Japanese Encephalitis (JE) viral disease is a mosquito-borne brain disease caused by the Japanese Encephalitis Virus (JEV). The disease is common in South East, East, South Asian countries, Western Pacific, Western India, and the Far East. The viral disease transmits from animals to humans, with mosquitoes being the vector. The Culex tritaeniorhynchus mosquito is responsible for spreading the disease in humans. Humans are the dead-end hosts for the JE virus, and the virus exists in a transmission cycle between mosquitoes, pigs, and water birds. People who are at risk of getting Japanese Encephalitis to include:

  • Children below ten years of age living in JE endemic regions
  • Older population
  • People living in rural areas and involved in fish and pig farming
  • People who do not adhere to cleanliness and follow preventive measures to stop mosquito breeding & mosquito bites

Mild fever and headache in adults, abdominal pain, vomiting, & seizures in children are the symptoms during the early stage of the disease. Without proper diagnosis and management, the disease can move towards the critical step where the patients show high fever, severe headache, neck stiffness, seizures, coma, and death.
The diagnostic tests carried out for Japanese Encephalitis include:

  • Laboratory tests to determine the presence of the Japanese Encephalitis virus-specific IgM antibodies in patients
  • CT or MRI scan
  • Nucleic acid amplification, histology with immunohistochemistry
  • Virus culture of autopsy tissues
  • Simple nitrocellulose membrane-based format

There is no specific medicine to cure Japanese Encephalitis. Vaccines have been developed, but their efficacy after a particular period decreases, and thus patients may need to get re-vaccinated. This article mentions the types of JE virus vaccine used to date and a summary informing the patients about the IXIARO vaccine approved by USFDA for Japanese Encephalitis.

Types of Japanese Encephalitis vaccine
Four types of Japanese Encephalitis vaccine are present, namely:

  • Inactivated mouse brain-derived vaccines are produced from infected adult mouse brain tissue. However, major manufacturers have discontinued production since new and improved JE vaccines are available in the market. Countries that used this vaccine were India, Japan, Malaysia, South Korea, Sri Lanka, Taiwan, Thailand, and Vietnam.
  • Inactivated cell culture-derived vaccines: This vaccine is manufactured from the P3 strain of the Japanese Encephalitis virus grown in primary hamster kidney cells. However, due to its limited efficacy and requirement of high doses, manufacturers stopped the production of the cell-cultured vaccine. A new and improved Vero-cell-derived inactivated SA14-14-2 vaccine overtook the cell-culture-based method using Tissue Culture. An example of a Vero-cell-derived inactivated SA14-14-2 vaccine is IXIARO, available in the USA.
  • Live attenuated vaccines: The live attenuated SA14-14-2 JE vaccine strain is manufactured after isolating the wild SA14 strain from a mosquito larvae pool and passing it multiple times in primary hamster kidney cells. The vaccine is safe and available in China, Nepal, India, South Korea, and Thailand.
  • Live Recombinant vaccines: It is also known as the chimeric YFV-JEV recombinant vaccine and is generated by the principle of reverse genetics. The chimeric YFV-JEV recombinant vaccine came into consideration after the regulatory agencies of Western Nations showed disagreement towards using live-attenuated SA-14-14-2 Japanese Encephalitis Strain.

IXIARO, the vaccine for Japanese Encephalitis
The Japanese Encephalitis virus vaccine is a suspension for intramuscular injection (given in muscles) vaccine containing inactivated, adsorbed, Vero-cell culture-derived SA14-14-2 virus strains. It is available in the USA under the brand name Ixiaro. The vaccine was licensed in 2009 for adults and in 2013 for children two months of age and older. It is used to prevent Japanese Encephalitis viral infection and is given only under the direct supervision of a registered physician.
The vaccine is approved for people who come under the following criteria:

  • People who are planning to shift to JE endemic countries
  • People who are frequent travelers to JE endemic countries
  • People who plan to visit a country where JE is at its peak and will be there for a longer duration
  • People who stay for less than one month in JE endemic countries and have an increased risk for mosquito bites can also be considered.
  • Laboratory workers involved in vaccine development and production

The Japanese Encephalitis virus vaccine is given in two doses. For children between 2 months and less than three years of age, the dose is 0.25 mL, and the gap between the first and second dose is 28 days. For children between three and less than 18 years, the amount is 0.5 mL, and the dosing interval is 28 days. For adults, i.e., 18 to 65 years, the dose is 0.5 mL, and the gap between two doses is 28 days. However, the vaccine can also be given to adults with an interval of seven days between two doses. For adults above 65 years, the dose is the same as for people between 18-65 years, and the dosing interval is 28 days. A booster dose is also recommended after one year for people who still risk getting exposed to viral infection.
Usually, the last dose is given at least one week before traveling. After the second dose, the body takes about one week to develop antibodies. It is necessary to develop antibodies towards the JE virus before stepping into a country where JE cases are prominent.

What information must people give a physician before taking a Japanese Encephalitis Vaccine?
Before taking the Japanese Encephalitis virus vaccine, people or parents of the child must let the physician know:

  • If the person (female of reproductive age) is pregnant
  • If the woman is breastfeeding
  • The person is traveling for less than a month to a country where JE infection occurs and planning to stay in urban areas of that country.
  • The occurrence of any allergic or life-threatening reaction after taking the first dose of the vaccine.
  • If the person to be vaccinated is severely ill.
  • Before taking the vaccine, tell your physician if you take any concomitant medication for a preexisting disease. Also, let the physician know your habits with alcohol and tobacco.

What are the side effects of IXIARO?
Scientific studies have found that severe reactions to the JE vaccine are infrequent. However, there is a very remote chance that the vaccine will cause severe allergic reactions, injury, or death.
However, the common side effects that a person may experience include:

  • Fever in children after the first dose
  • Headache and myalgia (pain in muscles) in adults
  • Some people may experience pain, swelling, redness, or tenderness at the injection site.
  • The common injection site reaction for infants of 2 months to less than one year is redness with adverse reactions like fever, irritability, and diarrhea.

Vaccinated people should report to a physician if the pain in the injection site remains for a longer duration or if they experience vision changes or ringing in the ears.
People should report to the emergency ward of their nearest hospital if they experience the following severe reactions:

  • Hives
  • Painful swelling of the face and the throat
  • Difficulty in breathing
  • Tachycardia (fast heartbeat)
  • Dizziness or feeling of being faint

How is the JE vaccine given?
The Japanese Encephalitis vaccine is administered as an intramuscular injection in the upper arm muscle of people aged between three years of age and older. For infants between 12 to 35 months of age, the vaccine is given either into the arm or thigh muscles. The vaccine is given into the thigh muscle for infants above two months and below 12 months of age.


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