01 Dec 2013

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 infection of the brain 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 when outbreaks are occurring. Those staying near to rice fields or pig farms for one month or longer are at greater 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 those travellers whose activities put them 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, Japanese Encephalitis Fact Sheet 386, March 2014 [1]
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 [2]. 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, recent estimates are that 67,900 cases occur annually in 24 JE endemic countries (annual incidence 1.8 per 100,000 population). 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 and there is widespread under reporting [4,5].

Factors favouring disease in these areas include: 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, usually coinciding with the rainy season. However seasonal patterns can vary within individual countries and from year to year [6]. May to September is the peak transmission season for the temperate regions of Asia such as Korea and Japan, and March to October for the more tropical countries of South East Asia such as Thailand, Cambodia, and Viet Nam [3, 6]. For Nepal and Northern India, the season is between September and December [3]. The transmission season tends to be year round in Malaysia, Indonesia, and the Philippines, where rain may fall throughout the year. Seasonal variations may be due to differing irrigation practices and migratory patterns of the susceptible bird hosts in endemic countries.

The Torres Strait Islands of Australia reported its first cases of JE in 1995 [7]. 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.

Risk for travellers

From 1973 to 2008, 55 cases of JE were reported in travellers from non-endemic countries [8]. 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. 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 [10, 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.

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 as a result of cardiac and respiratory complications [12]. The second was a woman who had been to Thailand in 1994; she recovered fully after four months [13].

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.

Signs and symptoms

The majority of cases of JE are asymptomatic (without symptoms) or present with non-specific flu-like symptoms. Children and the elderly most commonly suffer a clinical illness, which can be severe. Approximately 1 in 250 infections is estimated to become clinically apparent and encephalitis is estimated to occur in 1 in 300 patients [6, 9]. The incubation period is 5-15 days, and presenting symptoms include fever, headache, altered mental state, and convulsions. Approximately 20-30 percent of severe cases are fatal and 30-50 percent of survivors have significant neurological problems following infection [4, 5, 10].

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 [14].

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 which 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 [6]:

  • 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 who have potential exposure to the virus.

Availability

There is currently one licensed vaccine recommended for use in the UK, IXIARO® [15]. 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 [15]. 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 [6].

IXIARO® vaccine schedule

Age Range

Dose

Schedule

Reinforcing immunisation

Under 2 months of age

Not usually recommended

(no safety or efficacy data)

Children aged 2 months to under 3 years

0.25ml

(discard half of the vaccine)*

2 doses:

Day 0 and 28

No data**

Children aged 3 to 11 years

0.5ml

2 doses:

Day 0 and 28

No data**

Children aged 12 to 17 years

0.5ml

2 doses:

Day 0 and 28

See also accelerated schedule***

No data**

Adults aged 18 to 65 years

0.5ml

2 doses:

Day 0 and 28

See also accelerated schedule***

Single dose of IXIARO® at 12-24 months following primary course. For those at continuous risk a booster at 12 months is recommended.

Manufacturer recommends a second booster 10 years after the first booster dose, prior to potential exposure to JEV.

Adults aged 65 years and older

0.5ml

2 doses:

Day 0 and 28

See also accelerated schedule***

Duration of protection is uncertain, therefore a booster dose (third dose) should be considered before any further exposure to JE virus. Long-term seroprotection following a booster-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. 
**There are no data to permit recommendations for boosting in infants and children below 18 years of age. However, if sustained protection is required, a booster dose may need to be considered.
***See also accelerated schedule below.

Accelerated schedule

Adults aged 18-65 years can be vaccinated in an accelerated schedule according to the IXIARO marketing authority 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 [6, 15]. Use of this accelerated schedule can also be considered off license for travellers 12-18 years of age and those over 65 years of age when time is genuinely short [6].

Following a single dose of IXIARO®, 54 percent of adults had developed antibodies by day 28 in a clinical study [14]. 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® [15].

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 subjects experienced systemic adverse reactions and approximately 54 percent experienced injection site reactions. These reactions usually occur within the first three days after vaccination, are usually mild and resolve within a few days [15].

Pregnancy and breastfeeding

As a precautionary measure, the use of IXIARO in pregnant and breastfeeding women should be avoided [13,14]. 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 (6).

First Published :   01 Dec 2013
Last Updated :   23 Nov 2016

  1. World Health Organization Japanese encephalitis fact sheet 386. March 2014. [Accessed April 2015]
  2. Halstead SB, Jacobson J. Japanese encephalitis vaccines. 2008 In Plotkin S, Orenstein W, Offit P: Vaccines 5th edition p312- 352. Saunders Elsevier.
  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 April 2015]
  4. World Health Organization. Position paper on Japanese Encephalitis. Wkly Epidemiol Rec. 2015; 81:325-340. [Accessed April 2015]
  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 April 2015]
  6. Public Health England Immunisation against infectious disease. Chapter 20 Japanese encephalitis Updated 23 November 2016 [Accessed 23 November 2016]
  7. 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.
  8. Hills SL, Griggs AC, Fischer M. Japanese encephalitis in travelers from non-endemic countries, 1973–2008. Am J Trop Med Hyg. 2010 May; 82(5):930–6.
  9. Centers for Disease Control and Prevention. Japanese Encephalitis Vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report 2010; 59(No. RR-01):1-27. [Accessed April 2015]
  10. Shlim D, Solomon T. Japanese encephalitis vaccine for travellers: Exploring the limits of risk. Clin Infect Dis 2002; 35:183-8.
  11. Hatz C, Werlein J, Mutsch M et al. Japanese encephalitis: defining risk incidence for travelers to endemic countries and vaccine prescribing from the UK and Switzerland. J Trav Med 2009;16: 200–203.
  12. Rose MR, Hughes SM, Gatus BJ. A case of Japanese B encephalitis imported into the United Kingdom. J Infect. 1983; 6:261-5.
  13. Burdon JT, Stanley PJ, Lloyd G et al. A case of Japanese encephalitis. J Infect 1994; 28:175-9.
  14. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2014. New York: Oxford University Press; 2014. Chapter 3 Infectious diseases. [Accessed April 2015]
  15. Valneva Summary of Product Characteristics. IXIARO®. Last updated 20 July 2016. [Accessed 23 November 2016]

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