How would you perceive an illness risk of 1 in a million?

How about 1 in 20,000?

Or, 1 in 5000?

Unfair question? Yes. What kind of illness are we are talking about? Is it a mild fever with a runny nose? Or is it encephalitis aka inflammation of the brain?

Japanese encephalitis (JE) is the most commonly diagnosed viral encephalitis in Asia. Remember, encephalitis = inflammation of the brain. JE virus (JEV) is transmitted by Culex mosquitoes. JEV infects birds and pigs; the cycle among birds, pigs and mosquitoes spills over to infect humans. Antibodies against JEV protects against JE. Antibodies can be acquired through natural illness, or induced through vaccines.

Although the risk of JE among travelers to Southeast Asia is very low, those unlucky enough to catch JE can have devastating consequences. This paints the backdrop for our discussion: is it reasonable to bet on the very low risk of acquiring JE as a traveler and pass on vaccination, or is it reasonable to get vaccinated to avoid death and disability in case you are among the super unlucky few?

Risks....

Older estimates refer to a JE risk of 1 in a million among travelers. But who are these travelers and where are they traveling to? Clearly, someone from say Iceland traveling to Bangkok on a 3-day business trip (extremely low risk) will have different odds than a fellow Íslendingar on a 3 month backpacking trip through rural Asia or living in a bamboo hut next to a paddy field in Bali. When adjusted for duration, season and itinerary, the risk for non-immune travelers in JE endemic areas may be (a wild guess) 1 in 5,000 to 1 in 20,000 per each week of travel.

The issue of JE is four fold:

1. JE is widespread throughout Asia.
2. Travelers are very unlikely to contract JE.
3. JE vaccines currently available provide high rates of immunity; they are also expensive.
4. If you are unlucky enough to catch JE by being the 1 in 5,000 or the 1 in 20,000 this week, there is a 30% chance you will die. If you live, there’s a 50% chance you will have permanent brain damage.

Yup.

In my practice, I see two groups of people when it comes to JE:

1. The concerned group. “It is a severe disease, it can kill, if I survive I may have permanent brain damage, there is a good enough vaccine, I’m gonna invest in it, I want my bamboo hut next to a paddy field and I don’t want to freak out each time I get bitten by a mosquito…AND I met this really cool infectious disease doctor who has actually treated patients with JE..he said it is not for the faint at heart”.
2. The reassured group. “Nah, the risk to travelers is very low. I have a much higher chance of being mowed down by a scooter. Most infections have little or no symptoms. I read this super cool travel blog by this really cool infectious disease doctor who said only about 3% of mosquitoes in rural areas carry JEV; even if 10% of mosquitoes carried JEV, the chance that a single mosquito bite will transmit the virus AND cause symptoms is about 1 in 10,000. I’m good.”

OK stop. What is going on here???

Symptoms....

Let’s all take a deep breath and talk about the symptoms of JE first. JE usually starts just like most other viral illness: with fever. For most people, fever may be the only symptom. Chills, runny nose, diarrhoea and such may follow. After a few days, the really unlucky few will progress to brain inflammation: clouding of consciousness, vomiting, seizures, meningitis, abnormal posturing, and coma. Paralysis can easily be mistaken for polio. And of course a third will die, and half of the survivors will have permanent brain damage.

Vectors....

Who is the culprit? In science we don’t call them culprits. We call them vectors. The vector for JE is mosquitoes of the Culex species. In Asia, it is usually Culex tritaeniorhyncus - an ornithophilic (bird-biting) mosquito that breeds in rural areas (e.g., rice paddies and ditches) where birds are found. These mozzies are also found on the edges of cities. They feed at night, seek blood meals mainly outdoors, feed repeatedly during a brief life span, and disperse widely after a blood meal.

Nice.

Southern tropical areas are fair game: southern Vietnam, southern Thailand, Indonesia, Malaysia, Philippines, Sri Lanka, and southern India. However…

Mozzies don’t always follow the rule book.

You will find JE as far west as Pakistan, to Papua New Guinea in the Southeast, and Northern China, Korea and Japan in the Northeast. Cases occur sporadically throughout the year, with a peak after the start of the rainy season.

What happens to people who are born and raised in areas where JE is naturally widespread?

Easy.

Almost all humans are infected by the time they reach early adulthood. Half before age 4 years, and almost all before age 10. So, before you defend your ‘reassured group’ position by saying well Dr. Changa hasn’t had the JE vaccine so why should I, just remember that Dr. Changa was born and raised in JE country. He ran around barefoot in cloth diapers, stick in hand to ward off rabid dogs while chasing waterhens and mongooses (who also carry rabies..) the point is, Dr. Changa was more likely than not bitten by a thousand JE-weaponized mosquitoes by the time he was promoted from cloth diapers. Because he has in all likelihood acquired natural immunity to JE, the vaccine will be of no benefit to him. Let’s keep our apples to apples, ok? Meaning, when a non-immune traveler comes to a JE endemic country, the risk is the same as resident non-immune child.

High death rates among children in endemic countries call for mass immunization campaigns. However, these mass human immunization campaigns do not protect non-immune travelers. Why not? Herd immunity is a thing, you say. Here’s why not. You may vaccinate a million babies, but JE virus is still alive and well in that cattle egret or whatever white bird du jour on yon paddy field, or in the brand new family of cute little kampong piglets. To be protected from JE, one must acquire immunity - through natural infection, or through vaccination. Herd immunity won’t help you here - on in COVID for that matter…but I digress.

The vaccines:

Gone are the days of the old vaccines such as the Biken, made from formalin-inactivated JE viruses grown in brains of suckling mice (I kid you not). Unsurprisingly these vaccines caused terrible allergic reactions and horrible neurologic side effects that made people say who needs JE when you have Biken.

Fortunately, the JE vaccine landscape is now significantly better - something to keep in mind when pouring over Google searches for vaccine side effects. Make sure you are looking up the currently available vaccines and not the ones that have thankfully been discontinued.

Most travelers today receive one of the following types of JE vaccines:

1. Inactivated vaccines (i.e., vaccine has no live virus): IXIARO and JEVAC.
2. Live virus vaccine: IMOJEV and CD-JEVax. As with most live virus vaccines, avoid in pregnancy and in any situation with weakened immune systems (HIV/AIDS, immune suppressive treatments, etc).

The most common side effects of these newer JE vaccines include fever, headache, body ache, and pain/swelling at the injection site. Rashes and allergic reactions also may occur.

Do these vaccines still cause allergic reactions?

It is important to look at the product information leaflets of each vaccine - an easy online search away. For instance, IXIARO inactive ingredients include protamine sulphate, aluminum hydroxide, sodium chloride, potassium dihydrogen phosphate, disodium hydrogen phosphate (from IXIARO package insert). Anyone with serious allergic reactions to these ingredients should avoid the vaccine. Similarly, IMOJEV inactive ingredients include mannitol, lactose monohydrate, glutamic acid, potassium hydroxide, histidine, human serum albumin, and sodium chloride. No adjuvant or antimicrobial preservative is added (from IMOJEV product leaflet).

The Numbers Game in Real Life:

In 1994-95, two travelers staying in hotels in Bali developed JE:


1. March 1994: a Swedish woman, survived;
2. January 1995: in a Danish man, died.

The annual number of non-Asian tourists visiting Bali during this time was around 450,000.

An Israeli tourist developed JE while traveling in Thailand in 1989, and survived. Israeli public health authorities promptly recommend JE vaccine for all Israeli travelers to Thailand.

Life is full of numerators and denominators.

The issue of Japanese encephalitis, and the JE vaccine, is not as straightforward as say the yellow fever vaccine, nor nearly as controversial as the COVID vaccines. Each person’s risk perception is different. This is one instance where the healthcare provider and traveler / expatriate must sit down (or Zoom) and carefully go over risks and benefits.

Call your friendly neighbourhood super cool infectious disease doctor if you want to chat more about JE, JE vaccines, piglets and cattle egrets.