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Developing ASSETS to combat antimicrobial resistance in livestock

April 28, 2020

Researchers Cheryl Waldner and Simon Otto are harnessing genomics to help livestock producers quickly match diseases to the most effective drugs and, in the process, helping to combat a looming threat to animal and human health.

Since the first antibiotics were discovered in the late 1920s, researchers have engaged in an arms race of sorts as microbes (such as bacteria) developed resistance to existing drugs. Today, some microbes are resistant to commonly used antimicrobials, and a few are resistant to all known antimicrobials.

“If we don’t address the development of antimicrobial resistance, experts in a recent report to the Canadian government warned that 396,000 Canadians could die by 2050,” Waldner said. “The cost to hospitals could be an additional $120 billion and there could be a loss of $388 billion in GDP to the Canadian economy.”

Many of these same antimicrobials are used in livestock, so strategies to combat antimicrobial resistance in food animals are critical to both human and animal health.

“Antimicrobial stewardship is a shared responsibility between human and animal health professionals and the people that use the drugs – both patients and animal owners,” said Waldner, who is herself a veterinarian, a cow-calf producer and a professor at the Western College of Veterinary Medicine at the University of Saskatchewan. Otto is a veterinary epidemiologist and assistant professor with the University of Alberta’s School of Public Health.

The Genomic ASSETS (Antimicrobial Stewardship Systems from Evidence-based Treatment Strategies) for Livestock initiative aims to develop efficient new tools to help manage antimicrobial use. The Genome Prairie project is backed by combined $5.6 million in funding through Genome Canada’s Large-Scale Applied Research Project (LSARP) program, together with the governments of Saskatchewan and Alberta, and Agriculture and Agri-food Canada, as well as beef and feedlot industry funding partners.

Part of the problem in managing antimicrobial drugs is that health professionals have no fast, practical way to know which disease-causing microbes are present. Lacking this, physicians and vets must rely on experience, clinical data and product research. For example, if infectious respiratory disease is suspected, samples taken from the upper respiratory tract of humans and animals, are sent to labs to identify the pathogen and recommend appropriate antimicrobials. However, lab results can take several days.

To save lives – and prevent disease spread – physicians and vets often immediately administer broad spectrum antimicrobials. Livestock producers and feedlot operators have a different perspective. To protect the herd, and their investment, they often treat prophylactically using broad spectrum antimicrobials to reduce the potential for a disease outbreak.

However, the more often an antimicrobial is used, the higher the likelihood that microbes will develop resistance to the drug. This is the danger for both animal and human health.

Reducing the testing lag time eliminates the need for immediate and widely used administration. Waldner and Otto aim cut this down to hours. ASSETS uses metagenomics, an approach that identifies all the genetic material in a sample. This can be matched with a database of known pathogens and genes to identify not only microbes, but also what drugs they might be resistant to. This allows vets to choose the most effective drugs. Partners at Agriculture and Agri-food Canada are looking at a complementary rapid test known as RPA (recombinase polymerase amplification).

“Our first objective is to leverage genomic technologies for comprehensive one-step analysis to identify pathogens and antimicrobial resistance genes in the lab in hours rather than days,” said Waldner.

For beef cattle producers, this would allow them to sample a group of animals when they arrive at the feedlot and work with their vet to generate diagnostic information to inform treatment – something Waldner and Otto call pen-level precision medicine.

The researchers anticipate the ASSETS tools will be accessible to vets with timely results provided to producers. The beef and feedlot industry will be involved through engagement and field trials as end-users. For example, the researchers need to work out testing strategies such as how and when to best collect samples and how many cattle need to be sampled. All these elements will need to be tested on-site to make sure they yield useful information and are compatible with feedlot practices.

“Our research team includes practicing feedlot veterinarians that will implement the technology in pilot projects and inform its practical development,” said Waldner.

“There is the potential for metagenomics and other tools, such as RPA, to be adopted in veterinary clinics,” she said, adding that genomics benchtop equipment can be linked to diagnostic labs to interpret results and inform decisions on which antimicrobial to use in a given situation.

While antimicrobial resistance is the main target of ASSETS, the tools will also be valuable for managing other aspects of animal health.

“The primary result will be precision use of antibiotics – quick and accessible information for veterinarians to tailor antibiotic therapy for individual pens of calves,” Waldner said. “The same tools used to identify bacteria and potentially viruses identified in calves arriving at feedlots can also pinpoint vaccine gaps for cow-calf producers.”wcvm188-1592_49565274273_o.jpg

Photo: Beef calves in the Beef Cattle Teaching and Research Unit at the University of Saskatchewan’s Livestock and Forage Centre of Excellence (LFCE). Photo by Christina Weese.