Japanese%20encephalitis Management

• 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 dusk to dawn are the peak biting hours of mosquitoes that transmit Japanese encephalitis virus
• Use of mosquito nets, preferably those treated with insecticides, is advised
• 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
  • A strengthened surveillance system for at-risk countries is recommended
• Vaccination 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
  • Persons relocating to Japanese encephalitis virus-endemic countries with plans of settling there for ≥1 month 
  • Laboratory staff with potential exposure to infectious Japanese encephalitis virus

• Vaccination should be considered for the following:
  • Travelers spending <1 month in endemic areas during the transmission season, if their travel plans include activities to be conducted outside the city area, which puts them at risk of exposure to Japanese encephalitis virus infection
  • 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 who will be staying within city limits and not during high-risk period of Japanese encephalitis virus transmission
• Administration of vaccine in pregnant women should be deferred due to lack of clinical studies that have been conducted
  • Vaccination may be considered in pregnant women travelling to endemic areas if the risk of immunization outweighs 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

Types of Japanese Encephalitis Vaccines

• The 4 main types of Japanese encephalitis vaccines include inactivated mouse brain-derived, inactivated Vero cell-derived, live attenuated and live recombinant (chimeric) vaccines
• Vero cell culture-derived Japanese encephalitis vaccine (JE-VC), an inactivated vaccine, is the only licensed Japanese encephalitis vaccine in the United States, which was approved for use in the US in 2009 for individuals 17 years and older and in 2013 for use in children 2 months through 16 years of age
• Mouse brain-derived Japanese encephalitis vaccine (JE-MB) is an inactivated vaccine that was approved in the United States in 1992 for use in individuals >1 year of age but production was discontinued in 2006
• The Advisory Committee on Immunization Practices (ACIP) 2019 have the following recommendations for the use of  JE-VC vaccine:
  • Primary series:
    • For children 2-35 months of age: 2 intramuscular (IM) doses at 0.25 mL per dose given 28 days apart
    • For children aged ≥3 years and adults >65 years of age: 2 IM doses at 0.5 mL per dose given 28 days apart
    • For adults aged 18-65 years: 2 IM doses at 0.5 mL per dose given on days 0 and 7-28 (accelerated schedule)
    • All doses should be completed at least 1 week prior to potential JE virus exposure
  • Booster dose: If primary vaccination was administered ≥1 year ago after completion of primary series, a booster dose is recommended if anticipating possible exposure or is currently exposed to Japanese encephalitis virus 
• SA14-14-2 is a live attenuated vaccine developed in hamster kidney cells that is used in China and prequalified by the WHO in October 2013
  • 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
• Several randomized controlled studies conducted in Asia showed the seroprotective effect of JE-VC in subjects aged 2 months to 17 years after completion of the primary vaccine series and in adult test subjects given the 2-dose series
• In live recombinant vaccines, high seroprotection rates were reported from children from endemic areas and from adults from non-endemic areas 1 month after receiving a single dose of the vaccine
• 2 inactivated Vero cell-derived and 1 live attenuated vaccine have been reviewed by the WHO Global Advisory Committee on Vaccine Safety (GACVS) in 2013 and found that these vaccines have acceptable safety profiles

• 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 (ie upper and lower motor neuron weakness, cerebellar and extrapyramidal signs)
  • 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