According to Sydney ID Director Professor Ben Marais, a key example of One Health in action is the response by University of Sydney researchers to the deadly – and previously unseen – Japanese encephalitis outbreak in south-eastern Australia in 2022.

"The Japanese Encephalitis virus (JEV), the virus that causes the disease, is not transmitted among humans: it’s borne by mosquitoes (so it’s known as an arbovirus) but the virus is amplified in pigs and wild birds," says Professor Marais.

"When an animal with the virus in its blood is bitten by a mozzie that then bites a human, JEV can be transmitted to humans."

The 2022 outbreak in Australia resulted in 45 confirmed human cases, which included seven deaths. The alarm sounded when there was an unusually high number of stillbirths and piglet mummification in commercial piggeries.

It was there that JEV was detected, which helped to solve the mystery of healthy people with unexplained severe brain infection (encephalitis) that was occurring at the same time.

But how did it happen? And can we be better prepared for future infectious disease outbreaks?

With the One Health approach, old-school field surveillance and epidemiologic work in mosquitoes and animals has been combined with advanced genomics to produce a comprehensive new template for improving our response to arbovirus threats.

“We unpicked what it was about the Australian landscape that resulted in the outbreak so that we can improve surveillance for JEV and similar arboviruses," says Associate Professor Brookes.

"The team helped identify interconnected factors, with temporary wetlands and flooded areas having a greater risk than permanent wetlands, perhaps due to changes in waterbird distribution or increased opportunity for mosquito breeding than permanent waterbodies."

Ongoing mosquito surveillance is also critical, not just in Australia, but particularly in Southeast Asia, India and the Pacific region where Japanese encephalitis is more common.

Currently, research students supported by Sydney ID are working in countries in which JEV circulates continuously, such as the Philippines and India, as well as Australia, to investigate mosquito abundance and diversity and how that might influence JEV transmission.

“We're conducting what we call xenosurveillance in mosquitoes – we look at their blood meals and find out what species they've been feeding on.," explains Associate Professor Brookes.

"That can give you information about how well your mosquito control is going. If you've got a high human feeding index, your mosquito bite prevention is not going well. We can then work with social scientists to understand why that might be.”

While surveillance is one part of the equation, another is disease diagnosis, and the JEV outbreak spurred virologist Dr John-Sebastian Eden into action.

He specialises in bioinformatics and genomics and, through novel virus sequencing, was not only able to help diagnose the first JEV infections in humans but also track the outbreak’s progress through mosquitoes into humans and pigs. 

“Most diagnostic tests are not open-ended; they’re specific to the type of virus you want to detect. So because no one was looking for JEV in our part of the world when the first cases presented, it could easily be missed," explains Dr Eden.

Traditional health pathology labs examine human samples  around certain expectations of what they might find. Dr Eden’s work has resulted in a novel approach to diagnosing infectious disease that involves sequencing all genetic information in samples and comparing it to extensive databanks of parasites, fungi bacteria, and virus genome sequences to find a match.

“Instead of searching for a particular virus, we can process a sample and look for anything that’s there rather than looking for a needle in a haystack," says Dr Eden.

"The work then uses this genetic information to build large maps, or genetic trees to consider where the virus came from and aid the public health response.

“We can tell an evolutionary story to understand virus patterns. Now, we are much better placed to respond to an outbreak and we are partnering with human and animal health labs to set up a capacity for diagnosing novel disease events.”

Dr Eden says that, compared to many routine pathology laboratories, the University is best placed to offer the broad context needed for disease identification and response.

“All the hosts of a virus need to be viewed together to understand where it's coming from," says Dr Eden.

"The JEV case broke boundaries because most of what we were sequencing was from commercial pig farms. I'm like a middleman that has the flexibility and collaborative network to do both human health and animal health research.”

Dr Eden explains his work in Nature Communications on the emergence and spread of the outbreak, while his article published in Science outlines the impact the outbreak has had.

The One Health approach is helping us prepare for future disease outbreaks. A critical concern is so-called Disease X, the next unknown pathogen that will cause the next global pandemic.

“We use foresighting, where we give ourselves scenarios and ask what conditions could cause the next outbreak to occur, and what factors we could influence," says Associate Professor Brookes.

H5N1, a highly contagious strain of bird flu (avian influenza), is another key concern noted by the epidemiologist.

“It’s spread globally. It's in wild migratory birds flying around the world. It has spread into cows, people, cats, seals, and penguins," explains Associate Professor Brookes.

"And if it happens to be able to spread and sustain transmission in us, then that could be a very serious situation.”

When it comes to predicting future risks, one factor is the propensity of viruses to jump species.

“When looking at virus behaviours, many viruses tend to stick to what they know," says Dr Eden.

"Every virus that passes from animals to humans has its own little network of animals that it affects and how it's transmitted. And we know with viruses like influenza and coronavirus that they are risks for pandemics, because they’ve done it in the past. They are a worry.”

For Associate Professor Brookes, a critical technique to help tackle future risks is disease transmission modelling, in which computer models simulate how disease might spread in the population.

The work at the University of Sydney reflects the larger landscape. There is a One Health arm at the interim Australian Centre for Disease Control (CDC), with infectious diseases a top priority. The full CDC is scheduled to be up and running in 2026. 

Multidisciplinary collaboration is key for effective One Health research and this is what both Sydney ID, and the wider Faculty of Medicine and Health, support.

Projects span the globe, with collaborations throughout South East Asia across a range of infectious diseases, as well as further afield in Europe, Africa, and the Americas. A recent formal partnership with the Public Health Foundation of India is also strengthening collaborations. 

“The solutions that we find locally are translatable to solve regional and global issues and we are now regarded as leaders in One Health, especially in arboviruses and arbovirus surveillance," says Professor Marais.

“What we've demonstrated is that if we collaborate in strong teams, even if funding is split between the participating groups, the outcomes are better. You can do more impactful work, and ultimately, you'll have more success.”