Solving AMR through a One-Health lens

The newly-funded Antimicrobial Resistance – One Health Consortium managed out of UCalgary* is about to play an important role in how we safeguard the eroding ability of antibiotics to save lives and prevent illness. Its role will be to leverage the capacity and expertise across Alberta, nationally and internationally to find solutions to a looming antimicrobial resistance (AMR) crisis in humans and animals that spills over to the environment—hence the one health approach. Currently, several thousand Canadians die every year from infections with multiple drug-resistant bacteria, and the rate of increase is exponential. Worldwide, the economic impact of these infections is estimated at US$100 trillion/year.

“In the beef industry, there’s a lot we don’t know,” says Dr. Herman Barkema, Scientific Director of the Consortium and NSERC Industrial Research Chair in Infectious Diseases at UCalgary’s Faculty of Veterinary Medicine. “And we can’t even talk about cow/calf and feedlot operations in the same breath because antimicrobial use and resistance differs in each sector.”

For example, calves are treated with antimicrobials on arrival at the feedlot, then they get medicated feed for the duration of their stay. How much resistance that produces, and whether it causes problems in run-off? Who knows? Then, there’s the health of the animal to consider. The public is playing an enormous role in wanting meat products that are raised without antibiotics, which is reducing on-farm use—but perhaps at the cost of sick animals not getting the drugs they need to stay healthy and productive. And of course, there are people—the producers and their families, and the workers in the industry all of whom may be impacted by AMR.

“If we get resistance against frequently-used drugs in the feedlot, we have a problem—and emerging evidence shows that antimicrobials ARE becoming less effective,” says Barkema. “The only way to protect people will be with drugs of last resort, and we should really be careful not to overuse those because they are exactly that… last resort!”

The Consortium’s 27 projects focus on treatment optimization, AMR surveillance, and infection prevention and control under three thematic areas: innovation and commercialization, education and societal impact, and policy, economics and sustainability.

So why are pharmaceutical companies not investing in new antibiotics? Any new drug is likely to be safeguarded like gold, and used only to treat multi-drug resistant infections. So, minimizing drug use is one way to combat resistance—but it doesn’t result in the large sale volumes needed to recoup the $2-4 billion costs to develop and receive regulatory approval for use of an antimicrobial.

Instead, the Consortium is looking to alternatives like phage therapy, new targets, biomarkers, stewardship, the microbiome, as well as optimizing the use of current treatments. It is also developing protocols to change the prescribing habits of veterinarians, pharmacists and doctors, and the usage practices of farmers and people. Vaccine development, hygiene protocols for people and animals, and genetic selection for disease resistance can all lower antimicrobial use.

“We are excited to be involved in this initiative as we know that some animals are more resilient to infectious disease than others,” says Plastow. “Identifying them is the challenge; however, our work in pigs and cattle is helping develop tools to do this. The team. including others at UCalgary like Karin Orsel and Frank van der Meer. have generated phenotypes and samples to push this effort forward. And Gentec’s Janelle Jiminez will be working with these researchers from April to find new funding to exploit these resources.”

Use practices are already starting to change. As of December 1, 2018, the over-the-counter sale of medically-important antimicrobials is no longer allowed. Such products can only be purchased with a prescription issued by a veterinarian. Those are the (relatively) “easy” administrative changes. The Consortium’s innovative solutions will take years to develop, test and employ, although consumer and retailer push (A&W, McDonalds, Maple Leaf, Sobeys, etc.) may accelerate uptake.

“Then,” says Barkema, “we’d better be ready to follow. Our results in beef will apply to other livestock, and connect to people and the environment. If we use less antibiotics in agriculture, there’s less run-off and less soil contamination. That means better drinking water and environment. Everything is linked.”

* The Consortium is Alberta-wide, comprising the universities of Calgary, Alberta and Lethbridge as well as Lethbridge Research Centre, Olds College, Lakeland College, Southern Alberta Institute of Technology and Northern Alberta Institute of Technology.

1,600 chickens… and counting

Because the Leghorn chicken is so prolific (up to 320 eggs/year!), it is the darling of the egg industry, and produces the vast majority of eggs in Canada. They lay white eggs, so it’s easy to tell. For those who prefer a brown shell, you can thank the Rhode Island Red and a few other breeds. Between them, they’ve locked up the market.

So what happened to the breeds we used to see around farmhouses, back in the day? Some of them are in trouble, with few individuals left, certainly not enough for a healthy population. Ten of these breeds (1,600 chickens total) find a home within the Heritage Chicken program at UAlberta (with another population at UGuelph, in case of catastrophe at one location).

“Currently, in-breeding is high among four of the breeds because they’re randomly mated,” says Marzieh Heidaritabar, the Gentec post-doc trying to develop a funded project for the program off the side of her desk. “But this isn’t efficient. Ideally, we want a proper breeding program to select the best animals. Genomics is the best tool to help us select the most diverse sires and females as parents of the next generation.”

Eighty-five chickens have already been sequenced. “That’s how we knew inbreeding was high in the first place,” says Marzieh. Now, another $70K is needed to finish the job, and fund students and tests. She plans to apply to NSERC this year to, hopefully, get the project rolling in 2021.

The goal would be to keep the unique genes in the breeds and increase the number of individuals over 2-3 generations to assess the success of the breeding program—but it may make more sense to merge the breeds if they are genetically close. Secondary objectives would be to examine immunity and behaviour, both of which may increase the suitability of the breeds for certain environments. Two other ongoing projects are working on perching and gait traits.

While Marzieh will go through traditional Tri-Council channels and the higher-tech GoFundMe platform, the program has been creative about fundraising in a different way. $175/year will get you a dozen eggs every other week for 10 months. Or you can adopt-a-rooster instead (similar program minus the eggs).

“Every little bit helps,” says Marzieh, “and it’s a great way to get the public involved.”

Coronavirus: the latest zoonose

Coronaviruses are a family of zoonotic viruses; zoonotic meaning that they can pass from animals to people. SARS is one example, ebola, MERS and H1N1 are others. The sources have been animals as varied as pigs, monkeys, poultry, civet cats and camels. The strain of coronavirus (named COVID-19) currently in the news has been declared a “public health emergency of international concern.” The race to find a vaccine or prevent deaths is intense. To help us understand more about coronaviruses and zoonoses in pigs and people, Gentec spoke to Dr. Egan Brockhoff, Veterinary Counsellor for the Canadian Pork Council.

Gentec: How do we know that the source of a human disease might be animals? How do we know to do a “reverse diagnosis?”

Dr. Egan Brockhoff: Scientists do a whole-genome sequence of the bacteria or the virus, then they look for similarities with other known bacteria or viruses. That indicates where it’s most likely to have originated. It might sound simple but it involves significant scientific exploration. For COVID-19, the pangolin seems to be the animal source. The fact that these animals are eaten makes them a likely source of the jump, but that still needs to be confirmed.

Gentec: Porcine epidemic diarrhea (PED) virus, which is a pretty nasty pig disease, is also a coronavirus that could spread to humans. Why hasn’t it?

Dr. Egan Brockhoff: PED is a delta coronavirus. COVID-19 is a beta coronavirus. Even though they’re part of the same family, they’re only very distantly related. PED is an enteric virus that causes intestinal illness whereas the beta COVID-19 infecting humans is a respiratory virus. Because they’re so different, PED isn’t likely to jump over to humans.

Also, COVID-19 is a new virus. Once it has adapted to its host, it’s not likely to jump back to animals. To give you an example, MERS came from camels and can still be found in camels. But when viruses adapt to a new host, they don’t re-adapt to their original host as easily. Now that COVID-19 has become a zoonose and infected humans, we’re not very concerned that it will jump back. If it does, it would probably go to its most recent host.

Gentec: We’ve seen how fast and how wide zoonoses can spread. Which organizations are involved in containing an outbreak?

Dr. Egan Brockhoff: On a global level, the World Health Organization is responsible for human health, and the OIE (World Organisation for Animal Health) is responsible for animal health. At the federal level in Canada, Public Health Agency of Canada and Health Canada are the competent authorities for human health, and the Office of the Chief Veterinary Officer for Canada and the Canadian Food Inspection Agency are the competent authorities for animal health. Then each province has a chief medical and veterinary officer as well. In other words, many organizations must work together to find the best methods of control.

Gentec: So how do they talk to each other? What do they monitor? How do they decide on the best actions to take?

Dr. Egan Brockhoff: Both the WHO and the OIE are in constant back-and-forth communication with their member states. In terms of COVID-19, both were consulted, and the WHO has now landed a body of experts into China to work on this disease. In fact, renowned Canadian epidemiologist Dr. Bruce Aylward will be leading that team.

Canada and other developed nations have a very robust infrastructure for communicating with the WHO and OIE but in other countries, that may vary more. In this situation, China is working very hard with its public health authorities to understand and contain the disease, and the WHO is assisting and communicating back to the OIE. But let’s be clear, COVID-19 is not an animal health outbreak, it’s a public health outbreak. The OIE doesn’t have to be highly engaged beyond helping the authorities understand the coronavirus in its most recent species.

Gentec: What actions are being or have been taken to mitigate spread of PED in animals?

Dr. Egan Brockhoff: Again, let’s be clear. PED is not a zoonose, it’s a highly infectious enteric virus—for pigs. So bioexclusion, that is, the external biosecurity efforts to take to keep disease out of the farm are key. For PED, critical steps including washing all incoming transports to ensure they are virus-free, making sure you limit access to the controlled access zone around the farm, ensuring that people who must enter the farm wear boot covers, remove their footwear and clothing when they step over the line and go through a shower on the way back. And of course, wearing farm-specific clothing.

African swine fever kills nearly all infected pigs. The same measures of bioexclusion will keep it out of the farm. Because it’s not an aerosol virus (transmission through droplets or particles in the air), it moves by allowing infected animals or products to move on or off a farm. For example, feeding contaminated food items to healthy pigs will expose them to this disease. Because people can’t get it, good basic bioexclusion will keep the virus from affecting the population.

Gentec: The founding head of Ontario Public Health has spoken publicly that travel bans for zoonoses are ineffective, xenophobic and not evidence-based. Do you agree? 

Dr. Egan Brockhoff: Every disease has unique features in terms of infectivity rates and routes by which it infects, so the story changes a bit but in general, that’s accurate. The WHO echoed those sentiments as well. Travel bans are not necessarily effective. Typically, with infectious diseases, people are infectious before they have clinical signs. The flu is a good example. All the early work done on COVID-19 echoes that. So, people can move all over the world before they know they’re infected. At best, travel bans can slow the spread but not contain it.

Gentec: Do you find that the public are informed and correctly informed about zoonoses, particularly those coming from pigs?

Dr. Egan Brockhoff: The public has every opportunity to access good information from the competent public health authorities. But there’s absolutely no question that social media has made it challenging for the public because there’s so much non-professional information out there as well.

Gentec: What’s your message to the public about zoonoses?

Dr. Egan Brockhoff: Washing your hands is one of the most effective things you can do to protect yourself from all infectious diseases, whether they come from other humans or from animals. Use good sanitation in the kitchen. And cook meat to a temperature that kills bacteria and viruses. You can use a food thermometer for that. Meat doesn’t have to be burnt to a crisp to be safe. And you don’t have to become a vegetarian either. Plenty of foodborne illnesses come through plants.

Gentec: Thank you, Dr. Brockhoff, for taking the time to do this interview.