Catching the flu – early
By Chris Rodley
The flu has often been mistakenly considered more of a nuisance than a serious threat to human health, a relatively minor ailment to be endured with the aid of bed rest and chicken soup.
It’s curious that one of the world’s deadliest diseases has such an innocent reputation, says Kevin Downard, a researcher from the School of Molecular Bioscience who has been studying the virus for 15 years. “This is not an innocuous beast,” he explains. “Familiarity has bred complacency. You’d think very differently about it if you’d lived through the 1918–19 pandemic.”
As many as half a billion people became infected and up to 100 million people died in the Spanish flu pandemic that broke out at the end of the First World War. Among them was Associate Professor Downard’s own great-grandmother, a London charwoman. Another flu pandemic could happen at any time, he says, and it could kill just as many people again or even more.
Our main defence against it is an international surveillance network, overseen by the World Health Organization, which has served as an early warning system for influenza since the 1950s. Potentially dangerous outbreaks of flu are characterised using the polymerase chain reaction (PCR). A sample of virus is first collected then transferred to a laboratory, converted to double-stranded DNA, copied to increase the amount of DNA, then identified. The entire process can take several days.
But soon, thanks to a breakthrough by Professor Downard, health authorities may have access to a new testing protocol for influenza viruses that is faster and simpler while being just as effective. According to the scientist, that could make a big difference in the crucial early stages of a pandemic.
Professor Downard’s test relies on detecting signature peptides, or segments of viral protein. “In every type and subtype of influenza, there are peptides that have a conserved amino acid sequence and a unique mass that allow the virus to be characterised by their detection alone,” he explains. In his procedure, a sample of the whole virus is first broken down and then placed in a high-resolution mass spectrometer which reveals the mass of the constituent peptides. The technique is known as proteotyping.
In contrast to the time-consuming PCR method, Professor Downard’s approach takes less than a minute to analyse a prepared sample once the virus has been broken down by the enzyme. Even more importantly, the procedure is simple enough that, in the future, it could be carried out in a mobile laboratory on the front lines of an outbreak.
"The procedure could be carried out in a mobile laboratory on the front lines of an outbreak. There would be no need to fly a sample from a remote village."
That means there would be no need to fly a sample from the site of an outbreak – which could be a remote village – to a laboratory which could be thousands of miles away. Health authorities would be able to know almost immediately if a dangerous virus had appeared and where it had spread to.
Localised outbreaks or single, infected individuals could be isolated at once, and work on vaccines or distribution of antivirals could begin immediately. In combination with existing surveillance and response measures, it could help to slow a pandemic or perhaps even avert one all together.
As well as speeding up our public health response, Professor Downard’s method could also prove useful to the laboratories that develop new drugs to combat the flu. His lab has used mass spectrometry to show whether the proteins of particular strains interact with antiviral drugs and thus whether they are resistant. Its a procedure that could help in developing new, more effective antivirals. It may also shed new light on how strains are evolving from one lineage to another, potentially helping to predict how they will evolve in the future (a vital task when developing a vaccine).
The rapid testing procedure could also find a use in clinical settings. If doctors were able to quickly determine that a patient definitively has influenza, they would not need to follow the widespread practice of prescribing antivirals as an insurance policy to patients with flu-like symptoms. That would help to check the growing problem of antiviral-resistant flu strains, which mirrors the rise of antibiotic-resistant bacteria.
Currently, Professor Downard is continuing to refine his proteotyping procedure and perfecting the approach for testing nasal swab specimens, while exploring ways to widen the application of the method to study virus evolution. He has the assistance of two ARC Discovery grants, and is also looking for investors to help him commercialise the discovery and promote its use in flu surveillance.
The scientist credits his breakthrough to a long-held fascination for the mass spectrometer, a technology first developed nearly a century ago to identify isotopes and measure atomic weights. “I’m an instrument sort of guy,” he says. “I like playing around with equipment.”
Beyond the satisfaction of seeing his research bear fruit, he is also excited about the potential to make a widespread impact on human health: “Obviously it is too late to help my great-grandmother, but it’s nice to think that I’m working on something that could help others.”
He notes, however, that there are no guarantees the world will avoid another pandemic like the one in 1918–19. “Having all this technology still might not help you if a strain emerges that’s very deadly and spreads very quickly, and if your antivirals and vaccines aren’t effective,” he says. “Then you’ve got a problem."
The University of Sydney wasn’t spared when Spanish flu arrived in Australia in 1919, most likely brought back with the ANZACs from the Great War. As the pandemic raged across the city, afflicting almost 40 percent of Sydney’s population, the campus was shut down by government order along with schools, cinemas and racecourses across the country.
When it reopened five weeks later, emergency measures were introduced by the Professorial Board to curb the spread of the disease. Students were commanded to wear masks in class and all members of the University were asked to undergo repeated inoculations at the Department of Pathology. According to Kevin Downard, the bacterial vaccine used at the time, which was manufactured by the Commonwealth Serum Laboratories in vast quantities, may have been of some help against the virus, if only because it stimulated an immune response.
Meanwhile, many of the University’s medical students joined the army of volunteers staffing flu hospitals in temporary locations such as the Sydney Showground. Dr Cawley Madden, a third-year student at the time, later wrote of his experience tending the sick and dying in one of the makeshift hospitals. “I had had no clinical training,” he recalled, “but I was able to look like a young doctor, and dole out the stock medicines and the instructions I was handed. Perhaps I doled out a little confidence to the poor people too.