Diseases Info

Japanese Encephalitis

Description | Signs & Symptoms | Diagnosis | Transmission | Culex Mosquitoes | Prevention | Vaccine

Description

Japanese encephalitis (JE) is a common mosquito-borne viral encephalitis in Asia. Most infections are asymptomatic, but among patients who develop a clinical illness, the case-fatality rate may be as high as 30%. Neuropsychiatric sequelae are reported in 50% of survivors. In endemic areas, children are at greatest risk of infection; however, multiple factors such as occupation, recreational exposure, gender (possibly reflectingexposure), previous vaccination, and naturally acquired immunity, alter the potential for infection and illness. A higher case-fatality rate is reported in the elderly, but serious sequelae are more frequent in the very young, possibly because they are more likely to survive a severe infection.

JE virus is transmitted chiefly by the bites of mosquitoes in the Culex vishnui complex: the individual vector species in specific geographic areas differ. In China and many endemic areas in Asia, Culex tritaeniorhyncus is the principal vector. This species feeds outdoors beginning at dusk and during evening hours until dawn; it has a wide host range including domestic animals, birds, and humans. Larvae are found in flooded rice fields, marshes, and small stable collections of water around cultivated fields. In temperate zones, the vectors are present in greatest numbers from June through September and are inactive during winter months. Swine and certain species of wild birds function as viremic amplifying hosts in the transmission cycle. Habitats supporting the transmission cycle of JE virus are principally in rural, agricultural locations. In many areas of Asia, however, the appropriate ecologic conditions for virus transmission occur near or occasionally within urban centers.

Signs & Symptoms

• Fever
• Drowsiness
• Headache
• Confusion/fits
• Malaise
• Paralysis
• Confusion
• Coma

Diagnosis

Based on the typical illness and confirmed by special blood tests or post-mortem tests in fatal cases.

Transmission

• Japanese encephalitis cannot be spread from human to human.
• Eating pork cannot transmit the disease.
• The Japanese encephalitis virus multiplies in the pig’s body. When the female Culex mosquito sucks the blood of pig, she picks up the Japanese encephalitis virus.
• After an incubation period of 14 days, the Culex mosquito is able to transmit the Japanese encephalitis virus to a new host usually the pig.
• The Japanese encephalitis virus can infect human and horses if the infectious Culex mosquitoes bit them. Human and horses are the dead end hosts since there are no transmission from man to man or from horse to horse.

Culex Mosquitoes

Habits of mosquitoes which carry Japanese encephalitis

• Only the Culex mosquitoes can transmit the Japanese encephalitis virus.
• The Culex mosquitoes breed in dirty polluted water such ponds, pools, ditches, puddles, drains and rice fields.
• Culex mosquitoes bite between dawn and dusk (6.30pm – 6.30am).
• Culex mosquitoes prefer pig rather than human blood.

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Prevention

• Avoid being bitten by mosquito
• Sleep in mosquito net.
• Using insecticides to prevent insect bites (e.g. mosquito coil, repellent, aerosol spray and cream)
• Fixing wire netting at all windows
• Wear long sleeved clothes / trousers
• Eliminating all Culex breeding places
  • Providing good and proper drainage system
  • Drain or fill up all pools and puddles with sand
  • Maintain cleanliness in the piggeries
  • Conduct regular fogging exercise in and around the pig farms

• Who require the vaccination against Japanese encephalitis
  • Workers in the pig farms
  • People staying in or near the pig farms up to a radius of 2 km, especially children

Vaccine

JE vaccine licensed in the United States is manufactured by Biken, Osaka, Japan, and distributed by Connaught Laboratories, Inc. Other JE vaccines are made by several companies in Asia, but are not licensed in the United States. Vaccination should only be considered for persons who plan to live in areas where JE is endemic or epidemic and for travelers whose activities include trips into rural, farming areas. Short-term travelers (< 30 days), especially those whose visits are restricted to major urban areas, are at a lower risk for acquiring JE and generally should not receive the vaccine. Evaluation of an individual traveler’s risk should take into account their itinerary and activities and the current level of JE activity in the country.

Types of Vaccines

Three types of JE vaccine are currently in large – scale production and use, namely:

1. mouse brain – derived inactivated vaccine;
2. cell culture – derived inactivated vaccine; and
3. cell culture - derived live attenuated vaccine

The mouse brain – derived and inactivated vaccine based on the Nagayama strain (or Beijing – 1 strain) is currently the only vaccine available on the international market. China produces two JE vaccines for domestic use, an inactivated JE as well as a live attenuated vaccine, both grown in primary hamster kidney cells. Controlled studies have shown that the commercially available mouse brain-derived vaccine is efficacious and without serious side effects for childhood vaccination. Local reactions such as tenderness, redness and swelling occur in 20% of vaccines. A similar percentage may experience mild systemic symptoms, including headache, myalgia, gastro-intestinal symptoms and fever.

The mouse brain – derived vaccine is given subcutaneously in doses of 0.5ml or 1ml, the lower dose being for children aged 1-3. The manufactures recommended that 2 injections be given at an interval of 1-2 weeks in primary immunization followed by a booster after 1 year, with subsequent boosters every 3-4 years to maintain immunity. In several Asian trials, primary immunization has been a disease-preventing efficacy of > 95%; 91% efficacy was achieved in a placebo – controlled trial.

Population at risk and dosage for vaccination

1. Very high risk population
   Pig farmers and their families staying on the farm.
   Dose: Day 0, Day 7, Day 30, 1Year
   Booster: after every 3 years
2. High risk group
   All those staying within 2 km from the pig farms and below 15 years of age.
   Dose: Day 0, Day 7, 1 Year
   Booster: after every 3 years

Payment for vaccination

The Ministry of Health will bear the cost incurred to vaccinate this high-risk group.

Schedule

The recommended primary immunization 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 because of time constraints. Two doses given a week apart may be used in unusual circumstances but will confer short-term immunity in only 80% of vaccinees. The last dose should be administered at least 10 days before the commencement of travel to ensure an adequate immune response and access to medical care in the event of delayed adverse reactions.

Use in Children

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

Adverse Reactions

JE vaccine is associated with local reactions and mild systemic side effects (fever, headache, myalgias, malaise) in about 20% of vaccinees. More serious allergic reactions including generalized urticaria, angioedema, respiratory distress, and anaphylaxis have occurred within minutes to as long as one week after immunization. Such hypersensitivity reactions occur in approximately 0.6% of vaccinees. Reactions have been responsive to therapy with epinephrine, antihistamines and/or steroids. Vaccinees should be observed for 30 minutes after immunization and warned about the possibility of delayed allergic reactions. The full course of immunization should be completed > 10 days before departure, and vaccinees should be advised to remain in areas with access to medical care. Persons with a past history of urticaria appear to have a greater risk for developing more serious allergic reactions, and this 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 immunization.

Contraindications

Persons with known hypersensitivity to the vaccine should not be vaccinated. Persons with multiple allergies, especially a history of allergic urticaria or angioedema, are at higher risk for allergic complications from JE vaccine.

Pregnancy

Vaccination during pregnancy should be avoided unless the risk of acquiring Japanese encephalitis outweighs the theoretical risk of vaccination.

Preventive Measures

Travelers are advised to stay in screened or air-conditioned rooms, to use bed nets when such quarters are unavailable, to use insecticidal space sprays as necessary, and to use insect repellents and protective clothing to avoid mosquito bites

Table 1>Risk of Japanese encephalitis

Country	Affected areas / jurisdictions	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 on mainland Australia at Cape York Peninsula
Bangladesh	Few data, but probably widespread	Possibly July–December, as in northern India	Outbreak reported from Tangail district, Dacca division; sporadic cases in Rajshahi division.
Bhutan	No data	No data	Not applicable
Brunei	Presumed to be sporadic-endemic as in Malaysia	Presumed year-round transmission
Cambodia	Presumed to be endemic-hyperendemic countrywide	Presumed to be May–October	Cases reported from refugee camps on Thai border
Hong Kong	Rare cases in new territories	April–October	Vaccine not routinely recommended
India	Reported cases from all states except Arunachal, Dadra, Daman, Diu, Gujarat, Himachal, Jammu, Kashmir, Lakshadweep, Meghalaya, Nagar Haveli, Orissa, Punjab, Rajasthan, Sikkim	South India: May–October in Goa; October–January in Tamil Nadu; August–December in Karnataka. Second peak, April–June in Mandya district. Andrha Pradesh: September–December North India: July–December	Outbreaks in West Bengal, Bihar, Karnataka, Tamil Nadu, Andrha Pradesh, Assam, Uttar Pradesh, Manipur, and Goa Urban cases reported (e.g., Lucknow)
Indonesia	Kalimantan, Bali, Nusa Tenggara, Sulawesi, Mollucas, and West Irian Java, Lombok	Probably year-round risk; varies by island; peak risks associated with rainfall, rice cultivation, and presence of pigs. Peak periods of risk: November–March; June–July in some years	Human cases recognized on Bali and Java and possibly in Lombok
Japan*	Rare-sporadic cases on all islands except Hokkaido	June–September except Ryuku Islands (Okinawa) April–October	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–October	Last major outbreaks in 1982–1983. Sporadic cases reported in 1994 and 1998.
Laos	Presumed to be endemic–hyperendemic countrywide	Presumed to be May–October	No data available
Malaysia	Sporadic-endemic in all states of Peninsula, Sarawak, and probably Sabah	No seasonal pattern; year-round transmission	Most cases from Penang, Perak, Salangor, Johore, and Sarawak
Myanmar (Burma)	Presumed to be endemic-hyperendemic countrywide	Presumed to be May–October	Repeated outbreaks in Shan State in Chiang Mai Valley
Nepal	Hyperendemic in southern lowlands (Terai)	July–December	Vaccine not recommended for travelers visiting high- altitude areas only
Pakistan	May be transmitted in central deltas	Presumed to be June–January	Cases reported near Karachi. Endemic areas overlap those for West Nile virus. Lower Indus Valley may be an endemic transmission area.
Papua New Guinea	Normanby Islands and Western Province	Probably year-round risk	Localized sporadic cases
People’s Republic of China	Cases in all provinces except Xizang (Tibet), Xinjiang, Qinghai. Hyperendemic in southern China; endemic-periodically epidemic in temperate areas	Northern China: May–September Southern China: April–October (Guangshi, Yunnan, Gwangdong, and Southern Fugian, Szechuan, Guizhou, Hunan, Jiangsi provinces)	Vaccine not routinely recommended for travelers to urban areas only
Philippines	Presumed to be endemic on all islands	Uncertain. Speculations based on locations and agroecosystems: West Luzon, Mindoro, Negro Palowan: April–November. Elsewhere: year-round, with greatest risk April–January	Outbreaks described in Nueva Ecija, Luzon, and Manila
Russia	Far eastern maritime areas south of Khabarousk	Peak period July–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–January; secondary peak of enzootic transmission May–June	Recent outbreaks in central (Anuradhapura) and northwestern provinces
Taiwan*	Endemic, sporadic cases; island-wide	April–October, with a June peak	Cases reported in and around Taipei and the Kao- hsiung-Pingtung river basins
Thailand	Hyperendemic in north; sporadic-endemic in south	May–October	Annual outbreaks in Chiang Mai Valley; sporadic cases in Bangkok suburbs
Vietnam	Endemic-hyperendemic in all provinces	May–October	Highest rates in and near Hanoi
Western Pacific	Two epidemics reported in Guam & Saipan since 1947.	Uncertain; possibly September–January	Enzootic cycle may not be sustainable; epidemics may follow introductions of virus.
*Local JE incidence rates may not accurately reflect risks to nonimmune visitors because of high immunization rates in local populations. Humans are incidental to the transmission cycle. High levels of viral transmission may 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 may change. Tsai TF, Yu Yx, Japanese encephalitis vaccines. In: Plotkin SA & Mortimer EA. Vaccines. 2nd ed., WB Saunders, Philadelphia 1994:671–713.

Table 2>Japanese encephalitis vaccine

Doses	Subcutaneous route		Comments
	1–2 years of age	> 3 years of age
Primary series 1, 2, and 3	0.5 mL	1.0 mL	Days 0, 7, 30
Booster*	1.0 mL	1.0 mL	1 dose at > 36 months
*In vaccinees who have completed a three-dose primary series, the full duration of protection is unknown; therefore, definitive recommendations cannot be given.

Distribution of Japanese encephalitis in Asia,1970-1998