As Legionnaires’ disease outbreaks become more frequent, a team of NSW scientists are exploring whether genome sequencing could help pinpoint the source sooner.
Since July, researchers from NSW Health Pathology, Westmead Hospital and the University of Sydney have studied the potential of rapid genomic sequencing, a scientific technique that reveals the entire DNA signature of an organism.
The goal of this NSW Health-funded research is to create a surveillance tool that analyses both clinical and environmental samples for quicker confirmation of an outbreak’s source — a task often challenging and time-consuming for public health authorities to achieve.
The theory underscoring this study is genomic sequencing — which is largely known for its use in confirming genetic diseases, potentially in a matter of hours — could identify specific strains of Legionella pneumophila, known as Legionella, a bacteria responsible for Legionnaires’ disease.
“Genomics, in broad terms, have been [used] for confirming outbreaks and linking clinical cases to environmental sources for a long time,” Vitali Sintchenko, a microbiologist with both University of Sydney and NSW Health, as well as one the study’s co-investigators, said.
“The study aims at applying the genomic techniques to link Legionella cultures from environmental samples and cultures from clinical cases, and identify these potential clusters faster.
“We’re talking about building a system which is prospective, so it’s not [responding] to an already-established outbreak.
“You want to have a system which prospectively surveys clinical cases and environmental isolates and identifies links.”
Over the last three decades, the potentially lethal disease has become more prevalent. According to federal data, the annual number of confirmed cases lifted from 33 to 237 between 1997 and 2023.
During July and August this year, an outbreak of Legionnaires’ disease in Melbourne saw more than 100 cases of infection with two confirmed deaths.
“If successful, this research will enable public health authorities to confirm clusters of cases sooner, potentially helping them identify the source of infection and prevent further spread in the community,” NSW Minister for Medical Research David Harris said.
An accidentally-acquired infection
The difficulty in responding to a Legionnaires’ disease outbreak circles around how Legionella infections begin.
Rather than person-to-person, Legionella spreads through water, with contaminated cooling towers — including those found in the air conditioning systems used in offices or hotels — being the most common cause of outbreaks.
“It’s an accidental human pathogen. It hasn’t evolved to spread from person-to-person. It’s really an opportunistic, unfortunately accidentally-acquired, infection,” Elizabeth Hartland, a microbiologist and both the director and CEO of the Hudson Institute of Medical Research, said.
“When there’s one contaminated water source that then is aerosolised in a major way across a large region, then we see that as an outbreak.”
Physicians and microbiologists have long understood how Legionnaires’ disease spreads and the place of cooling towers in this equation. What’s more difficult is locating the exact origin of an outbreak.
One reason why is time, with symptoms of Legionnaires’ disease generally appearing within 10 days from initial infection. Then, once a Legionella infection is suspected, confirmation from a laboratory roughly takes seven days.
“Once somebody does start displaying symptoms, a lot of clinicians might not immediately jump to Legionella as the cause,” Professor Hartland said.
‘Outbreaks can be very complex’
Compounding this is the number of environments — specifically cooling towers, that Legionella can contaminate and spread.
“These outbreaks can be very complex, with hundreds or thousands of cooling towers potentially in an area that need to be tested and investigated,” Norelle Sherry, the deputy director of the University of Melbourne’s Microbiological Diagnostic Unit Public Health Laboratory, said.
“If we’re waiting seven to 10 days to get the cultures and the sequencing data and be able to bring that [information] together, that’s a long lead time for public health teams to be waiting for data.”
The current approach for public health authorities to locate the source of outbreak relies on interviews with the infected to discern potential areas of interest. If genome sequencing is used, it’s to discover potential links between cases after an outbreak or cluster is suspected.
“Anything we can do to shorten that time period means earlier public health actions and potentially fewer cases,” Dr Sherry said.
‘We can prevent cases of exposure’
In recent years, researchers have attempted to develop new tools to accelerate the investigation and confirmation process of an outbreak, including artificial intelligence as well as biosensing technology.
Professor Sintchenko sees his research, if successful, as enabling clinicians to routinely test samples to quickly and accurately identify whether infections in multiple infections are the result of the same strain. Even if the links aren’t obvious.
“We’ll have a system that can identify common sources of infection faster and with less resources from public health than we have now. And as a result of it, we can prevent cases of exposure,” he said.
“The game is really about [being] as quick as possible in recognising these clusters at the beginning. Not at the peak, but [at] the beginning and flatten the curve.”