Pinpointing pathogens

28 April 2023

As the leading Clinical Scientist of public health and epidemiology at SA Pathology’s Microbiology and Infectious Diseases (MID) laboratory, Dr Lex Leong is delivering pinpoint accuracy when it comes to COVID-19 infection.

Lex was working at SAHMRI when he first began exploring the use of genomics as a surveillance tool for pathogens – bacteria, fungi and viruses that cause disease in humans. It was this work that put him in contact with SA Pathology’s Dr Ivan Bastian.

Together, they envisioned a bright future for genomics in clinical microbiology and for public health surveillance, and it was this vision that prompted Lex to make the move to SA Pathology in 2018 to establish a Whole Genome Sequencing (WGS) program to improve the monitoring of pathogens in the South Australian community.

“I was a one-man band back then, where I did most of the genomics - wet lab, dry lab, analysis and also reporting and everything all by myself; now I have a team which is great!” says Lex.

He says the challenge now is keeping up with his team’s momentum. “We’re getting more scientists and postdocs coming into the laboratory, they bring a passion for research and for delivering translational science.”

Why genomics?

WGS offers significant advantages over traditional testing methods. Importantly, it increases the range of pathogens being tested.

“If previously we were testing specifically for 4 pathogens, with WGS we’re now testing for 20-30 plus pathogens from viruses, bacteria to fungi, and the workflow is pathogen agnostic, which means it will identity any pathogen present in a sample – including new and emerging pathogens.”

Using WGS provides much more information about the pathogen than traditional methods, including identifying changes in the genes of the pathogen, and where these changes might result in resistance to treatment or increased virulence.

This information is critical to identifying the epidemiology of a pathogen, how it is spreading through the population and who it is infecting, especially in a pandemic.

COVID-19: A proving ground

When COVID-19 started, SA Pathology investigated the deployment of WGS to type variants of SARS-CoV-2 and its potential to track the virus in South Australia’s population. With a heavy research focus, SA Pathology began sequencing all COVID-19 cases and rapidly enabling epidemiologists to track transmission.

“Interestingly, COVID-19 has a relatively stable genome, meaning that it doesn’t change very quickly, so you can easily pinpoint if person A has transmitted the virus to person B. That’s what enabled us to identify linkages between cases in quarantine hotels.

“We started with a cleaner in the hallway getting COVID-19; it turns out that it was from a COVID-positive person under isolation in the hotel. They were in their hotel room with their window open and when they coughed, the wind carried the virus and someone caught it. Without surveillance testing using whole genomic sequencing, which tells us the exact identity of the virus, we would never have been able to identify the origin of this outbreak.”

National surveillance

Since 2016, SA Pathology has been part of the national Communicable Disease Genomic Network (CDGN), aimed at promoting the use of genome analysis for the identification of communicable and notifiable diseases. Operating as an Expert Reference Panel of the Public Health Laboratory Network, CDGN reports findings to the Communicable Disease Network Australia which informs public health policy for Australia.

“SA Pathology has been collaborating with other states and jurisdictions to use genomic sequencing and increase genomic capacity in each state. We also share our genomic sequencing results across the network.”

South Australia was considered a small jurisdiction in the field of WGS of pathogens when they joined the CDGN, but through the work of Lex and his team, SA Pathology’s output is now almost on par with the eastern states.

Underpinning this model is AusTrakka, Australia’s national genomic surveillance platform that coordinates the rapid response to disease outbreaks across the country, including ongoing surveillance of the COVID-19 pandemic. The platform captures and shares the genomic sequencing results of pathogens from across the country and New Zealand, monitoring for any changes in frequency of occurrence or changes in the genome that might indicate an outbreak or increased resistance to treatment, or both.

The research team is also developing an understanding of how pathogens occurred in the Australian population in the past. Member organisations are sending WGS results of pathogen isolates from the past to AusTrakka, one pathogen at a time, to track early transmissions and outbreaks.

“Having the whole picture of the pathogen’s occurrence in the community enables us to see what an outbreak looks like in the past and going forward. Continuous surveillance is vital, without it, our information is far more fragmented.”

Translational science benefiting remote communities

CDGN’s capability was again proved during a recent tuberculosis outbreak on Anangu Pitjantjatjara Yankunytjatjara (APY) lands, involving communities in South Australia and Western Australia.

SA Pathology is playing a key role, working with Dr Simone Barry from the SA Tuberculosis Services at the Royal Adelaide Hospital, to better understand the cluster to enable an appropriate public health response.

This fundamentally important work, a combination of clinical service and complementary genomic investigation, is contributing to a national program and, in this case, having a profound impact on protecting our most remote communities.