Japanese encephalitis

JE is transmitted to humans in predominantly rural parts of Asia and the Pacific Rim where rice cultivation and pig farming are common Japanese encephalitis

 

Key Messages

Japanese encephalitis is a potentially severe viral brain infection usually transmitted through the bite of an infected Culex spp. mosquito.
The disease occurs in large parts of Asia and the Pacific Rim, usually in rural areas where rice cultivation and pig farming is common.
Japanese encephalitis virus is transmitted to humans from pigs and wading birds via the bite of an infected mosquito.
Most human infections with Japanese encephalitis virus do not result in symptoms. In symptomatic cases requiring hospitalisation, mortality rates are high and neurological complications are common.
The risk of contracting Japanese encephalitis for most travellers is very low, especially for short term travellers visiting urban areas. Individuals are at increased risk if they visit areas where Japanese encephalitis is known to occur, particularly during periods of increased transmission. Staying near rice fields or pig farms for one month or longer increases risk.
The risk of transmission can be reduced by insect bite avoidance measures, particularly between the hours of dusk and dawn when the mosquito vector is most active. An effective vaccination should be offered to travellers at increased risk.

Overview

Japanese encephalitis (JE) is a viral encephalitis caused by a flavivirus. Other examples of mosquito borne flaviviruses include dengue and yellow fever. The disease is transmitted to humans by Culex spp. mosquitoes in predominantly rural parts of Asia and the Pacific Rim where rice cultivation and pig farming are common.

Risk areas

Figure 1: Countries or areas at risk
JE riskSource: World Health Organization
Please check our Country Information pages for individual country vaccine recommendations.

Japanese encephalitis (JE) was first recognised in Japan in the late 1800s, but the first major epidemic (involving 6,000 cases) was described in 1924 [1]. Since then, JE has increasingly been recognised throughout most countries of East and South East Asia (see figure 1) where it is a leading cause of viral encephalitis. The global incidence of JE is unknown. However, it is estimated that 68,000 clinical cases occur every year in 24 JE endemic countries in the in the South-East Asia and Western Pacific regions [2]. China (excluding Taiwan) accounts for 50 percent of cases, and globally 75 percent of cases occur in children aged 0-14 years (annual incidence of 5.4 per 100,000 population) [3]. Most cases of JE are asymptomatic or mild and there seems to be considerable under reporting [4]. Of those who develop encephalitis, many die or are left with long term significant neurological problems [5].

The Torres Strait Islands of Australia reported its first cases of JE in 1995 [6]. The virus is found in pigs on the Islands of the Torres Strait, and the transmission season in this area is considered to be year round.

Factors favouring disease in these areas include: the presence of the vector (Culex spp. mosquitoes), environmental conditions necessary for the mosquito breeding cycle (rainfall, humidity, tropical temperatures), mosquito habitats (such as rice-growing fields, swamps, and marshes), and presence of the amplifying hosts (pigs and birds).

The incidence of JE in humans varies by country, higher incidence usually coinciding with the rainy season. However, seasonal patterns can vary within individual countries and from year to year [7]. Seasonal variations may be due to differing irrigation practices and migratory patterns of the susceptible bird hosts in endemic countries.

Risk for travellers

Cases of Japanese encephalitis have been reported in travellers [8 -10]. From 1973 to 2015, a total of 79 confirmed cases of JE were reported in travellers from non-endemic countries [10]. Thirty seven of these cases were reviewed and 24 (65 percent) had spent more than one month in JE endemic areas; most had factors that increased their risk of infection.

The risk to most travellers to Asia is very low, especially for short-term travellers visiting urban areas. The overall incidence of JE among persons from non-endemic countries travelling to Asia is estimated to be less than one case per one million travellers [9]. The risk varies on the basis of destination, duration, season, and activities. Typically the risk increases for persons who intend to live or travel in endemic or epidemic areas for long periods of time and have rural trips during transmission seasons [1, 11]. Certain activities, even during short trips where there is significant rural, outdoor or night time exposure e.g. fieldwork, camping, or cycling can increase the traveller’s risk [12]. However, it is not essential to have these risk factors, as JE has also been reported in two travellers with no apparent risk factors.

Japanese encephalitis in UK travellers

There have been two documented cases of JE in UK travellers. The first was a British woman who had been living and working in Hong Kong and was diagnosed with JE in 1982; she died because of cardiac and respiratory complications [13]. The second was a woman who had been to Thailand in 1994; she recovered fully after four months [14].

Transmission

JE virus is transmitted to humans from animals and birds via the bite of an infected Culex spp. mosquito. These mosquitoes feed predominantly during the night, from dusk to dawn; pigs and wading birds are the principle hosts. Culex spp. mosquitoes are prolific in rural areas where flooded rice fields and marshes provide breeding grounds; however, they have also been found in urban locations. In temperate regions of Asia, most cases occur in the warm season, when large epidemics can occur [2].

Cases of JE can also occur outside the normal high transmission season [8]. In the tropics and subtropics, JE can occur year-round but transmission often intensifies during the rainy season and pre-harvest period in rice-cultivating regions [2].

Signs and symptoms

Most cases of JE are asymptomatic (without symptoms) or present with non-specific flu-like symptoms. The incubation period is 5-15 days, and initial symptoms include fever, headache and nausea progressing to meningoencephalitis with convulsions and altered consciousness [5, 15]. Of those who develop encephalitis, approximately 30% die. In those who survive, it is estimated that 30-50% develop long term neurological or psychiatric problems [1].

Diagnosis and treatment

JE should be suspected in a patient who resides in or has visited an endemic or epidemic area who presents with typical symptoms of the disease (see above). Laboratory diagnosis of JE is made by detecting a rise in antibodies to JE in the blood or cerebrospinal fluid (CSF). These antibodies can be detected in the CSF of most patients by four days after onset of symptoms and in blood by seven days [12].

Treatment is supportive with severe cases requiring treatment in an intensive care facility. There is no specific anti-viral treatment. Long-term care for neurological complications may be needed.

Preventing Japanese encephalitis

The risk of acquiring JE can be reduced by insect bite avoidance methods, particularly between the hours of dusk and dawn, when the Culex spp. mosquito vector is most active.

A JE vaccine is available and is recommended for those intending to stay for long periods in rural endemic regions during the main transmission season, or whose planned activities will increase their risk (see vaccine recommendations below).

Vaccine information

All travellers should undergo a careful risk assessment which considers the itinerary, duration of stay, season of travel and planned activities. Country specific recommendations can be found in the Country Information pages.
 
Japanese encephalitis (JE) vaccine is recommended for [7]:
  • Travellers who are going to reside in an area where JE is endemic or epidemic.
  • Travellers staying a month or longer in the risk area during the transmission season, especially if travel will include rural areas.
  • Travellers with shorter itineraries if risk is considered sufficient. For example, those spending time in rice fields (where the mosquito vector breeds) or close to pig farms.
  • Laboratory staff with the potential to be exposed to JE.
     

Availability

There is currently one licensed vaccine recommended for use in the UK, IXIARO® [16]. The Green Cross (GC) vaccine and Biken vaccine (JE Vax) are no longer available in the UK.

IXIARO® is licensed for immunisation against JE in adults and children from two months of age [16]. This vaccine is distributed in the UK by Valneva. IXIARO® may be used as a booster for travellers who have received a course of GC or Biken vaccine previously [7].

 

IXIARO® vaccine schedule

Age range

Dose

Primary course

Reinforcing immunisation

Under 2 months of age

Not usually recommended

(no safety or efficacy data)

Children aged 2 months to under 36 months of age

0.25ml (discard half of the vaccine)*

2 doses: Day 0 and 28

See also accelerated schedule***

For those at ongoing risk** a single first booster dose of IXIARO® 12 months after primary immunisation is recommended.

Others should be offered a first booster dose at 12-24 months following the primary course, prior to re-exposure to JE virus.

Duration of protection, beyond two years after the first booster is uncertain.

Children aged 3 to 17 years

0.5ml

2 doses: Day 0 and 28

See also accelerated schedule***

Adults 18 to 64 years

0.5ml

2 doses: Day 0 and 28

See also accelerated schedule***

For those at ongoing risk** a single dose of IXIARO® booster 12 months after primary immunisation is recommended.

Others should be offered the first booster dose at 12-24 months following the primary course prior to re-exposure to JE virus.

A 2nd booster (4th dose) should be offered at 10 years for those who remain at risk.

Adults aged 65 years and older

0.5ml

2 doses: Day 0 and 28

See also accelerated schedule***

For those at continued/further risk a single dose of IXIARO® booster at 12 months should be considered.

The duration of protection is uncertain for the primary course.

The length of protection following a booster dose (3rd dose) is not known.

*See IXIARO® Summary of Product Characteristics for details on preparing the 0.25 ml dose for children aged 2 months to less than 3 years. 
** Long term travellers who expect to reside in endemic areas for appreciable periods of time
***See also accelerated schedule below.

In situations where the primary course (days 0 and 28 or days 0 and 7) plus the first booster has been interrupted, the schedule should be resumed, and not restarted.

Accelerated schedule

Adults aged 18-65 years can be vaccinated using a licensed accelerated schedule as follows: first dose at day 0, second dose: 7 days after first dose. With both schedules, the primary immunisation schedule (first and second dose) should be completed at least one week prior to potential exposure to JE [7, 16]. Use of this accelerated schedule can also be considered off license for travellers 2 months -17 years of age and those over 65 years of age when time is short [7].

IXIARO® is available in a small number of Asian countries currently. Therefore, travellers may not be able to complete their vaccination course overseas with this vaccine. It is recommended that vaccinees who received the first dose of IXIARO® complete the primary two-dose vaccination course with IXIARO®.

Contraindications for IXIARO® vaccine

  • Serious illness or acute febrile illness.
  • Hypersensitivity to any components of the vaccine.
  • Serious reaction to a previous dose of vaccine.

Post vaccination adverse reactions

In clinical studies, approximately 40 percent of vaccinated individuals experienced systemic adverse reactions, and approximately 54 percent experienced injection site reactions, such as pain, tenderness and muscle ache. These reactions usually occur within the first three days after vaccination, are usually mild and resolve within a few days [1].

Pregnancy and breastfeeding

As a precautionary measure, the use of IXIARO® in pregnant and breastfeeding women should be avoided [7, 16]. However, travellers and their medical advisers must make a risk assessment on the theoretical risks of JE vaccine in pregnancy against the potential risk of acquiring JE disease [7].

First Published :   06 Jul 2018
Last Updated :   06 Jul 2018

  1. Scott B, Halstead SB. Japanese encephalitis vaccines. 2018. In Plotkin S, Orenstein W, Offit P, Edwards KM: Vaccines 7th edition p511- 548. Elsevier.
  2. World Health Organization Japanese encephalitis fact sheet 386. December 2015 [Accessed 5 July 2018]
  3. Campbell GL, Hills SL, Fischer M et al. Estimated global incidence of Japanese encephalitis: a systematic review. Bulletin of the World Health Organization, 2011, 89:766-744E [Accessed 5 July 2018]
  4. World Health Organization. Japanese Encephalitis Vaccines: WHO position paper - February 2015. Wkly Epidemiol Rec. 2015; 81:325-340. [Accessed 5 July 2018]
  5. Solomon T, Dungc NM, Kneend R et al. Neurological Aspects of Tropical Disease Japanese encephalitis. J Neurol Neurosurg Psychiatry 2000; 68:405-415. [Accessed 5 July 2018]
  6. Hanna JN, Ritchie SA. Phillips DA et al. An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995. Med J Aust. 1996; 165:256-260.
  7. Public Health England Immunisation against infectious disease. Chapter 20 Japanese encephalitis Updated 11 June 2018 [Accessed 5 July 2018]
  8. Buhl MR, Lindquist L, Japanese encephalitis is travelers: review of cases and seasonal risk. J. Trav Med 2009. 16, 3: 217-219. [Accessed 5 July 2018]
  9. Erra EO, Kantele A. The Vero cell-derived, inactivated, SA14-14-2 strain-based vaccine (Ixiaro) for prevention of Japanese encephalitis. Expert Rev Vaccines 2015; 14:1167-79.
  10. Hills SL, Griggs AC, Fischer M. Japanese encephalitis in travellers from non-endemic countries, 1973-2008. Am J Trop Med Hyg 2010; 82:930-6. [Accessed 5 July 2018]
  11. Lindquist L. Recent and historical trends in the epidemiology of Japanese encephalitis and its implication for risk assessment in travellers. J Trav Med 2018, Vol 25, Suppl 1,S3-S9. [Accessed 5 July 2018]
  12. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2018 New York: Oxford University Press; 2017 Chapter 3 Infectious diseases. [Accessed 5 July 2018]
  13. Rose MR, Hughes SM, Gatus BJ. A case of Japanese B encephalitis imported into the United Kingdom. J Infect. 1983; 6:261-5. [Accessed 5 July 2018]
  14. Burdon JT, Stanley PJ, Lloyd G et al. A case of Japanese encephalitis. J Infect 1994; 28:175-9. [Accessed 5 July 2018]
  15. Ooi MH, Lewthwaite P, Lai BF et al. The epidemiology, clinical features and long-term prognosis of Japanese encephalitis in central Sarawak, Malaysia, 1997-2005. Clin Infect Dis 2008; 47:458-68. [Accessed 5 July 2018]
  16. Valneva Summary of Product Characteristics. IXIARO®. Last updated 20 July 2016. [Accessed 5 July 2018]

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