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Japanese Encephalitis

Actualizado: Enero 4, 2012

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    Entendiendo la enfermedad

    Japanese encephalitis (JE) is a mosquito-borne disease due to a virus similar to the virus that causes yellow fever. It occurs throughout most of Asia and parts of the Western Pacific. Only a small fraction of people infected with JEV develop encephalitis but it is estimated that there are 35,000-50,000 cases each year. Of those who develop encephalitis as many as 20-30% will die, and about half (50%) of the survivors will have permanent brain damage. In areas where infection is endemic, almost everyone has been infected by 15 years of age.

    JE occurs primarily in rural areas where pigs are intensively raised, particularly in regions with rice production. In vertebrate hosts, like pigs and wading birds, the JE virus is amplified, although the virus does not cause illness in pigs. Pregnant sows that are infected with JE virus, however, often have stillbirths so farmers often immunize their sows. JE virus is spread by infected mosquitoes which breed in pools of water: a single rice paddy, for example, can generate about 30,000 mosquitoes per day.

    During the first half of the 20th century, JE occurred primarily in Japan, Korea, Taiwan and China. Japan has greatly reduced JE as a result of widespread immunization of children and the protection of herds of pigs. Vaccination has also reduced JE in China. In recent decades, however, JE has spread to Southeast Asia, India, Bangladesh, Sri Lanka, Nepal, Saipan and Australia. The reasons for the spread are not certain but scientists think it may be due to increased pig farming near rural rice paddies in these areas, or the virus may be spread by migrating birds and wind-blown mosquitoes.

    In endemic areas, JE virus infection occurs primarily among children. However, travelers of all ages have become infected with JE virus. The military has estimated that among the unimmunized, between one and two people in 100,000 per week are infected with JE virus. Scandinavian tourists to these regions have been estimated to be infected at a rate of one in 275,000 with half developing encephalitis. The risk for travelers acquiring JE infection depends on the season of travel, destination (rural areas being much higher risk than urban areas), duration of stay, and likelihood of mosquito exposure (dusk and night time are the preferred times for biting mosquitoes).

    Vacunas disponibles

    Product: JE-VAX (inactivated virus grown in mouse brain vaccine (JE-MB))
    Manufacturer: Biken (distributed by Sanofi Pasteur)
    Licensed: 1992 (This vaccine is no longer available as all stocks of this vaccine in the US expired in May, 2011)

    Product: Ixiaro (inactivated virus grown in VERO cell tissue culture vaccine (JE-VC))
    Manufacturer: Intercell (distributed by Novartis)
    Licensed: 2009

    JE-MB contained 0.007% thimerosal preservative. JE-VC does not contain thimerosal.

    Historia de la vacuna

    A number of JE vaccines are available in Asia and elsewhere; there are two licensed in the US. JE-MB was licensed in the United States in 1992 for use in travelers over age 1 year who are considered at risk of acquiring JE. The JE-MB vaccine is no longer being manufactured and it is no longer available in the US. A new JE vaccine, JE-VC grown in cell cultures was licensed in 2009 for use in travelers aged 17 and older who are considered at risk of acquiring JE. The JE-VC vaccine remains under study in children but has not yet been licensed for use in children under 17 years of age.

    Quienes deben y quienes no deben recibir esta vacuna

    Who should receive the Japanese encephalitis vaccine?

    • JE vaccine has a good safety record; however, not all travelers to countries where JE occurs are at risk for JE virus exposure. As a consequence, travelers and their health providers need to weigh the risks and benefits of vaccination as well as the likelihood of exposure to the virus. The risks and benefit considerations are described in detail by the Centers for Disease Control and Prevention (CDC.2010. MMWR 59(RR-1)).
    • In general, JE-VC vaccine is recommended for travelers 17 years of age and older who plan to spend a month or longer in areas where JE virus infection of pigs occurs during the time of year when they will be travelling. Because the risk of JE varies based on destination, duration of visit, season of the year, and planned activities, travelers and their healthcare providers will need to weigh the overall risk for travel-associated JE, the high morbidity and mortality when JE occurs, and the low probability of vaccine-associated adverse effects.
      • o The safety of JE-VC among children has not yet been established. Until those data are available, JE-VC vaccination of children 16 years of age and younger is only available in the US by enrolling children in an on-going clinical trial or administration of vaccine “off-label.”
      • Other JE vaccines may be available at international travelers’ health clinics in Asia.
      • There are only limited data on the use of JE-VC in persons aged 65 years of age or older.
    • Laboratory personnel who work with JE virus would likely benefit by pre-exposure vaccination with JE-VC, although there are no data on the efficacy of JE-VC vaccine after percutaneous (needle stick) or aerosol exposure to JE virus.

    Who should not receive the Japanese encephalitis vaccine?

    • People who have had a severe allergic reaction after a previous dose of JE-VC or JE-MB should not receive additional doses.
      • JE-VC contains protamine sulfate, a compound known to cause hypersensitivity in some persons.
      • JE-MB contained thimerosal, proteins of rodent origin, and proteins of neural origin, which are known to cause hypersensitivity in some persons.
    • Children under 12 months of age should not receive JE vaccine. Although other JE vaccines have been safely administered to children 6-12 months of age in Japan and Thailand, there are only limited data on the safety or effectiveness of JE-VC in US children less than 17 years of age.
    • JE vaccination is not recommended for pregnant women because of a theoretical risk to the developing fetus. If you are pregnant and you must travel to an area in which the risk of JE is high, you should discuss the benefits and risks with your healthcare provider.
    • Breast-feeding is not a contraindication to vaccination but there are no data on the safety or effectiveness of JE vaccines during breast feeding.

    Calendario de dosis

    JE-VC is administered as 2 doses given by intramuscular injection 28 days apart. The series should be completed at least 1 week before potential exposure to JE virus. The dose is 0.5 ml.

    If the primary series of JE-VC was administered more than a year previously, a booster dose may be given before potential JE virus exposure. There are no data on the effectiveness of a JE-VC booster dose administered more than 2 years after the primary series.

    There are no data on the effectiveness of JE-VC as a booster dose after JE-MB. Therefore, CDC recommends that those individuals 17 years of age or older who have received JE-MB previously, receive a 2-dose primary series of JE-VC if they require vaccination against JE virus.

    Efectividad de la vacuna

    Several JE vaccines are available in Asia which are known to be effective. However, it is not possible to conduct efficacy trials in the US. Nevertheless it is likely that US travelers are protected by a 2-dose series of the US licensed JE-VC vaccine, because this vaccine induces JE virus neutralizing antibodies which are considered to be a reliable indicator of immunity. In addition, older studies of laboratory personnel and experimental studies with animals suggest that these vaccines should be protective. A 2-dose series of JE-VC is at least as effective as the 3-dose series of JE-MB was previously at inducing protective levels of antibody.

    Efectos secundarios conocidos

    People immunized with JE-VC or JE-MB may have local pain, swelling and redness, or fever. Some rare neurologic symptoms (such as encephalitis, gait disturbances and Parkinsonism) have been reported in some people who were vaccinated with JV-MB but the WHO Global Advisory Committee on Vaccine Safety determined that no causal link could be established. [link causality Issue] The newer JE-VC vaccine was tested on fewer than 5,000 adults, so that it is possible that rare, unexpected, serious adverse events associated with JE-VC could occur.

    Several JE vaccines are available in Asia which are known to be effective. However, it is not possible to conduct efficacy trials in the US. Nevertheless it is likely that US travelers are protected by a 2-dose series of the US licensed JE-VC vaccine, because this vaccine induces JE virus neutralizing antibodies which are considered to be a reliable indicator of immunity. In addition, older studies of laboratory personnel and experimental studies with animals suggest that these vaccines should be protective. A 2-dose series of JE-VC is at least as effective as the 3-dose series of JE-MB was previously at inducing protective levels of antibody.

    Asuntos relacionados

    Travelers to JE-endemic countries should take precautions to avoid mosquito bites by using insect repellent, wearing permethrin-impregnated clothing, sleeping under permethrin-impregnated bed nets, and by staying in accommodations with air conditioning or screens.

    Referencias clave y fuentes de información adicional

    • Centers for Disease Control and Prevention (CDC). 2010. Japanese encephalitis vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 59(RR-1).
    • Jelinek T. 2009. Ixiaro®: a new vaccine against Japanese encephalitis. Expert Rev. Vaccines 8(11): 1501-11.
    • CDC. 2011. Update on Japanese encephalitis vaccine for children—United States, May, 2011. MMWR 60(20): 664-5.
    • CDC. 2011. Recommendations for use of a booster dose of inactivated Vero cell culture—derived Japanese encephalitis vaccine—Advisory Committee on Immunization Practices, 2011. MMWR 60(20): 661-3.