Japanese Encephalitis Vaccine Needed for Southeast Asia. Guide for decision-making.

Introduction

Japanese encephalitis (JE) is a viral infection transmitted by mosquitos. About 68,000 people are diagnosed annually as having the disease, and over 20,000 of that number die from JE-associated health consequences.
The endemic sites for JE are Asian and Western Pacific countries where the infection is widely spread year-round. However, the optimal conditions for the epidemic are warm weather and rainy seasons in tropical and subtropical regions as this is when the number of mosquitos increases. As well, those areas where people are cultivating rice are more dangerous during the pre-harvest seasons.

What countries have an increased risk of contracting JE?

Initially, Japanese encephalitis had been only found in Japan, China, Korea, and Taiwan. Recently new cases have been reported all over the region.

Today, there are 26 countries in the Asian and Pacific regions where JE has become a public health issue. According to the Centers for Disease Control and Prevention (CDC), the list of high-risk countries for Japanese encephalitis includes:

What is the probability of contracting JE?

The risk of contracting JE depends on various factors, such as age (those under 15 years old are more susceptible), time of the year, location, etc. Out of 100,000 people residing in endemic countries, only 6 to 11 develop JE each year. The majority of those affected are children aged 15 years old or younger.
The risk for travelers from non-endemic countries is very low (1 in a million). However, if a person intends to stay in an endemic country for more than 30 days, their risk becomes equal to the residents of that country. There are high-risk areas, seasons, and activities that alter the probability of contracting the disease.
The CDC created a summary of high-risk areas and seasons for each endemic country, which is presented below:

What activities increase the risk of contracting JE?

Any activity is considered high-risk of being bitten by a mosquito. Just being in the area is a risk of contracting JE. The list of activities includes camping, cycling, hunting, and any other activity that requires spending time outdoors. The rural areas have proven to be more dangerous in terms of JE transmission.

How to minimize the risk of contracting JE

In order to decrease the probability of contracting Japanese encephalitis, travelers should be vaccinated against the disease, or protect themselves with mosquito repellant.

How to avoid mosquito bites

The Centers for Disease Control and Prevention suggests the following preventive methods:

• Use anti-mosquito sprays and creams that contain DEET, Picaridin, 2-undecanone, Oil of lemon eucalyptus, IR3535, and Para-menthane-diol.
• Avoid the high-risk activities mentioned above.
• Make sure your body is covered by clothing as much as possible.

The JE vaccine

The only Japanese encephalitis vaccine  available in the US is Ixiaro. In 2013, it was approved for vaccination among those aged two months and older.
The vaccine should be administered to all tourists from non-endemic countries (including the US), who intend to stay in high-risk geographic areas for more than a month. Moreover, those who intend to stay less than a month but intend to engage in activities where the probability of JE acquisition is high should be vaccinated as well. Vaccination is needless for those who will not visit rural areas and/or will leave the high-risk country earlier.
Allergic people and pregnant women should not be vaccinated against JE since no literature proves the safety of the vaccine among those populations. However, an individual approach is needed for pregnant women intending to visit the endemic regions since the benefits of vaccination may outweigh the risks.

Disadvantages of the JE vaccine

There are some vaccine-associated non-specific reactions, such as fever, muscle pain, and localized pain and redness. Serious adverse events are very uncommon after the administration of the JE vaccine.
In order to prevent unpleasant events, people who have allergies or who are pregnant should inform their doctor before receiving the vaccine.

Doses for full protection from JE

Two doses of the vaccine are needed for full JE protection. The second dose should be given four weeks after the first shot has been administered. However, for those aged 18 years or older, two JE vaccine doses may be given 1 week apart, which will give them 99% protection. It is important to know that the time interval between entering a high-risk country and vaccine administration should be 7 days or longer.
According to the CDC, individuals who received two doses of the vaccine given four weeks apart before their 17th birthday will develop immunity to Japanese encephalitis 28 days after administration of the second dose. This period is equal to 42 days for the majority of those aged 65 years and older.

Post-vaccine JE protection

About 70% of the US travelers who received both doses of the JE vaccine, will be protected against this disease for up to 5 years. 4 A third shot of the vaccine is recommended if more than 1 year has been passed since the last shot of the JE vaccine since the risk of contracting the Japanese Encephalitis Virus is still high.
A single shot of the vaccine for children aged two years or younger should be given a 0.25 mL dosage. The dosage is doubled for those aged three years and older.

Is one dose of the JE vaccine sufficient?

Not really. A single shot of the JE vaccine does not result in the development of full immune protection against Japanese encephalitis. 10 The estimated protection is about 29.4% from a single-dose of the JE vaccine ten days after the vaccine inoculation.
Those who were unable to have the second shot should try to avoid mosquito bites in order to guarantee that they will not contract the virus.

Second dose protection from JE

As it was mentioned before, people will achieve full JE protection 28 days after the administration of the second shot. However, there is evidence that the JE vaccine offers 97.3% protection 7 days after getting 2 doses of the vaccine 4 weeks apart. Moreover, about 99% of JE transmissions may be protected 7 days after the administration of 2 doses of the vaccine 7 days apart.

How many people in the USA opt for the JE vaccine?

According to the study conducted in the late 2000s, only 11% of US tourists whose destination was a JE-endemic country and who had an increased probability of JE acquisition (long stay, traveling to the risky regions, etc.) chose to get a JE shot.

Is the vaccine available in high-risk countries?

CDC does not suggest the US citizens be immunized in other countries since the vaccines available there may be a different type and/or have lower quality.
Travelers can find the closest clinic in their region and make an appointment for the JE vaccination by visiting the website of the International Society of Travel Medicine.
However, tourists should consider the required time interval between the two shots and the needed period of the full immune response development (at least 4 weeks after the administration of the 2nd dose).

Symptoms of JE

Less than 1% of JE-positive individuals develop encephalitis. People begin to experience JE-related symptoms 5 to 15 days after being infected with the disease.

JE-related symptoms and health complications

The most frequently identified JE symptoms include:

• Abdominal pain
• High fever
• Vomiting
• Headache
• Spastic paralysis
• Disorientation
• Coma
• Seizures
• Neck stiffness

Unfortunately, 1/3 of those having these symptoms will eventually die.

Treatment of JE

According to the World Health Organization, there is no cure available for Japanese encephalitis. Symptomatic treatment is suggested for the improvement of patients overall well-being.

Conclusion

Japanese encephalitis is an incurable, deadly disease widely spread in Asia and the Pacific regions. The best way to deal with this infection is to prevent it. There are several ways for protection from JE transmission including vaccination.
JE vaccines have been proven effective and safe worldwide. Thus, any traveler aged 2 months and older who is at high risk of contracting JE should have 2 shots of the vaccine to prevent the inevitable consequences.

References:

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4. Japanese Encephalitis - Chapter 4 - 2020 Yellow Book | Travelers’ Health | CDC.
5. GHO | By category | Japanese encephalitis - Reported cases by country.
6. Amicizia D, Zangrillo F, Lai PL, Iovine M, Panatto D. Overview of Japanese encephalitis disease and its prevention. Focus on IC51 vaccine (IXIARO®). J Prev Med Hyg. 2018
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13. Need travel vaccines? Plan ahead. | Travelers’ Health | CDC.