (CDC) recommendations for the use of the Japanese encephalitis vaccine are as follows:

• The vaccine is recommended for travelers who plan to spend one month or more in endemic areas during the transmission season. This includes travelers who will be based primarily in urban areas.
• The vaccine should be considered for short-term travelers (less than one month) who are planning to spend substantial amounts of time outdoors in rural or agricultural areas, those who plan to participate in outdoor activities and those staying in areas without air conditioning, screens or bed nets. It should also be considered in travelers to an area with a known outbreak and those with uncertain destinations, activities, and duration of travel.
• The vaccine is not currently recommended for travelers with short-term travel plans to urban areas only.
• Differential Diagnosis

There are many differential diagnoses of Japanese encephalitis; therefore, a careful travel history important. It includes:

• Murray Valley encephalitis
• West Nile virus encephalitis
• St. Louis encephalitis
• Herpes simplex encephalitis
• Western and Eastern equine encephalitis
• Venezuelan Equine encephalitis
• Ehrlichiosis
• Enterovirus meningitis
• Mycoplasma meningitis
• Cytomegalovirus infection in the immunocompromised host
• Typhoid fever
• Dengue fever
• Brain abscess
• Tuberculous meningitis
• Nipah virus infection
• Rocky Mountain spotted fever
• Fungal meningitis
• Leptospirosis
• Neurocysticercosis
• Amebic meningoencephalitis
• Lupus with central nervous system involvement
• Central nervous system (CNS) tumor
• Cerebrovascular accident

Only 1% of patients infected with the virus will progress to encephalitis. Unfortunately, mortality for patients who do develop encephalitis is 20% to 30%. While most cases will improve in 6 to 12 months, many patients who survive will have significant neurologic and psychiatric sequelae (30% to 50% of cases).

• Pearls and Other Issues

Japanese encephalitis is a potentially devastating but preventable disease. Travelers to endemic areas should review the CDC vaccination guidelines regarding immunization available at www.cdc.gov.

• Enhancing Healthcare Team Outcomes

The management of Japanese encephalitis is interprofessional. The infection has no cure and patients need support from a variety of specialists. The key role of the primary caregiver and nurse practitioner is patient education. Since there is no effective treatment prevention is critical. This is best accomplished by avoiding mosquito bites entirely. Even very short periods of outdoor exposure can result in bites, so proper protective clothing that includes long sleeves, long pants, socks, and closed-toe shoes should be worn.  Pant legs can be tucked into socks to prevent bites to the exposed ankles. Transmission is common during the warmer months and mosquitoes may bite through very thin clothing so treating clothing with repellents containing permethrin, DEET or other EPA-registered insect repellants will reduce this risk. Transmission is most frequent when mosquitoes feed, between dawn and dusk, so outdoor activities during this period should be avoided. Travelers should sleep in air-conditioned spaces or use mosquito nets or screens to prevent bites during sleep.

A safe, effective vaccine exists and may be administered in a short-course regimen. The vaccine is quite underutilized. 

The outcomes for patients with Japanese encephalitis are guarded. Recovery does occur but is often marked by residual neuropsychiatric deficits which may persist for months or even years. [11]

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Disclosure: Leslie Simon declares no relevant financial relationships with ineligible companies.

Disclosure: Divyajot Sandhu declares no relevant financial relationships with ineligible companies.

Disclosure: Amandeep Goyal declares no relevant financial relationships with ineligible companies.

Disclosure: Brian Kruse declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Simon LV, Sandhu DS, Goyal A, et al. Japanese Encephalitis. [Updated 2023 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Japanese Encephalitis VIS

Current Edition Date: 8/15/2019

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• More information about japanese encephalitis vaccination

Japanese Encephalitis Vaccine: What You Need to Know

Japanese encephalitis (JE) vaccine can prevent Japanese encephalitis .

• Japanese encephalitis occurs mainly in many parts of Asia and the Western Pacific, particularly in rural areas.
• It is spread through the bite of an infected mosquito. It does not spread from person to person.
• Risk is very low for most travelers. It is higher for people living in areas where the disease is common, or for people traveling there for long periods of time.
• Most people infected with JE virus don’t have any symptoms. Others might have symptoms as mild as a fever and headache, or as serious as encephalitis (swelling of the brain).
• A person with encephalitis can experience fever, neck stiffness, seizures, and coma. About 1 person in 4 with encephalitis dies. Up to half of those who don’t die have permanent disability (for example, brain damage).
• It is believed that infection in a pregnant woman could harm her unborn baby.
• Why get vaccinated?
• Talk with your health care provider
• Risks of a vaccine reaction
• What if there is a serious problem?
• How can I learn more?

Japanese encephalitis vaccine is approved for people 2 months of age and older.

It is recommended for people who:

• Plan to live in a country where JE occurs,
• Plan to visit a country where JE occurs for long periods (e.g., one month or more), or
• Frequently travel to countries where JE occurs.

It should also be considered for travelers spending less than one month in a country where JE occurs, if they:

• Will visit rural areas and have an increased risk for mosquito bites,
• Are not sure of their travel plans.

Many laboratory workers at risk for exposure to JE virus will also require vaccination.

The vaccine is given as a 2-dose series. A booster dose is recommended after a year for people who remain at risk.

NOTE:  The best way to prevent JE is to avoid mosquito bites. Your health care provider can advise you.

Tell your vaccine provider if the person getting the vaccine:

• Has had an allergic reaction after a previous dose of JE vaccine , or has any severe, life-threatening allergies.
• Is pregnant . Pregnant women should usually not get JE vaccine.
• Will be traveling for fewer than 30 days and only traveling to urban areas. You might not need the vaccine.

In some cases, your health care provider may decide to postpone JE vaccination to a future visit.

  People with minor illnesses, such as a cold, may be vaccinated. People who are moderately or severely ill should usually wait until they recover before getting JE vaccine.

Your health care provider can give you more information.

• Pain, tenderness, redness, or swelling where the shot was given are common after JE vaccine.
• Fever sometimes happens (more often in children).
• Headache or muscle aches can occur (mainly in adults).

Studies have shown that severe reactions to JE vaccine are very rare.

People sometimes faint after medical procedures, including vaccination. Tell your provider if you feel dizzy or have vision changes or ringing in the ears.

As with any medicine, there is a very remote chance of a vaccine causing a severe allergic reaction, other serious injury, or death.

An allergic reaction could occur after the vaccinated person leaves the clinic. If you see signs of a severe allergic reaction (hives, swelling of the face and throat, difficulty breathing, a fast heartbeat, dizziness, or weakness), call 9-1-1 and get the person to the nearest hospital.

For other signs that concern you, call your health care provider.

Adverse reactions should be reported to the Vaccine Adverse Event Reporting System (VAERS). Your health care provider will usually file this report, or you can do it yourself. Visit the VAERS website or call 1-800-822-7967 .  VAERS is only for reporting reactions, and VAERS staff do not give medical advice.

• Ask your health care provider.
• Call your local or state health department .
• Call 1-800-232-4636 ( 1-800-CDC-INFO ) or
• Visit CDC’s JE website

Many vaccine information statements are available in Spanish and other languages. See www.immunize.org/vis

Hojas de información sobre vacunas están disponibles en español y en muchos otros idiomas. Visite www.immunize.org/vis

Vaccine Information Statement Japanese Encephalitis Vaccine (8/15/19)

Department of Health and Human Services Centers for Disease Control and Prevention

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