Animal & Veterinary
Canadian Integrated Program for Antimicrobial Resistance Surveillance by Richard Reid-Smith, DVM, DVSc
DR. REID-SMITH: Thanks, Ezra. And thanks to the organizers for inviting me to present some of the information about CIPARS. So CIPARS is the Canadian Integrated Program for Antimicrobial Resistance Surveillance. And my intention with this presentation is not to cover a whole lot of results. I’m just going to maybe present a few examples primarily on, present the structure of CIPARS. You will get a little bit of the results from CIPARS in Lucie Dutil’s presentation tomorrow.
So, the development of CIPARS is similar to the development of NARMS. We started off with some consensus conferences including one in 1997, the same year as the Berlin Conference. In 2001 obviously the WHO Global Strategy came out.
And then in 2002 there was a Health Canada Advisory Committee Report on the impact of antimicrobial use in agriculture on human health. And both the 1997 Conference and the 2002 Advisory Committee Report recommended the establishment of a program to monitor antimicrobial use in food animals and to monitor antimicrobial resistance in the food chain.
So, in conjunction with that and following that there was some moves to put some funding in place, to develop a surveillance program.
Now, Canada already had a -- the Canadian Nosocomial Infection Surveillance Program, or CNISP which is a hospital based program that is run by the Public Health Agency or in partnership with the Public Health Agency with Mike Mulvey as the lead of that, which would look at the antimicrobial resistance organisms in the hospital acquired setting, particularly in the area of MRSA. So CIPARS wasn’t about that, it was about resistance in the food chain.
And so the preliminary objectives of CIPARS was to provide a unified approach to monitor trends and resistance and use in humans and in animals, but there again, the resistance in humans in the food chain, and to generate data to facilitate assessment of that public health impact described in the Health Canada Advisory Committee Report.
So, some of the things CIPARS set out to do, identifying trends over time, detecting the emergence of resistance through MIC changes, integrating the data. So trying to follow the example of what an integrated system would have, which was both human data, animal data, and resistance data and use data.
And it was a requirement at least by the Healthcare Advisory Committee Report that it be at least compatible with NARMS, to as great an extent as possible, methodologically, that it would be a source of information for risk assessment and a basis for research and we would have timely reporting and I’ll come back to that at the end.
So, the structure of CIPARS is it’s evolved over time. It’s a bit different than NARMS in that it -- the operational structure of CIPARS is primarily within the Public Health Agency of Canada. And there is some evolution over time accounting for that. It wasn’t by intent, but the Public Health Agency of Canada is essentially the counterpart of CDC.
So, all of the stuff that is done by FDA, or not all of the -- a lot of the work that here is done by FDA and also by USDA is actually done by the Public Health Agency of Canada. And supported by the Health Canada which is the FDA counter-part and by the Canadian Food Inspection Agency with is the FSIS counterpart.
In addition, there is the CIPARS Public Health Partnership, Canada as you probably know is a confederation of 10 provinces and three territories. And most of the healthcare public health is actually a provincial mandate, not a federal mandate. There are federal activities, but the primarily delivery is at the provincial level.
In addition, the regulation of veterinary medicine and the sale of antimicrobials on the animal side is also a provincial mandate even though the approval of the drugs for sale or for use is a Health Canada mandate, a federal mandate.
So, the Canadian -- CIPARS public health partnership is a collective of the 10 provincial ministries of health that contribute to the human arm of CIPARS.
And then the provincial ministries of agriculture help out as well, some are more actively involved then others, principally Quebec, Saskatchewan and Alberta and B.C.
And then the abattoirs that help would be slaughter sampling and farms that assist with the farm sampling, which I’ll come to in a moment.
Laboratory operations, we essentially have two main labs that are involved, the Lab for Foodborne Zoonoses, which is where I am, and the National Microbiology Lab in Winnipeg. So, LFZ is responsible for the food and animal components of CIPARS. In addition we have some work on the retail sampling in Atlanta, Canada that is done at the University of Prince Edward Island. And some of the molecular characterization of the food and animal isolates are done at the University of Guelph, Patrick Borland’s lab.
And then the National Microbiology Lab looks after the human side, including the molecular characterization. Susceptibility testing is the same as NARMS, Sensititre, NARMS plates and the same methods for both the human and animal arms.
So, schematically the integrated program on this quadrant, we have the human sample side so that provincial, those 10 provincial labs forward isolates to the National Microbiology Lab and the responsibility of that rests with the National Microbiology Lab and the Center for Foodborne Environmental and Zoonoses Infectious Diseases, to manage that.
And then on the animal side, we’ve got diagnostic samples, farm samples, slaughter plant samples and retail samples that go to the Laboratory for Foodborne Zoonoses.
Collection of human drug use data, that’s data that’s purchased through IMS, Health Canada and analyzed by the Center for Foodborne and Environmental Zoonoses Infectious Diseases. And then the animal data, such as it is, that’s collected through the Lab for Foodborne Zoonoses.
The Lab for Foodborne Zoonoses, is a bit different, it’s a lab it’s got both laboratory component and an epidemiologic component.
So, just to start out with some of the individual components, starting with the diagnostic animal side and I’m going to go basically up through the food chain. This is also the part, the component, the was first in existence because it was based on or evolved out of the work that ---used to do in testing Salmonella from animal sources on a regular basis and publishing those before CIPARS came into existence and some of you may be familiar with that.
So, it essentially started in 2002 with Salmonella isolates being forwarded from provincial animal health labs to the OIE Reference Lab at LFZ, and then those for serotyping and phage typing and then those are included in CIPARS. So we have some provinces that are sending everything and others that are just sending some select submissions.
And then in CIPARS we -- while we have data on other animals species in the CIPARS reports we typically only report on the cattle, the pigs, chickens and turkeys.
Moving on to the farm component, which is one of the newer components, and undergoing some changes right now which will come to in a moment, this was money from a particularly -- from a specific funding source that was sun-setted, so it was time limited. We had five years to set up and test a program. There was only really -- we looked at various options but we came to the conclusion we only had enough money to do one commodity well. And at the same time USDA was doing CAPS, so we basically tried to the -- take the same approach. And we set up approximately 100 sentinel farms across the country in the five major pork producing provinces.
In addition, the sixth providence, British Columbia, actually did the pilot for us so that they weren’t an ongoing participant.
And through the infrastructure that evolved we ran it through the swine veterinarians, so they were responsible for -- they were contracted and they collected the samples and the antimicrobial use data.
And then we had two supervisory veterinarians who were there basically as an independent part in between, us collecting the data and the corporate farms in order to add an extra level of protection for confidentiality.
So, the herds were allocated per province based on proportional to the number of Grower-Finisher Units in each province. We had two provinces that kicks in some additional money to add additional herds beyond the minimum required number for the program.
And so that collected data from 2006 and the data, sampling data collection is just winding up for 2010 and is subsequently undergoing some modifications because the core funding is now completed.
So, this is a distribution of where the five major provinces are, Quebec, Ontario, Saskatchewan, Manitoba, and Alberta, are to where the vets and their -- which is the smaller number, and the herds were.
So, that as an ongoing focus the funding we have now is insufficient to carry on doing routine sampling and we’re going to be focusing on collecting drug use data. If we’re going to do additional sampling it will be through research projects or grant applications unless we can develop some new funding.
In addition to the swine program, we’ve done some research projects, some larger and some smaller, in conjunction with the various partners. We’ve done two in dairy. One is just completing, two in beef, one is just wrapping up now, and two in sheep.
We have finally got to the point with the broiler industry that there is a pilot project starting now which will look at both -- there will be some antimicrobial use data collection and some samples collected and that is a -- externally funded project that is being run through the University of Guelph.
Moving on to the drug use data, because that’s linked to, as I mentioned, the On-Farm program, one of it’s primarily mandates was to collect on-farm drug use data. And this is -- and we have the same situation I think in the U.S., that the idea about where to optimally collect drug use data is not always clear because of the complexity of the routes by which drugs can get from the pharmaceutical manufactures down to the end users.
This was a schematic prepared by the Center for Coastal Health for British Columbia, under the various regulations and the various routes that they could get from the manufacturers down to the end users.
So, the optimal sites are a way of collecting drug use data, not always clear. And in Canada, at the moment, the Canadian Animal Health Institute, like the FSIS and the U.S. provides aggregated -- in the Canadian cases distribution data which is slightly different than sales data. And we have the CIPARS swine program providing on drug use data for those 100 sentinel farms.
We have also, as I mentioned, partnered in a variety of research projects that have generated antimicrobial use data on swine, beef, dairy, sheep, horses and companion animals. And so, because we have no process by which we can collect drug use data comprehensively, we’re still looking at combining these sources of information in the development of the use estimation model.
This is just an example of some of the data generated through one of the research projects showing ADD per cow month, Penicillin, Ceftiofur, Oxytetracycline, and Trimethoprim-Sulfate in 25 herds in Ontario, which basically just shows the large degree of variability from a farm that was using 2.5 ADD per cow month down to one that was almost using none.
Moving on to the slaughter component, this again is a little bit different than what happens in NARMS. When we set up CIPARS the activity of CFIA is a little bit different FSIS so we didn’t have an opportunity, or we didn’t have access to carcass samples, and we had to design this from the ground up. And so we elected to go with cecal samples because we weren’t sure that we would actually have a farm sample, so we knew we would have retail, we wanted to have something that was representative of what was coming off the farm rather than something that was in the middle of the slaughter process.
And so in 2002 when this started out, we started with 51 slaughter plants. The selection is based -- of the plants is random and based on slaughter volume. It includes cattle which includes dairy cattle, market hogs and broilers. And these are the -- the bacteria that is tested with each one is not -- they’re not uniform across all but CIPARS primarily is about E. coli, Salmonella and Campylobacter with some Enterococcus work.
And the sample sizes are primarily determined in order to generate 150 isolates of Salmonella and E. coli where those are being tested. There are some exceptions both here and in retail where if the prevalence is very low, if we’re actually going to be bothered to try to recover the Salmonella for example, Salmonella from pork, that because the sample size required with such a low prevalence, yield would be too expensive, so we just test what we get but it’s not to generate a prevalence estimates with decent confidence intervals.
So, it would be Abattoir Program is coordinated by fact. And by the CFIA. The CFIA provides oversight in the plants where the samples are collected and either collects the samples or a plants, quality control staff, collected and then the samples are sent on to our lab in Saint-Hyacinthe, Quebec.
A couple of other projects that are related or are the same sort of step in the food chain, because we weren’t particularly anxious and test table eggs, but we did want to have a look at eggs. We’ve tried to look at a couple of surrogates, pre-pasteurization, liquid whole eggs and cecal samples from spent hens, and those are projects that we did in collaboration again with the University of Guelph.
Moving on to the retail component, here it has gradually developed over time, we started in Quebec and Ontario and have added Saskatchewan in 2005, it’s the green one. And British Columbia in 2006. And three of the four Atlantic Provinces in 2007.
And this isn’t exactly by design, it’s just where we have the resources and the opportunities to collect the samples and where we have field workers available.
We have also conducted a pilot project with Agriculture Canada and Agri-Food, the Provincial Ministry of Agriculture in Alberta, which was a project of two years duration. This is now finished.
And so we collect, purchase, chicken here, it’s chicken legs with skin on. So it’s again a bit different than NARMS. Pork chops, ground beef, and these are fresh and raw samples. And again E. coli, Campylobacter, Salmonella and Enterococcus, with a goal of trying to get 100 isolates per commodity, per province, per year. It’s not exactly true for this, particularly for the Atlantic provinces, because they’re lumped into one.
And the stores, the sites for sampling are the -- the sampling is done within a Census Division, the census divisions are based on population randomly sampled, based on population, in order to try to represent exposure.
Since 2007 we’ve been looking at salmon, shrimp, domestic and imported salmon and shrimp, which can be fresh or frozen. But raw. And echoing the comments that were made earlier by -- in the CLSI presentation, what to do with the MIC values of Vibrio and Aeromonas is a bit of a -- it’s a bit difficult.
Other commodities we look at, primarily again through University based research projects, and that we have looked on and off at turkey, both milk-fed and grain-fed veal, lamb, goat, venison, trout, tilapia. CFIS is currently sampling bag lettuce, a number of produce commodities, bag lettuce, cantaloupe, et cetera. And we’re hoping shortly to be able to get access to the isolates coming out of those to test those for susceptibility as well. And in additionally, we’ve looked at a few pet related items.
On the human side that started in 2003 with Provincial Public Health labs forwarding human Salmonella isolates to NML as I mentioned. And it’s all isolates from the first half of the month plus all new S. Newport and S. typhi, that’s undergoing some, probably undergoing some change.Currently other bacteria are only looked at either, have been looked at or will be looked at in research projects.
This is just an example of some of the data showing changes in multi-drug resistant Salmonella over time mirroring some of what’s been shown from NARMS already with the decline in Typhimurium.
And then the drug use information comes through IMS Health. And is analyzed by CIPARS.
It’s just a couple of quick examples. Here is that sort of typical one of azythromycin, these are all the provinces that would be up and down associated with the seasonal respiratory illness, but then here is one, cipro, where we can see one outlier providence and that allowed that province to address the question of why it’s use was out of wack with the rest of the country.
And then with cipro, the primary thing is to get to the data integration point. Here we have S. enteritidis in red, Heidelberg in green and Kentucky in blue. Chicken diagnostic samples, chicken abattoir, chicken retail, and human showing the Enteritidis and Heidelberg, across the whole thing is mirrored across the four point of sampling. Whereas Kentucky is obviously a flatline in the human cases because you don’t see too many human cases coming through.
We do have a few non-food animal research projects. Including, there was a question earlier about wildlife, so we do do a bit of wildlife, of course companion animals. This is a wildlife surrounding at sample. And some water work. Again, primarily grant projects.
And the intent with most of those is just to try to provide some data to fill in some of the gaps on the confuse-o-gram or complex-o-gram, whatever you want to call it.
And just to wrap up, just to show a few examples of some of the results that we get from some of these other projects. I would like to show this one mostly because I did the project and never got around to publishing it, so this is the only way I can show it.
This was a survey we did of antimicrobial drug use from Canadian companion animal vets that, the scenario with cats, with feline, upper -- mild feline upper respiratory tract infection. And it shows in purple vets that would consider doing nothing, amoxicillin, amoxi-Cl, fluoroquinolones, cephalosporins, versus the blue that would make it their top choice. So there are some that would choose drugs when in this scenario antibiotics are pretty universally considered to be inappropriate.
And even though only 70 percent say that they would make nothing their top choice, 93 percent recognized that they should do nothing. So they’re similar to physicians.
And this is some of the data from a horse project looking at resistance in equine E. coli from Western and Atlantic Canada and quite low levels of resistance.
Just to wrap up, some of the other work, a lot of work around molecular characterization. We do some work with lab and epi methods develop, in mathematical and risk modeling. And then some work on some of the emerging or current issues of MRSA and C. difficile and so on.
And the international collaborations, most of which are being mentioned already.
So, we produced an annual report. It takes us a while to get it out because of the complexity of the analysis, which a lot of the rest of you are familiar with. We’re currently working on getting our 2008 report out.
But because we wanted something a little bit more timely, a few years ago we started releasing a preliminary report and the intention -- and that is a reduced report that just has data in it and no interpretation and we try to get that out within six months of the end of the calendar year. And so we currently have the 2009 preliminary report went up on our website in June.
And that’s it. Thank you very much.
DR. BARZILAY: Thank you very much for an interesting presentation. I will ask in the interest of time that if there are any questions we address them at the end of the next session, which will be the roundtable and Q and A session of the day.
(Whereupon, the luncheon break was taken at 12:41 p.m.)