The science of Japanese encephalitis

Japanese encephalitis has catapulted seemingly out of nowhere and into Australian headlines in recent days. With the disease having now reached four states and sadly caused two confirmed deaths, many Australians are looking to answer questions about this new-to-us viral infection.

So, what is Japanese encephalitis, why is it spreading in Australia now, and is there anything we can do?

What is Japanese encephalitis and what causes it?

As the name suggests, Japanese encephalitis is a type of encephalitis, or inflammation of the brain. Symptoms of the disease include fever, headache, vomiting and seizures.

It’s caused by the Japanese encephalitis virus (JEV), an RNA virus in the Flaviviridae family. Other viruses in this family include dengue virus and Zika virus. They are what’s known as arboviruses – short for arthropod-borne viruses, referring to the fact that they are spread by insects like ticks and mosquitoes.

Specifically, JEV is spread by mosquitoes in the Culex genus. Pigs and wading birds like herons and egrets are “amplifying hosts”: that means the virus can infect them and replicate to levels high enough that it can go on to infect a mosquito that bites the larger animal.

Humans and horses can both be infected by the virus via a mosquito bite, but we are what’s known as “dead-end hosts”: the virus can’t replicate to high enough levels in our blood to transfer to a mosquito if we’re bitten again.

Scientists aren’t quite sure of why JEV replicates better in pigs than in humans. Ali Zaid, a viral immunologist from the Menzies Health Research Institute Queensland at Griffith University, says that viruses usually have preferred host species that are best for them to replicate in – which is known as tropism.

“There’s most likely something about the cell entry receptors in humans compared to what is in a bird that makes it easier or more difficult for a particular virus to get in,” he says.

You can’t catch the virus from another person or by eating pork products from an infected pig. That’s because the route of infection matters. JEV needs to be spread by mosquito bite and particularly to get into the blood – so it can’t do you any harm if you just breathe it in or eat food containing it.

The vast majority of JEV infections are asymptomatic – the Australian Immunisation Handbook says that only between 1 in 25 and 1 in 1000 infections actually cause clinical disease.

But for those who are unfortunate enough to develop the disease, it’s often very serious. Between 20% and 30% of symptomatic cases are fatal, and 30–50% of people who survive the acute illness experience ongoing neurological symptoms.

We’re not really sure what causes some people to have a severe response to JEV infection.

Like many viral diseases, the more dangerous symptoms like fever or encephalitis are actually part of our body’s response to the viral infection, not directly caused by the virus itself.

“Most of the time the virus will go into its preferred cell, infect it, replicate – and if it has evolved to sort of be sneaky, it will leave the cell relatively unharmed,” says Zaid.

“But what happens is the immune system will trigger a knee-jerk reaction, which is designed to brace every other cell in the body against future viral infection. This inflammation is there to essentially kill any cell that may be infected.”

Children and older people seem to be more vulnerable. For older adults, that’s probably down to ageing.  

“Your immune system ages and it’s less able to fend off an explosive infection, and your organs are less likely to handle the damage and inflammation that results from an immune response against the virus,” says Zaid.

Zaid points out that in many other countries where Japanese encephalitis is endemic, it’s primarily a disease of childhood.

Australia is a bit of an outlier in only experiencing cases in adults, and also in having a better-resourced health system than many countries in South and Southeast Asia where JEV is more widespread – so it can be difficult to translate knowledge from other parts of the world to our context.

Why is Japanese encephalitis spreading in Australia now?

Japanese encephalitis has been present in Australia for a while, but largely confined to tropical areas – small corners of the Cape York Peninsula and the Torres Strait. Vaccination programs instituted following the first recorded outbreak in the Torres Strait in 1995 have provided protection for humans, and Queensland health department mosquito control activities helped keep the disease, if not the virus itself, largely at bay in those areas.

For Nigel Beebe, an associate professor at the University of Queensland and CSIRO working on several mosquito-borne diseases including JEV and malaria, the current spread to the south is unfortunate but not exactly surprising.

“We have been thinking that this was going to happen since around 2000,” he says.

“In Australia we have access to wading birds that fly in from Papua New Guinea, we have a large feral pig population – so they’re both amplifying hosts – and we have a very good mosquito vector.”

That vector is Culex annulirostrus, or the common banded mosquito – a freshwater mosquito found widely across the eastern half of Australia, as well as in Papua New Guinea. Beebe says the species has been shown to be able to transmit JEV in laboratory studies.

His lab is currently working on population genetics to try to identify different strains of C. annulirostrus and understand whether they have different capacity to transmit viruses. There are other flaviviruses that are already present in these regions and transmitted by local Culex mosquitoes.  

Several experts have suggested that climate change and Australia’s recent weather conditions could have tipped the balance in favour of the virus’s southwards spread.

“The reports of multiple cases of Japanese encephalitis acquired in Australia occurring at the same time as severe flooding serves as a warning of the significant potential for new human health threats associated with climate change, including the emergence of new pathogens and the appearance of known infections in new localities,” says Karin Leder, a professor in the School of Public Health and Preventive Medicine at Monash University.

The current La Niña cycle has likely influenced migration of birds that carry the virus and increased the abundance of mosquitoes. Rain and flooding can create wetland environments in new places, which draw birds and mosquitoes together and potentially bring them into closer contact with both humans and pigs.

“Regardless of La Niña, if our climate is to become warmer, and challenged by flood events, we may find that JEV will circulate widely and continuously,” says Gregor Devine, group leader of the Mosquito Control Laboratory at QIMR Berghofer.

What can we do to protect ourselves and each other?

Unfortunately, there are no specific treatments for Japanese encephalitis, but that doesn’t mean we’re powerless against the virus.

There are two vaccines against JEV currently approved for use in Australia, and they’re both highly effective.

Both are based on the same strain of JEV and derived from virus grown in a cultured cell line developed from African green monkey cells. The major difference is that one vaccine (Imojev) contains a live attenuated virus, and the other (JEspect) contains an inactivated virus.

According to the Australian Immunisation Handbook, a single dose of Imojev generates protective levels of neutralising antibodies against four strains of JEV in 85% of adults, and about 65% of adults maintain these protective antibodies against at least three strains five years after vaccination. Young children maintain protective antibodies for at least 12 months after a single dose. The vaccine is approved for use in people aged nine months and older in Australia.

JEspect is delivered as two primary doses, like most COVID-19 vaccines. It’s approved for use in people aged two months and older, with a smaller dose being used for children aged two months to three years. At least 83% of adults have protective levels of neutralising antibodies six months after vaccination with two doses of JEspect, and 48% maintain these levels after two years. Protection also remains high in children for at least six months. JEspect can also be used as a booster if there is a high ongoing risk of JEV infection.

“Those are some of the best vaccines we’ve got,” says Zaid. “They work quite well and they’re available. They’re not cheap, that’s the only problem.”

The Victorian state government has recently flagged that it wants to make JEV vaccines more broadly accessible, given the current outbreak.

Zaid agrees that this should be considered, especially for people who are exposed to areas with both mosquitoes and animal hosts like pigs and wading birds.

He also points out that, while Japanese encephalitis is in the news, many strategies to reduce the risk of JEV infection will also help counter other mosquito-borne flaviviruses such as Murray Valley encephalitis and Kunjin virus (a West Nile strain). These are already established in southern Australia, they’re also likely to increase with the current favourable mosquito breeding conditions – and we don’t have vaccines for them.

Targeting the mosquitoes, rather than the virus, then, is a worthwhile strategy. That includes taking extra care to avoid mosquito bites by applying strong insect repellent and eliminating pools of stagnant water that promote mosquito breeding.

Avoiding the outdoors at dusk and dawn, when mosquitoes are most active, and wearing long, light-coloured clothing (mosquitoes are attracted to dark colours) also help.

There are also strategies to control the mosquito population, like insecticides that kill larvae – but they can be difficult and expensive to implement over a broad area, especially when weather conditions favour the mosquitoes.

Beebe says that the affected states have come together effectively to deliver a coordinated health response to JEV; in addition to that, he’d like to see the creation of national centre of disease control.

“There’s a lot to learn now if Japanese encephalitis is going to stay on mainland Australia and continually cycle,” he says. “We really need to work out its ecology in our particular landscape.”