japanese%20encephalitis%20virus
JAPANESE ENCEPHALITIS VIRUS

Japanese encephalitis virus is an RNA flavivirus that causes virus encephalitis across Asia, the western Pacific region & parts of Australia.

It is transmitted in an enzootic cycle and the virus is transmitted to humans through the bite of infected Culex tritaeniorhynchus mosquitoes.

There is no specific antiviral treatment for Japanese encephalitis virus and management is mainly symptomatic treatment and supportive care.

Personal protection from mosquito bites in endemic areas and obtaining vaccination are the primary strategies to control Japanese encephalitis virus infection due to lack of specific antiviral therapy, high case fatality, & substantial morbidity.

Prevention

  • Personal protection from mosquito bites in endemic areas and obtaining vaccination are the primary strategies to control Japanese encephalitis virus infection due to lack of specific antiviral therapy, high case fatality, substantial morbidity

Protection from Mosquito Bites

  • It is advised to use insect repellent when going outdoors in endemic areas
    • Insect repellents containing DEET, IR3535, picaridin or oil of lemon eucalyptus is recommended
  • Wearing permethrin-impregnated clothing will give extra protection from mosquito bites especially when wearing thin clothing
    • Wear long sleeves, long pants and socks when outdoors if the weather permits
    • Permethrin repellents should not be applied directly to the skin
  • Avoid exposure during peak mosquito biting hours
    • Cooler hours from dust to dawn are the peak biting hours of mosquitoes that transmit Japanese encephalitis virus
  • Travelers in endemic areas are advised to stay in an air-conditioned or well-screened rooms or use bed nets and aerosol room insecticides in order to avoid exposure to vector-borne diseases

Vaccination

  • World Health Organization (WHO) recommends that in all areas where Japanese encephalitis is recognized as a public health priority, Japanese encephalitis virus vaccination should be integrated into national immunization schedules
    • Vaccination should be considered, even if the number of Japanese encephalitis-confirmed cases is low, where there is a suitable environment for Japanese encephalitis virus transmission
  • Obtaining vaccine is recommended for the following:
    • Travelers who plan to stay for ≥1 month in endemic areas during the Japanese encephalitis virus transmission season that includes long-term or recurrent travelers or expatriates who will stay in urban areas but most likely to visit an endemic area during high-risk period of Japanese encephalitis virus transmission
    • Laboratory staff with potential exposure to infectious Japanese encephalitis virus
  • Having vaccination should be considered for the following:
    • Travelers spending <1 month in endemic areas during the transmission season, if they plan to travel outside an urban area and their activities will increase the risk of Japanese encephalitis virus exposure
    • Travelers to an area with an ongoing Japanese encephalitis outbreak
    • Travelers to endemic areas who are uncertain of specific destinations, activities or duration of travel
  • Japanese encephalitis virus vaccination is not recommended for short-term travelers whose visit will be restricted to urban areas or times outside of a well-defined Japanese encephalitis virus transmission season
  • Administration of vaccine in pregnant women should be deferred due to lack of clinical studies that have been conducted
    • But pregnant women who must travel to an area where risk for infection is high should be vaccinated when the theoretical risk of immunization is outweighed by the risk of infection
      • It is preferred that inactivated Vero cell-derived vaccines be used over live attenuated or live recombinant vaccines based on the general precautionary principle against using live vaccines in pregnant women especially if alternative types of vaccines are available
  • Two vaccines that have been licensed in the United States (US):
    • JE-MB is a mouse brain-derived formalin-inactivated vaccine that showed efficacy in a randomized, double-blind trial in Thailand and is approved in United States in 1992 for use in individuals >1 year of age; production was discontinued in 2006 and remaining vaccine is reserved for use in children 1-16 years of age
    • JE-VC is an inactivated Vero cell culture-derived vaccine which was approved for use in the United States in 2009 for individuals 17 years and older and in 2013 for use in children 2 months through 16 years of age
  • The Advisory Committee on Immunization Practices (ACIP) 2013 have the following recommendations for the use of inactivated Vero cell culture-derived Japanese encephalitis (JE-VC) vaccine:
    • Primary series for JE-VC is administered in two intramuscular (IM) doses given 28 days apart
    • For children aged 2 months through 2 years, each dose is 0.25 mL
    • For adults and children aged ≥3 years, each dose is 0.5 mL
    • For persons aged ≥17 years, ACIP recommends that if the primary series of JE-VC was administered >1 year previously, a booster dose may be given before potential Japanese encephalitis virus exposure
  • SA 14-14-2 is a live attenuated vaccine developed in hamster kidney cells that is used in China
    • Has been shown to be safe and immunogenic, and has been given to over 100 million children in China
    • Efficacy was demonstrated in a relatively simple and inexpensive control study with effectiveness of one dose was 80% and 2 doses of one year apart to be 97.5%
  • A live attenuated, recombinant (chimeric) Japanese encephalitis virus vaccine was created by replacing the premembrane and envelope coding sequences of the yellow fever live attenuated 17D vaccine virus with the analogous sequences coding for the antigenic determinants from SA 14-14-2 live attenuated Japanese encephalitis virus vaccine
    • It was licensed in Australia in 2010 and since used in a growing number of Asian countries
    • The vaccine virus is produced in Vero cells

Immunogenicity and Safety of Japanese Encephalitis Virus Vaccines

  • There is no efficacy data for Japanese encephalitis virus vaccine but was licensed based on its ability to induce seroprotective Japanese encephalitis virus neutralizing antibodies as a surrogate for protection and safety evaluations of 5000 adults
  • In adults, studies evaluating individuals receiving Japanese encephalitis virus vaccine or placebo adjuvant have described comparable rates of local and systemic reactions
  • In the largest pediatric trial of Japanese encephalitis vaccine done in the Philippines among children assigned to receive 2 age-appropriate doses of JE-VC, 384 of 385 were seroprotected at 28 days after the second dose
    • At 6 months after completing the primary series, 134 of 152 children aged 2 months through 2 years and 224 of 237 children after 3-17 years had protective neutralizing antibodies
  • In a randomized, controlled trial conducted in India among children aged 1 and 2 years, 22 of 23 children were seroprotected at 28 days after receiving two 0.25 mL doses of JE-VC
    • No statistically significant differences were detected in the seroprotection rates between this group and children who received two 0.5 mL doses of JE-VC or 3 doses of JE-MB vaccine
  • In live recombinant vaccines, high seroprotection rates were reported from children from endemic areas and from adults from non-endemic areas 1 month after giving of a single dose of the vaccine
  • The two inactivated Vero cell-derived vaccines, live attenuated vaccine and live recombinant vaccine has been reviewed by the WHO Global Advisory Committee on Vaccine Safety (GACVS) and found that these vaccines have acceptable safety profiles

Prognosis

  • Infection with Japanese encephalitis virus thought to produce lifelong immunity
    • The different flaviviruses share antigens and induce cross-reacting antibodies
  • Patients having multiple, prolonged seizures, raised intracranial pressure, respiratory pattern changes, flexor and extensor posturing changes, and abnormalities of the pupillary and oculocephalic reflexes have poor prognosis
  • Mortality among hospitalized patients is about 20-30% and 50% of survivors have severe neurologic sequelae
    • Young children <10 years of age have a greater risk of residual neurologic, psychosocial, intellectual and/or physical disabilities and a higher case-fatality rate
  • Status epilepticus, brain hypoxia, increased intracranial pressure, brainstem herniation and aspiration pneumonia are the most common complications associated with poor outcome and death
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