Infectious Diseases, Vaccine/Immunization, ID Snapshot
Which travelers should consider Japanese encephalitis virus vaccine?
by H. Cody Meissner M.D., FAAP
Dr. Meissner
Japanese encephalitis (JE) is the most common vaccine-preventable encephalitis throughout most of Asia and
parts of the western Pacific. In endemic countries, 35,000 to 50,000 cases occur annually, with most cases
occurring in children.
Approximately 20% to 30% of cases are fatal, and up to 50% of survivors experience neurologic involvement.
Among travelers, infection can occur in people of any age.
Which two of the following statements regarding Japanese encephalitis are not correct?
a.) Japanese encephalitis virus (JEV) exists in an enzootic cycle between mosquitoes and vertebrate hosts,
mainly pigs and birds, where the virus is amplified.
b.) JEV is transmitted to humans by the bite of an infected mosquito, mainly Culex species.
c.) Disease develops in more than 70% of infected people.
d.)Viruses that cause Japanese encephalitis, yellow fever, West Nile, Zika, dengue, hepatitis C and St. Louis
encephalitis are classified as flaviviruses.
e.) Two JE virus vaccines are available in the United States: Ixiaro and JE-VAX.
Answer: c and e are not correct
Fewer than 1% of people infected by JEV develop symptoms, which range from an undifferentiated febrile
illness to acute encephalitis. Encephalitis is the most commonly identified syndrome. Symptoms generally begin
with fever, headache and vomiting, then progress to mental status changes and focal neurologic deficits. JEV
infection should be considered in any traveler returning from an endemic area with acute neurologic symptoms.
Only one Japanese encephalitis vaccine, Ixiaro, is licensed and available in the U.S. Ixiaro is an inactivated
Vero cell derived vaccine (JE-VC) manufactured and distributed by Valneva. In May 2009, the Food and Drug
Administration licensed JE-VC for use in people older than 16 years of age, and in May 2013, this vaccine was
licensed for use in children 2 months through 16 years of age.
JE-VAX was an inactivated vaccine prepared by intracerebral inoculation of mice with Japanese encephalitis
virus. Infected mouse brains were harvested, and virus was inactivated with formaldehyde. Production of JEVAX was discontinued in 2006, and all remaining vaccine in the U.S. expired in May 2011.
The primary series for JE-VC consists of two intramuscular doses administered 28 days apart. For children 2
months through 2 years, the dose is 0.25 milliliters (mL) and for children 3 years and older (and adults) each
Copyright © 2015, The American Academy of Pediatrics
Infectious Diseases, Vaccine/Immunization, ID Snapshot
dose is 0.5 mL. No efficacy data are available for Japanese encephalitis vaccines. Recommendations for
vaccine use are based on the ability of the vaccine to produce a protective neutralizing antibody concentration.
Immunogenicity studies demonstrated that the antibody response to JE-VC is non-inferior to that of mouse brain
derived vaccine. Local and systemic adverse events caused by JE-VC are similar to those reported after mouse
brain derived vaccine. However, mouse brain derived vaccine has been associated with serious allergic and
neurologic adverse events. Encephalitis, seizures and gait disturbances have been reported at a rate of less
than two cases per 100,000 vaccinees. Acute disseminated encephalomyelitis had been associated temporally
with administration of mouse brain derived vaccine. JE-VC vaccine is recognized to have fewer serious side
effects than mouse brain derived vaccine.
The overall incidence of JE among travelers to an endemic country from a non-endemic country is estimated to
be less than one case per million travelers. The risk depends on the destination (endemic areas shown in map),
duration of visit, season of the year and activity (travel to rural areas, proximity to farms or jungle,
accommodations without window screens and participation in outdoor activity increase the risk). All travelers
should be advised about the importance of personal protective measures to prevent mosquito bites.
From 1973 to 2008, 55 cases of JE were reported among travelers from non-endemic countries. JE-VC vaccine
generally is not recommended for short-term travel (less than one month), especially if the trip is restricted to an
urban area or the visit takes place outside the JEV transmission period.
Recommendations for use of JE-VC in travelers are based on the overall low risk for travel-associated JE and
the high morbidity associated with infection. Considerations for vaccine recommendations include: itinerary and
activity, the lack of treatment once symptoms begin, the severe outcome among infected people (encephalitis
and death), the low incidence of serious adverse events associated with JE vaccines and vaccine cost. JE
vaccines generally are paid for by the traveler (travel vaccines are not covered by the Vaccines for Children
program or insurance plans) at a cost of up to $500 for the series. For many if not most travelers, the risk of an
adverse reaction to the vaccine exceeds the risk of infection.
JE vaccine should be considered for travelers who will spend longer than one month in an endemic area during
JEV transmission season. Those who are traveling for less than one month should consider immunization if
travel includes an increased amount of outdoor time in a rural or agricultural area or if they are staying in an
accommodation that lacks screens or bed nets.
Dr. Meissner is professor of pediatrics at Floating Hospital for Children, Tufts Medical Center. He also is an ex
officio member of the AAP Committee on Infectious Diseases and associate editor of the AAP Visual Red Book.
Resource
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CDC Health Information for International Travel (Yellow Book)
Copyright © 2015, The American Academy of Pediatrics