Detecting levels of a single biomarker in the blood can identify which patients will develop dangerous influenza infections
Australian researchers have developed a blood test that provides an early warning signal for life-threatening respiratory tract infections.
By spying on the severity of the immune system’s response to the influenza virus, the test can specify the risk of pneumonia and death over the coming days or weeks with a high level of accuracy.
Researchers found that patients with severe influenza infections tended to upregulate the expression of a single gene biomarker IFI27 compared with people with other viral or bacterial infections.
“We can see a beautiful trend,” lead researcher Dr Benjamin Tang, from the Westmead Institute for Medical Research in Sydney, said.
“If someone is infected with influenza then we can see the signal start to go up within the first day.”
In patients with mild influenza infection, IFI27 levels are usually around 10 to 20-fold higher than in healthy individuals.
Severe influenza that results in hospitalisation or presentation to emergency department is associated with at least a 74-fold increase in IFI27.
Usually, a dozen or even hundreds of biomarkers needed to be mapped out to determine an immune response to a pathogen, which was impractical in a clinical setting, Dr Tang said.
But through a series of discovery cohorts, validation tests and in vitro experiments, the researchers found that the single biomarker, IFI27, was as diagnostically powerful as multi-gene biomarkers.
In a prospective study published in Respiratory Infections, the team tested for IFI27 using existing real-time PCR technology in more than 400 patients with respiratory tract infections.
They found that IFI27 could distinguish between influenza and bacterial infections with a sensitivity of 80% and specificity of 90%.
The biomarker could also separate other viral infections from influenza.
Crucially, IFI27 could also stratify patients with influenza based on their risk of complications and death, Dr Tang told The Medical Republic. However, this important application of the research was buried in the supplementary material of the paper.
The researchers were asked to rewrite their paper to focus on the capacity for IFI27 to reduce unnecessary antibiotics prescriptions during the peer review process.
But an upcoming paper will provide new details, such as the fact that 85% to 90% of patients with IFI27 levels increased 74-fold develop serious infections.
If a doctor knew a patient had an influenza infection and that symptoms were unlikely to resolve on their own, they could prescribe antiviral medication, such as Tamiflu, much sooner, Dr Tang said.
“There have been quite a lot of large studies coming out in the last few years showing that the sooner you start antivirals, the more likely that you are going to save a life and prevent complications such as viral pneumonia down the track,” he said.
The second paper will also reveal that testing for high IFI27 levels can predict the risk of a patient dying with 85% to 90% accuracy.
“If there is a high risk of death you are obviously not going to send the patient home,” Dr Tang said. “You want to admit the patient or you want to alert intensive care doctors to keep an eye on this patient.”
While this new technology was exciting and had been patented in Australia, Dr Tang said the test needed at least two to five years of further development.
One big unknown is how long a patient has after testing positive for high levels of IFI27 before they develop a serious illness.
Due to budget constraints, the research only took blood samples at one time point instead of daily, which would have divulged this time lag, Dr Tang said.
The study also needed to be replicated in other patient populations and across different clinical settings but so far the results were promising, he said.
“We are being cautiously optimistic.”
Respiratory Infections 2017, 15 June
