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Whole-Genome Sequencing Gaining Traction in Public Health, Outbreak Surveillance

ATLANTA (GenomeWeb) – Whether or not whole-genome sequencing is ready to be applied to public health questions may no longer be up for debate, according to speakers at the ASM Microbe 2018 meeting here.

Though the technology is still evolving, speakers during a session on next-generation sequencing in clinical practice said that questions of whether whole-genome sequencing might be a beneficial tool for public health microbiology may be moot as it is already being applied in the field. Researchers from across the globe are using sequencing approaches for public health surveillance to identify clusters of infectious diseases and trace them to their sources.

"Genomic surveillance is neither hope nor hype, it is a reality," said the University of Oxford's Martin Maiden during his talk.

During that same session, the Public Health Agency of Canada's Celine Nadon noted that her agency has relied on whole-genome sequencing to uncover sources of Listeria monocytogenes, Escherichia coli, and Salmonella enteritidis outbreaks. In some cases, she said they found sequencing to be better than conventional approaches.

For the Listeria outbreak, she and her colleagues relied on both pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing to analyze cases. They found that PFGE gave a large number of false positives — only about half the clusters were true clusters. This, she said, could explain why they had difficulty deciphering some past outbreaks, as they might not have been true ones.

At the same time, Nadon also said that whole-genome sequencing was much better able to detect S. enteritidis outbreaks — including a number of small outbreaks — than conventional approaches.

Similarly, in a separate poster talk session on outbreak detection, the US Centers for Disease Control and Prevention's Lavin Joseph described how he and his colleagues used whole-genome sequencing to trace a multidrug resistant Campylobacter jejuni outbreak in the US that was linked to pet store puppies. Dogs, he noted, can be healthy carriers of C. jejuni.

He and his colleagues sequenced and performed PFGE analysis of isolates from the outbreak. Their whole-genome multi-locus sequence typing analysis split their isolates into three clades, which Joseph said had a better concordance with the epidemiological data they collected than did PFGE results.

Brent Gilpin from the Institute of Environmental Science and Research in New Zealand used both multiplex binary typing and whole-genome sequencing to examine Campylobacter jejuni from an outbreak. He noted during the poster talk session that this enabled the researchers to narrow the exposure window and link the outbreak to a well that had been contaminated by a nearby sheep farm after heavy rains, as the water and sheep harbored nearly indistinguishable C. jejuni genotypes.

Likewise, Anthony Smith from South Africa's National Institute for Communicable Diseases and his colleagues used whole-genome sequencing to trace an L. monocytogenes outbreak to a single source, bologna processed by a particular company. This, he said, led to a recall and the shuttering of the company's facilities for cleaning.

However, there are still challenges to using whole-genome sequencing in public health applications, researchers said. During the clinical practice session, University of Oxford's Derrick Cook noted that a knowledge base still needs to be built up. He has been working on building such a capacity to use whole-genome sequencing to diagnose mycobacterial infections and determine their antimicrobial susceptibility. It has been, he said, an eight-year endeavor during which they had to develop new tools, but he and he colleagues recently reported in the Journal of Clinical Microbiology that whole-genome sequencing can accurately predict species and drug resistance.

But, the accuracy for other pathogens, he noted, would be only as good as the catalog to which samples are compared.

Others also wondered whether sequencing would be as capable as current approaches for detecting antibiotic resistance.

In his talk, BioMérieux's Alex Van Belkum noted that current approaches for antibiotic susceptibility testing are well fixed, accepted, and cheap. He also noted that not finding a resistance marker or gene in a pathogen doesn't necessarily mean that it won't be resistant, as there are unknown resistance genes.

He added that sequencing would have to overcome all the same issues facing classical testing approaches as well as additional ones, including regulatory hurdles. "We still have a long way to go," Van Belkum said.

Other speakers during that session countered that the use of sequencing in public health surveillance and investigations is already underway. "I can't think of a single area of what a public health microbiology lab does that hasn't been touched by whole-genome sequencing," Nadon said.