Japanese Encephalitis

Description

Japanese encephalitis (JE), a mosquito-borne flaviviral infection, is the leading cause of childhood encephalitis in Asia, where up to 50,000 cases may be reported annually. Most infections are asymptomatic, but when encephalitis develops, the case-fatality rate can be as high as 30%. Neuropsychiatric sequelae are reported in 50% of survivors. Although children are at greatest risk of infection in endemic areas, outdoor occupation, recreational exposure, and male gender are also risk factors for infection. Immunity to JE virus from previous vaccination or naturally acquired immunity reduces the risk of illness. Although most adults living in endemic areas have acquired natural immunity and older persons rarely develop illness, a high case-fatality rate has also been reported in the elderly.

JE virus is transmitted chiefly by mosquitoes in the Culex vishnui complex; the specific species depends on the geographic area. In China and other endemic areas in Asia, C. tritaeniorhyncus is the principal vector. This species feeds outdoors beginning at dusk and during evening hours until dawn. Larvae are found in flooded rice fields, marshes, and other small stable collections of water found around cultivated fields. In temperate zones, this vector is present in greatest density from June through September; it is inactive during winter months. It has a wide host range that includes domestic mammals, birds, and humans. Swine and certain species of wading birds are the amplifying hosts in an enzootic transmission cycle. Because JE virus primarily cycles among animals and mosquitoes and because national JE vaccination programs are present in many affected countries (e.g., Thailand, Taiwan, Japan, Korea), the absence of human infections alone should not be used to gauge a traveller's risk for infection.

Occurrence

JE transmission principally occurs in rural agricultural locations where flooding irrigation is practiced. In many areas of Asia, these ecologic conditions may occur near or occasionally within urban centers. Transmission is seasonal and occurs in the summer and autumn in the temperate regions of China, Japan, Korea, and eastern Russia. Elsewhere, seasonal patterns of disease may be extended or vary with the rainy season and irrigation practices. Risk of JE varies by season and geographic area (Table 4-1 and Map 4-3).

Risk for Travellers

The risk to short-term travellers and those who confine their travel to urban centers is very low. Expatriates and travellers living for prolonged periods in rural areas where JE is endemic or epidemic are at greater risk. Travellers with extensive unprotected outdoor, evening, and nighttime exposure in rural areas, such as might be experienced while bicycling, camping, or engaging in certain occupational activities, may be at high risk even if their trip is brief.

Table 4-1. Risk of Japanese encephalitis, by country, region, and season

Country	Affected Areas	Transmission Season	Comments
Australia	Islands of Torres Strait	Probably year-round transmission risk	Localized outbreak in Torres Strait in 1995 and sporadic cases in 1998 in Torres Strait and one case on mainland Australia at Cape York Peninsula
Bangladesh	Little data, but probably widespread	Possibly July to December, as in northern India	Outbreak reported from Tangail District, Dhaka Division in 1977; more recently, sporadic cases in Rajshahi Division
Bhutan	No data	No data	No comments
Brunei	Presumed to be sporadic-endemic, as in Malaysia	Presumed year-round transmission	No comments
Burma ( Myanmar )	Presumed to be endemic-hyperendemic countrywide	Presumed to be May to October	Repeated outbreaks in Shan State
Cambodia	Presumed to be endemic-hyperendemic countrywide	Presumed to be May to October	Cases reported from refugee camps on Thai border
China	Cases in all provinces except Xizang ( Tibet ), Xinjiang, Qinghai. Hyperendemic in southern China. Endemic-periodically epidemic in temperate areas. Hong Kong: Rare cases in new territories Taiwan: Endemic, sporadic cases islandwide1	Northern China: May to September Southern China: April to October (Guangxi, Yunnan, Guangdong, and Southern Fujian, Sichuan, Guizhou, Hunan, and Jiangxi provinces) Hong Kong: April to October Taiwan: April to October, with a June peak1	Vaccine not routinely recommended for travellers to urban areas only Taiwan: Cases reported in and around Taipei and the Kao-hsiung-Pingtung river basins
India	Reported cases from all states except Arunachal, Dadra, Daman, Diu, Gujarat, Himachal, Jammu, Kashmir, Lakshadweep, Meghalaya, Nagar Haveli, Orissa, Punjab, Rajasthan, and Sikkim	South India: May to October in Goa; October to January in Tamil Nadu; and August to December in Karnataka. Second peak, April to June in Mandya District Andrha Pradesh: September to December North India: July to December	Outbreaks in West Bengal, Bihar, Karnataka, Tamil Nadu, Andrha Pradesh, Assam, Uttar Pradesh, Manipur, and Goa. Urban cases reported (e.g., in Lucknow)
Indonesia	Kalimantan, Bali, Nusa, Tenggara, Sulawesi, Mollucas, Irian Jaya (Papua), and Lombok	Probably year-round risk; varies by island; peak risks associated with rainfall, rice cultivation, and presence of pigs Peak periods of risk: November to March; June and July in some years	Human cases recognised on Bali and Java, and possibly in Lombok
Japan1	Rare-sporadic cases on all islands except Hokkaido	June to September, except April to December on Ryuku Islands (Okinawa )	Vaccine not routinely recommended for travel to Tokyo and other major cities. Enzootic transmission without human cases observed on Hokkaido
Korea	North Korea: No data. South Korea: Sporadic-endemic with occasional outbreaks	July to October	Last major outbreaks in 1982 and 1983. Sporadic cases reported in 1994 and 1998.
Laos	Presumed to be endemic-hyperendemic countrywide	Presumed to be May to October	No comments
Malaysia	Sporadic-endemic in all states of Peninsula, Sarawak, and probably Sabah	Year-round transmission	Most cases from Penang, Perak, Salangor, Johore, and Sarawak
Nepal	Hyperendemic in southern lowlands (Terai)	July to December	Vaccine not recommended for travellers visiting only high-altitude areas
Pakistan	May be transmitted in central deltas	Presumed to be June to January	Cases reported near Karachi; endemic areas overlap those for West Nile virus. Lower Indus Valley might be an endemic area.
Papua New Guinea	Normanby Islands and Western Province	Probably year-round risk	Localized sporadic cases
Philippines	Presumed to be endemic on all islands	Uncertain; speculations based on locations and agroecosystems. West Luzon, Mindoro, Negros, Palawan: April to November Elsewhere: year-round, with greatest risk April to January	Outbreaks described in Nueva Ecija, Luzon, and Manila
Russia	Far Eastern maritime areas south of Khabarousk	Peak period July to September	First human cases in 30 years recently reported
Singapore	Rare cases	Year-round transmission, with April peak	Vaccine not routinely recommended
Sri Lanka	Endemic in all but mountainous areas Periodically epidemic in northern and central provinces	October to January; secondary peak of enzootic transmission May to June	Recent outbreaks in central (Anuradhapura) and northwestern provinces
Thailand	Hyperendemic in north; sporadic-endemic in south	May to October	Annual outbreaks in Chiang Mai Valley; sporadic cases in Bangkok suburbs
Vietnam	Endemic-hyperendemic in all provinces	May to October	Highest rates in and near Hanoi
Pacific Islands	Two epidemics reported in Guam & Saipan since 1947	Uncertain; possibly September to January	Enzootic cycle might not be sustainable; epidemics might follow introductions of virus.

1Local JE incidence rates may not accurately reflect risks to nonimmune visitors because of high vaccination rates in local populations. Humans are incidental to the transmission cycle. High levels of viral transmission can occur in the absence of human disease.

NOTE: Assessments are based on publications, surveillance reports, and personal correspondence. Extrapolations have been made from available data. Transmission patterns can change.

Map 4-3. Geographic distribution of Japanese encephalitis

Map 4-3. Geographic distribution of Japanese encephalitis

Prevention

Vaccine

An inactivated JE vaccine produced from infected mouse brains has been licensed for use in the U.S. civilian population since 1992. This vaccine is manufactured by Biken (Osaka, Japan) and distributed in the United States by Aventis Pasteur. Other JE vaccines are made by other Asian companies but not licensed for use in the United States.

Vaccination should be considered by persons who plan to live in areas where JE is endemic or epidemic and by travellers whose activities include trips into rural farming areas. Short-term travellers, especially those whose visits are restricted to major urban areas, are at lower risk for infection and generally should not be advised to receive the vaccine. Evaluation of an individual traveller's risk should take into account itinerary and activities and the current level of JE activity in the travel area (see Table 4-1).

The recommended primary immunisation series is three doses of 1.0 mL each, administered subcutaneously on days 0, 7, and 30. An abbreviated schedule of days 0, 7, and 14 can be used when the longer schedule is impractical. Both regimens produce similar immunity among recipients. Two doses given a week apart may be used in unusual circumstances and will confer short-term immunity in 80% of vaccinees. The last dose should be administered at least 10 days before beginning travel to ensure an adequate immune response and access to medical care in the event of any delayed adverse reactions (Table 4-2). Many Asian countries have adopted a schedule of two primary doses approximately 4 weeks apart, followed by a booster after 1 year, with subsequent boosters at 3-year intervals. The duration of immunity after serial booster doses has not been well established.

Immunisation routes and schedules for infants and children 1-3 years of age are identical except that 0.5 mL doses should be administered. No data are available on vaccine efficacy and safety in infants <1 year of age. The full duration of protection is unknown; however, preliminary data indicate that neutralizing antibodies persist for at least 2 years after primary immunisation. In infants and children whose primary immunisation series included 0.5 mL doses, a 1.0 mL booster dose (0.5 mL for children <3 years of age) may be administered 2 years after the primary series.

Table 4-2. Japanese encephalitis vaccine

Doses1	1-2 years of age	3 years of age	Comments
Primary series 1, 2, and 3	0.5 mL	1.0 mL	Days 0, 7, and 30
Booster	0.5 mL	1.0 mL	1 dose at 24 months or later2

1Administered by the subcutaneous route
2For vaccinees who have completed a three-dose primary series, the full duration of protection is unknown; therefore, definitive recommendations cannot be given.

Adverse Reactions

JE vaccine is associated with local reactions and mild systemic side effects (fever, headache, myalgias, and malaise) in approximately 20% of vaccinees. More serious hypersensitivity reactions, including generalised urticaria, angioedema, respiratory distress, and anaphylaxis have occurred within minutes to as long as 1 week after immunisation. Such hypersensitivity reactions have occurred in up to 0.6% of vaccinees. Reactions have been responsive to therapy with epinephrine, antihistamines, or steroids, or a combination of these. Vaccine recipients should be observed for 30 minutes after immunisation and warned about the possibility of delayed allergic reactions. The full course of immunisation should be completed at least 10 days before departure, and vaccinees should be advised to remain in areas with access to medical care. Persons with a history of urticaria or angioedema appear to have a greater risk for developing more serious allergic reactions; this factor must be considered when weighing the risks and benefits of the vaccine. A history of allergy to JE or other mouse-derived vaccines is a contraindication to further immunisation.

Although the use of mouse brains as the substrate for virus growth has always elicited concern about post-vaccination neurologic side effects, the evidence of an association between JE vaccine and demyelinating neurologic events such as acute disseminated encephalomyelitis or polyneuritis remains circumstantial and primarily based on case reports

Precautions and Contraindications

Persons with known hypersensitivity to the vaccine should not be vaccinated. Persons with multiple allergies or with a history of urticaria or angioedema for any reason are at higher risk for allergic complications from the JE vaccine. Vaccination during pregnancy should be avoided unless the risk of acquiring JE outweighs the theoretical risk of vaccination.

Personal Protection Measures

Although JE vaccination is very effective against developing infection, travellers should still avoid mosquito bites to reduce the risk of other vector-borne infectious diseases. Travellers should be advised to stay in screened or air-conditioned rooms, to use bed nets when such quarters are unavailable, to use area aerosol insecticides and mosquito coils as necessary, and to use personal insect repellents containing DEET and protective clothing to avoid mosquito bites (see Chapter 2, Protection against Mosquitoes and Other Arthropods).

Bibliography

Burke DS, Leake CJ. Japanese encephalitis. In: Monath TP, editor. The arboviruses: epidemiology and ecology, Vol 3. Boca Raton, FL: CRC Press; 1998. p. 63-92.
CDC. General Recommendations on Immunisation Recommendations of the Advisory Committee on Immunisation Practices (ACIP). MMWR Recomm Rep. 1994; 43(RR-1):1-38.
Halstead SB, Jacobson J. Japanese encephalitis. Adv Virus Res. 2003;61:103-38
Konishi E, Shoda M, Kondo T. Prevalence of antibody to Japanese encephalitis virus nonstructural 1 protein among racehorses in Japan: indication of natural infection and need for continuous vaccination. Vaccine. 2004;22:1097-103.
Monath TP. Japanese encephalitis vaccines: current vaccines and future prospects. Curr Top Microbiol Immunol. 2002;267:105-38.
Plesner AM. Allergic reactions to Japanese encephalitis vaccine. Immunol Allergy Clin North Am. 2003;23:665-97.
Tsai TF. New Initiatives for the control of Japanese encephalitis by vaccination: minutes of a WHO/CVI meeting, Bangkok, Thailand, 13-15 October 1998. Vaccine. 2000;18 Suppl 2:1-25.
World Health Organization. Japanese Encephalitis vaccine [monograph on the Internet]. Geneva: WHO; 1998 [cited 2004 Nov 5]. Available from: http://childrensvaccine.org/files/JE_position_paper_WHO.pdf

- Michael Bunning and Anthony Marfin

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