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Japanese encephalitis (JE) is the leading cause of viral encephalitis (brain infection) in Asia. The disease occurs chiefly in China, Korea, Southeast Asia and the Indian subcontinent (see map showing distribution of Japanese encephalitis in Asia). Japanese encephalitis is transmitted by Culex mosquitoes, which breed in ground pools, especially flooded rice fields, and bite primarily after dusk. The virus lives principally in domestic pigs and Ardeid (wading) birds. Transmission of Japanese encephalitis is therefore greatest in rural, agricultural areas where rice paddies and pig farming co-exist. The risk may be increased by heavy rainfall and irrigation. Most infections are asymptomatic. But encephalitis, when it occurs, is severe and frequently leads to death or permanent brain damage.
The risk of Japanese encephalitis for most travelers appears to be very small. From 1992 to 2008, only four cases were reported in U.S. residents. All were Asian immigrants or family members who traveled to Asia to live or to visit friends or relatives and who had not been vaccinated against the disease (see MMWR). From 1973 to 1992, only 11 cases of Japanese encephalitis were reported in U.S. residents, five of whom were civilians.
Japanese encephalitis vaccine is recommended for those who expect to spend a month or more in rural areas where Japanese encephalitis is reported and for short-term travelers who may spend substantial time outdoors or engage in extensive outdoor activities in rural or agricultural areas where the disease occurs, especially in the evening. For those age 17 or older, the recommended vaccine is IXIARO, which was approved by the U.S. Food and Drug Administration in March 2009. The vaccine consists of purified, inactivated JE virus proteins. The recommended dosage is 0.5 cc given intramuscularly, followed by a second dose 28 days later. The series should be completed at least one week before travel. The most common side effects are headaches, muscle aches, and pain and tenderness at the injection site. Safety has not been established in pregnant women, nursing mothers, or children under the age of 17. The duration of protection after immunization is not known.
For those younger than 17 years of age, there is no FDA-approved vaccine in the United States at the present time. An older vaccine, called JE-VAX (Aventis Pasteur), is no longer manufactured or available in the United States. There are limited data regarding the safety of IXIARO in children, but it will likely be several years before IXIARO is licensed for use in children in the United States. Because it is a licensed product, a healthcare provider can purchase the product and choose to use it off-label in children less than 17 years of age. The manufacturer is currently studying a 0.5mL dose (regular adult dose) for children 3 years of age and a 0.25mL dose (half adult dose) for children aged 2 months through 2 years. For additional data and information regarding the use of IXIARO in children, healthcare providers can contact Novartis Medical Communications at 1-877-683-4732 or firstname.lastname@example.org.
There are two other options for obtaining JE vaccine for children:
Enroll in the ongoing IXIARO pediatric clinical trial at one of five U.S. sites. The study is open-label and all enrollees receive two doses of IXIARO administered 28 days apart. A third study visit is required at 56 days after the subject receives the first dose of vaccine. Additional information is available on the NIH clinical trials webpage. A list of U.S. clinical trial sites and contact information is available on the CDC website.
Receive JE vaccine at an international travelers' health clinic in Asia. JE vaccines available at international traveler's health clinics in Asia include inactivated mouse brain-derived vaccine manufactured in South Korea, live attenuated SA 14-14-2 vaccine manufactured in China, or inactivated Vero cell culture-derived vaccine manufactured in Japan. Each of these vaccines is licensed for pediatric use in one or more Asian countries; however, these vaccines are not licensed by the U.S. FDA. The recommended number of doses and schedule will vary by vaccine and country. A partial list of international travelers health clinics in Asia that administer JE vaccines to children is available on the CDC website.
There are no recommendations concerning booster doses. No information is available on the safety of the vaccine in pregnant or breastfeeding women. IXIARO is classified as pregnancy category B. Japanese encephalitis may cause fetal death in the first and second trimesters, so the risk of the vaccine must be balanced against the risk of illness in a pregnant woman traveling to an endemic area.
Insect protection measures are essential in areas where Japanese encephalitis is known to occur.
From the World Health Organization (WHO)
Japanese encephalitis (background information and vaccine position paper)
Safety of Japanese encephalitis vaccine
Japanese encephalitis vaccines: WHO position paper (PDF)
Japanese encephalitis: disease burden and vaccines
Japanese encephalitis (background)
From the Centers for Disease Control (CDC)
Japanese encephalitis fact sheet
Japanese encephalitis frequently asked questions
Inactivated Japanese Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices (PDF) (most complete summary)
From the National Travel Health Network and Centre (U.K.)
From the New England Journal of Medicine
T.Solomon, "Control of Japanese Encephalitis â Within Our Grasp?"
(NEJM 2006; 355:869-871)
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