New genomic technology to fast-track detection of Legionnaire’s disease

To help to detect Legionella bacteria more quickly and protect public health, researchers, supported by NSW Health’s Translational Research Grant Scheme, are setting up a new surveillance system that can also identify different DNA strains.

Rapid medical detective work is needed when a person is diagnosed with Legionnaire’s disease, a severe type of pneumonia that results from exposure to contaminated water vapour droplets or dust. Timely identification of the source of the Legionella bacteria that causes the infection, is critical to preventing further cases and minimising outbreaks, which can occur in clusters, affecting numerous people at once. 

In the future, this work will also be supported by a NSW Government investment of $492 million in a new NSW Health Pathology Statewide Hub in the Westmead Hospital Precinct. Investment in the new hub is essential for the delivery of new and enhanced pathology services and includes a new build for the Institute of Clinical Pathology and Medical Research. 

In addition, and to speed up containment of diseases linked to Legionella bacteria, the Office for Health and Medical Research is supporting a research project to establish and trial a new laboratory-based surveillance system for disease prevention, control and management. The Office has provided funding support through the Translational Research Grants Scheme. To learn more about this project, the Office spoke to Professor Vitali Sintchenko and Dr Eby Sim about their collaborative research. Both are based at the Westmead Health Precinct.

Legionella bacteria impacts and public health protection  
Vitali Sintchenko is a Professor from the School of Medical Sciences at the University of Sydney and a Clinical Microbiologist at the NSW Health Pathology Institute of Clinical Pathology and Medical Research. He is an expert in the bio-surveillance of communicable diseases that impact public health. Using up-to-the-minute tools and information, he is improving accuracy of predictions about the behaviour and modes of transmission of microbial pathogens, such as Legionella bacteria:  
 
Where is Legionella bacteria often found? 
“Legionella pneumophila, can grow in water cooling towers used in air conditioning systems in large buildings and also in artificial water sources.”  

What health issues can this bacteria cause? 
“Symptoms, which often occur two to 10 days after exposure, may include fever, chills, coughing, headache, muscle aches, lethargy and shortness of breath. The Legionella bacteria either causes Legionnaire’s disease, or Pontiac fever, which is a milder respiratory infection.” 
 
What are the aims of your research project?  
“Our team is developing a diagnostic workflow to assist rapid genomic (DNA) analysis of Legionella bacteria from respiratory samples taken from patients. An anticipated project outcome is the integration of legionella whole of genome sequencing. 

Recent advances have made it possible to sequence DNA of different pathogens found in patients’ clinical samples, to decipher their genetic code. This direct sequencing is beneficial for detection of Legionnaire’s disease as Legionella bacteria is notoriously difficult to culture in the lab. Our research also aims to provide proof-of-concept evidence for statewide implementation of this new Legionella surveillance system. This new system is designed to improve patient outcomes and reduce public health risks by adopting these faster methods for linking human cases to environmental sources.” 
 
How has the Office funding supported your work? 
The Translational Research Grants scheme has provided us with funding which has been used to employ a team of dedicated research staff and also procure consumables and re-agents that are needed to conduct lab experiments. This support has been instrumental for the project and for the translation of the project’s findings into lab practice.” 

What happens when Legionella related infection is suspected? 
“Laboratories and hospitals are required to confidentially notify the cases to Public Health Units in NSW. Staff then interview patients about their illness and possible exposures, to start trying to join the dots to track down possible sites of contamination and take samples from them.” 

Identifying Legionella bacteria DNA for surveillance 
Dr Eby Sim is a Research Fellow from the School of Medical Sciences at the University of Sydney. He is based at the NSW Health Pathology Institute of Clinical Pathology and Medical Research. His work involves the use of DNA sequencing to investigate the genetic make-up of microbial pathogens such as Legionella, to help detect their emergence and spread.

How do you extract DNA information to identify different strains of the bacteria? 
“Currently, to identify Legionella bacteria, respiratory samples are taken from the patient and placed on agar plates in the lab to see if the bacteria can grow, which can take one to two weeks. Instead of doing this, the new system uses those samples for ‘DNA extraction’.  

For this process we break the cell apart, use chemical and physical means to release the DNA and purify the DNA to convert it into a molecule. This is then run through a machine called a DNA sequencer, which performs whole genome sequencing. The subsequent analysis provides information about variations, insertions and deletions to the Legionella bacteria DNA, which can help shed light on the origins of the outbreak.” 

How will your approach speed up Legionella bacteria detection? 
“With this surveillance system, if numerous people have developed illness but are carrying different Legionella strains, we know there are likely two different sites of exposure, not one. We can then look for patterns of geographic movement or other connections within each patient group to help track public outbreaks faster and help prevent further cases.”