Key points
- When a suspected case of H5 bird flu arrived in Australia, CSIRO scientists knew the first hours would matter.
- Working through the weekend inside Australia’s high containment laboratory, the team confirmed the virus and rapidly decoded the genetic clues governments needed to respond.
- Their response was built on years of preparation, specialist expertise and people ready to act when a virus Australia had long watched finally reached our shores.
When a suspected case of H5 bird flu arrived in Australia, CSIRO scientists knew the first hours would matter.
Working through the weekend inside Australia’s high containment laboratory, the team confirmed the virus and rapidly decoded the genetic clues governments needed to respond.
Their response was built on years of preparation, specialist expertise and people ready to act when a virus Australia had long watched finally reached our shores.
On a Thursday afternoon in June, Dr Vidya Bhardwaj received an email from Western Australia’s animal health laboratory.
A sick migratory bird had tested positive for highly pathogenic H5N1 avian influenza (H5 bird flu).
This is the strain of bird flu that has caused mass animal deaths around the world over the last few years, but had yet to reach Australian shores.
"The states are our frontline detectors," explained Dr Bhardwaj from CSIRO’s Australian Centre for Disease Preparedness (ACDP).
"When they identify something of concern, our role as Australia's animal health reference laboratory is to confirm what they've found and provide the detailed information needed for decision-making."
ACDP combines cutting-edge science, rigorous quality controls and international collaboration.
First things first: confirming with PCR
Most people are familiar with PCR tests as they’re commonly used to test for viruses in people: a sample is added to the test and if the virus/bacteria is present, a reaction will occur indicating a positive result. These tests provide a quick answer, which is very important, but they provide no extra detail.
If you imagine a virus’s genome like a book written with a mix of four letters: A, C, G, T (or sometimes U), PCR tests are set up to look for a short, specific phrase in that book.
“With PCR tests, all it will tell you is if that part of the gene is there or not. Your test has to be well designed to only give positives for the specific virus that you’re looking for. The test needs to be specific.
“For example, if your test uses a phrase of genetic code that is in H5 bird flu, but that same phrase can also be found in the common cold, your PCR will show positive for either of those viruses,” Dr Bhardwaj explained.
Knowing H5 bird flu would likely one day reach our shores, ACDP researchers developed an additional PCR test that shows not only positive for H5 bird flu, but specifically the strain found in sub-Antarctic colonies late last year.
Once the samples had arrived at ACDP, the countdown to get results began.
“We needed to move quickly with these first important samples of high suspicion, so we began sequencing tests at the same time as PCR testing,” Dr Bhardwaj explained.
Reading the genetic story
Unlike PCR tests, where you simply get a positive or negative, genome sequencing tests provide a lot more information. They give you the virus sequence; you can read the entire genome ‘book’ full of phrases using those four letters.
This can then be compared to reference samples from other confirmed cases to give you information such as where the virus is likely to be from and how it has or hasn’t changed.
“There are some important patterns we looked for immediately,” said Dr Bhardwaj.
"The first pattern showed what clade it was (what group of viruses it’s most closely related to) – we could quickly confirm that it was indeed the 2.3.4.4.b. strain of bird flu.
“We also checked what scientists call the cleavage site: a small but important part of the virus’s genetic code that can influence how severe the disease is in birds. If that section had changed, it could have been a sign the virus was behaving differently and needed closer investigation.
“In this case, it matched the virus seen in sub-Antarctic birds, which meant we did not need to do further research into the severity of this sample.”
The next significant piece of information is determining the genotype.
“The genotype basically is a system of classification to name viruses. We were able to look at the virus’ genetic data and confirm the first WA sample was the exact same strain that had been found in sub-Antarctic animals.
“By knowing the specific genotype, researchers have a much better understanding of how the virus is expected to behave including which species it’s likely to infect, if diagnostic tests will work to pick it up or if it’s likely to be drug resistant.
“Within 12 hours we were able to report on three things: The clade, which is 2.3.4.4.b., the severity of the virus and the genotype. Together, these details give governments enough information to assess risk and make important decisions about surveillance, biosecurity and response next steps.”
“Sequencing was confirmed around 9pm Friday. I stayed until it was done, I was too anxious to see the results to leave work,” said Dr Bhardwaj.
“The minute I got the report, I was able to think, ‘ok, now we know, let’s activate the next steps’.”.
Being an accredited reference lab, there are checks and controls at every point of the reporting and testing process.
“I think it was close to 11, 11.30pm before we were able to send through our report,” Dr Bhardwaj said.
We’re just getting started
Once the urgent information was reported, the team continued.
“We took the virus again and looked at other things that people might find useful. Things like if it is avian or mammalian adapted (more likely to infect birds or mammals), can we see any glaring drug resistance markers changing? This information becomes important if the virus spreads to humans,” Dr Bhardwaj said.
Within one business day of sequencing and analysis, the team uploaded the full genome of the virus to the Global Initiative on Sharing all Influenza Data. This means other governments and health researchers can look at the genome as well to support rapid global risk assessments.
“Our counterparts in New Zealand were able to use that genome sequence to compare it with their first cases that arrived not long after,” Dr Bhardwaj said
Another task that takes a significant amount of time is the phylogenetic tree. Essentially, figuring out the family tree of the virus.
“That's really helpful for us to understand where the virus came from, how closely related it is to known viruses, and if it has changed. That's really important. If it’s suddenly more distantly related, we're like, oh, we need to look into this further,” Dr Bhardwaj explained.
Ongoing preparedness, rapid response
CSIRO researchers are also working with collaborators to analyse bird movement, epidemiology and environmental data to better understand and predict how H5N1 may spread in Australia. The work requires multiple disciplines, bringing together bird ecologists, epidemiologists and meteorologists to build a clearer picture of risk.
“All these experts come together to help predict how the virus may move through Australia. Our coastline is so big, so this helps authorities identify where to focus surveillance efforts to best prepare.
“Australia has unique wildlife. There are many unknowns about how H5 will affect our marine mammals, birds and other animals,” Dr Bhardwaj said.
With H5 bird flu now being detected in land and sea mammals, the work at ACDP remains critical to Australia’s ongoing preparedness and response.
“We will keep working to test, sequence, analyse and model to help Australia respond to this virus.”