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2011 NARMS Scientific Meeting Wednesday, July 20, 2011 Held at the Holiday Inn Express St. Louis, MO Audio Associates 301-577-5882 2 2011 NARMS Scientific Meeting July 20, 2011 I N D E X Page Welcome by Heather Tate, MS, PhD 4 NARMS Overview by Patrick McDermott, MS, PhD 4 USDA Slaughter Sampling by Emilio Esteban, DVM, MBA, MPVM, PhD 21 Question and Answer Session 35 USDA On-Farm Sampling by Paula Fedorka-Cray, PhD 44 FDA Retail Sampling by Emily Tong, MPH 66 Question and Answer Session 74 Evolution of CIPARS Retail and Food Animal Sampling by Lucie Dutil, DVM, MSc 78 Sampling Methods Used by EFSA for Antimicrobial Resistance Monitoring by Pierre-Alexandre Beloeil, PhD 98 Pitfalls of Sampling by H. Morgan Scott, DVM, PhD 112 Panel Discussion: Improving NARMS Sampling 137 Comments by Scott McEwen, DVM, DVSc 137 Comments by Randy Singer, DVM, PhD 143 Comments by H. Morgan Scott, DVM, PhD 147 Comments by Bayleyegn Molla, DVM, MSc, PhD 149 Open Discussion 150 Audio Associates 301/577-5882 3 I N D E X (continued) Page Comments from the Beef Industry by Elizabeth Parker, DVM 169 Comments from the Swine Industry by Paul Sundberg, DVM, PhD 175 Comments from the Turkey Industry by Brian Woo-Ming, DVM 183 Comments from the Chicken Industry by Al Yancy, DVM 00 Public Comment Period 191 Comments from The Animal Health Institute by Thomas Shryock, PhD 192 Comments from STOP and Keep Antibiotics Working by Susan Vaughn Grooters, MPH 198 Comments from the National Pork Producers Council by Liz Wagstrom, DVM 211 Comments from APHIS by Bruce Wagner, MS, MA, PhD 216 Focused Discussion Moderated by Heather Tate, MS, PhD 219 Keynote: “---” indicates inaudible in the transcript. “*” indicates phonetically spelled in the transcript. Audio Associates 301/577-5882 4 M O R N I N G S E S S I O N (8:11 a.m.) Welcome by Heather Tate, MS, PhD DR. TATE: Okay, good morning everyone and welcome to the 2011 NARMS Scientific Meeting. My name is Heather Tate and I am the NARMS Coordinator at FDA. I am going to introduce our first speaker Dr. Patrick McDermott who is the Director of NARMS and he is also located at FDA in Laurel, Maryland. NARMS Overview by Patrick McDermott, MS, PhD DR. McDERMOTT: Thank you Heather and good morning everyone and thank you everyone for coming today. My purpose this morning in starting off our meeting is really just to try to give a little bit of background and show you where we have been since a major review of the NARMS program back in 2007 by the FDA Science Board. And also try to give context to show why we are here today and what has led up to this meeting today which is intended to focus on the sampling scheme in NARMS. I also want to say I like the size of this group. I hope everyone will feel emboldened to participate and speak up and add to the conversation. And I think we can have a really good discussion today that could benefit the program and help Audio Associates 301/577-5882 5 FDA do its job and we are always looking for better ways to do that. (Slide) So the context of NARMS, I think most of you are probably familiar with NARMS very well but it seemed appropriate to give a little context to those who maybe are less familiar with it. And it is really driven by the impact of antimicrobial use in food animal production and how that practice or those practices affect the evolution of resistance in pathogens transmitted through the food supply; that is the regulatory scientific umbrella under which NARMS is a part if you will. And a corollary to that question is what is the impact of this on public health? So it is definitely a focus on public health. And this whole issue which has been with us for a long time now is addressed at CVM in a multi-pronged approach that includes a revised safety assessment process and this is the Guidance for Industry 152. It includes enhanced surveillance, and NARMS is sort of born with that intention in mind, expanded research activities which are important, I think, critically important to sort of filling some of the gaps that surveillance cannot fill and also to help in the safety assessment process. It includes an international component to make sure that data generated in NARMS are Audio Associates 301/577-5882 6 comparable and validly comparable data from other systems and other international activities as well. And then education and outreach which has mainly been in the form of prudent use guidelines in other guidances. (Slide) In the Guidance for Industry 152, this is a qualitative risk assessment process where new animal antimicrobials are evaluated for their potential to impact public health and I am sure many of you are familiar with it. It includes a Release Assessment that has a probability that resistant bacteria are present in the animal as a consequence of drug use and you need something of a research component to understand that at the microbiological level, basically understanding the mechanisms of resistance and how they evolve. There is an Exposure Assessment which is the probability for humans to ingest bacteria in question from the relevant food commodity. NARMS can help provide data to address that question as well. And then the last one, the probability that human exposure to resistant bacteria results in an adverse human health consequence, we are less directly involved in but it is part of the overall HHS approach to understanding the risk. (Slide) So with that in mind NARMS has four operational Audio Associates 301/577-5882 7 goals if you will. To monitor trends in resistance among foodborne bacteria from three different sources of samples, human clinical isolates, retail meats purchased at grocery outlets and food animals which has mainly, as you will hear later from Paula Fedorka-Cray, been measured using the surrogate of slaughter isolates. The second goal is to disseminate timely information on resistance to promote interventions to reduce it, so an attempt to use the data for action if you will which is the purpose of all surveillance. Conduct research to better understand how resistance evolves and spreads. Again, I think that is an important component. And assist FDA in making regulatory decisions on the save and effective antimicrobial drugs for animals. That includes the Qualitative Risk Assessment I just described. So these data are provided to FDA and FDA uses them at their own discretion. (Slide) So as a starting point for today’s discussion, I think it is useful to start with the FDA Science Board Review of NARMS which concluded in March of 2007 and they addressed four different components of the program; data management, sampling, research activities, and international activities. Audio Associates 301/577-5882 8 And we are really here today to focus on the second one. And they made some general comments about the program. That it has become mission critical for FDA, it needs to make sure it keeps its focus on public health, it should evolve and become more predictive, responsive, and expansive, it needs a strategic plan and business planning processes, and then endorses development of a 10-year strategic plan with public involvement. We just recently drafted and published a 5-year strategic plan and the comment period on that recently closed. (Slide) As far as sampling goes, so forgetting the data management, research, and international part, as far as the sampling part goes the Science Board said that the current sampling strategies all have degrees of bias which is no surprise. We need to critically re-evaluate the sampling to assure data can withstand scientific, legal and regulatory scrutiny and challenges. In other words we need to make it better, more defensible data. We need to transition to national, random sampling strategies when we do not have that. When this is not feasible, data should be stratified or sampling should be limited and focused on specific hypothesis- driven research. And we do in NARMS, and have in the recent past, done sort of some work like that for example looking at MRSA in meats. Where biases cannot be corrected, the Science Audio Associates 301/577-5882 9 Board says the methodology should be designed as an early warning system for emerging resistances. (Slide) On the animal sampling, speaking of the slaughter isolates, the Science Board comments where sampling needs to be nationally representative. Biases occur because processing plants are not randomly selected and Paula will probably expand on this. But FSIS has moved more and more toward risk- based sampling and revisiting plants that have failed the last inspection and so that has added a little bit more of a skew to the data. Alternatively we could consider ongoing “baseline” type sampling schemes as is done right now in the USDA. (Slide) They also commented that on-farm data are essential in understanding the movement of resistance from farm to fork. NAHMS data are potentially useful but samples fail to provide a true national sample, was the comment of the Science Board. It may be best to limit on-farm samples to specific research studies. And then at the time we were including diagnostic samples in NARMS, we are no longer doing that. They thought that it should be sort of considered separately. (Slide) This shows the flow of the animal samples through Audio Associates 301/577-5882 10 FSIS and the regional labs and they are received by Paula Fedorka-Cray’s group at ARS in Athens and the testing is done there. (Slide) And then for the Campylobacter, Enterococcus, and E. coli isolates, there are chicken carcass rinsates from the Eastern Lab where those organisms are recovered only from chicken samples. I should have emphasized this is Salmonella, Campylobacter, Enterococcus, and E. coli. (Slide) So I am focused on the animal component because the Science Board is focused on the animal component. My intention today is to focus on the animal component. We are not going to consider the human sampling right now. We think it is probably hard to improve on it the way it is. We are still having some discussions about it but it is less of a monumental challenge if you will than the animal component. In the retail meat part we also want to talk about today, the Science Board had fairly few comments on it. They noted that retail meat sample size is relatively small and the lack of national sampling limits broader interpretation. And also it may be useful to adjust sampling to help answer specific hypothesis-driven questions. This is a theme that came up over and over again that if you cannot really give us national trends, maybe you can go and answer specific research questions that could be extrapolated. Audio Associates 301/577-5882 11 (Slide) So I mentioned that we drafted a Strategic Plan fairly recently and the public comment period closed on it. (Slide) It had four goals that were derived from the Science Board Review. To develop, implement and optimize a shared database with advanced data acquisition and reporting tools. We are still making progress on that; It is quite expensive. We have had some IT issues that have kind of slowed us down a little bit but we are still dedicating resources to that process and think it will help us a lot. To make sampling more representative and more applicable to trend analysis which is what we will focus on today. Strengthen research and support international activities. So those were the four main goals. (Slide) So in the Strategic Plan as far as sampling is concerned, there are five objectives. In the draft listed here we have not incorporated the comments into revising the plan as of yet; we will do that when we return. But Objective 2.1 and 2.2 are really what we are focused on as I said. To increase the geographic representativeness and total number of retail meat isolates by increasing the number of participating states. Audio Associates 301/577-5882 12 So one thought in this regard is the power to be gained from more isolates might be the most important question. I just offer that up for your consideration. There are other possibilities that are dependent on variables such as whether or not the regional differences in resistance among retail isolates are that substantial. The second objective, to modify animal sampling to overcome biases resulting from the current FSIS HACCP compliance sampling which is risk-based and post-processing. And then there are a couple other objectives under sampling related to human testing; to expand the Campylobacter component, to add animal feeds, and to try to reinvigorate the commensal monitoring in human isolates. (Slide) So what we have done since the Science Board Review is tried to take these things in stages. And sort of beginning with the low hanging fruit, it is nice that we have gotten all this advice on all the things we should do differently but we have not gotten additional resources to try to address those until Fiscal Year 2011. So what we have done leading up to today is we had a Methods Meeting among the NARMS partners in September 2008 in Athens, Georgia. And listed here are the things that were addressed in that meeting. It was really focused on laboratory issues and along with that some research issues. Audio Associates 301/577-5882 13 So we had a lot of issues we wanted to discuss about quality control and some really fundamental elements. We took advantage of the meeting to revise the NARMS goals. We thought the language was ambiguous and weak and probably some will argue it is still not explicit enough but we think we improved them a little bit. But a lot of emphasis on sample and isolate processing in the lab to make sure we are doing things comparably. And at that time we established research working groups for laboratory, microbiology, epidemiology, and molecular biology and then the other things that are listed here. Out of it came a laboratory manual for NARMS Methods and Sample Processing. (Slide) After the Athens meeting we met again. Among the NARMS partners from CDC, USDA and FDA we met in Rockville in 2009 and spent most of that meeting really focused on the database, in developing an integrated database and the analytical tools. And really querying everybody to make sure that the trajectory we were on at that time was going to meet the needs of everybody in the program. It included another IT challenge at CDC, namely linking NARMS and PulseNet data and really you could go beyond that and say tried to integrate more the different monitoring programs at CDC so that you can get the synergy from the different datasets that are available there. The working groups got together for follow-ups. We Audio Associates 301/577-5882 14 did talk about sampling at that meeting and strategic planning as well. (Slide) Then we met last year in Atlanta and the focus really was on the international part of NARMS and we had speakers from the countries and organizations listed here. And then we spent quite a bit of time talking about molecular biology research of resistance and strain typing. (Slide) And that really brings us to why we are here. We are really here to focus on really the hardest question and the one that requires more resources which is revising sampling. Because it is obvious that we want to make that as robust as possible because from that we get data derived that are as defensible as possible. This just sort of encapsulates again some of the Science Board comments but the move to risk-based sampling has necessitated a new animal scheme. It should represent food production and consumption within a region as much as possible. And you can see some of the things here. And a major consideration, I think Paula you will probably emphasize this as well and Paula has done work in this area to highlight these issues, is depending on where you sample in the food and animal production continuum if you will, you will get different results. So if you sample on- Audio Associates 301/577-5882 15 farm you will get different serotypes and resistance patterns than you will when animals come off the truck, when animals are in lairage and at different points in the abattoir so it does matter where you pick samples. And that is always going to be a problem and a challenge for comparing results of animal sampling internationally. And then a couple considerations, on-farm sampling is probably most representative of the prevalence of resistance where the antimicrobials are being used. And there is a possibility to get drug use information which again has been a major difficulty to obtain that type of information. And we will have denominators by commodity. Right now with the abattoir sampling we are just getting the positive Salmonella strains that are recovered from the abattoirs and we do not really have denominators by commodity that would give us the prevalence information. And then the considerations for sampling the retail meat, it is closest to the consumer and reflects in part the strains that persist in the slaughter. So it is the things that happen in the abattoir that are also going to impact and influence the patterns and strain types we find in retail meats. National meat production is extensively integrated and distribution is broadly deployed. And I just put that in there to remind myself to I guess repeat what I said before Audio Associates 301/577-5882 16 which is maybe just getting more isolates is one of the best solutions to increase the power of the analysis we can do for retail meats. And because we have looked at some of the packaging information, you do see that there are sort of regional distributions of meat so that what you see in one state is not going to be wildly different from a state right next door but might be substantially different in a different part of the United States. So the geographic part may be captured already or are less challenging, but that is my own bias so please just shoot it down if you think I am mistaken there. (Slide) So we have tried in a series of meetings to revise our goals, to address issues in the laboratory, to find ways to work more efficiently in collaborative research projects through establishing the working groups and other mechanisms. We have put a lot of effort and a lot of resources into the database development, international harmonization, but not sampling until today. (Slide) Resources, of course, are the bookends to all of this. This shows the NARMS funding since 2006 and the first four or five columns are all identical. The program has not gotten any additional resources until Fiscal Year 2011 and we got them this year, as you know, from the budget process that Audio Associates 301/577-5882 17 has become more complicated and delayed. We got it late in the year but it seems to be a permanent addition to the base of NARMS and so we have gone from 6.7 to 7.8 million. And when you look at these numbers in the last column for Fiscal Year 2011, the CDC numbers include support for the FoodNet sites so they send at least 50,000 dollars out to 11 of the different sites so that goes straight out the door. And then the FDA funds -- we buy all the susceptibility testing panels and reagents as well so there is some explanation for why those are different but that is what we are working with, 7.8 million dollars in resources. (Slide) So here is what we did with those funds this year. And again we did not have a lot of time to plan this and to deploy these funds but working with CDC it has been a real question for a long time about testing outbreak isolates and CDC is going to expand their antimicrobial susceptibility testing of isolates from outbreaks. That comment also showed up on our Strategic Plan and so I am glad we are thinking in parallel on that. And this additional testing will allow CDC to more fully use the rich epidemiologic data that is typically available for outbreak investigations so that will be very helpful. And as I mentioned before, we had discussed at a previous meeting to link NARMS with FoodNet and PulseNet and Audio Associates 301/577-5882 18 other datasets just to try to get some synergies there. Also working with USDA we initiated four on-farm pilot studies in dairy cattle, beef cattle, broilers and turkeys. And these data will be analyzed along with Dr. Fedorka-Cray’s on-farm pilot in swine that is ongoing. So we are trying to get out on to the farm and see what the logistics look like, what the expenses are, how frequent the sampling can be done, and how we can divide responsibilities. At FDA we do plan to add retail testing sites in 2012, three of them we are planning right now. Emily Tong will talk to you a little bit about that. It is not simply a scientific question of well gee we really need the Chicago- land area because the laboratory there may simply not be willing to participate so it is not as simple as going out and identifying a region you would like to sample but you need laboratory infrastructure in place, you need the budget, you need the buy-in of the administrators, and so on. And then also we are using some of the funds to continue the development of the database. So that is from my perspective sort of the context I see for framing our discussion today. That is what we have been focused on, following the Science Board. We have tried to do what we can without any additional resources and still maintain the testing that was historically how NARMS operated. But we have an opportunity now to really I think address the Audio Associates 301/577-5882 19 sampling issues and meet some of those recommendations that came from the Science Board and others about the importance of getting on-farm isolates if possible and making the animal component more representative and making the retail meat component more robust and representative as well where we can. So I look forward to today’s discussion. I am really happy to see a lot of familiar faces and I am glad some of those who may be new to the program have joined us and I look forward to your participation and contribution. There are a lot of possibilities, there are a lot of things we could consider as options and success has a lot of different faces to it. So for example on the retail meat, we could add sites, we could add commodities, we could test more of the current meats that we are doing right now. Some people suggest that we look at other pathogens so all of these things I think are on the table and I would love to hear people’s input and their opinion on these different options. (Slide) With that I will just wrap up and remind you of the agenda this morning and we have a fairly full agenda. We have a couple areas though where we will have panel discussions, public comment periods and focused discussions; that is what I am looking forward to most of all where we can sort of hammer out some of the options that are before us. (Slide) Audio Associates 301/577-5882 20 A couple of housekeeping issues, refreshments will be here in the morning and at breaks. Lunch is on your own. And I think, what do we have for lunch, we have an hour and fifteen minutes Heather, that is still right, so that will give us a little more time to get down the street to some of the restaurants. It is a public meeting so it is recorded and transcribed and there will be a transcript available on the website after the meeting. And the docket will be open for 30 days after the meeting where you can make comments to the docket that you think maybe were not fairly treated here or there was no opportunity to raise a given issue. (Slide) I would like to quickly also thank Heather Tate the NARMS Coordinator who really keeps the program functioning in so many ways and was instrumental in getting this meeting together today. Katherine Bond at the FDA Office of International Programs has been very supportive for our meetings recently, Aleta Sindelar at the FDA Center for Veterinary Medicine who we always go to for all our questions on logistics, Kelly Covington who is out front and has helped us a great deal with this meeting, and the Seamon Corporation who is a contractor for logistics. So those people deserve thanks and made this meeting possible. So with that I guess I could entertain a question or two if anyone has one or we can just move on to the topics. Audio Associates 301/577-5882 21 Okay, that is fine, thank you very much. (Applause) DR. TATE: I just want to let folks know that we do have ample time built into the schedule particularly in the afternoon to have discussion and questions can be answered and things like that so we will have time available later. I also wanted to bring to your attention the materials that were out front that you should have picked up along with the agenda, was the actual summary report from the external subcommittee that reviewed the NARMS program. It was published in 2007 so that is your background for this meeting. And then there is also a slide on all of the steps throughout farm animal production at which we might possibly want to sample from so that is something to keep in mind also as we move through today’s agenda. Okay, the next speaker is Dr. Emilio Esteban. He is the Scientific Advisor for Laboratory Services for the Office of Public Health Science which is in the Food Safety Inspection Service of USDA and he is located in Athens. USDA Slaughter Sampling by Emilio Esteban, DVM, MBA, MPVM, PhD DR. ESTEBAN: Good morning. I am the first one to come to slaughter so this is good. I am used to it see. When I accepted this invitation, I was not aware that I was going to be speaking to this kind of group. I was thinking of five Audio Associates 301/577-5882 22 of us around the table drinking coffee so I am going to have to edit my slides as I go because if this is transcribed I will be fired. (Laughter) DR. ESTEBAN: But I am going to say it anyway so Paula, save me okay? DR. FEDORKA-CRAY: (Away from microphone) DR. ESTEBAN: My slides are not going to cover 30 minutes so I will have plenty of time for questions. The way my slides are are quite simple and straight forward so if something is not clear, ask somebody else in the agency because I will not have the answer. (Slide) I am going to go really down to what we are doing here which is sampling. And I am going to first describe a little bit of what we do in the agency right now, then I am going to talk about what we might be doing in the future in the agency, and then I will tell you what I would like to do in the agency. So I do not know which one of those three is going to be the reality but one of those three is going to be the reality. What I know for a fact is that on the average every year for the last 10 years we have collected anywhere between 45,000 and 35,000 samples for HACCP. And basically the purpose of the sampling is to verify that the plant’s HACCP is Audio Associates 301/577-5882 23 under control. We do not do process control. We do not do this because of a huge public health need. The first goal of our sampling for HACCP is to verify that the plant’s HACCP is under control. We have individual sampling frames for broilers, turkeys, cow/bull, steer/heifer, hogs and then we have separate HACCP programs for ground beef and for beef trim. All of these different sampling frames we sample on the basis of sets. For example a broiler HACCP set has 51 samples. A heifer/steer may have 83 samples in a set. And the pass/fail ratio is based on the baseline that we did back in the late 1980s when the prevalence was very different than it is today but we still have those same pass/fail rates for each set except for turkeys and broilers where we just released new standards this first of July a few weeks ago. (Slide) So what would be an ideal program? We would like to have a nationally representative sample so we also need to select the proper material to test. We would have to have a very nice test that has very good sensitivity and good selectively and we would have to have a defined period in which to sample, basically the principles of epidemiology; person, place and thing right? You have to have those three variables in there. (Slide) Audio Associates 301/577-5882 24 So what does the real program look like right now? Well I do believe that -- and I do not want to contradict the Science Board because they are the Science Board and they know more than I do but I do think we do have a nationally representative sample and I will try to say why I think we do have a nationally representative sample. Every single plant that we have in the United States under federal inspection is identified and segregated and identified in a sampling frame. So in essence we actually have a census of our plants. We document for each time we sample the volume that that sample represents. So for example when we issue an inspector an assignment to collect a sample, one of the fields in the sample form is what is the size of the lot that the sample came from? So the only thing that we cannot do right now simply because of the logistics at the plant is randomly select which lot we are going to sample. That part of the sampling is at the convenience of the inspector. When they have time to sample, is when they collect that sample at that moment. So for example if you have a plant where they are producing beef trim, the plant may produce thousands of lots each one of 2,000 pounds of combo bins, we select a combo-bin or five combo-bins to sample from and those five combo-bins are selected by the inspector, not randomly but it is a Audio Associates 301/577-5882 25 convenient sampling. And for me it is essential for me to differentiate between convenient sampling and random sampling. A lot of times we refer to random sampling as walking in and collecting a sample, that is not random that is convenience. Random sampling would be identify all the lots that day and mathematically pick which one you are going to sample, we do not do that. At the plant we do not do that, so it is convenient sampling. The essence of the sampling point is convenient sampling. (Slide) This data goes back to 2007-2008. We roughly have 180 establishments under the broilers inspection. They, at that point back in 2008-2009, were classified by production size, not by category that we have today but by production size; small, very small and large. Roughly you can see, and I do not have a pointer with me, but the second column -- the first, second and third columns basically tells you the large plants, the small plants, and the very small plants. And obviously the large plants represent only 20 percent or 17.8 percent of the establishments but represent close to 40 percent of the product. And so when you are going to use a data point from a sampling, and they call it risk-based, people I think Audio Associates 301/577-5882 26 misunderstand the concept of risk-based. Risk-based, the way we think about it when we use the term, is a volume adjustment. It is not anything other than a volume adjusted. So in essence if you are trying to see how much product goes out into commerce, volume adjusted actually gives you a very good reflection of prevalence because you are adjusting for the volume, the exposure the person is going to have when they consume that product. So volume adjusting is in fact adjusting correctly. (Slide) So if you have the sampling universe and you can actually have a census of plants and you know how much each plant produces, then the next thing is what are you going to sample? And I guess a convenient sample is based on a risk- based algorithm but a risk-based adjusts for how large a plant is and how much it is producing. The sample set is going to be depending on the product you are sampling like I said before. A swab sample is different in the number of samples than a trim sample, than a ground beef sample, than a broiler sample. And the sampling window, even though the set size is 51 and the theory is 51 consecutive production days would be when you sample, on the average it takes between 90 days and over 2 years to complete a set. So again while the intention of the program is to have a very nice tight window, the Audio Associates 301/577-5882 27 implementation of the program is not that way. So for carcass rinses for poultry and for hogs and for turkeys we do swabs; petty much it is the same thing. Now for trim we do have a little bit of a different approach. And for ground beef we have a different approach and that is truly a more risk-based algorithm. The algorithm that is used for the ground beef samples, that one actually has an additional weighing value for plants that have failed before, plants that have a previous positive. And that is a little bit more weighted to what you would understand the traditional concept of risk. And then in a lot of these plants we do actually environmental swabs. And Paula you do not get those in your lab which would be another nice thing to have; what happens in the plant besides the product that may be contaminating the product. (Slide) Again traditionally, you guys are familiar with the concept of a Category A or a Set A and the least biased population estimate would be of Sample Set A. We do not call them A, B and C anymore. And Set A is you have 200 plants, everybody has a Set A. Those that fail get a Set B. But right now more than 90 percent -- our standards are developed such that statistically 90 percent of the plants are supposed to pass the standard. So at least 90 percent of a universe of Audio Associates 301/577-5882 28 plants have been sampled unbiasly; every single plant has been sampled. So if you fail Set A, you get a Set B. If you fail Set B, you get a Set C. And I read the report from your Scientific Board and one of the recommendations it has is to just use the Set A. Well that would be good but we no longer have the concept of Sets A, B, and C so that recommendation is no longer applicable. We do not have Set A, B and C anymore. (Slide) Moving on to what we have today which is categories and these are risk categories, Category 1, 2 and 3. Every plant starts as a Category 1 plant. If they fail, then in this case they are moved to a Category 2. It is very similar to what we had before with Set A, B, and C except to be in Category 1 -- and if you can see the footnote, it may be too small to read, but a Category Plant 1 establishment will have six or fewer positives in two consecutive sets to be in Category 1 and that is the key for this. And as you can see, up to 2010, 90 percent of the plants were in that category and the expectation is that by 2013, 95 percent will be in Category 1. The last two rows on that chart are volume adjusted and not volume adjusted. There is not a huge difference in doing the volume adjustment but we do have that information. (Slide) So we have identified the plants, we have identified Audio Associates 301/577-5882 29 how we are going to sample them, we then need to decide about the method of what we actually get from that sample once we collect it. Ideally I would collect the whole chicken, and I am going to use the example of chicken a lot, and incubate the whole chicken and my laboratory will smell to high heaven but I would get everything that possibly can grow on that chicken, it would be the ideal approach right, but we cannot. We shake the chicken in a bag, not to bake it, just to get the rinsate back. We send about 400 ml of rinsate, we only get about 30 of it back and then we go through the whole method. And we had an experiment or study going on with Paula so we picked -- one colony we picked out of that plate and the assumption is that colony is the representative colony. And actually Paula I think you picked 20 and Paula you are going to talk about this later. We went to then pick 20 additional colonies to see if they were the same as the one that we had picked and reported to be the one serotype and I think 15 percent of them had a mismatch. So 85 percent of them, that one colony was in fact representative of the serogroup that was in the entire chicken so it is not all that bad. Now having said that, whatever came out of those birds was depending on the transfer medium we used, the VPW, on the enrichment media we used, and the selective media we used. So all these things introduce a bias into what we are Audio Associates 301/577-5882 30 seeing in the population. And the current model is we pick one colony out of the plate. (Slide) So the new standards, the ones we started now on July 1st. Every single plant, ---, is not a random selection of plants; every single plant. For me you only do randomized sampling when you cannot do a census. We are doing a census so what is the point of randomizing anything? Every single plant will need to have two complete sets done. So within the following 2 years, starting July 1st of this year through July 1st of 2014, every single broiler and turkey plant will be having two sets done. This is a unique opportunity for VetNet because you will have a census for --- sampling. It will be truly representative of what is out there at least on the establishment level. We are going to continue to do rinses on the broilers and we will do swabs on the turkeys. We are analyzing these samples for Campylobacter and for Salmonella. And ARS is going to get all those isolates, the positive ones. So it is a unique opportunity window over the next two years to do a lot of good work at least for those production places. And the method we are going to be using at this point is the same method we have used for the last few years, the --- system. We do not plan on changing the media right now. So you can actually do some trend comparisons. Audio Associates 301/577-5882 31 (Slide) The only two conditions that I want to point out that we would not sample are establishments that have very low production volumes but we have assumed that those very, very small establishments produce so little that it is really not relevant what they contribute to the risk. And the second is the frequency of production. When an establishment produces less than 26 days a year, again it will take us too long to collect a sample set so we are probably not going to be sampling it. So when I say census it will be a census with the exclusion of these types of establishments. (Slide) Another opportunity to get samples that are nationally representative, we are currently in the shakedown time of a chicken parts study so we are actually conducting a nationally representative baseline of chicken parts. So the issue is not having a random nationally representative sample, this baseline is supposed to provide us with isolates that will be nationally representative. Another great opportunity for VetNet to get those isolates and actually have chicken part comparisons with the whole carcass rinsates that we get; we have never done that before. It will go for a year. The second thing that we are about to start is an egg baseline. And of course as you know FDA and FSIS have dual jurisdiction there. All the cracked eggs are ours, all Audio Associates 301/577-5882 32 the processed eggs are ours, and all the whole eggs are FDAs. We are going to do a national baseline on processed egg products which is what we are responsible for. The shakedown should start over the next couple of weeks and it will go on for 18 months. Another opportunity to get whatever comes out of those processed egg products to feed into the national prevalence estimate for Salmonella. There are two tentative studies that we have thought about that budget-wise we have not been able to kick[sic]. One is to do a lymph node study. The theory is that the lymph nodes, as physiology mandates, they filter everything in our systems and they accumulate all the bad stuff so we wanted to see if we could actually conduct a study on lymph nodes to see what prevalence of pathogens are there, E. coli and Salmonella, and which types were present. And the other one is MDR on the West Coast. Our data for the last few years has suggested that for some reason happy California cows seem to have much more MDR than the non- happy cows in the rest of the United States. And so we wanted to do a study to see what is unique and if it has to do with the drylot dairies versus the free-range dairies and things like this, we have not really kicked that off again. Collecting the samples there was a large burden on the inspection force and we could not do that but it is still there on the books. And again all the isolates could possibly Audio Associates 301/577-5882 33 go to VetNet. (Slide) This is just to point out that all sampling aside VetNet is a tremendous public health help for FSIS. We use it for trace back and we use it to enhance our epidemiological investigations. It is an invaluable resource. (Slide) So the question was are our HACCP samples compatible with the intention of NARMS? And again I would say yes, specifically these next two years. We will have a census of plants. It will be extremely nationally representative, it will be all the plants. In addition we have a new program that we are going to be working on on ground product. Traditionally we have not sampled ground chicken or ground turkey products too much but the positive rates for those two products is much, much higher than the carcass or the carcass parts. So if you are looking at increasing the number of isolates, sampling of those two products, the ground products of chicken and ground turkey, will give you a lot more positives to work with real fast. And the other thing is we cancelled the HACCP programs for swabbing for cow, bull, steer, heifer and hogs. We were getting basically almost no positives from those programs. So what we are trying to do then is move those resources into sampling the trim that comes from those Audio Associates 301/577-5882 34 carcasses. Rather than swabbing the carcass, we will do N-60 of the trim and analyze those trim samples for both E. coli and Salmonella. But this is still in the works; it is not something that the agency has already approved but it is sort of where we want to go to. It seems much in line with what AMS is doing for the school lunch program. And we are comparing what they are getting with what we are getting and it seems that the resources would be best aligned if we were to sample the trim instead of swabbing the carcasses. Plus it is much more efficient for the inspector. (Asides) (Applause) Question and Answer Session DR. WAGSTROM: Hi, Liz Wagstrom from the National Pork Producers Council. What are the plans for anything with the pork baseline that is going on now? DR. ESTEBAN: The market hog baseline, we are going to extend it until the end of August to collect enough samples. We will analyze it, publish the results on the web and share it with you. My desire would have been to be sharing data with you quarterly but that was not the way that obviously the agency felt so we will finish it in August, clean the data, and free it up as soon as possible. And I will go back tomorrow to Washington and make sure that we have a timeline and we can communicate --- meetings. Audio Associates 301/577-5882 35 DR. McEWEN: Hi Scott McEwen, University of Guelph. I just had a question regarding the risk-based sampling plan. I am going to read a statement that I found on the NARMS website concerning the sampling from FSIS. It said “beginning in June, 2006 sampling was scheduled using risk-based criteria designed to focus FSIS resources on establishments with the most samples positive for Salmonella.” So that implied to me that sampling is more or less exclusively directed to those high-risk plants. But from your presentation I got the impression that maybe all plants are being sampled. Is that the case for poultry and for other major production species? I think what is important to find out is if samples are in fact available from all the plants, it is just that there may be some weighting for high-risk plants. I think that is important in terms of the overall sampling. DR. ESTEBAN: Yes, I guess that is what I was trying to get across which is when people say risk-based, the risk algorithm basically is risk because it is volume adjusted, there is a factor for that, and there is another factor for previous positives, previous failures. There is an adjustment for plants that have a notice of intended enforcement meaning that they have something else, not the sample result but something else in the plant that seems to make that plant riskier. All that goes into the algorithm and that is how we sample them. Audio Associates 301/577-5882 36 However, since we went to the category approach, every single plant is to be sampled to be part of a category. So yes it could be risk-based in a sense that you give priority sampling to the riskier plants but every plant gets sampled anyway. DR. McEWEN: And you were talking about poultry. What that also the case for beef and pork? DR. ESTEBAN: (Nodding of head) DR. McEWEN: Okay. DR. KARP: Beth Karp from CDC. I actually had a very similar question. I think the next sentence in the report talked about serotypes too, that the sampling was based on the serotypes as well that were found in the plants; those that are most commonly found in humans. DR. ESTEBAN: I do not know if that report says that but the idea is the agency has a strong interest in actually drilling more into detail and do serotype and attack first those plants that seem to have a serotype associated with public health ahead of those that are not. What we have to understand is that when you do these algorithms, you can pull these things in there but the net result it might be the same one, same result that you would had you not done all those adjustments. I mean really think about it, there are say 200 plants possible in the sampling frame. If you had the resources to sample every plant, and we Audio Associates 301/577-5882 37 do sample every plant almost every year unless they are in Category 1 and they pass. Right now if a plant is in Category 1 and it has passed the last two sets, we do not sample them again for another year. But we do have the resources to sample every plant every year regardless of the serotype, regardless of the volume, regardless of whatever. I think Patrick had mentioned one thing that I don’t want to be lost. There is a whole different program for follow-up sampling. When a plant fails, when a plant fails the standard and has a positive in the case of E. coli or trim, then there is additional follow-up sampling that is done on that plant which is obviously a much riskier plant. In the case of E. coli, for the 120 days that follow the positive we document that this is a high risk plant to have a second positive so we do a 60 sample follow-up sample set for 16 weeks after that first positive and those samples should be excluded from the VetNet that you want to take away that excess risk. If I confused people, I can talk during lunch time or whatever. DR. LOBSTEIN: Yes Mark Lobstein from the Poultry and Egg Export Council. I am just curious if there is a rationale behind the slide you had up basically directing sampling toward broilers and not for turkeys. Was it based on volume or -- I did not know why broilers were targeted over turkeys. Audio Associates 301/577-5882 38 DR. ESTEBAN: It was because I did this last night and I was falling asleep. No there is no picking on broilers. Turkeys and broilers will have to follow the same Category 1, 2, and 3. They will have a different pass/fail standard than they do because the sample set is larger. It is 56 samples versus 51 samples, the pass/fail rate is higher and there will be a separate standard for Campylobacter. And as of this year the pass/fail applies to -- if a plant passes Salmonella but fails the Campylobacter, the whole plant will be re-sampled for both pathogens again. So they have to meet the dual standard. DR. LOBSTEIN: That is understood. I was just curious because you just specifically mentioned broilers. DR. ESTEBAN: I just did not put the other bullet for turkeys. DR. SCOTT: Morgan Scott, Kansas State University. Would you mind going back to the table? I am going to sort of follow-up on Scott’s question just to make sure I get this right. It is the table that had the three levels of production size and the sampling and then the isolates of Salmonella that arose from I think like 10 or 12. (Slide) DR. SCOTT: So you are describing a sample-based surveillance system and a positivity and negativity based on Salmonella growth or not in this situation. But what goes to Audio Associates 301/577-5882 39 USDA ARS at NARMS is actually the row that says number of positive results. So 53 from the large plants, 191 from the mid-size plants, and 233 from the small plants that if I am not mistaken is not proportional to the samples that have been taken. And I guess my question further on this risk-based is is that wrapped up in this? I am not pointing a finger at small, medium or large but the fact that you have a proportionate sampling system but that what ARS receives is actually only the positives makes it in effect a risk-based sampling strategy. DR. ESTEBAN: Okay, again, risk is based on exposure to humans. And so if you sample the larger plants more -- the 1200 samples that we collect from large plants are in a different risk level than the ones that would be in the smallest ones and the medium ones obviously because you can see the small plants seem to have a much dirtier product, seem to have. But they represent less exposure to humans. DR. SCOTT: (Away from microphone) DR. ESTEBAN: That is correct and that is why -- due to the volume adjustments so that the one sample you collect it represents -- it is volume adjusted basically. But I understand your point I mean that sample represents a different risk because it is a different plant and it has to be different because the production practices in the large plant are very different than a small one and the intervention Audio Associates 301/577-5882 40 is going to be different. And the serotypes may be different. DR. McDERMOTT: Emilio when you mentioned that you are moving away from swabbing carcasses to ground product and things of that nature, you are talking about swabbing carcasses post-prod, basically post-processing, post evisceration, post chill, whatever it is, you are close to the back door of the plant. DR. ESTEBAN: When the cow is hanging up front -- and actually not at the end of the product. It can be post- interventions and it can be pre-interventions. The point is we are not doing it anymore. DR. McDERMOTT: No, I understand but my question was one of the discussions that we have had about animal sampling is to sample the animals at abattoir but before lairage, post shipping. I think it would be good for the audience to hear what the problems are with putting something like that in place. So in other words you do not have on-farm -- okay you do have issues associated with stress of shipping and things and maybe your sampling unit is now a truck instead of an animal and maybe you lose -- there are going to be trade-offs wherever we collect the sample. But an advantage here is that you are at a final point where animals are coming to you and is there a way to take advantage of that and get true animal samples rather than -- to me it looks more like retail meat samples that just have not been cut up and put in the bag yet. Audio Associates 301/577-5882 41 DR. ESTEBAN: Yes, I think the reason we have not done that is it is extremely resource intensive. There is no easy place in the plant to get in and collect that sample without posing additional risk to our inspector. And our inspection force is in theory driven by an idea that they are doing what they are doing because of public health, not for research purposes. So one of the things we find in the agency all the time is the argument that I get is, are we a sampling agency or an inspection agency? Because there is just so much we can get away with as it is right now. That is why I want to use the one sample we collect for as many things as I possibly can and then adjust statistically at the back end. If I can prevent the bias of the collection, I can adjust for the bias as much as possible statistically at the end. Ideally I would like to take a sample at the truck, at the holding pen, a hide sample before they get stripped, one post-dehiding and one at the end; that would be sweet. If I could do that even at 10 plants, rotating those 10 plants in a sentinel fashion, randomly selecting regions during the year, that would be fantastic but that is more of an academic exercise that we have to be associated with universities or something because our inspection force is not going to do it. It is going to be a hard sell. I am not going to save never but it is going to be a hard sell. Audio Associates 301/577-5882 42 DR. TATE: Okay, last question. DR. WAGSTROM: I follow-up on your moving away from carcass testing to ground product testing and I understand that you think you will get a bigger yield of Salmonella isolates out of those samples. In pork there are very few servings of ground pork that are served. It goes to sausage; it goes to something else that is going to have kill steps associated with it so the public health implications of getting an isolate from a carcass versus ground pork are much different. So can you kind of expand on why within pork we have moved away from what I -- what I hear you say is we are moving away from any carcass testing. DR. ESTEBAN: Pork is a special situation like you said. The US consumes a lot of ground beef; we do not consume a lot of ground pork. It is pork chops basically, it is pieces of flesh. But we moved away from the HACCP sampling which is basically --- the size of the hog. You guys are doing such a wonderful job there is not enough economic value in that activity because we do not get any positives, nobody fails a set. So we had to take a step back and reassess whether our set approach is correct and what might be the alternative for that slaughter class to monitor that your HACCP is under control. We have not designed a ground pork program yet. We just have not decided what is it that is going to replace the Audio Associates 301/577-5882 43 swabbing. The swabbing was not giving us the return that we needed so rather than keep the faucet open until I think of something else, we decided to shut that faucet and put the resources into something else while we come up with a better program. Thank you. DR. TATE: Thank you Emilio. Our next speaker is Dr. Paula Fedorka-Cray who heads the Bacterial and Epidemiology and Antimicrobial Resistance Unit at the Agricultural Research Service at the USDA in Athens. USDA On-Farm Sampling by Paula Fedorka-Cray, PhD DR. FEDORKA-CRAY: I would like to thank everybody for being here and I would especially like to thank Heather and Pat for putting this together. It is always a monumental job to have this happen over a period of time. And I am really excited to be able to sit here and discuss a lot of the issues with everyone. As Pat and I have discussed over time, the goal is really have a solid system that everybody is happy with and that is representative of truly what the program has set out to do and to answer the questions that we have established. Emilio, I have learned something, I have learned a lot. I am going to have to take his slides and study them. But I have learned something too about the FSIS sampling and so I am not going to spend a lot of time over that but I want Audio Associates 301/577-5882 44 to clarify a couple of things. One is that we do get all of the isolates that FSIS collects. So we don’t get some, we don’t get a portion, we get all of them okay so we test everything that we get. We have been working with Neena Anandaraman and Niel Golden to in fact look at how we tease out those extra samplings, so those extra 16 if there are samples or isolates that may be associated with add-on testing so that we have only a single testing point for all of the plants over a period of time. And hopefully that exercise will be completed sometime in the early fall. And the intention is to go back and do all of the years that way and see how the data changes or does not change over that period of time. The other thing is that we get all of the Salmonella isolates. We actually do the culturing for E. coli, Campylobacter and Enterococcus from the Eastern Lab rinsates that are leftover from the Salmonella testing and these only comes from broilers. So those are the composition of the E. coli, the Campylobacter and Enterococcus isolates that we have today and we recognize the bias that is associated with those. However I am happy to say that we will start getting all of the Campylobacter isolates from FSIS as part of their new initiative which my understanding is is more along the lines of a baseline type study and will be representative of Audio Associates 301/577-5882 45 production. And we will get every isolate that they have for that too. So just keep that in mind. I think that a lot of people have a misperception or do not quite understand that we do take all of the isolates and that we do the testing for all of the isolates. And we do have -- we can ask FSIS, we do not have plant information, but we do have information associated with a very large, a large, and a small plant. We do have regional information. We do have the information by year. And a lot of that information is available and we can certainly do some things with that too over time. So with that then, that is really all I am going to talk about for the testing that we are doing as far as the FSIS. That will continue. No matter what we move to over time to have some continuity, we are going to continue doing what we are doing until we have a change. And it may be a combination of everything at the end. So let me just talk a little bit about what we are doing now and sort of what my vision is. And like Emilio, this is the way that I see it and what I would like to do and that is all very subject to change. (Slide) NARMS is now a separate CRIS project within our unit. This is something that is different within the agency in that it is totally a dedicated project now. It does Audio Associates 301/577-5882 46 include USDA VetNet, and it is focused on primarily initiating standard methodology, reevaluating and evaluating methodology continuously and redesigning the sampling scheme and moving it back to whatever is most representative of the farm level, whatever that is going to look like. And I say move it closer to the farm or add in plant prior to interventions, that is what Pat was asking for. We have lots of lively debates about whether we should collect at lairage or whether we should collect on the truck or where might we collect that would be most representative of what we need. And then evaluate new and existing culture methods. Randy has done a lot of work, we have done a lot of work, FSIS does a lot of work, and we know that as microbiologists, the best thing about job security is that essentially if you want to find something or if you do not want to find something we can make that happen. So the most important thing is to have transparent methods that demonstrate the best possible results that we can get and to describe the limitations within those. We cannot do everything; it is just too resource intensive to do everything so we have to agree to some methodology, some sense of what we are going to do over time that again answers the question. And one of the things that I see that I missed is that it is really important for us to ask what is the question, what do we want to have at the end? Do we want to Audio Associates 301/577-5882 47 be able to link use with the isolates that we get? Do we want a representation of production? Do we want to look and use Salmonella as the sentinel organism or are we going to just look at Salmonella prevalence then and whatever resistance we get associated with that? Do we look at specific resistance attributes? Do we look at specific commodities, one more than the other? So again it is formulating that type of question. And like I said, we are going to continue the current testing simply for continuity until we have some change over time. (Slide) This is a very busy slide. This was put in the CRIS project and this was –- again the way I kind of viewed how we might approach re-evaluation and design of the animal sampling. So just very simply I am going to extract some things from here so you do not have to read it so don’t bother looking at it trying to figure it out. That, what I just circled, is continuing the sampling as we have it now. And we have in there the biggest limitation is detection of trends. You know we have to be able to tease all this data out to look at trends over time. And so that is – I think Emilio did a very nice job, better than I have over the years of defining exactly what risk-based really means because I think people have the misconception that you focus in on something that is bad and Audio Associates 301/577-5882 48 that is not the case. So again I think it is important for us to define all of these, Pat, at some place on our website; we should probably do a better job of that and clear it up so everybody is on the same page. So the other point is that, this is continuing along the FSIS lines, and we need to explore ways in particular to minimize the bias in the data analysis. And Emilio talked very nicely about looking at doing mini-baselines. We do have all of the baseline data that is available. We have talked about what we should do with it and we need to come to some decision at some point in time about putting that separately as a separate report in NARMS if that will work recognizing that that is a standalone that was done one time at that period of time, kind of like a NAHMS study is done. We could look at sampling at pre-intervention and there is always a question of does it link to the farm and to use? So again, what do we want to have answered? This middle part I think is one of the most critical parts; it is the on-farm sampling. This is really contingent upon having a strong university and commodity group collaboration. And I will be heavy on the commodity group collaboration because I do not think that we can get this done cost effectively without having the commodity groups involved in this. And I think that it is really important to look at how we get these samples, how we can get the wide Audio Associates 301/577-5882 49 representation, and how we get the buy-in and I will give you an example of how it is working so far. Having the universities involved is critical in maintaining confidentiality and we will also describe -- and in getting the expertise at levels that we do not have access to. It is mutually beneficial. Everybody has got a stake in this and I would like everybody to have buy-in. And in my opinion it is the only true link to use that you are going to have. So if you want[sic] sampling on the farm, anything else that you get out is going to have some disequilibrium associated with use at some point in time. And one of the questions that I would have is can we get enough sampling in collaboration with cooperator so that in fact it does have a national representation that we want over time. And these slides will be available on the web so you can read the fine print later on. And then the third leg is to continue the NAHMS collaborations. These are national representations. They are studies based on the entire commodity. And it is a convenient sample, it does have limitations associated with it and the biggest is just the frequency of data. These are very costly and time consuming studies. And Bruce Wagner I am happy to say is here from APHIS and could speak to any and all of the studies and I would hope that would be -- I know he will be very involved in the discussions here as we move on with the Audio Associates 301/577-5882 50 program. And again it is going to end up being some combination of these approaches. I do not think any one approach is the way we are going to end up although I could be surprised. (Slide) Now you had the opportunity to pick up copies of this so you have -- I consider this is something that Pat and I agreed on when we were using this as an AGISAR document. These are some of the approaches that we can use. The cohort of animals on-farm, at lairage, and post- slaughter, this addresses what is on-farm, transport/lairage exposures and what contaminates meat prior to retail. The cost of this may hinder the ability to be geographically representative. So if we do this across all commodities, we know how much it is going to cost and we are talking millions of dollars over a period of time. So if we look to the far left and in my house we talk about mom’s left and mom’s right and this is usually mom’s left and this is usually mom’s right so I have to point and also talk about what I mean over a period of time. But we have animals on-farm. This does not always reflect the pathogens that will be covered post-slaughter. And this is true, however, there was a presentation at ABMA that in fact did talk about that there is a high correlation between what Audio Associates 301/577-5882 51 is on-farm and what is coming out post-slaughter and it was presented by Bailey and I am going to get his slides. Allen Byrd was also presenting some of this work because he was involved with it. So in fact there is a correlation at least based on the studies that they have done and we will take a look at that. It is the most direct indication of resistance arising from on-farm antimicrobial use but it may not address resistance from historical use or from exogenous sources. When we look at in-plant, it reflects -- when we look at lairage, it is what is expected to contaminate retail meats but it has the confounder of cross contaminations by strains persisting in lairage that can confound analysis. So it may be less indicative of current antimicrobial use on-farm and again it is a trade-off. We move to post-slaughter, it addresses what has contaminated meat but it may overlap with retail meat sampling. Although I will say that I find it quite interesting that the numbers post-kill tend to be much, much lower than what they are at retail as far as prevalence goes so there is something going on and I think that there is a culture but non-viable state, there is a stress state for the bacteria, and this is going to affect then what you see pre and post. So it may be a very good indication of what is making it through and when you add that to some of what we see Audio Associates 301/577-5882 52 with retail, it can give us a very good idea of what may have more importance than others. And then retail meats have the same limitations as lairage. (Slide) So let me talk just a little bit about what we are doing now or what we have planned to do. So this is a proposal that we put in the CRIS project. Wondwossen Gebreyes is the university collaborator. We are talking about sampling operations with 5000 head which represents about 61 percent of the total inventory which is 68 million total. Ten states account for 85 percent of total inventory and those are listed there. And we propose to start in three states, the top three states, Iowa, North Carolina, and Minnesota and capturing 95 percent of the 37 million hogs that are in production in those states. And this then represents 51.5 percent of total production. And this is about the same level that is represented in a NAHMS study if you do the same type of calculations because the calculations were based on some of the NAHMS calculations. (Slide) Now when we look at how many isolates do we actually need for the database? There are a lot of articles out there in Europe, they say 170. If we talk about looking at a minimum of 300 isolates, and that is a number that we have kicked around, how many, what is the minimum that we need. Audio Associates 301/577-5882 53 Prevalence, if we use 7.2 percent which is an average that is gleaned from the publications, from the literature, we need about 4200 pen floor samples to achieve the 300 isolates. And I just rounded up to 4500 for even distribution because it is easier to think that way and that equal about 150 barns if we collect 30 pen floor samples per barn, 3 samples from each of 10 pens. So right now we are looking at about 45 barns per state, 15 farms per state. These will be collected within 7 to 10 days of transport, collected seasonally so the farms will be distributed seasonally, and what is left will be collected in Ohio because then we begin capturing some of the smaller and mid and niche market production systems. (Slide) We do intend to look at balancing production systems. So if 30 percent of overall production is mid-sized and niche market, then this is what we would want to capture in a proportion and 70 percent large production. Again it is a convenient sampling. There is no way that I can figure out short of a Congressional Act how to do a complete random sampling that is mandated. So we have to look at convenience sampling over a period of time. We do have questionnaires to capture management and biosecurity information and antimicrobial use information including co-factor information such as disinfectant protocols and chemicals that will be Audio Associates 301/577-5882 54 used, any type of heavy metal use and at what stage and what level over a period of time. (Slide) So what do we do for this? We actually ship the boxes to the -- these are shipped to Wondwossen. Wondwossen then distributes them to the collaborators who will actually set up the collections. These sampling boxes contain everything that you need including the directions, the collection form that they end up sending back, a place for a kit ID which is blinded so when we get it back, the shipping label is back to us, the return labels are from us and billed to us so we have no clue where they are coming from; all we get is a kit ID. The university collaborator Wondwossen will hold the key. In this way, our working with industry helps to guarantee that there is confidentiality. And then we put anything else that we need to in there, tubes, knives, swabs, PBS if we are going to have any kind of chicks necropsied or swine necropsied or anything on site. So it is again -- and I hope that you see the importance of the commodity groups impressing upon the industry the importance of them participating in the collection of these samples. This is a significant, significant cost savings and their involvement is critical to this. And it also ensures that we have a wider distribution Audio Associates 301/577-5882 55 because we simply cannot pay enough people and reach enough farms over a period of time that will ensure the representativeness that we need. (Slide) So the collector freezes the cool packs, collects and ships the samples back to us where we use a standardized protocol to look at the four main bugs and then any other additional bacteria that we may sample that is important for that period of time. For instance in swine we may look at some samples for MRSA or C. difficile. These isolates are characterized and serotyped. We have our serotyping in house which we hope to have validated through standard protocols and this costs us a couple bucks an isolate to serotype. This has been tested against NVSL and right now we are having 100 percent concordance as long as we have a smartcode[sic] for it. The data is recorded in the database. It will be sent back individually to Wondwossen, Wondwossen will distribute it back, so it is sort of an added value back to the farm, back to the participants. We will aggregate everything and put it into the NARMS database which will become the on-farm information. And it will not be broken down by region or any other descriptor until we have a large enough subset to be able to adequately blind all of that information over a period of time. Audio Associates 301/577-5882 56 Our intention then is to have regular, and what do I mean by regular? Hopefully we will have at least monthly calls at some point just to say does this work, is it working, and what do we need? Monthly data back to all of the participants, monthly postings into the NARMS website, and then more intensive meetings with hopefully all of the collaborators and collectors over time to give feedback to look at what might be working in some operations versus other operations to then be able to suggest ways that improvements can be made on specific operations that could lead to a reduction in pathogen levels over time. So again it is this partnership. You have to be getting something; everybody has to have mutual benefit from the entire program. And the most important thing is that we maintain confidentiality. (Slide) All of the swine sampling will actually start within the next two to three weeks. We are sampling right now in poultry. It is very similar to swine in the overall design. We use a 20 percent Salmonella prevalence as a minimum and we only need 1500 samples with that kind of prevalence. In fact we will end up collecting a lot larger number of samples simply because production is so much larger in poultry than it is in swine. The major poultry producing states are Georgia, Audio Associates 301/577-5882 57 Arkansas, Alabama, Mississippi, North Carolina, Michigan, Maryland and California. Our goal is to enroll at least the top 10 companies or as many of those as we can over a period of time, getting in maybe the top fifteen. We initiated sampling in April in one company and a second company sampling is to start the first week of August. While at this meeting I was actually approached by two other companies who would like to also start sampling in mid to late August and our goal is to enroll two additional companies by September. So we will be looking at a total of six poultry companies that we would be partnering with at that time. I did talk to Chuck Hofacre who is going to be the university collaborator and coordinator and we will figure out how to get the boxes to him and the boxes will get distributed out to where they need to go again to ensure confidentiality over a period of time. And I do have to say that everybody in both commodities has been extremely interested, on-board, and willing to participate to get all of this sent back to us. (Slide) When we started in April we started in pullets and breeders. It is interesting what you get out in pullets and breeders so that we know -- and in discussion with the companies in particular, there is merit in looking at pullets Audio Associates 301/577-5882 58 and breeders in addition to broilers over a period of time because the pullets and breeders are going to have Salmonella associated with them. These do already have some antimicrobial resistance associated with them. And unless we know what is happening throughout production, then it is pretty hard to tease out what you are seeing at the end associated with transport. These kits are sent to the collaborators for blinding. The farm managers have been collecting on the one farm and shipping samples to us. The other farm that will start, their managers already have boxes. We have designed a spreadsheet to capture the results and we have sent back monthly results and we have routine discussions with them tweaking the system as we need to. (Slide) This just gives you an idea of what we are doing in the houses although these are boots wrapped with booties. This is the best that I could do for feet. So they walk up one side and walk down the other; we have two pair of booties. We have been taking two nipping waters, one fan dust and when found insects, rodent droppings, and any carcass/ceca from dead birds and there are always a couple of dead birds over a period of time. Since these are integrated poultry operations, we have agreed to get feed monthly when we get up and rolling. Audio Associates 301/577-5882 59 It will be quarterly until we get going but it will include the ingredients so we will know what is going into the birds over a period of time too. And we do have antimicrobial use information that we will be able to associate with all of this in addition to the management information; the same that we have for the swine industry. (Slide) Now based on what we have done for the last couple of months, we have already decided that we can change our sampling protocol and what we are going to end up doing is just looking at pullets at 4 weeks, breeders at 44 weeks, and broilers within 1 week of transport, two pairs of booties with each being cultured individually and 2 samples from cecal droppings. That is going to be the main composite. Those are most likely to be positive and I was happy to see that at the three talks I went to at the Poultry Science Association, those are also the samples that they recommend that have the highest correlation with in fact what comes out at slaughter at the end. We will always take some ceca from dead birds if available because they tend to produce just slightly different results and we will see how all of that fits in. And then particularly in the breeders over a period of time, darkling beetles may be our major source for control and representation of different serotypes that come in to the production Audio Associates 301/577-5882 60 facilities. We are going to look at 2 houses per farm. We will have 6 minimum samples, the booties and the cecal droppings, 8 maximum per house. Right now we are talking about looking at a majority of the houses within an operation sent over a period of time. And again the biggest part is covered in that they are collecting the samples for us. They are excited because they are getting that information back to them which gives again the partnership aspect to it. And we are looking at the feed again. (Slide) So some of the questions that I have is when we set up these types of studies, who collects the samples? For us it is the commodity groups who have been spectacular cooperators. We hope to be able to go into cattle and turkeys at some point in time. It is the most cost-effective way to get the largest number of samples that we can. Who has to provide buy-in? Well we hope that everybody provides buy-in to this or whatever scheme we end up with over a period of time. And do we have the correct level of confidentiality? We hope we do right now but we are always open to other layers, other ways to protect the ID of the cooperators involved. The ID numbers I think help a lot in none of our notebooks in the laboratory have any farm names associated Audio Associates 301/577-5882 61 with them. And again we have to agree, no matter which system, no matter who is involved, looking at comparable culture methods because if one is culturing one way and another is culturing another way, if more than one lab is involved, it is going to be like comparing apples to oranges over a period of time. Which bacteria do we do and then how many isolates? We have talked about some of the studies that we have done. We do know that if you take 5 isolates you are likely to get 3 that are very similar. Eighty-five percent of the time 5 of them will end up being the same, 15 percent of the time you are going to end up with something different. How many isolates do we need to collect and what does it really mean when we go down on the end? And again this should be done across the entire system. We may need to look at discussing more sample collection with CDC and more isolate collection in retail as well. (Slide) So eventually what we hope to be able to do is to sort everything by species, production type, region, serotype, season, phenotype and genotype. We would hope that it could be predictive. Predictive of what? Predictive of at least what is going and most likely to end up in retail, predictive of what we need to work on, and maybe predictive of emerging Audio Associates 301/577-5882 62 patterns that are going to come about as far as antimicrobial resistance goes. The use and management information I think will be most beneficial not only to FDA but back to the farm themselves. If you can offer to a production system a way to improve and make some things better, the groups that we have worked with, the farms that we have worked with, they are welcome to those types of suggestions and look forward to implementing and making the changes. (Slide) As Pat discussed there is a parallel on-farm pilot just to be able to spread out our resources. This is to pilot other processes to see if long-term networks of scientists -- it is a little bit of a different model in that there is a network of labs and university collaborators that will be collecting samples individually. This is being led by Dr. Mary Torrence who is our national program leader at the request of the FDA. This is a four-month pilot from September to December. This network of university and ARS food safety researchers will do the sampling; Texas Tech, Minnesota, and Georgia and then ARS at Clay Center, College Station, and Beltsville. And all of these programs have some long-term sampling programs or industry collaborations on board right now. Samples, ours are strictly on-farm. Theirs may be Audio Associates 301/577-5882 63 on-farm, at the truck or at the slaughter door. (Slide) The details have not been worked out yet but in principal the sampling will be done on feedlot and dairy and poultry that represent the geographical regions with food animal production. This network will collect the samples, do the cultures and characterization. The difference here though is that these isolates are being sent to FDA for sensitivity testing and further characterization. The process will be evaluated in mid-December and then we will take their results and what we have been doing and look at, hopefully sitting down with a group of advisors, in looking at what might be the best way to sample to meet the needs of the program. And again if this network succeeds, it will be revised to include more sampling and researchers to meet the NARMS needs. (Slide) So where am I coming from? Well the reality of the situation is that we do not have enough money to do this in one lab in one way alone. I mean this just is not going to work. And that is one of the reasons that we agreed to have a meeting and to come together and look at what will be the best way to do things. So it is going to likely be a combination of sampling protocols maybe from different places across the food production arena. It might be a combination of sampling methods and it might serve different types of core purposes. Audio Associates 301/577-5882 64 It might have ongoing evaluation necessary with the partners, not might, will have ongoing evaluation. No matter what scheme ends up being used, this is something that is going to have to be done. I think that it is critical to have this synergy of partnerships. At a minimum we are going to have to meet more regularly, a yearly meeting whether it be a large NARMS meeting to talk about results and other issues that may come up. Some component of it is going to have to just address I think sampling and any revisions or challenges that we have met throughout the year. My goal is to build this on-farm program to capture the present status of production as well as detect emerging trends over a period of time. It must mesh with the human and retail sampling as well as the current public health efforts within FSIS. And I think that that is incumbent upon us because we are all part of the public health mission. I know that was really fast but hopefully we will have the rest of the day to look at answering any questions that you need. (Applause) DR. TATE: Are there any questions? And since we are a little behind I would entertain one or two. (No response) DR. TATE: Okay, the next speaker will be Ms. Emily Audio Associates 301/577-5882 65 Tong who is an epidemiologist at FDA Center for Veterinary Medicine and she is responsible for putting together the retail meat report. FDA Retail Sampling by Emily Tong, MPH MS. TONG: Thank you Heather. Today I will be presenting the retail meat sampling in a little bit more detail than Pat described earlier. (Slide) First I will be going over the history of the retail meat program and pretty much how it started. Then I will talk about some of the recommendations that were made for the retail sampling. And then describe in a little bit more detail about the actual sampling that we currently have. And finally we will talk about some of the considerations that we would like to discuss later in this meeting. (Slide) So the NARMS program, as you may know, started in 1996 with the initial selection of Salmonella from animal and human origin. And then later in 1998 we did Campylobacter and in 2000 we did enterococci and E. coli. During this time an inter-agency taskforce was established to create a blueprint for a specific coordinated federal action to address the emerging threat of antimicrobial resistance. Audio Associates 301/577-5882 66 And in 2001, the World Health Organization recommended that resistance be monitored from farm to fork by a three-pronged approach which included the animal isolates, human clinical isolates, and finally the retail meat isolates. So consequently in 2002, the retail meat program was added to the NARMS program. It was built on an existing public health infrastructure by using state public health laboratories that were already in the Foodborne Disease Active Surveillance Network which you guys know as FoodNet. And because of time and budgetary constraints, leveraging existing collaborations and infrastructure proved to be the most efficient way to start the retail program. So over time, NARMS has since evolved in size, awareness and importance. And to meet the NARMS objectives that Pat stated earlier, we have made sure that the methods and procedures have been standardized among all the participants in the NARMS retail meat program. (Slide) So the Science Board’s recommendations, they found potential areas for bias in our sampling scheme including a small sample size when the data was stratified and the lack of a statistically valid national sampling strategy that can limit broader interpretation of the data. And the final recommendation was to use a random sampling scheme when possible. And when this was not Audio Associates 301/577-5882 67 possible, they recommended that we further stratify the data to adjust the sampling strategy to answer specific hypothesis- driven questions like source and risk factors for resistance. And as Pat mentioned earlier, we recently did a one- year pilot study on methicillin resistant Staphylococcus. And from the data that we have analyzed so far, we have seen a prevalence of 4 percent in the retail meat that was sampled. (Slide) So what exactly are our retail sampling objectives? We really want to highlight the first one which is to primarily detect the temporal changes in resistance. And secondly we want to determine the prevalence of antimicrobial resistance among Salmonella, Campylobacter, enterococci, and E. coli. (Slide) So this slide is a really excellent representation of how we have expanded over time. The NARMS Retail Meat Program began in 2002 with five FoodNet sites including Connecticut, Georgia, Maryland, Minnesota and Tennessee. And later in 2002 Oregon joined. And over the time we have added new surveillance sites including New York and California in 2003, Colorado and New Mexico in 2004, and finally in 2008 we added Pennsylvania. As you can see in the last bullet, in 2012 we are planning to add three additional sites to our program for Audio Associates 301/577-5882 68 testing Salmonella and Campylobacter and I have highlighted these with the plus signs. And pretty much we have invited all of the sites that are participating in the NARMS human clinical isolates to participate and we established that these are the sites that have interest in joining the Retail Meat Program. Those are Texas, Kansas, Michigan, Louisiana, Iowa, and Ohio. And what you can see here is that geographically these sites would fill the surveillance gap that we currently have in the Midwest. (Slide) So this shows us the retail meat surveillance coverage. From the 10 FoodNet sites in Pennsylvania, we know that the surveillance area includes approximately 4 percent of the United States population. Those totals that are there with the zip code areas, it is about 12 million. (Slide) So how are the sampling locations actually determined for the retail meat? We start with saying that our grocery store locations prior to 2005 were selected by convenience sampling. After 2005, we changed our sampling scheme to address the Science Board’s recommendations and we are now using a stratified random sampling scheme. So right now each of the 11 sites identifies a minimum of three strata to sample from which we are designating by the leading 3 digit zip code areas. So I have Audio Associates 301/577-5882 69 included an example here of California. What we do is give each site a map and it has all of their zip code area locations and they are able to pick zip codes that are around their surrounding Department of Public Health and it has to be a minimum of three zip code locations. So in this example, California chose 941 and zip codes that were between 945 and 948 and those are highlighted with the red dots. Once we receive these zip code areas, we then purchase a list of grocery stores from the Chain Store Guide and they give us a list that are within each of those zip code locations, all of the grocery stores that are within those zip code locations. And I have included a little insert of what the data looks like from the Chain Store Guide. It includes the company’s name, their address, and their zip code location. Also it has latitude and longitude data so that we could possibly use this in a geographic information system. So once we receive this list from the Chain Store Guide, we then analyze the data where we are able to separate the list for each site into quadrants and then we use stats to randomly select the grocery stores that the sites will have to go to on a monthly basis. We pick 10 grocery stores per month with 5 primary and 5 secondary stores to sample from. (Slide) So this is just an outline of the current retail Audio Associates 301/577-5882 70 meat sampling scheme. We request that each site sample at least twice a month. And then once they do the sampling, they need to go to at least five grocery stores per month where they will purchase a maximum of two samples each of chicken breasts that have the skin on and bone in, ground turkey, ground beef, and pork chop. There then is a meat selection priority where we request the site to sample two different brands from any given store. And in the event that a site cannot sample two different brands, then we ask them to select on another priority where they are to select two brands that have two different establishment numbers and two different sell-by dates. And finally if they go to the grocery stores on the primary list and they are unable to find these meat commodities, we request them to go to the secondary stores. And so following this sampling scheme, each site would end up collecting 10 samples each per meat type and this equals 40 meat samples per month. If you multiply that by 11 laboratories and 12 months, that will result in over 5200 meat samples per year. (Slide) So some of the strengths and weaknesses that we have noticed in our sampling scheme is that although we have moved away from the convenience sampling scheme we still have a few things that we could be working on. As the Science Board Audio Associates 301/577-5882 71 pointed out, there is limited population coverage. And the Chain Store Guide where we are receiving the grocery store lists do not include sales volume which would be really helpful. We have done some research to try and find the sales volume information and it has been very difficult finding it. And finally the exclusion of certain membership stores; removing these stores may give some bias in having a sub- population missing. (Slide) We are going to look at some of our data. We think that the sampling that we have done so far has been pretty good. I mean you can see here from 2002 we had 600 samples and as we increased over time and added more sites we are now sampling over 1300 samples per year. And in 2012 we will be adding three more sites so we can expect another increase there. (Slide) This is our Salmonella prevalence from 2002 to 2010 and we just want to note that our 2010 data that is there is preliminary. And here you can see that the prevalence is highest in chicken breasts and ground turkey. And over time we can see that the percent positive has remained relatively stable and increasing slowly over time. For ground beef and pork chop, we can see that it has been less than 5 percent since the beginning of the NARMS Audio Associates 301/577-5882 72 program. (Slide) And with Campylobacter you can also see the consistency in our data. For chicken breasts you can see that it was declining over time but for the most part, with the exception of 2004, it has been between 40 and 50 percent. Also ground turkey has been less than 10 percent. And ground beef and pork chop the prevalence has been so low since 2002 that in 2008 we decided that we would stop testing for campylobacter in ground beef or pork chop. (Slide) Now to the reason why we are here; we would like to improve the NARMS program and we would like to solicit your support and expertise in addressing some of the following considerations and questions. The first one is what pathogens or commensal organisms should we monitor? For example we did the pilot study on MRSA and we determined there was 4 percent in the samples that we tested. Is it possible that we should add this to our program or continue the pilot study? Secondly should we expand or replace the commodities to include seafood? Many of the sites have asked us questions about why are we still sampling from ground beef and pork chop as they have low prevalence. Is it possible that we could sample a different commodity such as imports or seafood? Audio Associates 301/577-5882 73 (Slide) Next, what should be the selection criteria for the additional sites? As you saw, we had a number of sites and we can only add three sites in 2012. So how should we determine that? Should it be based on population, should it be based on the consumer and what are they purchasing, is it volume of the state and how many meat samples that they are selling? And finally should we increase the number of samples for the current sites that we have? So as we move out through the rest of this day, we would like to solicit your comments and expertise on answering some of these questions that we would like to address when we move to the future. (Slide) And finally I just want to acknowledge all the FoodNet sites that have helped us do our retail meat sampling and the CVM NARMS Team and the NARMS working groups that include our collaborators and many of you. Thank you. (Applause) Question and Answer Session DR. TATE: Thanks Emily. Are there any questions for her? DR. ESTEBAN: I am very curious. You have about 40-50 percent prevalence of Campylobacter in chicken breasts? MS. TONG: Yes. Audio Associates 301/577-5882 74 DR. ESTEBAN: The reason I am curious is because when we did our in-plant national prevalence estimate we were around 10 to 20 percent. So who is injecting the chicken with Campylobacter? (Laughter) DR. ESTEBAN: I am just curious. I do not know whose write up was wrong but I would love to see if we have the same method because if we have different analytical methods it is going to be kind of embarrassing to explain to the stockholders, you know industry and the consumer groups. I don’t know how -- so if we could share methods that would be great. MS. TONG: Okay. DR. ESTEBAN: Thanks. MS. VAUGHN GROOTERS: It is Susan Vaughn Grooters from STOP and Keep Antibiotics Working and I am just wondering about these graphs. Do you then break them down to multi-drug resistance strains and other strains? This is just a capture of all Campylobacter and Salmonella, correct? DR. : (Away from microphone) MS. VAUGHN GROOTERS: Sorry, you do break these down for multi-drug resistant strains and you go beyond this. This is just a capture of what Campylobacter and Salmonella are from what you are getting in retail samples correct? MS. TONG: Yes, we have an annual retail meat report Audio Associates 301/577-5882 75 where we do break down Campylobacter by C. jejuni and C. coli which has this information in more detail. MS. VAUGHN GROOTERS: But you are not sharing that information today? MS. TONG: No. DR. McDERMOTT: (Away from microphone) MS. VAUGHN GROOTERS: (Away from microphone) DR. McDERMOTT: (Away from microphone) DR. YANCY: Al Yancy, US Poultry and Egg Association. I do think it is important to look at the testing methods for the baseline on Campylobacter as well as the testing methodology that you are using. But I also think it is critically important and you can certainly add this to the list of number of samples for the current sites, I do not think it is safe to assume that that which is produced in the plant is what ends up in the retail case because there are all those steps throughout the cold chain that have to be looked at. Also whether or not product gets abused through that cold chain process or whether it gets abused at the retail site that repacks the product that may be bulk-packed to them. And so that is critically important and assumptions should not be made that whatever is in the retail case is absolutely positively what was shipped out of that plant because it may not and in some cases absolutely is not the case. Audio Associates 301/577-5882 76 MS. TONG: Thank you, excellent comment. DR. McDERMOTT: (Away from microphone) DR. : (Away from microphone) DR. McDERMOTT: (Away from microphone) MS. TONG: Right, we are actually doing -- our summer intern is working on gathering all that organic information because the sites when they collect the samples they save the labels but they do not forward it to us so we are actually working on that to complete our database with organic and inorganic data. DR. MOLLA: My question refers to the point you raised particularly with MRSA from your pilot study point of view. Did you detect in all commodities of retail meat samples or was it limited to one commodity only? MS. TONG: I believe it was two commodities, do you remember? DR. McDERMOTT: (Away from microphone) MS. TONG: I can look into that and – DR. McDERMOTT: (Away from microphone) DR. MOLLA: We did a pilot study, the same, on retail meat samples particularly on pork and to detect MRSA ST398 and I was wondering which of the commodities were positive in your pilot study. Thank you. MS. TONG: Okay, I can follow up with you. DR. TATE: Okay, is that it? Audio Associates 301/577-5882 77 (No response) DR. TATE: All right so we have a break until 10:15 and then we will reconvene for our next speaker Dr. Lucie Dutil. (Whereupon a break was taken) DR. McDERMOTT: We will move on to our next presenter today, Lucie Dutil, from the Canadian Integrated Program for Antimicrobial Resistance. She is going to talk to us about the evolution of CIPARS retail meat and food animal sampling and some of the lessons they have learned in developing CIPARS. Evolution of CIPARS Retail and Food Animal Sampling by Lucie Dutil, DVM, MSc DR. DUTIL: Thank you for the introduction and also thank you for the invitation. It is always a real pleasure for me to get another occasion to meet with NARMS colleagues. (Slide) So I have been asked to talk about the evolution of the CIPARS program. As most of you know, CIPARS is doing surveillance of antimicrobial use and antimicrobial resistance. And on the antimicrobial resistance side we have passive surveillance and active surveillance and I will be focusing on active surveillance today because that is where most of the thinking has been done in terms of sampling strategies. And I will be focusing on abattoir and retail as Audio Associates 301/577-5882 78 well more than the farm although we have a farm sample. It is more based on convenience sampling and I do not have enough time to talk about it so I will be focusing on abattoir and retail meat sampling. (Slide) Back before we started -- we initiated the program in 2002, before that point there were several reports and meetings that happened before then that were highlighting the need for active surveillance. And in 2000 an AMR steering committee in Canada identified three broad goals that the active surveillance should be able to achieve which were to detect temporal and geographical trends, assess AMR pressure coming from food, and from animals. So to be able to achieve those goals, estimates that were derived from those surveillance components had to be representative of the target population and they also had to be precise enough to allow the detection of differences with a certain degree of confidence. (Slide) For the abattoir surveillance, our unit of analysis is the bacteria from food animals raised in Canada. We decided to go for this surveillance component at the national level for the representation of the estimates. So this component is measuring the contribution of domestic food animals to AMR versus retail that also includes some imported Audio Associates 301/577-5882 79 elements. So we are achieving that by sampling the cecal content at the abattoir level and not the carcass rinse so it is something totally aside from what the regular activities of the abattoirs are. We wanted, by doing that, to avoid cross- contamination that we see and you know avoid the confusion that could come from cross-contamination from the environment of the abattoir. We considered that as being a representation of a -- you know it is a pre-harvest sample and a representation of the farm level of AMR although there are a few differences, as close as possible to the farm level but yet being at the abattoir level and the ease of sampling at that level. We are currently only looking at federally inspected abattoirs. We consider that as being adequate because 90 percent of our animals slaughtered in Canada go through those abattoirs. And also we have the support of the Canadian Food Inspection Agency that makes it easier to implement and also to do the follow-up on that component. (Slide) So before establishing the sampling scheme there have been various simulation models that were run. And in those models we included the variables such as the cost of the various testing, the cost of sampling, estimates of prevalence that we had at the time for the bacteria prevalence and the AMR prevalence, and also we tested at various geographical Audio Associates 301/577-5882 80 scales, so that was the input information. And the output we had two informations which were the powers to detect differences and also the mean cost. And through this we had various outputs. (Slide) And we finally established that our target number of isolates would be 150 isolates per year per commodity per bacteria and that it would provide an acceptable precision and power at an affordable cost. Of course it is not a lot of isolates and you have to believe in random sampling and sampling strategies. And in this case, for example, if you have two groups of 150 isolates with one showing a prevalence of 50 percent, to be able to detect significant differences prevalence would have to be 39 percent roughly or below in the other group to be able to say it is significant. So the power to detect differences is not very, very big when you are around 50 percent prevalence. What is nice with that is when you are in lower prevalences, the same sample size will give you a lower range between the two so you can detect significant differences between two populations with 1.5 and 7 percent prevalence. Some people will say it is still not enough but you have to think also that stakeholders are not ready to move whenever there is a little 1 percent change in prevalence. So realistically do we really need to go more than that? It Audio Associates 301/577-5882 81 would be nice sometimes to have more than that especially when we get into Salmonella and we want to dig down into serotypes and all that but for now, for the time being, this is what we have established as a target, a realistic target according to the costs. (Slide) The important thing is to get to that representative set of isolates and there are various steps that we have to go through including selection of abattoirs, allocation of the samples and the definition of a sampling schedule, selection of the lots at the abattoir level, selection of the animals, and also some selection that happens at the lab level like Emilio was saying this morning, or and Paula was saying, you know depending on the method, but that is something that you have to live with. And we also have some samples that we test and some samples that we do not test that we have to -- we are going to go through that but at every step we try to either go randomly with some sort of random sample or at least try to avoid systematic bias and ensure representativity when a true random process is not possible for various reasons. (Slide) So the first step at the abattoir level is to sample and select our abattoir. So at the very beginning in 2002 what we used was a weighted/proportional random sampling of Audio Associates 301/577-5882 82 abattoirs, so bigger abattoirs with bigger slaughter volume had greater chances of probability of being selected. So initially we selected 65 plants, 2 plants declined participation and 12 had to be replaced mainly because they were the wrong commodity. They had switched commodity between the time we had the list and the time we contacted them. And some were considered not representative; they were university plants used for practice and things like that. So we ended up with 51 plants, 20 chicken, 20 pigs, and 11 cattle plants. Those remain in the program until now unless they were dropped. Most of the drops were due to plant closure, there has been a lot of reorganization at the plant level for all of those commodities through time. Some change commodities, one burned down, and we did drop 2 because they had low compliance; they would not follow the protocol that we had established. One came back later with better compliance. And for each of the plants that we lost we tried to find replacement plants that were randomly selected. And sometimes to replace a big plant we need to bring back more than one plant. So when there is a big plant closing, there is not always a big plant available or that comes randomly so sometimes we had to replace it with a greater number of plants. (Slide) Audio Associates 301/577-5882 83 So this is a picture of 2009-2010. In the square boxes you have the number of plants included in our sampling and below you have the total number of possible plants. So yes in Canada there are not that many abattoirs which makes it nice. So in 2009-2010 we had roughly half of the abattoirs in our sampling plan and that represented between 63 and 69 percent of the slaughter volume. (Slide) Once the abattoirs are selected, we need to define how many samples they will be collecting and they are not collecting isolates they will be collecting cecal samples so we need to identify how many cecal isolates will be sampled to get to the 150 isolates. And like it is for your sampling program, we base it on bacteria with the lowest prevalence. So as an example, for chicken here, the lowest prevalence is Campylobacter at 19 percent so we would require 790 samples total for all of Canada, all slaughterhouses. And in pigs the lowest prevalence would be Salmonella, we currently do not sample Campylobacter in pigs, so with 333 samples needed. (Slide) Once we have that we allocate all those samples across all abattoirs and this is proportional to the sampling volume so bigger abattoirs get more sampling. So a big abattoir, the most that they can sample is every other week; Audio Associates 301/577-5882 84 we do not go over that. And some small abattoirs may contribute only once during the year. But we do try to allocate it across the year so that at the lab level we do not have a big blob of samples coming all at once and also because we do not want seasonal variation or artificially due to the fact that we have a cluster in space or something like that. And each time abattoirs are requested to send five samples for each of those sampling periods which are basically a week. (Slide) When they are on a sampling week, they need to select first 5 different lots during the week so we do not want all the samples coming from the same lot. Often it is the first lots of the week that they select. This is a convenience sample. We have not found any way to randomize that at the abattoir level and make it easy across all commodities and across all abattoirs. So we give guidelines to try to avoid systematic bias. But basically it is when the QA person has time to sample because it is an extra activity. And sometimes it can be all lots of the week. Some of those abattoirs have very, very large lots and for the same day they will be killing only one lot so sometimes there is no selection to make. And there are a few cases, but rare cases, where there are only 4 or 3 lots during the week, they may not slaughter the whole week either, so in those very few cases Audio Associates 301/577-5882 85 they are allowed to send 2 samples for the same lot but this is indicated and this is something we take into account. We look if this is something that has to be taken into account. And then for each of those lots there is one animal “randomly” selected in each lot. So this is not a true random selection, again, there is not a list and we tell them to pick this one but you know how fast it goes on the chain especially for chicken so it is basically the animal that comes by when they are available. They do not have information on its origin, it cecal content, they cannot be influenced by the appearance of the carcass because at the level where they take that they do not have this. So we consider this as probably fairly representative although it is not random. (Slide) And then at the lab level, in addition to having the methods that will use a certain level of selection, for E. coli in chicken and in pigs we ask the lab to select 1 out of 4 samples and 1 out of 2 samples respectively because we do not want to test all of the samples because we want to get 150 isolates to stay within budget. But all samples are tested for pathogenic bacteria and all beef samples are tested for E. coli. (Slide) So there has not been much change in the strategies, in fact there hasn’t been any changes in the strategy but what Audio Associates 301/577-5882 86 happened in terms of changes at the abattoir level is more the number of plants, you know plants dropping and having to be replaced. And as you can see, at the very beginning we did have to increase the number of plants included because we had underestimated the true prevalence of Salmonella. The data we had were regional and when we came with national data we had lower prevalence -- sorry that was the other way around, we overestimated, so we had lower prevalence of Salmonella so we had to increase the number of plants. Over the year for all of those commodities there has been a consolidation so a reduction in the number of plants that we had to live with. Like I said we tried to replace -- it does not show which plants, it shows the total numbers so it does not show how many were dropped and how many were replaced. But in general it did not have much impact on the total number of samples that we had, we did reach our target except in 2010 for beef cattle where we lost a big plant early during the year and we were not able to replace it by a similar volume after that so we basically almost cut it by half our target for beef cattle. And that is something we are actually looking at which is what was the impact on the estimates that are derived. This is a year that will be a bit special and we will probably have to take into account. Luckily in 2011 we have been able to enroll a big plant. We are now at 95 percent of the sampling volume in Audio Associates 301/577-5882 87 beef cattle so it really moves and that is something we have to follow. (Slide) So there are strengths and limitations to that component. The strengths being the direct national representativity unless you lose a very big plant and then you have to work a little bit harder to get the adequate estimates. It does inform on animals raised in Canada. For us it is very important to be able to provide this information back to our stakeholder and not having the confusion that comes from imported meat. It is relatively inexpensive because it is centralized, we do not have to go on-farm and it is not a huge volume of samples. It is an easy way to obtain “farm level” information regarding AMR. And we put it in the strength, the direct involvement of the industry which raised the awareness of AMR in the industry. And we have had a fairly, fairly good collaboration from the industry and I think a good reputation also. We have had people not wanting to embark on the program, calling a plant on the program, and then embarking after just being convinced by the other plant that the program was easy to follow so we think it is going well. There are limitations. It requires agreement with the plants, it is not mandatory. It requires a visit at each plant to identify an acceptable sampling location because we Audio Associates 301/577-5882 88 are sampling ceca, we are opening ceca, so we do not want that to make a contamination in some places at the plant. We do have to provide sampling training. It is sensitive to large plant closures and it is only right now in federal plants but it is not really a limitation for those three commodities because that is mainly where those animals are going. (Slide) So now for retail, our unit of analysis is enteric bacteria on raw meat purchased in Canadian retail stores. There we seek provincial or regional representativity. We want to measure the consumer exposure on the same geographic scale as what we have on the human side. We have ground beef, chicken legs, pork chops, and recently added turkey. Those are cuts that are frequently consumed and also where we have a relatively high bacterial recovery. Like I said it may include imported beef and pork meat. For those commodities, ground beef can be mixed with cull dairy so there is also a mix with other commodities. But for chicken it is vastly domestically produced so on that side it is interesting, it is on a quota system, so there is a bit of mixing but there is not much and probably not enough to worry about. And we sample in chain or independent stores and butcher shops. (Slide) Audio Associates 301/577-5882 89 There we are, again through simulation models, we established 100 isolates per year per province per commodity per bacteria would provide this acceptable precision at affordable cost. Here we have to balance between precision and the need for data from multiple regions. We would love to have 150 isolates like on the abattoir side because that would help us detect changes in trends more rapidly and currently we are not reaching the target in some of the less populated provinces because of budget constraints. So there is an impact on precision. Like I said, it is lowering our capacity to detect trends however there is no impact on the representativity or not so much because we do follow the same sampling scheme as we are in the bigger populations. (Slide) So again something similar to what you saw on the abattoir side, we also base our sampling volume and the number of meat samples that need to be collected on the bacteria with lowest prevalence. But also we need to take into account the number of store visits, the lab capacity, and the budget so that is also the reason why we are not getting 100 isolates everywhere. (Slide) So again like on the abattoir side we need to get to that representative set of isolates and we have several steps. So the selection of census divisions which is similar to ---. Audio Associates 301/577-5882 90 In each of the provinces the allocation of those samples in each division and the definition of the sample schedule, the selection of the source, the selection of the meat in the store, and then another selection at the lab level. And again we try to avoid systematic bias and ensure representativity as much as possible. (Slide) Currently we are in 7 provinces or 5 regions. The Maritimes are all pulled together; those are small provinces with low population. (Slide) And in each of those provinces we use a stratified weighted sampling of the census divisions. So bigger census divisions -- well the first thing we did is we ordered all of those divisions by increasing size and population; we created the 4 strata of populations that have the same weight in terms of population. And within those strata the divisions were selected and had a greater probability of being selected according to their weight in terms of population. So this is an example for the province of Quebec where for example for the first strata we had a total of 72 divisions and we selected 10. And we had the fourth strata where we only had one division, the city of Montreal, and obviously that one was included. There are some cases in Quebec where we had selected Audio Associates 301/577-5882 91 a very remote place like Northern Quebec where there is almost no one living there and I am not even sure they eat chicken so we finally excluded those but in some provinces we do have a collaboration from the local health authority. So in Ontario and British Columbia for example we were able not to exclude those remote census divisions. (Slide) Then we have to allocate in each of those divisions a certain number of samples that we will have to collect from those divisions. And this is an example, here in the first strata -- each of the strata get the same amount of samples to collect because it is the same weight in terms of population. So here in the first strata we had 10 divisions where we had to collect 240 samples. So that for each division we visited them twice with 4 stores at each visit and 12 samples at each visit compared to the Montreal city where we also had 240 samples to collect but there we went 26 times and did a visit for 4 stores and 12 samples at each time. (Slide) So once we have that then we need to identify the sampling schedule. Basically we are sampling every week in Ontario and Quebec and every other week we see Saskatchewan and the Maritimes. The samples from the large divisions where we sample more often we try to distribute it evenly across the year, which is indicated by the little arrows of colors. Audio Associates 301/577-5882 92 Those are the same divisions where we go more frequently. We do have to group those divisions that are close in distance to try to reduce the cost of travel or those that are on the route but other than that we try really to allocate it equally during the year to avoid confusion between temporal or seasonal variations and cluster in space. (Slide) The stores, unfortunately we do not have a list. There is no good list of the stores. There is no list also indicating their sales volume or their meat sales volume which would be the ideal thing. So far we have not been able to do any random selection of the stores. So instead we give directives to our field worker. In some divisions there is no choice, there is not that many stores anyway so they basically sample from every store available. And in other places where there are choices, we tell field workers not to go more than once a year as much as possible and they have to also travel and you know travel within the division to try to change location from time to time. (Slide) At the store level, again at that level, it is not totally randomized how we pick the sample. When we are in a butcher shop it is basically the clerk that selects for us so that is like if you and I were to go shopping, it is probably the most representative way of sampling. Audio Associates 301/577-5882 93 And in the other shops we do ask field workers to collect small packages just for budget purposes. We do not have any indication that this is much different from the family size, it looks like it comes from -- the information we have from the same pool of meat at least in our reality. And we ask them to alternate between store brand and name brand because we do not only want to have store brand or just name brand. We ask them not to purchase any packages that are for rapid sale because it might be closer to the expiration date, the best before date, and that could bias the data. And so it not random selection but we do try to limit the sources of systematic bias. (Slide) And then again at the lab level we have something similar as for the abattoir where for chicken we ask the technician to only pick one out of two samples and test that for E. coli. It used to be a systematic sampling but we realized that our field workers were becoming wiser and they started going into butcher shops before going into the chain stores so we were starting to include more butcher shops just because of the systematic sample so we changed that for a truly random sample. Now they are getting a list and we tell them okay you select store 1, 3, 4 and 6 and then the following week it is another order. It is just a random number just to avoid that possible bias there. Audio Associates 301/577-5882 94 And there is no selection done for pathogenic bacteria. And all beef and pork are sampled for E. coli. (Slide) So there have not been any voluntary changes to the program other than adding new provinces or other new commodities. But what we have had to live with is sometimes interruptions in sampling mainly due to staffing issues. A field worker leaving and we have to replace them but we cannot replace them as fast as we want. Or some unforeseen events like a car accident and problems with insurance. So the main impact of those is again on the precision of the estimates but there could be a potential impact on the accuracy if there happened to be a very rapid drop or some temporal changes during that year that had happened. (Slide) So we plan in the future to try to expand in British Columbia and expand the sampling size so that we can reach our 100 isolates. We want to revisit our store list and explore how we could select more randomly because now we sort of have a store list that we have established ourselves. (Slide) The strengths and limitations, it is a good measure of exposure, the methods are harmonized across provinces and regions, it is a good infrastructure too that we use often to Audio Associates 301/577-5882 95 pilot other projects in collaboration with universities, and we handle all of the components of that so that is nice because we can react quite rapidly with that. (Slide) There are limitations of not being in all provinces, not being able to sample as much as we want in some of the provinces, and some distant divisions are not included which is not a big issue. (Slide) And just rapidly, we do have evidence that the sampling that we do is probably adequate either because the accuracy of the estimates seem to be accurate, that is by the small numbers or coherence across components and across time. (Slide) Here we have data that come from abattoir surveillance in 2002 and from HACCP surveillance in 2002 as well. We only had 78 isolates in abattoir surveillance and 2953 in HACCP. And if you look at the confidence interval, the abattoir is the red line and HACCP is the yellow one, so what we see is that we do not have -- you know the confidence intervals overlap so we are getting pretty much the same estimates. But when we compare that to an Ontario Feedlot Study, so a different geographical scale, a totally different sampling protocol, there we were finding significant differences in the estimates. Audio Associates 301/577-5882 96 (Slide) And if we take farms and abattoir surveillance, we get very similar estimates as well so we think farm abattoir surveillance is probably pretty good. (Slide) And just one last slide just showing that there is coherence across components here. It is showing chicken clinical cases, chicken abattoir and retail cases. The changes in the proportion of S. enteritidis in red and S. heidelberg in green, and S. Kentucky in blue where we see that when one is going down, it is going down in all components or when it is going up it, is going up in all components. And also in human on the very far right, we see similar things except S. Kentucky does not seem to be causing a lot of problems in humans. (Slide) On that I will thank you for your attention and acknowledge all the people that work on CIPARS and I do not think we have time for questions, sorry. (Applause) DR. McDERMOTT: Thank you Lucie. I think we will try to stay on schedule for now and perhaps if you have questions you can hold them for some of our panel discussions and we can raise them again there. It is my pleasure to introduce our next speaker, Audio Associates 301/577-5882 97 Dr. Pierre-Alexander Beloeil from EFSA, the European Food Safety Authority. And Pierre is going to talk to us about the work they have done in the EU to try to I think in part harmonize their surveillance systems and discuss ways in which they designed their sampling to meet the needs of EFSA’s programs. Sampling Methods Used by EFSA for Antimicrobial Resistance Monitoring by Pierre-Alexandre Beloeil, PhD DR. BELOEIL: Thank you very much for the introduction and I am very pleased to participate in this conference. (Slide) So indeed I will start the presentation with a short introduction about the European Food Safety Authority. So the European Food Safety Authority is a European Union Agency responsible for risk assessment regarding food and feed safety. In the European Union EFSA provides independent scientific advice, scientific and technical support and among that in particular data collection on the ---, zoonotic agents, foodborne outbreaks and as well antimicrobial resistance in food and animals and food producing animals, and as well EFSA provides clear communication on existing and emerging risks. (Slide) Audio Associates 301/577-5882 98 The aims of the monitoring of the resistance in the European Union are to understand the development and dissemination of resistance among food-producing animals and food. To inform the risk managers, the European Commission and the Member States on the current situation and trends, to provide relevant data for risk assessment, and to measure the effects of possible interventions and control measures. (Slide) But indeed according to the European Union legislation, the monitoring of antimicrobial resistance at the EU level is based on the Member States monitoring systems. And indeed again the legislation is a little bit more specific and it lays down that Member States must provide information with regard to a representative number of isolates of Salmonella, Campylobacter jejuni, and Campylobacter coli from cattle pigs and poultry and from food of animal origin from those species. So it is quite indicative. So monitoring resistance for those zoonotic agents is mandatory for Member States however the monitoring of commensal E. coli and enterococci is volunteer. (Slide) So EFSA is involved in the collection of the data reported by the 27 EU Member States and as well as 2 other European countries, Norway and Switzerland, and those data are collated and analyzed. Audio Associates 301/577-5882 99 (Slide) But to improve the comparability and the quality of the data on resistance collected by Member States, EFSA has issued harmonized specifications for monitoring and reporting of resistance for Salmonella in fowl, turkeys and pigs and for C. jejuni and C. coli in broilers, and as well as for the indicator[sic] bacteria. And two scientific reports we have published and the representation on the sampling strategies would be based on those two documents. (Slide) And in the framework of those recommendations for the monitoring and reporting of resistance in the EU so the objectives were to quantitatively monitor temporal trends in the occurrence of resistance and distribution of resistance to antimicrobial agents, allow the identification of the emergence of resistance, and as well to detect specific patterns of resistance or specific multi-resistance patterns. For this we are not yet at this stage. And again in the framework of those documents and in the framework of the monitoring at the EU level, the resistance is defined as the proportion of resistant bacteria and we are not yet combining prevalence in proportion of resistance. (Slide) Audio Associates 301/577-5882 100 So those documents consider detailed specifications for the different elements needed for a monitoring scheme. And among those I would like to insist on the fact that we use interpretive criteria, the epidemiological cut-off values defined by EUCAST which is the European Consortium for Antimicrobial Susceptibility Testing. And this is in line with the objective of early detection of emerging resistance or early detection of the increase in the number of bacteria with limited susceptibility. And of course those documents and those technical specifications address sampling strategies and sample size. (Slide) So mainly, chiefly, the active monitoring programs are recommended and they should be based on the randomized sampling strategy of healthy animals. And the isolates should be collected from either flocks or holdings and healthy animals should be considered. And this allows for the representativeness of the entire population, is a reflection of the variability in managerial and hygienic practices. And of course with an approximately equal distribution of the samples, over the years you can cover the different seasons and account for any seasonal effect. And as well the interest of an active monitoring program is to be able to determine the bacterial prevalence in the studied animal population. And again our further objective is to be able to combine Audio Associates 301/577-5882 101 proportion of resistance and prevalence of bacteria. So we have different kinds of active monitoring program. It is based on the collection of isolates in randomly selected holdings or flocks and those isolates collected from a random selection of carcasses within the slaughterhouses. For the selection of carcasses, a two-stage sampling is recommended and it has been previously described by at least two previous speakers. Typically it is proposed to involve in the program the slaughterhouses representing 90 percent of the national --- and then to select slaughter batches randomly and for this a random selection of working days and then a random selection of slaughter batches. And one carcass per batch should be selected to avoid any clustering. Regarding the selection of the holdings or for flocks, for the selection of the holding pigs then it is recommended to follow a simple random selection of holdings. We know that some Member States may use as well a sampling plan based on a cluster sampling. First they select area and then they select randomly holdings in this area. And for the poultry flocks, indeed it is in Europe I would say a real random selection as it is a census sampling of poultry flocks. Because we have -- the main idea is to build on other existing monitoring programs for the control of Audio Associates 301/577-5882 102 Salmonella in poultry. (Slide) It is mandatory that in all Member States national control programs are in place for the reduction of prevalence of Salmonella in breeding flocks of Gallus gallus, laying hen flocks of Gallus gallus and broiler flocks. And the same for breeding and fattening flocks of turkeys. And according to the detailed specifications for the testing of Salmonella status of flocks --- into legislation, so all flocks in production should be sampled so it is a census sampling. And regarding the sampling plan we have harmonized sampling procedures in terms of samples collected of frequency of sampling. And as well the laboratory methods are harmonized and standards are used. The main idea was to fuel the resistance monitoring programs with isolates of Salmonella collected in the framework of the Salmonella control programs and the same for Campylobacter. Fecal samples collected from poultry flocks can be tested as well for Campylobacter. (Slide) Of course in some particular cases passive monitoring is used as well. We know all the limitations of the passive monitoring but for example in a number of European Member States the passive monitoring is used for monitoring resistance in Salmonella in dairy cows. Audio Associates 301/577-5882 103 (Slide) So regarding the study populations focused by the monitoring programs of antimicrobial resistance. So focusing on animal populations and food thereof to which the consumer is most likely exposed. And again we find those foreseen by the legislation of course the fowl, the turkeys, the pigs. But that is true that in a number of Member States other animal species should be addressed to have a full picture of the risk of transmission of resistant isolates and we have the sheep, veal cows, and rabbit. And for those species either herds or carcasses at the slaughterhouse are randomly selected. And regarding the sampling of food thereof broiler, pig and bovine meats, carcasses at the slaughterhouse are selected. So the rationale for the choice of those epidemiological units, either flocks or carcasses, is that for the poultry flock we have typically an all-in, all-out production in the holdings in question. And then all the animals of the same flock share the same managerial practices. And we considered that to focus on isolates selected from flocks is of importance to further analyze in the future the relationship between resistance and use of antimicrobials. It is one of our other or new objectives. And regarding the isolates collected from carcasses, Audio Associates 301/577-5882 104 we consider those samples as a reflection of the human exposure. And as well this way to collect isolates for monitoring antimicrobial resistance has been chosen for practical reasons because in all slaughterhouses meat inspectors of the competent authorities are there and it is easier for the collection of isolates. (Slide) So in terms of a sampling frame and sampling plan in particular for those poultry flocks, the sampling frames are maintained by the National competent authorities in charge of the National Control Programs and all flocks in production of laying hen are involved. Indeed the real definition is all flocks of laying hen supplying an egg packing center should be included in the National Control Programs. Again for broiler flocks or fattening flocks of turkey, all flocks in production with more than 250 animals should be involved in the National Control Programs for Salmonella. The laying hens are sampled every 15 weeks during the laying phase and the broiler flocks and the fattening flocks of turkeys are sampled within 3 weeks before slaughtering and this is more or less harmonized throughout Europe. And regarding the carcasses, we have as described previously a two-state sampling plan and carcasses are sampled at the end of the slaughterline meaning before killing. Audio Associates 301/577-5882 105 So one isolate should be tested per positive epidemiological unit either considering as an epidemiological unit carcasses, flocks or holdings to avoid any clustering. And of course in the framework of the monitoring of Salmonella and the Campylobacter by the National Control Programs we have an additional step which is to randomly select among all the Salmonella isolates collected those which will be offered to the antimicrobial susceptibility testing. (Slide) And this we have to address, the question of the sample size. So a number of previous speakers have already addressed this issue. So the sample size is the number of isolates to be tested. And this number should allow with a predetermined accuracy the calculation of the proportion of resistance and as well the detection of changes in this proportion over time. Indeed the sample size is a compromise and two calculations should be made. The first one, the calculation of a sample size to assess prevalence, to assess the proportion of resistance again with a predetermined accuracy and as well a prevalence, you need to have an idea of the prevalence you want to assess. And a second calculation should be made which is the number of samples needed to assess a difference between two prevalences or between two proportions of resistance so that you are able to detect a Audio Associates 301/577-5882 106 change over time in this proportion of resistance. (Slide) And based on the results of those two calculations you have to make a choice and again it is a question of compromise. Regarding the calculation itself, the sample size depends on the proportion of resistance in the bacterial species and study population to be monitored, the magnitude of the change in proportion of resistance which should be detected by the monitoring program, the desired precision for estimating a proportion of resistance meaning the maximum acceptable error of the prevalence estimate, and as well the statistical confidence level and the required statistical power. (Slide) And again in the European context, EFSA had to propose the Member States with a minimal target sample size. And again this minimal number should account for the financial issues and for the cost. So we made a number of assumptions to make this calculation and to propose this 170 isolates. So those assumptions are an infinite bacterial population size per study population per Member State, a confidence level of 95 percent and a power of 80 percent, those are quite classical assumptions, and as well a perfect sensitivity and a perfect specificity of the antimicrobial susceptibility testing. Audio Associates 301/577-5882 107 And based on those basic assumptions we have proposed 170. Knowing that those 170 per study population, per country, and per year allows to detect a change of 15 percent in the situation of widespread resistance meaning a proportion of resistance of 50 percent, allows us to detect an increase of 5 percent in the situation of few pre-existing resistance so a proportion of resistance of 0.1 percent, and allows as well a precision in the estimation in the proportion of resistance of 8 percent and this for the worst case scenario of a resistance of 50 percent. But of course before -- I would say that it needs that number of isolates. You should take into account the prevalence of the bacteria in the number of samples to be collected so that at the end of the exercise you achieve those 170 isolates. But those 170 isolates are really a minimum requirement and a number of Member States test for resistance a higher number of isolates, 300 to 400, and this depends again on the existing proportion of resistance against a number of antimicrobials for which they want their program to focus on and as well considering the power to detect any emerging trends or decreasing trends. (Slide) Regarding the, you know, the particular case of isolates selected from all the isolates isolated in the framework of the National Control Programs of Salmonella in Audio Associates 301/577-5882 108 poultry for example, you need to perform a random selection. But if you have a very low prevalence of Salmonella, of course you should test all the existing isolates. And in the case of very low prevalence, the guidance document proposed a systematic sampling or targeted sampling to be sure to isolate Salmonella. (Slide) These are general recommendations of EFSA to Member States. The Member States apply those recommendations but again there is room for offered flexibility. And based on the data collected by the Member States and then collated by EFSA, those resistance data are analyzed at the EU level in close collaboration with ECDC, the European Center for Prevention and Disease Control in Europe. ECDC provides for and analyses the data on isolates from human cases. And the 2009 report published last week was or is the first joint report on resistance in Europe considering the resistance in Salmonella and Campylobacter in humans and as well in food producing animals and food. And as well indicator isolates in food and food producing animals are considered in this report. (Slide) In terms of specificities of the national monitoring programs of resistance, a number of national programs are publicly available; they are published on the web. And you Audio Associates 301/577-5882 109 may find more detailed information regarding the sampling strategies used in those countries. For example you have the DANMAP made by Denmark, FARM made by France, MARAN made by the Netherlands, and SVARM made by Sweden. (Slide) And just before I finish this presentation I would like just to tell you about our new objectives. So far I have presented some indications regarding the sampling strategies at Member State levels so 170 isolates to be tested, it is a recommendation at the national level. And we would like to work more and to establish an indicator of resistance at the EU level, typically a weighted means of those different proportions of resistance assessed at the national level but we are discussing about the best weights to use. We would like as well to combine resistance and prevalence. So far we have only presented proportion of resistance but again and as underlined previously by other speakers the interest of random programs is to assess as well the prevalence of the bacteria and the resistance among those bacteria so combining those we may assess the prevalence of resistant bacteria. And as well we would like to go further with ECDC on an integrated monitoring of resistance and usage both in animals and in humans. And the final goal is to analyze the Audio Associates 301/577-5882 110 relationship between use and resistance. And for the purpose, a pilot collection of data on use of antimicrobials in animals has been recently launched by EMA, the European Medicines Agency which is another agency of the European Commission based in London. And for the purpose of this future analysis of the relationship between use and resistance, we are improving as well our monitoring system of resistance at EU level by implementing the collection of resistance data at isolate level. So far EFSA received from the Member States aggregated data and we have this year a pilot collection including 12 volunteer countries. And in the future if we need that, we will be able to have isolate-based data reported by all Member States so that we can analyze the relationship between use and resistance. (Slide) Thank you for your attention. (Applause) DR. McDERMOTT: We can entertain one or two questions if anybody has any. (No response) DR. McDERMOTT: Okay, thank you Pierre. We will move on to our last speaker before lunch. Dr. Morgan Scott from Kansas State University is an epidemiologist and is going to talk to us about, well Pitfalls Audio Associates 301/577-5882 111 of Sampling is his title. I think we asked Morgan to just give us sort of his views on things to be considered just from strictly scientific or if you will --- point of view and not encumbered by all these other limitations of participation that we face in trying to do our sampling so Morgan we look forward to hearing your thoughts. Pitfalls of Sampling by H. Morgan Scott, DVM, PhD DR. SCOTT: Thank you Patrick. I am very pleased to be asked to present and I have to say the title was given to me and so I had a conception of maybe what you wanted and I think in some regards I may have hit the target and in other regards I may be way off. But what I will try to do as the last speaker before lunch is at least being with a light note and maybe end with a light note. Where there has been some duplication, skip over those subjects. There has been a lot of coverage of a lot of issues relating to sampling both from what I would call a biological as well as a statistical sense. But I will point to a couple of things that will at least hopefully get the audience thinking so that when we have the discussion after lunch maybe these will be some talking points. I will say at the outset I am not particularly wedded to any one of the ideas or opinions you might hear but I think they are food for thought particularly as it relates Audio Associates 301/577-5882 112 to the opportunities to maybe change NARMS as you go forward as you are thinking about doing. (Slide) So as an overview I would like to discuss this idea of pitfalls, perils or pitfalls, whether they be biological or statistical. I think the key issue here of course, and lots have talked about it, is avoiding bias and I will talk about external bias, or external validity and internal validity, as they relate to sampling for resistance in particular. I think there are some unique issues that we face with respect to sampling for antimicrobial resistant enteric bacteria. And I think when we heard the first speaker speaking about -- well the second speaker talking about the sample to determine whether Salmonella are present or not and secondarily whether those are resistant or not, creates some unique problems that we may have to consider as we deal with this issue of sampling for resistance. I will talk about the issues of estimation versus detection. I think most of the talks have been focused on providing prevalence estimates or maybe making comparisons, do things differ over time, do they differ amongst commodities, but we have not talked much about detection of emergence of resistance. And finally I will just touch on some ideas I have that might be useful for considering optimizing sampling Audio Associates 301/577-5882 113 protocols for NARMS. (Slide) So pitfalls of biological sampling, the first thing I thought about was having to go out and collect these samples. And I have to say I was the one armed with the camera so my colleague who ended up being the star of these photographs is Bo Norby previously from Texas A&M and now at Michigan State. Obviously the first pitfall is hard work and getting dirty, working in a sweaty, hot environment at 4:00 in the morning before these animals are fed. This is literally on- farm sampling. If you want to go to the individual animal level, this is what you have to do. However when they stand in line they often void the intestinal contents and so the second part of biological sampling at the individual animal level is boredom. You actually get to use four out of your five senses. You get to use your ears, your eyes, your nose, your touch, you do not want to taste this stuff, but to actually make sure you get a sample from an individual animal and relate that to the antibiotic that that animal may have been treated with in a trial or otherwise is a lot of work and a lot of boredom but it may be worth it in the long run. I am not sure at the national scale it is. (Slide) Audio Associates 301/577-5882 114 So what is the other pitfall? Well the other pitfall is the sample itself. And for those of you who have not spent a lot of time working with feeder cattle on high concentrate diets, this is not the most pleasant smelling material. But I do not think that was the pitfall we were concerned about here. I think what we were actually mostly concerned about was things that probably while they relate to the logistics of taking these samples, they are largely related to making sure that what we are doing has statistical validity. (Slide) And in essence the first half of this is probably making sure you do not commit deadly sins as they relate to the data themselves and the second part is making sure you do not do something wrong with them. Okay, so let’s talk about some of the examples of these. (Slide) I guess what I would ask with respect to NARMS is what do we expect the bacterial isolates and the resistance data to represent? If we can figure that out, I think it is a good first step. Then we ask, well what do they actually represent? And if they actually represent what we hope NARMS will do, then we all can go home. Okay, so that is the second question. And if the third was if what they could represent Audio Associates 301/577-5882 115 was something else, if changes were made would that make things better? (Slide) So I guess in essence the question is, are pitfalls really trade-offs? Because the other side of this is it is not just going out and getting dirty early in the morning it is deciding what you are going to do and with a fixed resource such as a fixed budget you kind of have to make decisions; everybody does that. And I think one think we are going to recognize is that if you make a choice in one direction you are probably going to inadvertently negatively affect another. Okay, that is going to happen here. But maybe there is a way to optimize the strategy and I think I have seen several opportunities where once the fixed costs of sampling are borne, I mean biological sampling whether it be FSIS taking the samples, maybe there is some room to actually do something with those samples that not only cuts costs or keeps costs to a minimum but leaves some room for serendipity and perhaps some discovery along the lines. (Slide) So I will not go through this, we have already talked about what CDC, FDA, and USDA contribute to this. I will make note of the slaughter sample versus diagnostic lab isolates which has been discontinued in the animal arm. (Slide) Audio Associates 301/577-5882 116 But what we are talking about here is, we want to talk about the animal arm is -- it is achieving external validity. In essence that is the ability to generalize to a broader population of interest. So I am going to use cattle examples, mostly it has been poultry this morning, I am going to use cattle because I am most comfortable with that, I do research in that area. And if we just consider the problems that are present in a relatively -- in that niche we can consider that there are probably similar problems across the commodity groups. We like to depend on a representative random sample. I think USDA-NAHMS is a really good example. It may not be done every year, it may not be done regularly, but there are examples of how representative samples of states that have a substantive amount of the commodity in question can be randomly sampled on a rotating basis. In terms of sources of bias in this sort of sampling we do have to think about what goes on. And the key ones are selection bias in terms of the farm, the slaughter plant, the animal, or the fecal sample that gets chosen. And the other forms of selection bias might be related to the lab in terms of bacterial isolation methods; I know Randy Singer has done a lot of publishing on that, the choice of isolates to be analyzed and so on. (Slide) Audio Associates 301/577-5882 117 The second type of bias which we will not spend much time on because it sounds like NARMS has had a meeting to deal with this is the internal validity and I would say a lot of that has to do with the lab. The choice of internal controls, the choice of methods, instrumentation, dealing with inter- operator differences, and of course they apply to statistical analyses and interpretation in an epidemiologic sense. We are going to assume for the rest of this presentation that that has all been dealt with or will hopefully be dealt with. (Slide) So the unique issues I think in sampling for resistance from the standpoint of dealing with enteric bacteria are as follows: That the structure of each of the animal industries and the particular unit of concern that we might be thinking about or talking about may not be the same across those industries. So the idea of a herd, of an animal, of the meat product, we have heard how important that is today already, of the bacteria or the bacterium if that is your unit of concern, maybe it is the plasmid, maybe it is even the gene that you are interested in. Most of what we talked about here tends to be bacterial-level prevalence estimates but that might not always be the case. There are also examples of multiple streams that feed into a common finished product and if they were all the Audio Associates 301/577-5882 118 same animals there would not be a niche market at all. But from the beef standpoint, at the very simplest, we can consider that what ends up in ground beef is not just what you call fed beef from feeder steers and heifers but dairy beef is a large component of it as are cull beef cows. We have issues of organic, antibiotic free versus conventional. We have issues of extensive and intensive agriculture so the question is what does that final sample represent and/or does it matter so long as it represents proportionally what the public is exposed to through consumption. (Slide) This might be an example of the flow from extensive agriculture on the left through intensive agriculture in the middle in feed yards and on to slaughter for example where the bulk of the dollars occur in the retail product that flow back up through this food chain. (Slide) The alternate model, again providing beef, would be the dairy industry where most of the adult dairy cows are producing milk as the revenue product on these operations and culled to dairy beef is more seen as recouping or minimizing losses. Certainly it is income but it is not the vast majority of the income of these operations. (Slide) Audio Associates 301/577-5882 119 So why does it matter? Well we have validity of long-term monitoring for trends and even detection depends on stable and representative sampling protocols. And we have had some discussion today about whether stable estimates and stable prevalences over time are a good thing. Do they just mean we are doing the wrong thing all the time repeatedly or does it mean we are actually getting a good estimate and they are stable estimates? I would like to think it is more of the latter but we always have to be fearful that there is some of the former in that. I think that we have to be aware of that industry- wide mega trends can impact this and can make us get complacent. So too can inadvertent changes in the people that are cooperating with us, if we do decide to go to on-farm sampling. (Slide) One example of extreme and I just used this as an illustration, since we have moved on from diagnostic lab samples it is probably a historical artifact. But just the idea that variation in prior treatment could impact what we are measuring. And that is fine if that is the purpose of your sampling. But if you are dealing with looking at slaughter samples, this would be an extreme that we hopefully would not see which is the observed NARMS differences between diagnostic and slaughter samples. Audio Associates 301/577-5882 120 These data are extracted from the website that Paula’s group maintains and they are wonderful in terms of access. They allow us to compare the blue line which is basically the prevalence to tetracycline resistance amongst Salmonella from slaughter cattle from 1997-2009 and the diagnostic results. And you can see that this is a stable, flat estimate of about 20 to 30 percent. But amongst the diagnostic labs, it was typically 10 to 20 percent higher. So that is probably the extreme orders of magnitude difference that one might expect if your sampling was not consistent and was not representing slaughter samples particularly well. (Slide) I do think there is value in knowing the sources and the magnitude of variance in each of the levels of the hierarchical structure of the animal industry because those help you to identify bias-vulnerable sample areas. If there is not a lot of variability in a certain area, it does not suggest there is much potential for bias in your sampling. But if you go all the way through the hierarchy and perhaps down through the food chain, you might discover there are certain areas that are highly variable with a consistent sample size and those would point to the areas that you have to be extra careful about your sampling to make sure you do not introduce bias. I think it is clear that vertically integrated Audio Associates 301/577-5882 121 industries have a greater potential to vary across each of those vertically integrated sectors, if you will, by corporation than you might expect perhaps in non-integrated industries where there is a constant flow of new animals in and out of each chain. (Slide) I think there are a couple things we can consider that are probably true. That where the sample is taken in the food chain relative to farm increases our ability to relate levels of resistance to usage but closer to slaughter or retail may increase our ability to relate them to human health isolates. I think that is likely to be true. I am not sure I can stand up here and prove that to you as a fact. If we focus on the biological sample versus the isolate, however, then that would be premised on the idea that the animals entering the food chain should be healthy themselves, then the bulk of the enteric bacteria that are present in a sample should represent normal flora. That is not to say that there are not pathogens in there or that there are not bad things in there but these animals are not clinically ill with those bacteria. And so if one believes that the proportion of the bacteria that during contamination in food processing would be proportional to what the bacteria are in the animal’s gut, then that might be a good representation of what finds its way Audio Associates 301/577-5882 122 into the food chain. (Slide) One thing again I would like to emphasize is that most of these surveillance programs are set at estimating the prevalence of resistance. They are not designed to detect resistance. Now if resistance is there and it is there to stable equilibrium, a reasonably high level, you will find it through NARMS, you will find it through CIPARS, you will find it in Europe. And I think the last speaker pointed out in one slide the idea that there are low level prevalences such as 0.1 percent but at least we know it is there for which that program will provide a prevalence estimate that is reasonably stable. The problem with that is that if something is new or if we do not know if it is there and we rely entirely on passive surveillance or surveillance of non-selective media, we may have the false assumption that we do not have that particular resistance present in our country. Now obviously sample sizes and approaches to those can be a problem. And if you rely on a common framework for both of those objectives, you may have problems. (Slide) Prevalence estimation is simplest in terms of describing it statistically. We have standard sampling schemes, they are relatively straight forward. Audio Associates 301/577-5882 123 (Slide) This is an example from my grad student, somebody who knows how to do graphics. These pink cows or whatever color they are are presumably the affected and out of the population it is easy for anybody to tally up the affected over the total and estimate the prevalence. The standard errors are maybe a little more complicated. The confidence intervals to do them right are even more complicated yet but it is not that difficult to do. The challenging part is actually getting a truly random sample. (Slide) So thinking back to this tetracycline example, these are stable estimates, there is not much change, but we have a pretty good chance of sampling and getting good, robust prevalence estimates with reasonable standard errors over time and pretty good confidence that this is what is going on in Salmonella in cattle. (Slide) What about the situation like ceftiofur introduced in 1988 for the first time. A second formulation introduced in 1996, a third in 2003. NARMS would indicate that the estimated prevalence of resistance from 1988 through -- well NARMS did not start in time I guess I should say so from 1988 through 1996 we do not know anything but it was zero the first year and it has been rising consistently ever since. Audio Associates 301/577-5882 124 One question we have to ask is would NARMS, if it had been around in 1988 through 1996, would we have been able to rely on it to reliably say that this resistance was not present. We now know we are getting relatively stable prevalences amongst slaughter cattle isolates, again mixed of dairy and beef but we do not know much before that. We also tend to, at least in dairy and beef animals harboring ceftiofur resistance, that it is almost always tied to this ACSSuT --- resistant type. And so that makes the previous graph on tetracycline all the more interesting because we know that some of those tet resistants are also now incorporating this ceftiofur resistance gene. (Slide) We have already talked about different random sampling mechanisms. Simple random sampling, most difficult to do, systematic, stratified, clustered, they have all been talked about for Europe and Canada and they are wise because often times we can more efficiently sample from multiple steps and multiple criteria in populations of interest. We are not going to talk about any of these things because you do not want to see any formulas today. (Slide) One thing we do need to think about though is that panels such as are used for NARMS and also CIPARS test multiple antimicrobials across a fixed isolate sample size. Audio Associates 301/577-5882 125 We have heard the number 150, we have heard 300, and we have heard 170. What that means, and that is fine, is you have to pick a number that gives you the best you can do for 15 antimicrobials and for different bacteria. And the varied prevalence with a fixed sample size basically yields different levels of precision. As long as you know that, that is fine. But if you look at the problems that occur when you do sub analyses, so for example when you go for all Salmonella to certain serovars or if you have a situation like ground beef in retail meat with Salmonella, you get really low numbers, it can really affect your confidence intervals and your standard errors. And so your precision of these estimates becomes really problematic sometimes. It is not to say and I am not naive enough to not know that in the binomial your largest standard errors occur --- 50 percent. But what happens is when you end up down at really low levels of prevalence, your standard errors may be smaller than they are at 50 percent but they put you awfully close to zero in many instances. (Slide) So that is the NARMS panel from 2003, not the updated panel. It has 15 antimicrobials, different levels of MIC potentially measured, and different interpretations. (Slide) This is quickly to show you that the standard errors Audio Associates 301/577-5882 126 are relatively small when we look at all 532 E. coli from the Platt et al., 2008 paper that I like to show everybody. You will notice that at the bottom on ceftiofur you have about 7 percent estimated for prevalence and a .01 standard error which means it is reasonable. You look at for example tetracycline at 56 percent and .02, as a relative proportion of the mean it is actually quite small. (Slide) If we only take a random sample of 50 of those instead of 532, you will see that the standard errors do not seem to have inflated that much, it does not have a big effect on your interpretation of tetracycline or sulfisoxazole, but now it has a huge effect on ceftiofur. I would also note for the statisticians in the audience that clearly this software package uses the wrong calculations for the confidence interval. It is showing a negative value for the confidence interval on ceftiofur prevalence and that is because it has used aWald* instead of something more appropriate like an Agresti-Coull and others which I am not going to talk about because that is going to make your head spin. (Slide) But I do want to spend a few minutes talking about detection. We have I think about 10 minutes left. For those of you who have seen me do I guess the traveling road show, this is something that I think we need to at least consider, Audio Associates 301/577-5882 127 is there a role for NARMS in other surveillance programs beyond just prevalence estimation? Do we need to be looking for certain things beyond commissioning research projects? So if we are going to say that resistance is not present in a certain country, region, industry, farm, and animal you know we may not have the capacity to do it unless we look at samples rather than isolates. Okay, just receiving isolates from other providers allow you to detect resistance when it first emerges, is at very low quantities or concentrations. You may ask, well is that even important? Well it depends. If you think that there is a chance to mitigate against resistance, it is likely that it is possible and is most possible early on before these strains adapt and become as fit as their competitors. (Slide) They are also used to estimate resistance prevalence which is present at aggregated levels. Is it present or not at the herd level? Is it present or not at the country level? Do we have ESBLs in the US in agriculture? Do we have VRE in the US in agriculture? These are real questions that people talk about but we do not know that we have actually spent any time really evaluating it. They involve different approaches both in the lab and statistically. And I think they are worth considering. (Slide) Audio Associates 301/577-5882 128 Again I am going to skip the formulas. We do not need to know whether you can use the binomial approximation even if you are replacing or the hypergeometric but we do need to know that it is a different formula for calculating sample size than what you do for prevalence estimates. (Slide) So why would we want to talk about detection in a surveillance system like NARMS? Well a new drug might be introduced. We now have a Guidance Document 152, it talks about risk, it does it qualitatively, high, medium, and low. But post-marketing surveillance might involve not just tracking trend because if it is 0 percent is it really 0 percent, but actually detecting its emergence before it is picked up in standard surveillance. There may also be unexplained geographical disparities that exist in agriculture like we have with VREs with the European history of avoparcin use, vancomycin- resistant enterococci in animals and in humans. We have a divide that would be interesting to explain. We also have an ESBL divide that we would like to keep there. But we have to ask ourselves, what do we really know about the situation in the US? (Slide) And I throw out these two examples. You probably cannot read them but these are examples of researchers on the Audio Associates 301/577-5882 129 left from Michigan who found VREs in show swine in Michigan counties and CTX-M which are ESBLs in Ohio dairy farms by using methods that include broth, if you will, enrichment and also selective media. Again we could argue about is it important that it is there or not? Isn’t it just important that it has been tamped down and is a really low level? But is that not the role of potentially of monitoring to include? I will say at the outset that if you want to have detection as part of your surveillance system, you cannot likely rely on people sending you isolates. You will actually need to receive the samples and possibly bank those samples for future use. (Slide) This are just examples of what we did with feeder cattle. The left is a blue line that is basically looking at direct plating onto MacConkey. We estimated ceftiofur resistance in 2009. Incoming feeder steers off grass into an experimental feedlot at 10 percent. Okay, that would be our estimate of the bacteria-level prevalence. (Slide) If we plate them instead directly onto MacConkey that has ceftiofur at the CLSI break point, we have 90 percent of the steers harboring ceftiofur resistance among steer E. coli. (Slide) Audio Associates 301/577-5882 130 If instead we broth enrich those, we put them in broth, we treat them really nicely, we have 100 percent. One hundred percent of steers and this is not from a mutation occurring in the animals, this says that 100 percent of steers arriving at feedlots in the Texas panhandle have ceftiofur resistant E. coli. Again, so what you may ask? But because it is a really low prevalence, it is less than 10 percent; the point is that it essentially is everywhere now that we are aware of. And these data are courtesy of a graduate student James Graves who did this as part of a Master’s project at West Texas A&M University. (Slide) So I guess I will close with saying here is what I would like to think that a sampling scheme for the animal arm of NARMS could be. Obviously, and these are going to be motherhood statements, it should be representative of the studied populations. There should be repeatable sampling and biological methods. I think sustainability of this which has been the marvel of NARMS and CIPARS and the European systems like DANMAP is that they have been sustained. And for somebody who works outside of that, I marvel at how much information is actually contained in these programs that have not been around Audio Associates 301/577-5882 131 that long if you think about it; 15 years maybe. It is just a wealth of information and sustaining that though beyond just being economic; if you move back into the farm, sustaining the representation of that becomes a challenge in terms of cooperation and people’s willingness to do that. You do not have an infrastructure established to ensure you can do that. I am not saying not to do it but just to be very careful. It should be precise when and where it is needed for prevalence and it should be sensitive when and where it is needed for detection which is going to involve sample-level considerations and not just isolate-level considerations. So again, you have heard me say it, I think there should be some more sample focus and maybe a little less isolate focus. And I would ask at the outset is there any reason why FSIS could not be sharing rinsate samples and not just the isolates or at least storing them. And I know there are losses with storage and freezing but just as a talking point is that something that could go on. (Slide) So there we go, I have said this, I have said it, I have said it. Okay so you have to talk about the future and the future might be articles in Science that have great color graphics. You know, you have probably all seen this. This is a scientist I think at Harvard. They have sampled their own Audio Associates 301/577-5882 132 poo. They did a metagenomic analysis, they cloned in all these genes they found, and found that there is probably in terms of the dark gray and black, identified beta-lactamases that we do not even know about because they have been hiding in the broad metagenome of the unculturable fraction of enteric bacteria. Now they saw the downside, this is just Armageddon waiting to happen because this could transfer into the aerobic fraction that causes all the disease in humans. You know the optimist, and I tend to be an optimist, would say well there is some natural barrier in there that maybe we should spend a little bit of time learning about. But the point is that historical samples have value because we could actually go back and maybe figure out why we are in the condition that we are in now and we will not know that unless we can go back and catch that information. I know that CIPARS has been storing some of those cecal and rinsate samples for as long as they have been in existence. Which again you could say well do we have the freezer space? Or you could say maybe we ought to expect changes in microbiological methods? Things are going to change and we are going to have better tools. Let’s think ahead a little bit. (Slide) So I will leave the final word on sampling and data to Dilbert and Wally in particular. It is nice to know that even though I did not take on a career in computer science and Audio Associates 301/577-5882 133 information technology and all I do is study feces that I too can contribute to the knowledge and data worldwide. Thank you. (Applause) DR. McDERMOTT: Well thanks for ending on a fecal joke right before lunch. You gave us a lot to think about as we go into the afternoon discussion so thank you. Any questions for Morgan before we break for lunch? (No response) DR. McDERMOTT: Okay so we are back here in about an hour and 15 minutes and we will resume at 1:00. And we will start talking about some of the information we have heard this morning. (Whereupon a luncheon recess was taken) Audio Associates 301/577-5882 134 A F T E R N O O N S E S S I O N (1:04 p.m.) DR McDERMOTT: Okay, if I could have your attention please. We will get started again with the afternoon session. What we had planned for the next part in the Panel Discussion was something of a free-flowing exchange of ideas and we have invited speakers and others that are experts in this area to consider the issues before us. And before we met, Heather had shared with them the questions that you see on the screen up here. Using the information we hope was explanatory enough this morning to address these questions. How should NARMS define adequate sampling for resistance trends? And I should say I think there is agreement at least within FDA that our goal here is to establish the prevalence of resistance in the different commodities or sources if you will and the ability to detect changes or trends over time. So similar to what Pierre presented for EFSA I think is our goal here. Morgan’s point about detecting something new emerging with enrichment and things like that I would say is part of targeted research but not the goal of NARMS. So it is prevalence and changes in resistance. And so what is the adequate sampling for doing that; for determining the prevalence and the resistance trend? So maybe I have modified Audio Associates 301/577-5882 135 the first question slightly. What are some additional sources for unbiased food animal samples? What additional information should NARMS collect and report? And these are really just to get the conversation started. And our panelists today, I guess you have not met all of them yet but I will introduce them shortly, have been mulling these over ahead of the meeting as a way to start this conversation. So you met Morgan Scott who just presented. Also on the panel is Scott McEwen from the University of Guelph and Scott has been doing and thinking about these sorts of things for a long time. Randy Singer from the University of Minnesota joins us and brings a lot of expertise in epidemiology and the statistics side. And then at the end we had invited Wondwossen Gebreyes and Paula told you about the collaboration with Wondwossen at Ohio State University. Wondwossen was not able to join us but thankfully was able to send a colleague who is going to join us as well and you will forgive me if I cannot pronounce your name correctly but I will try. DR. MOLLA: Bayleyegn. DR. McDERMOTT: Bayleyegn, thank you for joining us. I am going to just turn the podium over to Scott and he is Audio Associates 301/577-5882 136 going to show a few slides to get the conversation going and we will go from there. Panel Discussion: Improving NARMS Sampling Comments by Scott McEwen, DVM, DVSc DR. McEWEN: Thanks very much Pat and thanks for the invitation to join the panel and attend today; it has been a great meeting. And I agree with Pat’s comment earlier that the smaller group, it is a bit more amenable to getting conversations going and discussion and debate. And I have enjoyed tremendously the presentations this morning and I put a few things together before the meeting. The panelists, we really did not get together and plan things and none of us were sure quite best how to handle this. So I put some thoughts down and some of them are things that were discussed this morning already and I think I will try to add a few reflections that I have come up with I guess in the course of this morning’s conversation. (Slide) So this first slide is the -- most of it, the background is sort of the document you were given at the door in advance sort of mapping out the various levels of the food animal production and slaughter distribution system. And I just highlighted a couple of things I just wanted to briefly reinforce I guess. Audio Associates 301/577-5882 137 And one point I think is that the post slaughter or slaughterhouse is a point at which most surveillance monitoring programs in this area gather samples. And I think one of the reasons, and all of these have been talked about, but an important reason is that represents the sort of isolates I guess that are on human -- the food, the carcasses, some programs sample cecal contents but it is also a convenient point of convergence of the food system. So we have many thousands of farms out there producing animals and a much smaller number of slaughterhouses and abattoirs and so that is a convenient sample collection point that I think is important in each sort of sampling program to bear in mind. And one of the thoughts I had this morning is it would be -- and we talked about this back in Canada as well. It would be very useful if someone would sort of map out the larger food distribution system. It is probably available some place and it would be great if it was a software-based thing where you had the sort of various pathways that animals and products can take. That would help us in furthering our sampling program designs in order to identify other points of convergence such as, I think Pat talked about the possibilities of centers of retail, cut up and packaging prior to distribution to retail outlets might be another such point. Another point I wanted to reinforce I guess is that to the right hand side of this diagram we have points in the Audio Associates 301/577-5882 138 exposure pathway which are closer to human consumption. And from a sort of risk analysis standpoint then, they have I think a higher level of importance in terms of human exposure so that is a thing to bear in mind. Some of the other issues that have been talked a bit about, and I do not have anywhere else to discuss it but I think I will mesh them here, is the fact that as we all know antibiotic resistance is an ecological sort of issue or problem. And this makes it very interesting to study but it also makes it very complicated in order to try and get a grasp on. And I like to always contrast the situation we have with resistance to that of residues of antimicrobials. So antimicrobial use can lead to residues, it can lead to resistance. In the case of residues, it is comparatively easy to couple together a treatment event, an exposure of an animal to an antibiotic, and a residue of violation or occurrence in an animal because the chemical behaves in a very predictable fashion in the animal. It is distributed and eliminated and it is not -- with the exception of things like sulfa’s which can be sort of picked up, it is not transferred to other animals or other populations. But in contrast, bacteria, microorganisms of course do that all the time. And these genetic constructs, these resistance determinants, take in some cases many years and Audio Associates 301/577-5882 139 many geographical locations, and many different species of animals in which to develop. So they are not as easily coupled to a treatment event, any one treatment event, which complicates this whole business of trying to better understand the relationship between treatment and resistance. So where am I going with that? I am just saying that I agree that going back to the farm level is important with respect to trying to better understand treatment and resistance but we need to bear in mind that there is a lot more going on than just the exposure of that animal or that group of animals on the farm and the development and spread of resistance. There are all the things that have gone on before that. The other animals that are on that farm, the other treatment events that have taken place on that farm, the other inputs that may have a bearing on what is on that farm. A good example I think is in the case of the poultry industry. If we were to study the relationship between drug use and resistance in some broilers on a farm, to do our job properly we also have to look at previous flocks in that establishment as well as where those hatched chicks came from and what they were exposed to and their parent flocks are exposed to and so on. It is hard to know where it ends. You know we can go back to the farm but then there is going back to that farm history and the other inputs on the farm, it gets to be challenging sometimes. So whether we can do all of that Audio Associates 301/577-5882 140 in a monitoring program is an open question. (Slide) So back to the questions briefly; I have pretty much used up my time already. To answer this, how should NARMS define adequate sampling for resistance trends? My approach was to back up to I think what Morgan and others did, and that is to first principles in general. For me the most appropriate sampling plan is the one that best addresses the program objectives given the available resources and opportunities that exist in terms of collecting isolates and that sort of thing. So I think for trend data which is the prime objective, we should strive for a nationally representative sample. And I think the highest priority, in the monitoring program whose purpose is public health, should be healthy animals at slaughter and retail foods, meat and poultry. And that going back in the system is laudable and I think it should be encouraged. But I think until we better understand what advantages there are to ongoing monitoring at those higher levels or earlier levels, that we should focus on the hypothesis-driven studies like Paula described this morning that help us sort of better understand those farm level sort of dynamics. I think for me we have a long way to go in terms of better understanding the place of farm samples in sort of regular routine monitoring. Audio Associates 301/577-5882 141 (Slide) And again I reiterate the importance that for trends samples should be taken using sampling plans that are consistent with sound epidemiological/statistical principles and those have been well described already. (Slide) What are some additional sources for unbiased food animal samples? Again I had a few points here; I am not sure whether to sort of pursue them. I think again it depends on whether we are doing the on-farm sampling for monitoring purposes or for testing hypotheses/investigations. I think if it is the former, if it is monitoring, I think it has been touched on already today that we should be looking at a formal representative sample and a modest level of testing of each farm in order to get a representative sample. But that is obviously not going to be sufficient to allow you to do things like evaluate the role of drug use on a given farm for resistance if you only have a small level of isolates. At the abattoir level it occurred to me in listening to Lucie’s presentation which I should have known but it did not click for some reason, that in Canada the abattoir isolates are actually collected by the industry, that is the packing plants. And that was developed, and it might be worth discussing some time with Lucie a bit more about how this was done, through some early sort of gardening or fence mending or Audio Associates 301/577-5882 142 building good relationships with the actual packing plant people to get them onside with collecting these samples and making the job easy for them so they do it. The inspection staff does not do it. They are kind of there, as I understand Lucie, to sort of help out, troubleshoot, and that sort of thing but it is not an extra burden on the inspection staff. What burden exists is on the industry and so I think that may be an opportunity that NARMS sort of -- and USDA might look to. And I think I should probably just stop here because of time so I will turn it over to the next person. Comments by Randy Singer, DVM, PhD DR. SINGER: All right, well I also appreciate the invitation to speak here on this panel. (Slide) I will start with a point that I think is, well it is really important for me, is still to understand the goals of the NARMS program. I guess it was stated that we are really focusing here on trends but if we look back to these three questions, our first is adequate sampling for resistance trends but number 3 is additional information. Additional information to me gets at this issue of risk factors which has been stated in the Science Board report, that perhaps we could be incorporating some risk Audio Associates 301/577-5882 143 factors for changes in resistance trends. I do not think that fits well with the discussion we have been having here today though about how we are going to sample. If we listen to the talks from for instance from Canada and from Europe, where they gave sample sizes that they carefully worked through with either simulation models or other statistics, those sample sizes are for estimating trends with prevalence. If you want to start risk factor studies, one major issue is going to be your sample size calculations are going to be very different and that is going to be dependent on things like the variability in that risk factor and how its variance structure is related across your sampling frame. Things like how common are these different risk factors and what exactly is it that you are trying to show. So first is I do not think that questions 1 and 3 necessarily fit well together. Just because you can collect additional information, it does not mean you are going to be able to use it to address some of the things you might expect like risk factors for changes in those trends. Related to that as well -- so one issue is sample size, one issue is related to the variability or variance in the risk factors themselves, but a final piece is the structure of the commodities themselves. They are very different. You have some that are very vertically integrated and others that are much more extensive. And how you actually Audio Associates 301/577-5882 144 start sampling for information related to these additional -- how is it phrased again? The additional information, what might become these risk factors, it is complicated. If you take the poultry industry, it is not just that these companies are vertically integrated but it is who is actually making the decisions about what interventions or what management strategies to put into place. If it is a nutritional decision within a single company, that might be a decision that comes from the very top of that integrated company. But if it is a specific question about how are you going to disinfect this farm, that might be a farm manager decision and so it might vary across farms within the company. So just because you can collect additional information, does not mean that you will have something based on your sampling design that will be useful for predicting changes in resistance. You really have to have an understanding of how that company or how that industry has been designed and who is making the decisions with respect to those management decisions. So I struggle a little bit with question 3. I think the focus of NARMS has been to try to estimate these changes in resistance trends over time. But I do not think we are really set up to address why might we predict those changes and what information can we collect to do that. I think if we want to go that route it is going to require a different kind Audio Associates 301/577-5882 145 of sampling design and a huge increase in the sample sizes. A comment that relates to one of Scott’s points that he just made about the ecological study, and I completely agree with what he said so I am just going to reinforce that, is that those types of studies -- I mean resistance, especially on the farm, is an ecological process. It is a dynamic issue; it is the host and the environment with all the other factors that are going on on that operation. It is not just about are they using an antibiotic, yes or no, on that farm. If we really wanted to go that route, these are incredibly complex, incredibly expensive studies to perform and they are probably outside the scope of what NARMS is set up to do. What I would encourage though is that NARMS, as a program, link with those researchers who are doing those studies and those types of links are already forming. Some of them are based within the universities. To determine how can you better conduct those studies so that the data that come from them or the isolates that are being collected from those ecological studies might be things that would tie into some of NARMS’ goals but again that requires a very clear statement up front of what the goals are and can you get industry participation then. Because someone who is doing an on-farm study for an ecological aspect of resistance and has gotten the permission of those producers, is not necessarily going to Audio Associates 301/577-5882 146 be able to give all that information up to a program such as NARMS that is run by government agencies. So I think what we need to do is continue to develop those collaborations between government and academia as well as industry to see how you can better conduct those studies but I do not think the ecological piece is necessarily a focal point for NARMS. I was going to make comments about the estimation versus detection issue that Morgan brought up because I think it is a really important point but then I guess we have just received the clarification that the detection issue is not really a primary goal of NARMS, we are more into the estimation of prevalence so I think I will skip a couple of my points unless they come back. And I am assuming that there is going to be more dynamic in this conversation so I will just at this point yield. Comments by H. Morgan Scott, DVM, PhD DR. SCOTT: I am going to make one quick point, I already had the bully pulpit for half an hour and then Bayleyegn can come on. I just wanted to clarify with what Randy said and what Patrick had mentioned at the beginning. It is prevalence oriented but there are aspects of how the assays are designed that suggest that detection or emergence is certainly part of Audio Associates 301/577-5882 147 what may be sought. So for example, if it was just prevalence of resistance susceptible, you would have two concentrations on each plate or maybe three like there is for tetracycline. But you have some of them like amikacin, or had, and you have cipro, and you have a number where you have a full very wide range from extremely low to extremely high, suggesting that at least for some of these and based on the processes, that you were interested in observing shifts in MIC and other things. So I know that is not purely a detection in using selective media to identify extremely low prevalences of new resistance types but it does suggest that the design of the NARMS panels had more than just a prevalence in mind when they were developed. And again I am not trying to counter your point, I take it fully well, but I do think we need to remember that some of the design features of it go beyond prevalence estimation of a binary classification. DR. McDERMOTT: I guess I should make a few comments. The plates are really designed, and I have to go back and look at it because it has been a few years since we looked at it closely, but it is really set up to make sure we capture the QC ranges and then the full range of testing that incorporates any change in phenotype. So it is really not exactly as you characterized it. I think it is driven more by Audio Associates 301/577-5882 148 making sure that it is quality controlled for all the drugs and that those QC ranges also include the interpretive breakpoints. As far as whether detection should be an element in our consideration for sampling, in my mind, and that is why we are having this discussion so I am open to other possibilities, I see that more as a research sort of thing that you would do periodically. That perhaps you would go out and do you know selective enrichment for a class of interest maybe at a few sites for a few months and then evaluate but maybe not there all the time. You know it is an interesting question because part of that is a workload that we place on the people that are doing the testing on our behalf so there are a lot of things to consider. So I would not say NARMS would not have a role or is not interested in that but perhaps it would not be done as routinely as the other types of tests. DR. SCOTT: Could samples be banked for such purposes for historical -- I know it is expensive and unwieldy to have a -80 freezer churning away but just throwing that out. Comments by Bayleyegn Molla, DVM, MSc, PhD DR. MOLLA: Thank you very much for the invitation. It was mentioned earlier that Dr. Wondwossen Gebreyes was Audio Associates 301/577-5882 149 planning to attend this meeting but he was not able to be here due to other activities so he asked me whether I would be able to come to this meeting. I said yes but I thought I was not going to be on the panel because I am not the right person maybe for the sampling strategy. However, I would like to complement some of the issues which have been raised and in particular with the involvement of industry in order to make the programs which NARMS has in place, to make it more sustainable. The involvement of industry is very important and that has I think been taken into account with the presentation we heard in the morning by Dr. Paula Fedorka-Cray. Another issue which also is important is that some of the risk factors which are associated with antimicrobial resistance could also be integrated into those programs like what has been presented in the morning. The involvement of factors such as transportation trucks, lairage, and crates, those could also provide some additional information in addition to the --- samples which NARMS is planning to collect from various commodities. Otherwise I do not have any other different opinion. Open Discussion DR. SCOTT: Yes, and I guess -- and this is not just to be contrarian. I just want to throw out a couple of thoughts about maybe furthering what Scott had mentioned about Audio Associates 301/577-5882 150 the diagram and the modifications he had made and the value of near slaughter sampling with respect to public health risk or exposure you might say. I agree and I do have some concerns about moving too far back up the food chain if you will. Not that I do not see the value and I am one who has done a lot of on-farm studying. And as you saw, even though it was my colleague taking the samples, I see value in that particularly from a research standpoint. From a standpoint of monitoring for public health purposes, that is where things get a little cloudy for me. And my experience is in trying to do studies looking at current antimicrobial use and consumption and relating them to current antimicrobial resistance. It is often a futile exercise. And that is largely because most of what drives the current levels of resistance that are out there is past, I think, cumulative use of the product. And so if you take the product away and the resistance does not go away, which is the same as saying so basically what you are seeing out there is not a function of what is currently being utilized. If you really think it is important to capture that information, then you better be willing to do it for a long time in terms of usage data so that you can generate those valid, historical usage patterns and then go back and use some large scale ecological model to determine the relationships. That is my Audio Associates 301/577-5882 151 view. Now if I do not think that is so valuable, should there be on-farm regular prevalence studies through something like NARMS? Actually I think there should be but I think the beauty of what NARMS has had is it has been built on an infrastructure in many cases of existing FSIS, public health and FoodNet sampling. And I would ask the question especially given that Bruce Wagner is here, NAHMS does this every five years and they use a valid random sampling mechanism. Is it not something that once every five years would be enough to know about trends that are going on further upstream on-farm. I am not saying I do not see the value in annual testing upstream of slaughter and other things, but in terms of allocating resources do you need annual testing of farms with the knowledge that you may not have the compliance and the continued support of those. And so in some industries especially the variation that would go on if you simply lost one cooperator in terms of the prevalence estimates, could be dramatic. I just raise that as a thought. DR. McEWEN: I have another thought regarding the on-farm part. It was one of the slides that I skipped. And we have talked a bit about monitoring I guess or measuring qualitatively and quantitatively antimicrobial use on farms and Paula referred to this in her presentation. I think that Audio Associates 301/577-5882 152 is one of the great opportunities that arises from the on-farm initiatives that have been described and are possible. Because I think that is probably the biggest gap that exists currently in NARMS, is the lack of antimicrobial use monitoring in any meaningful way. And I think that that would be a big opportunity to get that farm-level data which can be used then to better refine I guess or to partition the national level use data that I think FDA now have and publish, is it annually? DR. : (Away from microphone) DR. McEWEN: It is not broken down by species or in any sort of sub-categorization of that type. And I think that is another opportunity to supplement and complement the NAHMS studies of specific commodities where there is antimicrobial use information given at least in terms of general practices and policies on farms in terms of whether they use metaphylaxis and if so what and that sort of thing. But there is much more degrees of sophistication I guess that could be entered into if you are able to do on-farm investigations. DR. SINGER: I guess the function of NARMS as a program, is it really to estimate a public health risk? And if so, I agree that the sampling most proximate to the consumer is where the sampling efforts should be focused. With that said, it gets back to this issue of, for me, estimation and detection. Audio Associates 301/577-5882 153 If you wanted an early warning system, as I know the diagnostic lab samples have been called, of what resistances are emerging, things we should be worried about, that that is one area where those diagnostic samples could be used. I do not think that they are a part of NARMS as a monitoring system; they are not going to help you assess trends. But there is a piece of the on-farm sampling that does that as well. I think almost every study that goes on-farm, if they have sampled a variety of aged animals on the farm, finds that age especially the very young, those neonatal animals, have the highest levels of resistance on the farm if it is a farm again with multiple ages on that farm. And that has been seen since -- well the first papers I have read of that are in the 1970s. There is a lot of work by --- and those groups showing that the very young animals have the multidrug resistant strains and it is not necessarily tied to antibiotic use. If you again were interested in an early warning system on-farm, perhaps you would then target sampling based around an age structure that is going to give you the most resistant isolates from that farm and in many respects those are going to be those very young animals. So depending again on what the focus is, is it the public health risk or is it as a detection system, you may Audio Associates 301/577-5882 154 choose to design a sampling strategy that reflects that. And again detection, early warning, could be around the very young animals. Another piece that has me a little confused is I have heard in two different talks, should imports be included? Well one was a question, should imports be included and should seafood be included? But another, and a discussion that I had over lunch, was that CIPARS does include some imported retail meats partly because they have to, there is the way that the meat is sold and the quantities sold in Canada. But again it gets to this fundamental question of what is the purpose of NARMS? If it is to assess a public health risk at consumption, then we might say sure imports should be included because that is, especially with respect to seafood, a major source for the consumer, the imported side. But if it is to do a relationship between farm to slaughter to consumer, then obviously you would scratch your head and say I do not see any purpose for the import side. So this is again where I have a slight disconnect with the NARMS program in trying to understand what it’s purpose is, who are we trying to serve. And if it is the public health risk, then perhaps we begin to focus more on the products that are consumed most in this country which would include some of those imported products including seafood. Especially given how antibiotics are used in some of the Audio Associates 301/577-5882 155 countries that produce much of the seafood, those might be products of most interest to us on their antimicrobial resistance profiles. DR. McEWEN: Maybe at this point we should ask if anybody has any questions that they would like to put to the panel. Just as you are thinking about that I had a point that I think sort of follows nicely on Randy’s, and that is in the sort of Vet/Epi world there is an area of interest I guess called risk-based surveillance. And Katharina Staerk from, it used to be the UK but now it is Switzerland, is one proponent of it. My basic understanding of it is the application of risk analysis principles to surveillance in terms of helping to determine priorities and helping to make the choices in terms of allocation of resources and that sort of thing. And as I was thinking about this this morning, it seems to me that NARMS management have been sort of doing that all along in many ways in terms of if you think about risk analysis that is identifying hazards of interest, exposure, and pathways. Trying to identify those hazards I guess and exposure pathways that together provide the highest probability and impact of adverse human health outcomes. That is kind of what risk analysis, risk assessment at least, is kind of about. There are management communication aspects. So I think that it is already part of that but I think, as I tell students, I think it helps to apply that risk analysis Audio Associates 301/577-5882 156 framework to an issue like this just to sort of help you check off the boxes that you are maybe doing things most efficiently. And sort of one way I think that might -- and again I think you are always doing this but for example if you are seeing that one exposure pathway is probably not yielding very much in terms of providing a venue of contamination of human food, then you can de-emphasize that in the monitoring program and shift those resources somewhere else. And again an example that comes to mind is -- I am just trying to remember whose presentation it was, stopped monitoring, was it Salmonella in pork chops, because they just were not turning -- DR. SCOTT: (Away from microphone) DR. McEWEN: Well thanks, wrong species and wrong organism but you know what I mean. So I think then coming around full circle to Randy’s point about the imported products from a public health standpoint and using risk analysis principles, then yes you probably should be looking to some of the other commodities and pathogens. But again I think that is a natural application of some of the pilot studies. Having the flexibility in the program to engage in pilot studies to allow you to sort of look and see what might be there and to sort of pilot partnerships to see what might bear fruit in terms of Audio Associates 301/577-5882 157 acquisition of samples and expertise and so on. The CIPARS groups has done that and Pat and others talked about pilot studies and Paula did this morning. And I think that is a very important part of a robust program like NARMS, is to have the built in capacity to do some of those, not really curiosity driven, but certainly exploratory question and answer type studies that may or may not lead anywhere because they often are useful. DR. SCOTT: I would like to actually follow up on Scott’s point there. One thing I noted and maybe I misinterpreted, but there does seem to be a greater emphasis for example in CIPARS on indicator organisms or commensals. So while they stopped looking for Salmonella in the ground beef, they have continued with E. coli if I am correct. Again I cannot remember the exact details Emily about the retail meat but are E. coli a component of the ground meat sample? MS. TONG: (Away from microphone) DR. SCOTT: But I guess I am a big fan of well if you cannot find the pathogen it does not mean you should, using that risk approach, just stop looking in there. I think there is value in knowing what is going on in terms of resistance amongst all the commodities. It is great that there is no pathogen and that is something that we should really be proponents of, but it does not mean that there is not selection pressure going on amongst the gram negative Audio Associates 301/577-5882 158 enterics and gram positive enteric commensals. And I think there is value in NARMS still tracking that because the thing about Salmonella is you know the serovars are going to change. The dominant serovars in both the animals and the humans is going to wax and wane and you just hope the next one is not a bad one. So I think there is value there. The other thing I guess -- I will leave it at that in case somebody else has a comment. DR. SHRYOCK: Tom Shryock, Elanco Animal Health. Astute observations for all of you guys. One thing that Lucie mentioned in her presentation this morning was simulation modeling. And I wonder if you would see a role for that, not knowing what that modeling is Lucie, but would that be an opportunity to kind of draw some of the bits and pieces we have been talking about together in terms of the questions and how we might interface some of the different components through the food chain? It is kind of an open question but is that a tool that could be explored further and bring us closer together? DR. SCOTT: Tom thank you, actually that was the thought that had left my head. It related to the other value and lest you do not think I see the value in on-farm surveys, I do. The one thing we do not know much about but that would be needed for simulation modeling is some idea of the various sources of variance. It was a bit in my talk but we do not Audio Associates 301/577-5882 159 have that information in many instances. So at each step in the food chain and amongst the hierarchies, where are the sources of variation or resistance amongst pathogenic commensals. And you will not get that unless you go back in the food chain. Unless you have that information you cannot actually construct a reasonable simulation model I think. Correct me if I am wrong anybody else. DR. SINGER: Well I agree with what Morgan is saying. I think there would be a lot of utility to incorporate simulation modeling into a sampling redesign of NARMS. I actually was asking over lunch if those models were publicly available. I think there might be ways around some of the uncertainties of that variance structure. Worst case scenarios and you can always take conservative estimates. Maybe you can get even, whether it is from researchers or from companies themselves who may have looked at some of these issues, but there would be utility to designing a system and testing it with a known set of samples, meaning simulated datasets, to see how well your system is actually performing. So I would hope that before NARMS decides to shift, or add or change something in its sampling design that it could actually be tested in silico to see if it is working. DR. McEWEN: These are just kind of random comments to take it to another direction. I thought it would be worth Audio Associates 301/577-5882 160 pursuing this point about the USDA isolates and whether or not there -- you know this risk-based business because as I said when I asked the question here of the speaker, it was my impression that essentially all the samples, all the isolates were from these plants that were deemed high risk because they were not -- I guess were getting too may positives. So after the presentation and the subsequent discussion, it seemed that it was not entirely true. That there are samples taken still from all the larger abattoirs in the United States and so that is good. And then in follow up to Morgan’s question, I think the way I left that discussion was that well yes, but most of the Salmonella isolates still come from those plants which have a higher degree of sampling and it had trouble I guess with repeat positives. So I think it would be important to try to drill down a little bit more into that and see whether you would still have enough Salmonella isolates overall to do some sampling of all the Salmonella’s that come in in order to get a representative sample, a more representative sample of the US population. And then you could actually see if it was different than those extra Salmonella which came from the high-risk plants. Try to resolve that issue a bit about whether it is a bias, whether it is indeed a biased sample or not. And aside from the issue of Salmonella, I guess it Audio Associates 301/577-5882 161 would be nice if you were able to get samples from a representative -- if you could get the biological samples from representative slaughter animals in the United States. And I think Paula you pointed out that you do get the samples from chickens that come into the Eastern Lab that you can culture for Campylobacter and other things, is that right? DR. FEDORKA-CRAY: Right. DR. McEWEN: But not from the beef and the pork and so on. DR. FEDORKA-CRAY: Right. DR. McEWEN: That is an area that I am a little bit fuzzy in terms of what is the current availability of representative isolates and samples from slaughter animals in the US. And maybe there is something that can be done to use the existing machinery that is in place given that all the plants are sampled at least once every two years as I think it was stated. DR. ESTEBAN: Those samples arrive at one of the three labs in FSIS and those samples are always available to Paula. The convenience of the ones that she gets from this lab is we get them in and we move them one floor upstairs and give it to her; it is quite simple. But the other two labs that do the other two-thirds of the samples, and we collect as I said 35 to 45,000 a year, are available. Once we use them we discard them. So yes we can store some for you Morgan. I Audio Associates 301/577-5882 162 am not going to store 45,000 every year. We could definitely store the rinsates. And for the other tissues, we actually have the tissue, not the rinsate. We actually have the ground beef or the trim or whatever and we store the positives for a while but we do not store all of them. So samples are available, it is what we do with them afterwards. And to address the other question that you said, when the prevalence for Salmonella gets low enough, we are going to have to switch to an indicator organism to still monitor process control. So there is no reason why we should not start doing right now antimicrobial resistance on the indicator organisms not just on the Salmonella. I know it is not a public health issue but it is another organism that we could look at pressure for antimicrobial resistance. DR. SINGER: Can I ask a follow-up question to this though. One concern I had when I was thinking about the use of the FSIS samples is that if performance standards change or if regulatory issues change, would that end up directly then impacting NARMS and its ability to have a consistent set of samples over time? Whether it is adding in a new organism or dropping some frequency of sampling because again you are combining regulatory issues with a monitoring system. DR. ESTEBAN: Obviously that risk always exists. But with the speed with which we move in the Federal Government, it would not be immediate. I guess I would not be Audio Associates 301/577-5882 163 too concerned about that unless there is a dramatic change. For example, the latest dramatic change is we started measuring Campylobacter two weeks ago. That is a big shift. I would have loved to have those samples as well, MLS for enterococcus and something else. --- that is a limitation of how much my lab can actually analyze. But again the material to test is there. DR. FEDORKA-CRAY: This is Paula Cray from USDA. When we get the spent rinsates from you, they do not always have enough liquid to do -- so we cannot test every cup that comes in because sometimes there is not enough fluid. So there is that issue that we would have to address. But the other thing is that you know culture is a big factor and Lucie and I were having a discussion about when you hold samples, when you freeze samples, you know, what are you recovering, how are you recovering it? If you have rinsates, they are going to be different than if you are holding feces or ground meats or something else. So you have to start looking at some of those trade-offs over a period of time too. It is not just a well we can save these rinsates and then we can just do whatever we want with them later, it does not work that way. So that is a consideration that you have to have. And then the other thing is that I am curious as to what your thoughts are on the total numbers of bacteria that Audio Associates 301/577-5882 164 you need in a monitoring system. I mean we have some that in CIPARS that do not reach 100 and that is a national monitoring. And we have hundreds, I mean I think the only one, turkey might have 111 isolates or something like that for 2010 and the others would have several hundred Salmonella isolates. So how many isolates and then we have not talked about representation across serotypes, we have not talked about other culture issues. I see you put up you know well you do not want to pick one isolate per farm. I have heard arguments well you could pick five or six then is that more representative or less representative? And so I think that in some of these discussions I think we could talk about what might not work. What I would like to hear is what will work or what should be considered along those lines, what is realistic, given the current funding and workload levels and everything too. Even with having a network of laboratories, it still costs something and so I would like to hear some of those types of discussions too because that really factors a lot. If we only need 100 poultry isolates, heck I can get those down the street. And if you need 100 isolates, you look at the distribution, we can get those in a day from 100 different places. So what do we really need? DR. SCOTT: And if you want the number 42 I cannot give that to you. But if you want me to -- Audio Associates 301/577-5882 165 DR. FEDORKA-CRAY: I want 111. DR. SCOTT: That is another story. But I think that actually the EFSA was fantastic in showing -- often times I am guilty of putting up this is the sample size to achieve this level of precision for this question and oh by the way we didn’t think about the issue of very, very low prevalence situations or detecting change. On that one slide that was presented, he had three objectives achieved with one sample size and that is probably what you need to start thinking about. Because otherwise it just becomes a -- and I actually had a slide where I said well you know what usually if you choose to do this, you are going to be giving up something for that. So I think -- and I am not saying the number is 170 either although that seems to be a pretty good number. But what happens is exactly what you said. So you choose 170 and you use that for Salmonella. But then you discover that oh well there are four dominant serovars and wouldn’t it be great to present it by those so now you have 60, 42, and 32. And then the question is well do we attach confidence intervals about that? And what do we do if those numbers change dramatically next year? Is it important or isn’t it? And so you have these apriori things that you must do and then you have these adhoc analyses that graphically look brilliant until you put the confidence intervals around Audio Associates 301/577-5882 166 them. So I guess what I would say is I have not answered your question but I think you have got -- actually the first question was trend or the last of the three. I think you are actually really on track for trend particularly for established prevalent resistances. I do not think anyone is going to challenge you on those. I mean you are tracking trends. You are tracking no trend in tet, you are tracking a trend in ceftiofur in the examples I gave. The issues might be -- you had one example I think from EFSA about the .01 prevalence, I am just not sure about those. So I am not going to give you a solid answer for everything. But you have identified the problem. Another good example is even if it was not serovars of Salmonella, if you do not get enough Salmonella from a certain commodity, it may not be enough for anything. So even though you may continue to sample for Salmonella, if you get 10 isolates one year from ground beef, I mean why even report it, it is almost not helpful at that point; you are better with the indicator. DR. FEDORKA-CRAY: (Away from microphone) DR. McEWEN: Personally I think you could also think about contracting some of this out to other groups. Isn’t that was CIPARS did, there was a contract to do some of the initial sample size work to Andre Rivel*? You know, get some university people, some PhD student, whatever. And it might Audio Associates 301/577-5882 167 involve some simulation work, it might involve just application of basic epi stats principles around various scenarios for sample size. But as soon as you start doing hypothesis testing then that multiples the sample size requirements like Randy said through the roof because of the numbers of organisms, the number of animal species you are talking about, the different levels of commodities, and the wide spectrum of antimicrobials, it can pretty quickly get out of hand unless you have some established priorities for what you want to do as has been talked about. DR. SINGER: I guess I have a question back to the NARMS folks. It would be -- it is called a National Monitoring System but is the prevalence estimate you desire truly a national estimate by commodity? I mean yes you can have a precise estimate of prevalence perhaps with 170 isolates but if you base that number of isolates as a function of the amount of product produced in the country, the US is very different from some of the countries we are comparing ourselves to. And so would you prefer something that is more regional than national although some of the commodities are very regional as well. Would you like an estimate that is a function of what we talked about earlier, a volume adjusted type of estimate? So just to talk about a strict number of isolates, while you might have a precise prevalence estimate, Audio Associates 301/577-5882 168 it still may not be very predictive of any level of risk associated with the commodity just because of the amount of that commodity this country produces. DR. McEWEN: Okay, Pat should we call it quits? Thanks very much ladies and gentlemen. (Applause) DR. FEDORKA-CRAY: We are going to move to comments from the commodity groups. And they were given a series of questions that -- without reading all the questions though, basically if you want to come up all of you that would be great. What essentially the commodity groups were asked to address was what they expect to see from a NARMS sampling system or what they see a NARMS sampling system should look like. And then how they might contribute to such a system and what they expect to get out of such a system for participation as part of the program. With that I think we will just go down in the order that they are sitting here then. So the first person would be Dr. Elizabeth Parker representing the National Cattlemen’s Beef Association. Comments from the Beef Industry by Elizabeth Parker, DVM DR. PARKER: Thanks Paula. I am Elizabeth Parker and I am Chief Veterinarian for National Cattlemen’s Beef Audio Associates 301/577-5882 169 Association. I represent about 140,000 beef producers across the US. Paula I failed you in your task you gave me. I really could not answer the three questions. But the reason I could not answer them were one you have heard quite a bit from several speakers today and the other one you probably do not want me to say but I am going to have to. I do not think we have a good enough understanding of what the goal and the purpose of NARMS is. I have read all the documents; it has been around a while. The advisory committee, that was very helpful Patrick this morning for you to go over that 2007 report of things that needed to be addressed, what you all have done. I think it would be more helpful to have further information on that. Because the answer to all of the three questions Paula talked about hinges on that, what is the goal of the program and the purpose and the intent? The other one is -- no one has mentioned today so being from the beef industry it is incumbent upon me to do so or else my guys will fire me. Antimicrobial resistance is extremely complicated. I mean the last panel, you could sit and listen to those guys forever and all the stuff you work on and think about and all the answers we need. The challenge with this topic has been over the last decade and especially over the last few years, instead of it Audio Associates 301/577-5882 170 being a scientific discussion which is so nice and refreshing it is a political discussion most days. And I bring that up because it directly ties into your third question which is what do we expect out of it and how can we collaborate and work together? And because it has become a political football, it has made it extremely difficult to have discussions like these and have productive conversations on what we need to do especially when you talk about on-farm. Because these people you are talking about and their farms, they are actually making a living and raising families as well as the beef cattle that feed all of us. So everything that is done, whether it is through a research function, a regulatory function, or what I think now is a study in trends and prevalence, affects other things. So in order to make some progress on this topic we need to remove the politics from it. And I know the folks in this room, that is not -- you have suffered from the consequences of that just as much as the industry does but it still has to be addressed. And another thing it goes to -- several people have talked about is the collaboration you need. If you are going to get samples anywhere along the food chain, not just on farms but also at the slaughter plants, and the lairage is a very interesting new component, you are going to need collaboration. And to get good collaboration you need trust and everybody needs to understand the goals and the intent and Audio Associates 301/577-5882 171 the uses for that information. And there could be multiple uses. So that is really important. The other things I would like to bring up, one is depending on what the goal is, one area we have talked about we need more information on is on specific bug/drug combinations. How you are using a certain antimicrobial in a certain species, in a certain setting that is going for food production, how is that affecting that particular thing? And until we get some more clear, detailed answers on that I think the rest of it we are just all kind of talking in circles in order to make good progress on this topic itself. The other thing is we talk about resources and money. It is not just the current economic environment. I think historically for NARMS it has seemed to be so broad and there is never enough people resources or money so how do you figure out based on your goal and your intent to prioritize that, to get the most answers both immediate and then longer term based on the resources you have? And we probably need to have a lot more discussions on that to better identify what those are and to help all of us with that. It is also a global discussion and one thing I do is both domestic and international work for cattle health. And people move -- I have been to three countries in the last two weeks and so have several other people in this room and therefore bacteria move as well. So working on maybe more Audio Associates 301/577-5882 172 collaboration with what is going on in other countries. I know there are quite a few different monitoring systems like this, they are all different. I think it would be helpful to have more conversations on the differences and the similarities. Not only movement patterns, I think Randy you brought it up, beef is extremely complicated in this; the complexities of it from farm to fork and how things move around the commodities and ground beef versus other. And I think we should have that on a global discussion as well because products that all of us -- our producers raise, they are not just here. And on ground beef, we actually import a lot of trim to make up the combination we need. And I think that will help us all in what we learn over the long term and maybe with smaller resources we can better utilize the funds and enhance those collaborations. The last thing I will touch on is protocols and methodology. I am not clear on the three different agencies particular with NARMS that collect samples and analyze them, if the lab methodologies and protocols are all the same. I would think they need to be but I would leave it up to Randy and Morgan and those guys to tell me if that is -- maybe I just do not know enough. But there is certainly transparency in what all of those are so that way when you are analyzing the data or industry is analyzing the data or whoever, that Audio Associates 301/577-5882 173 you actually know what you are analyzing and if you are comparing apples to apples and apples and oranges and what valuable information you can learn out of that or not. The last thing would be this is not just about antimicrobial resistance, it is not just about livestock. Bacteria surely don’t see the world that cleanly so I know that is today’s topic, but we need -- if we are going to find the answers we need to, it needs to be looked at by all species and uses of antimicrobials and how that affects resistance. And I know livestock is the easy target, but there are human uses, there are other animal uses, and there are industrial uses. And if we want to move the ball forward and have a productive conversation and get information that we all need, then we need to look at those things as well. There are going to be hard discussions but we need to have them. So I think I will finish up with hopefully that has been put in a positive framework. And we do have -- while this topic is extremely difficult because it has been politicized, we have examples of things in the past that have been challenging that because of good communication and collaboration, we have had tremendous success for the beef industry. The TB and brucellosis, we are less than .001 percent TB prevalence in the US cattle herd. That is because of a lot of hard work with federal and state governments as well as industry. And when they first started the TB and Audio Associates 301/577-5882 174 brucellosis programs -- brucellosis we now just have in the wildlife in the US, it is eradicated from the US cattle herd. When they first started that, the government folks would come out on the ranches and they were met with shotguns. So we came from there to a tremendously successful program. Another thing on food safety, E. coli 0157, because of the tremendous amount of work on the industry side on research that we have funded, we have had a 70 percent reduction based on FSIS’s own numbers between 2000 and 2010 of the positives on that. And that was industry working hard and our government folks working hard and us collaborating together. So I guess I am going to leave you on that. I put up a lot of hurdles and questions and things we need to work on but they are not insurmountable, we can do it if we actually work together and have it as a scientific discussion. DR. FEDORKA-CRAY: Thank you Elizabeth. Next is Paul Sundberg representing the National Pork Board. And he will speak on the swine industry. Comments from the Swing Industry Paul Sundberg, DVM, PhD DR. SUNDBERG: Thank you Paula. So first of all thank you for the opportunity for the swine industry to come and provide comments on NARMS and maybe a little bit of input as well. The National Pork Board is funded wholly by Checkoff Audio Associates 301/577-5882 175 funds and as such our job is research, education and promotion and so we are not the lobbying part of the industry. I want to make that clear, that I am here to provide comments based on that research, education and promotion type of charge and philosophy for our organization and for pork producers. I do not know if you read, if everybody has got the three questions. Do they have the three questions? Your industry’s needs for antimicrobial resistance monitoring? What an on-farm sampling program might look like for you? And how industry is willing to contribute? Those are the three things. Okay so I am going to address those three probably not unlike -- I am going to put them in the framework of those three but I think the comments in there you are going to hear this over and over again many times and I am going to add to it I guess. Your industry’s needs for antimicrobial resistance monitoring? The pork industry, I don’t know Paula, were we the first ones? If we were not the first we were darn close to it. Many years ago we sat down with Paula and talked about antimicrobial resistance monitoring; we have been in this for a long time. And our needs are there not unlike nature, politics abhors a vacuum and without good data, without scientific data, somebody is going to fill it and somebody is going to fill it with opinion and somebody is going to fill it with rhetoric and that is the value of NARMS. Audio Associates 301/577-5882 176 Your industry’s needs for antimicrobial resistance monitoring is data. We need data so we can ensure that we have a scientific basis for our programs, for our industry, for policymakers and others to consider as they do their job. So that is the easy one. What an on-farm sampling program might look like to you is much more difficult because just like the last panel and some of the things that you have heard today, that is really a difficult question. I was a lot clearer on that when I came than what I was by lunch because this morning -- I think the answer to that question is really dependent upon what the objectives are going to be. What do you want for the objectives for this thing and then I will tell you what it can look like. This morning I got very confused. I heard a lot of different things. You heard about surveillance, you heard people talk about surveillance. And the first thing is in any surveillance program, before you are going to have any surveillance program you better darn well have a response program. You better figure out what the response is going to look like before you start surveillance and I am not so sure that we have a response program for this thing. So I do not know if it is a surveillance program or not. You also heard that it is a monitoring program well that is different than surveillance. Monitoring is Audio Associates 301/577-5882 177 monitoring, it is watching it. It may be analyzing it but it is a monitoring function, that is not surveillance and response. And the third thing I heard this morning was well it is a research program, that there are elements of research in this and I do not know if it is a research program or not but certainly there was a lot of research program ideas that were presented this morning as part of NARMS. And so what it is going to look like is going to depend upon what the real objectives are. And way back when we may have started with this idea of we need to be monitoring antimicrobial resistance because we need to have some data so we can use that for developing more researchable questions and we can use that to help answer the questions by the policymakers of what should happen when and what should happen if and that was the monitoring function. And then there was that research offshoot because you find out that there are a lot more questions that you have than what you originally set out to answer. And so that all comes back around to -- as far as the pork industry goes. As far as my producers go, this idea of it is a national antimicrobial resistance monitoring program and monitoring system, the monitoring system provides the data. The monitoring system also provides some additional Audio Associates 301/577-5882 178 researchable questions that we have had a history of helping to fund and we have had a history of asking those because we want to have sound scientific data. I think that is probably where we come from a lot with this versus this surveillance program that I am not so sure that we have a clear understanding or appreciation for the response part of what surveillance would mean. All of that around there, and that is why I am confused because everybody -- and you have brought up good questions about this surveillance monitoring and research and what kind of samples do you take, and is it prevalence or is it incidence, well what do you get. Well that depends on what you want to have for surveillance monitoring and research. And I am not sure that we have that any more. It may be a little mission creep or maybe it was just me that was confused from the switch of uses of those words through this morning and even into this afternoon. So with that what do we want from the pork industry perspective, from the Checkoff perspective, what do we want in an antimicrobial resistance monitoring program? The first thing I think that the pork producers are going to want is they are going to want a program that is sustainable. If you are going to have a monitoring program that is going to be worth anything, you are going to have to have this, trends. You are going to have to have trends analysis Audio Associates 301/577-5882 179 and that means you have to have longevity. So the thing has to be sustainable and be able to have a life that will provide that data for you. A one shot deal is not going to help a whole lot and so one is sustainable. As we work through different programs for our industry, animal welfare, and others, our definition of this type of sustainability has become what is credible and what is workable and what is affordable and that is really where our definition of sustainability comes. Because you have to have credibility otherwise nobody is going to listen to it, it has to be affordable for everybody, producers as well as researchers as well as whoever else is involved so for all the stakeholders, affordability, and for all the stakeholders as well, doable. If working on -- if this thing about antimicrobial use and antibiotic resistance on the farm versus public health and antimicrobial resistance trends and public health, those are separate questions. But no matter what the question is you are going to go after, it has to be doable for all of the stakeholders. So on the farm if we are looking at these samples on the farm and we are looking at trying to get more information about antimicrobial use and resistance trends, it has to be doable for producers as well. The second thing is that you will not get producer or industry cooperation unless there is a consideration for Audio Associates 301/577-5882 180 the producer of what the cost benefit is of doing this. Really you are talking about convenience samples because you are talking about producers that are willing to participate in the program. And in order to make them see the light, to use the term, and participate in the program, they are not going to do this just because. There is going to be a cost benefit thing. How much is it going to cost me both in time and in material and in trouble and what is the benefit I am going to get back? And there may be a higher benefit of information of antimicrobial resistance trending and that is good. But I will tell you for a lot of them, where they live is -- the benefit for me is what are you going to tell me that is going to help me either with animal health on my farm or with production of my animals because that is really where I live and that is what I am doing for my family and what I am trying to do. So we have to figure out this cost/benefit thing for producers in order to incentivize them to produce. Least intrusive is the cost. I mean the cost side is what is the least intrusive thing you can do for producers as the program would go forward? And the benefit side, like I said, is what is the clinical or what is the production positive things that you can provide back to the producers. As an example, we heard about pathogen reduction this morning. A lot of different terms, pathogen reduction, Audio Associates 301/577-5882 181 antimicrobial resistance, all these things, it should have some clinical or some production outcome for producers. But I will tell you that I am not so sure that there is a pork producer in the country that is concerned about antimicrobial resistance in enterococcus in his pigs. That is not the benefit part. There may be some higher level benefit to that and certainly there can be food safety implications and all that and pork producers are supportive of all of that. But now you are asking them also to give their time to work on the farm for whatever the project is. The last one is clear objectives. We need to have these clear objectives. Like I said the National Antimicrobial Resistance Monitoring System, analyze for trends, and this public health versus on-farm use resistance question is something that has to be within the objectives and we have to figure that out to make progress. And to help the program, we have in our animal health side -- are forming for example veterinary sentinel clinics that can give us early warning systems of animal health issues. Well maybe as part of this sustainability thing, we have to think about how we could incorporate NARMS within things that are already happening. Whether it is HACCP, whether it is the collection of samples through veterinarians, through diagnostic stool, whatever is already happening how can we make it the least intrusive as possible? Audio Associates 301/577-5882 182 Third thing is the industry willing to contribute -- see that was the longest one in the middle; this one is not hard either. Because Paula talked about collaboration and certainly we are willing to contribute. We want to contribute to this. We have historical buy-in into this program. The ultimate decision about participation is going to be with the producer however. The Checkoff has contributed funds to go along with this as researchable questions and how we can contribute. Yes, we are willing to contribute but the devil is going to be in the details and we have to get all of that figured out on these individual projects and we are looking forward to discussing the projects, the outcomes, the reasons, the objectives, and the details. DR. FEDORKA-CRAY: Thank you very much Paul for following the trend line of anyone who has P-A-U-L in their name and extending a little bit beyond their time. DR. SUNDBERG: I didn’t have any slides; I had no slides. (Laughter) DR. FEDORKA-CRAY: Our next speaker is Dr. Brian Woo-Ming and Brian is representing the National Turkey Federation. Thank you Brian. Comments from the Turkey Industry by Brian Woo-Ming, DVM DR. Woo-Ming: Thank you Paula, that was pretty Audio Associates 301/577-5882 183 impressive, I did not think you would remember me. My name is Brian Woo-Ming and I am a veterinarian with Cargill Turkey. I was asked to do this because we have unfortunately had a change in our staffing at the NTF and lost Dr. Thesmar and unfortunately no one from the NTF could make it here so I was volunteered seeing as I live locally and I will do my best to entertain you. I am going to make a few general comments from the NTF and then I am going to add a few additional comments based on the meeting of all the turkey vets that occurs annually at the AVMA. Most of us in production were unfortunately unaware of the three questions because of the change in personnel. And our first introduction to the request came about 4 days ago and accordingly it was very difficult I think to provide you with the answers that I know you all want. As such, I am going to give you the canned answers from the NTF and then some suggestions from us in production. So the generic statements that we are going to make -- guys we support the basic principles of the NARMS system but we would like to see you include all the risks and not just focusing in on animals. And certainly the turkey group is one of the smallest livestock groups. We feel that we would like to hear more information regarding the human side to this. Very little of that filters down to us in Audio Associates 301/577-5882 184 production; I am being very honest with you all. We would like to see HHS and the USDA work together to focus on the reduction of foodborne pathogens whether resistant or not and I think a lot of that is already being done. And finally we would like to see more of a quantitative assessment on the risk of antibiotic usage in food animals and its impact on human health. Okay, those are my statements from the NTF. Now a few comments from the group of veterinarians that actually work in production. I am going to echo the concern about not fully understanding the goals and objectives of this new program or extension of the existing program. Those of us in production focus on a variety of things and we are at the end of the communication pipeline. Paula I would like to see the protocol that we discussed back in the workshop. Let’s disseminate that to all of us in production. We can discuss it over the next year. We probably visit monthly at the best on a conference call and then once again in person at the AVMA. Let’s discuss what cannot be obtained from the current system of retail sampling and what you hope to get out from the on-farm sampling and clearly define that prior to us giving you or trying to give you the answers. Secondly we are concerned on how the data is going to be used, shared, and made available to other stakeholders. Audio Associates 301/577-5882 185 We would like to understand where that data is going to go and how any confidential or proprietary data can be protected. So once again, those two statements came out of our meeting 4 days ago and we would like to get some sort of documentation on that. And I would be happy to provide that through our group to try to get you the answers that you want. I apologize for not having a prepared set of answers as my colleagues in the pork industry had. But we probably move as slow as you described in government and it is going to take a little more than 4 days for us to get together and give you what you want. So once again, thank you for letting us come here and we look forward to being here next year I guess. DR. FEDORKA-CRAY: Thank you Brian. And last but not least, Dr. Al Yancy from the US Poultry and Egg Association is going to present comments on behalf of the National Chicken Council and AABP. And Kurt Dobson was supposed to present. He was here this morning and had to leave and I grabbed Al this morning and so like Brian unfortunately he was put on the spot too so thank you to both of you for filling in and I know it is not an easy situation. Comments from the Chicken Industry by Al Yancy, DVM DR. YANCY: Your welcome and no it is not. Very quickly and I know that this will count as part of my time but I think it is important. Audio Associates 301/577-5882 186 I serve as the Vice President of Food Safety and Production Programs for the US Poultry and Egg Association. We are the umbrella trade association on the feathered side. It covers broilers, turkeys and eggs. We are not a lobbying organization. We are basically the science and research; the Paul Sundberg type approach from the pork side, we take the same approach, in other words from the feathered side. And so I came today to get educated and I am getting educated and this part is certainly going to be an education as well. So I am probably not the best person to be up here making these comments. Obviously those who were scheduled to be here would have been but were it not for me speaking on this, then the feather side minus the turkeys of course would not have not -- the broilers certainly would not have had a voice. And so yes these are comments that I have gone through and unfortunately I will try the best I can to paraphrase them. These are National Chicken Council comments and American Association of Broiler Veterinarians, that is the two groups -- Broiler Production, excuse me, whose comments these reflect. And then if there are a few minutes remaining, which I hope there will be, then I will tell you from my perspective what the US Poultry and Egg Association’s opinion is. I actually just started having conversations with Audio Associates 301/577-5882 187 Paula about this issue, the antibiotic resistance issue, NARMS, the changes that were proposed in NARMS in December of last year so obviously 7 months by far does not make me anything close to a knowledgeable person by much measure and certainly not an expert. But obviously the broiler industry wants to partner and does partner with government scientists to help support public health missions and produce safer poultry products, that is all of our goals and so we share that of course with our friends in the government and of course our friends in the trade, those to whom we sell our products, and of course consumers as well. Therapeutic antibiotic choices are exceedingly limited for our industry and so therapeutic use of antibiotics is -- a use in general of antibiotics is markedly restricted. Now that is not to say that we do not use them and it is not to say that it is not conceivable that antibiotic resistance -- we could be in fact contributing to antibiotic resistance. But to the points that have been made by my three predecessors, I think we do not know, by a long shot we do not know how much we contribute, to what extent we contribute, and if in fact we do contribute. So obviously our desire would be to support public health missions whatever they may be related to foodborne illness and to learn the ways in which poultry products could Audio Associates 301/577-5882 188 be made safer for consumers and do so in a collaborative way. And in this case the collaborative sampling and research. So having said that we think that broiler and breeder flocks would in theory be something that should be tested. We also believe that the best testing methods should be used and that we should have clear goals and clear responses to the findings delineated before we actually get into the program. In other words, we do not want to get into the program and not fully understanding what the program is going to be and have it changed. Furthermore we do not want to do something, and we are not insinuating that is the case here, but we do not want to do something that is politically driven; we want to do something that is scientifically driven. What could the industry contribute? Expert knowledge of poultry husbandry and production systems to assist in the design and implementation of a practical and sustainable sampling protocol or protocols, the labor to obtain and provide the samples to the labs, and a willingness to help design and participate in a collaborative research project to develop high-value sampling schemes that will enable resources to be used judiciously and have more total samples ultimately be tested. Obviously we agree with, this is now US Poultry and Egg Association, with these comments that I have just read to you which represent the National Chicken Council and the AABP. Audio Associates 301/577-5882 189 And we also agree with the comments that have been made by those prior to me on the panel. Much more definition has to be provided. We obviously are interested in having as much of an opportunity in helping create such definition as is humanly possible under the circumstances. What we would not like to see is the data used to create policy. We understand that the data would and should be used to inform policy. And I think there is a definite difference between creating policy based on the data you find and actually informing policy. And I think to some of the points that Paul made, for the producers to want to get into this program they have to have their fears alleviated that the data and the information that comes from this will be used against them. And I think that goes to the heart of the discussion of creating policy versus informing policy. And so I think the National Chicken Council certainly would enjoy further involvement in this program as far as collaboration. I can tell you the US Poultry and Egg Association would as well. And we are appreciative of the opportunity despite the stress that it caused me this morning when I was given the opportunity. And I apologize, although not entirely in my control, for our performance but if there is anything we can do to take part in this, we certainly would like to do so and we appreciate the opportunity. Audio Associates 301/577-5882 190 DR. FEDORKA-CRAY: So I would also like just to put on record that I do have slides that were submitted from the National Chicken Council and I would like those to be -- they complement exactly what Al said. So I will give you those Heather to put in there. And I would like to take the opportunity to thank each of them for coming and voicing their opinion on the subject. And the only thing I guess I would ask after break is that I would like to extend the invitation to Dr. Bruce Wagner that if he does have any comments on the APHIS program or policy or involvement, that he be given a few minutes to make those comments and I see him nodding so that is a yes. So with that please join me in thanking our representatives. (Applause) DR. FEDORKA-CRAY: And we will take a five minute break. (Whereupon a break was taken) Public Comment Period DR. TATE: So now we are entering the public comments section period. The first person that -- well actually we have two people who have submitted interest in giving some comments at this talk and so we are going to have them come up and then if there are any additional folks who needed to say anything during the public comment period, they Audio Associates 301/577-5882 191 can afterwards. So first we will have Tom Shryock come and you can say where you are from. Comments from The Animal Health Institute by Thomas Shryock, PhD DR. SHRYOCK: Thank you Heather. I am Tom Shryock with Elanco Animal Health. I am speaking here today as a representative of the Animal Health Institute and not Elanco which is the national trade association representing manufacturers of animal health products for pharmaceuticals, vaccines, and feed additives used in modern food production and the medicines that keep the livestock and pets healthy. AHI has long supported the US NARMS program. Public health, food safety, and animal health and welfare continue to be key areas in which AHI and its member companies seek to make a positive contribution by a variety of means. AHI welcomes discussions on better ways to interact and to be a resource with farms leadership in the future. AHI has participated in all of the NARMS public meetings, has provided constructive written suggestions via the docket submission on the recent federal register call for input on the NARMS Strategic Plan. The purpose of this statement is to address three key topic areas. First is industry needs for NARMS. AHI believes that it is first necessary to clearly establish how Audio Associates 301/577-5882 192 NARMS data will be used so that appropriate methods and strategies can be prioritized for implementation. To that end, the veterinary pharmaceutical industry has a need for trend data to track antimicrobial resistance or the lack thereof and key foodborne bacteria which can be a fundamental component upon which risk management interventions, FDA CVM ONADE product approvals, and judicious use practices and research studies can be based. Specifically AHI would like to use NARMS data to 1) support responsible use programs on-farm; 2) to include in Guidance 152 submissions; and 3) to support research on AMR. Although it would be ideal to have data generated that could be used in risk assessments, it is not clear at this time as to what extent that may be possible with the current sampling strategies and resources available. Industry views regarding sampling strategy and components. Given the current economic constraints in the government budget for new emphasis on food safety which were not present at the time of the 2007 FDA Science Board Review, it is now essential to prioritize limited resources to achieve fundamental goals. Accordingly, the core focus of NARMS should now be concentrated on susceptibility testing of isolates for foodborne pathogens obtained on-farm, at retail, and from ill humans; a completely redesigned, purpose specific, epidemiologically based and statistically Audio Associates 301/577-5882 193 representative sampling program. To maximize efficiency with existing resources several new approaches will be proposed for discussions. On-farm sampling. AHI believes that on-farm sampling is best conducted by USDA ARS researchers with hypothesis driven collaborative research programs and conducted outside of the NARMS program. The former CAFHES program and current USDA CRIS program overseen by Dr. Paula Fedorka-Cray is an excellent example of how this can be conducted. As proposed, a closer interaction and coordination with NAHMS should be considered so that additional information can be complied. There are several benefits to this approach. First on-farm access by USDA ARS researchers and university collaborators is likely to be viewed in a positive light by producers. On-farm access by regulatory agencies should be limited to for-cause purposes and not as a part of NARMS due to the perception that enforcement actions may result. Second, the value of a separate on-farm program outside the jurisdiction of NARMS is that it will allow sentinel site studies to be done that can collect the context data on disease outbreaks, antibiotic use practices, and can be designed to be representative and statistically meaningful. This data can guide responsible use programs. Isolates Audio Associates 301/577-5882 194 collected from the on-farm sampling can be provided to the NARMS collection. Third, this type of data will not fit into the format of the early NARMS reports or will it produce national prevalence rates and therefore should be published on its own merits and shared in appropriate forums. We recognize these epidemiologic studies do not provide national prevalence rates for antimicrobial resistance on-farm. The magnitude of the efforts to provide such estimates could be cost prohibitive. We believe that an analysis by NAHMS leadership investigators would give insight as to the cost and resources associated with providing true prevalence rates for resistance on-farm. Lairage, AHI views sampling at lairage as inappropriate and cannot support it within NARMS. The reason for this is simply that animals in lairage will be stressed, comingled and contaminated with bacterial strains that may not have originated on-farm. Thus the investment of resources into this sampling point will not generate data that will be informative or applicable to assess antibiotic resistance on- farm. Hypothesis-driven research projects would be a more appropriate means to explore the situation. Post-slaughter, AHI believes further discussion is necessary for this sample point because it has the best potential to provide representative data in a statistically Audio Associates 301/577-5882 195 meaningful way. The USDA microbiological baseline studies that have been conducted in cattle, swine, chickens and turkeys appear to provide a feasible means to obtain the type of data NARMS needs. There is already access to facilities, the sampling design, a proven microbiological methodology and a baseline of data to build upon. AHI strongly encourages NARMS leadership to carefully read the baseline data, study protocols, and look at the data and ascertain how this program might be adapted. Post-slaughter isolates may not relate to on-farm antibiotic practices and may have other limitations. However, other national monitoring programs have chosen to use this sample point as it provides the best information for what is likely to become retail meat. Since carcasses may be shipped in pieces or parts or made into ground meat and then distributed nationwide, this sampling point potentially offers the advantage of capturing the national prevalence data. Retail meat, it seems retail meat samples are primarily collected at FoodNet sites. Further discussion on the representativeness of the meat samples collected is needed to better understand what can be done to improve the program and whether the meat samples can be linked in any way to the human isolates collected in that geographic area. It may not be necessary to increase the total number of samples but for improved representativeness, samples may need to be increased Audio Associates 301/577-5882 196 for more sites in more states. Industry commitment, AHI proposes the following next steps as one means to help improve NARMS. First, comments submitted to the docket on the NARMS Strategic Plan need to be summarized and communicated perhaps in a future workshop. Second, NARMS leadership should carefully extract from AMR programs in other countries what has worked for sampling. Resources from OIE Terrestrial Code, WHO surveillance, CLSI, et cetera, et cetera may be reviewed. Input for this meeting should also be taken into account. Third, additionally there are numerous resources within the US government that should be able to collaborate on designing an appropriate sample collection system. Statisticians, epidemiologists, and others within USDA, FDA, or CDC or even other government agencies should be organized perhaps into a taskforce to design a workable system that can be proposed to stakeholders. Fourth, a workshop should be organized to discuss the fundamental operations, sampling design, logistics, laboratory activities, data capture analysis or reporting. Perhaps this could be as part of input on the strategic plan. A facilitated, multi-disciplinary small group approach might be one way to advance the revisions. AHI remains committed to support the NARMS program Audio Associates 301/577-5882 197 and is willing to contribute to the improvement by various means. In conclusion, AHI would like to obtain consensus on the purposes for which NARMS data will be used because that will help to define sampling points and strategies. Utilizing existing resources as the USDA for on-farm research is supported, both ARS and NAHMS, as a separate program outside of NARMS. Opportunities for post-slaughter sampling along the lines of USDA baseline microbiological studies should be explored. Retail meat sampling strategies require further understanding and discussion. AHI appreciates the opportunity to provide its views on the support and program. Thank you. (Applause) DR. TATE: Thank you Tom. The next speaker is Susan Vaughn Grooters from the STOP Organization. Comments from STOP and Keep Antibiotics Working by Susan Vaughn Grooters, MPH MS. VAUGHN GROOTERS: Good afternoon. I am Susan Vaughn Grooters. I am the Director of Research and Education at STOP. I received my public health training in epidemiology from the University of Massachusetts Amherst and my undergraduate degree in food sciences from the University of Audio Associates 301/577-5882 198 Vermont. Therefore I come to the conversation today from both disciplines. Keep Antibiotics Working and I appreciate the opportunity afforded us to offer comments today at the NARMS 2011 Scientific Meeting. Today I not only represent those individuals that have become ill from antibiotic resistant infections from foodborne illnesses that work with STOP but also as a member of Keep Antibiotics Working or as I will refer to the group as KAW. KAW is a coalition of health, consumer, agricultural, environmental, humane and other advocacy groups with more than 11 million supporters dedicated to the preservation of antibiotics for use in human and animal medicine. (Slide) For those of you who may be unfamiliar with STOP’s work, we are a national nonprofit public health organization dedicated to the prevention of illness and death from foodborne pathogens by advocating for sound public policy, building public awareness, and assisting those impacted by foodborne illnesses. STOP has been supporting those who have fallen sick and those who have lost their loved ones from foodborne illnesses, their families, friends and larger communities of Audio Associates 301/577-5882 199 concerned consumers for the last 18 years. (Slide) I imagine some of you may not have heard of STOP before today or know about some of our volunteer advocates so I would like to introduce you to some of them. These are toddlers, children, college students, parents and grandparents. They are teachers, real-estate agents, truck drivers, lawyers, retirees, homemakers, and farmers. They are victims of Salmonella, Vibrio, Listeria, Campylobacter, Norovirus, Hepatitis A and E. coli. They became sick from eating hamburgers, lettuce, chicken, melons, berries, water, juice, and many became ill from unknown sources. Some of them have long-term complications, some have recovered, and some of them are no longer with us. (Slide) Since its early inception, STOP has been committed to preventing illness and death from foodborne pathogens including antibiotic resistant ones. STOP believes that everyone deserves safe food and that includes food that is not contaminated with antibiotic resistant bacteria. I could spend the time allotted me today sharing the story of Debra and her children in North Carolina who were all sickened with multi-drug resistant Salmonella infections and the agonizing illnesses that were challenging and difficult to treat. Audio Associates 301/577-5882 200 Or I could spend my time sharing the story of James from Tennessee who was also sick with antibiotic resistant Salmonella. Or of Lara from California who had a resistant infection from Campylobacter. Or Russ who contracted MRSA from working on his farm right here in Missouri. The families that work with STOP and KAW are very special. They relive their grief and the painstaking details of what happened during their illnesses so other won’t ever have to go through what they did. (Slide) I could go into detail about any of these illnesses and the people that make up the cases and the statistics that we have heard some mention of today. But instead I am here to help in the discussion of the topic at hand, animal and retail sampling methods. (Slide) I would like to expound on the topic as well as encourage inclusion of a few other areas where there are needs for improvement within NARMS. It seems like the mission of KAW, STOP and NARMS are all aligned for antibiotic resistance is unequivocally a food safety and public health issue that deserves the attention of leadership that is in this room today. Audio Associates 301/577-5882 201 When it comes to accomplishing the Strategic Plan on NARMS, there are certain goals that deserve more priority than others. The second goal in the Strategic Plan, to make sampling more representative and more applicable to trend analysis, KAW believes needs to be given higher priority than other goals. The goals should be modified to make clear that the intention is to create nationally representative, statistically valid sampling strategies for all branches of NARMS as previously recommended by the reviewing FDA Science Board. KAW recognizes that it is difficult to change what has been done in the past but it is critical for these changes to take place. It seems that based on many of the conversations today that sampling is based on convenience except in retail sampling; if we can do it in retail, why not in slaughter? (Slide) For example, the Strategic Plan has a goal of improving geographic representativeness of meat samples but then falls short for making a commitment to basing samples on population or consumption and could be loosely interpreted to mean that only more sites would be added which would not comprise a truly more geographic representative sample. Similarly the plan for USDA sampling is just to make changes to overcome biases of the current system but does not Audio Associates 301/577-5882 202 mention creating a sampling plan based on a representative sample of animals slaughtered. Creating statistically valid sampling programs for all data collected as part of the NARMS program should be the priority for any changes to NARMS. (Slide) It is encouraging to have had representatives from the Canadian program here today for the agencies participating in NARMS should look closely at this program and others around the world to see what other countries have done that works. The Canadian integrated program for antimicrobial resistance surveillance provides a good example of a surveillance program based on nationally representative sampling which also seeks to balance the cost of sampling with statistical validity. This system has a sampling design based on a two- stage sampling scheme of food animals and slaughterhouses. The first stage is a random selection of federally inspected slaughterhouses. The probability for selection is proportional to the slaughterhouses’ annual slaughter volume. The second state is the systematic selection of animals on the slaughter line. The annual number of specimens collected is proportional to slaughter volume. This sampling scheme then seeks to minimize the financial burden of shipping costs by defining a collection Audio Associates 301/577-5882 203 period that identifies the importance of maximizing diversity and avoiding bias due to overrepresentation of particular producers. Collection periods occur over a twelve-month course and avoid any potential seasonal bias in bacteria prevalence and in susceptibility test results. This predetermined protocol also accommodates for various line configurations and is designed to avoid conflict with current inspection methodology. Also of note is that the sampling was designed to avoid cross-contamination. And the samples are collected by industry personnel under the oversight of the veterinarian in charge not federal employees or inspectors. (Slide) I appreciate the many presentations of this morning. We heard in Paula’s presentation that there is an importance in linking drug use with isolates. Antimicrobial drug use data should be included within the NARMS program and FDA should collect from feed mills to provide information on drug use at the animal species level. The FDA should explore other sources of data on antimicrobial drug use that are needed to fulfill the mission of NARMS. Drug use data should be included in the NARMS database as recommended by the reviewing FDA Science Board. The Strategic Plan should be modified to include specific objectives related to antimicrobial use data under all four goal areas. It is encouraging that EFSA in future ideal plans Audio Associates 301/577-5882 204 will need to look at resistance at the isolate level as well. (Slide) The next slide I obviously prepared before the discussions of what prevalence is being considered by NARMS though I do think it is worth going through because I think it has bearing on some of the confusion that some of us may have been sensing today. So recognizing that no data collection or analysis is ever perfect, is always fraught with some element of uncertainty and will have critics at every turn, I still think it is important to think of an ideal plan. And this is how I would start. NARMS, in goal two of the Strategic Plan, states that NARMS is working towards improving and expanding sampling schemes so that the data will best reflect the US food producing animal production and distribution system and capture data on the prevalence of antimicrobial resistance among enteric bacteria along the farm to work continuum. This begs the question; do we have a good prevalence rate by pathogen food product combination? If not, how do we get there? Is it appropriate to set goals without a well- regarded prevalence rate? So let’s first identify the problem. Well that is easy. Antibiotic resistant infections are causing illness in humans as a result of food consumed. How does this occur? Audio Associates 301/577-5882 205 Well one line of thinking is that antimicrobial drugs are administered in varying doses, in varying applications, in feed, water, individual treatment, et cetera to food animals. So now we know how this occurs and if our goal is to ultimately reduce illnesses, a good place to start is understanding and having an accurate antibiotic resistance prevalence rate which in turn helps determine an accurate sampling size and therefore a valid sampling plan. Looking at assumptions, it is also important to understand distribution. Likely we are not looking at normal distribution of antibiotic resistance because as we have identified, drug use data is a key component in understanding what resistance profile any given foodborne illness pathogen will have. Stated very simply, if you give an animal a drug, you are more likely to see resistance to that drug. So it is imperative, since drug use will be dependent upon the producer, veterinarian, and feed purchased, that we acknowledge a one size fits all approach may not be appropriate here for a sampling plan since we are not going to have normal distribution of any antibiotic resistance profile in any given pathogen throughout the entire food supply. Unless administration of drugs is incorporated into the data plan and we can understand that all producers of any given food commodity all administer the drugs in the same way, which we know they do not if we consider sustainable and Audio Associates 301/577-5882 206 organics, so it is more appropriate to assume that distribution varies and a sampling plan will have to address this variance. Then with all sampling plans there is a need to acknowledge potential biases and to seek to minimize those biases. So again an idea for an ideal plan is to acknowledge that there is a need for representative sampling and usage data to be incorporated. And because we are dealing with animals that live in different locations, in different climates, and that these climates vary by season and so does bacterial shedding, we would likely want to include seasonal and geographic sampling into a plan as well. And ideally this would ultimately help get us to where we all want to be, targeted interventions to minimize the risk to public health. (Slide) So recognizing that we are not in an ideal place now, what are some concrete steps that could be taken with sampling of animals or meat and either improve analysis or current data or reincorporate sampling to help understand what targeted interventions might be. Too few isolates found in beef and pork, it seems that resistant Campylobacter would only exist in chicken? However, maybe we should look at sampling from different sources or at the very least collect and report on data that may exist from these alternative food sources. Audio Associates 301/577-5882 207 (Slide) There is a value in knowing what is going on even at very low levels to understand what could be coming down the pike. There are recent papers finding that cattle in addition to poultry can be an important source of human Campylobacter infections. Reincorporating samples may show that Campylobacter and resistant infections can be associated with illness for those that consume beef or those in close proximity to farms such as farm workers. This is one inclusion that may be further explored from a proof burden determination from Campylobacter especially in light of the discrepancies we see in retail versus slaughter sampling of Campylobacter. (Slide) So what data might we have now that would be beneficial to incorporate? Well KAW would also like to see incorporation of resistance data collected as part of outbreak investigations and food recalls to be included in NARMS reports from FDA as a separate section. This type of data is particularly important because foods other than meat are being increasingly identified as a source of foodborne illnesses. Information on the resistance of isolates causing illnesses in foods other than meat is necessary for interpreting the retail meat data as a point of comparison. Additional objectives under Goals 1 and 2 of the Audio Associates 301/577-5882 208 Strategic Plan should be included that address the collection and reporting of outbreak data. Based on the medical records of STOP members and other publicized sources, we have seen resistant infections from food sources of which FDA has oversight from cantaloupes and cheese, seafood, or joint oversight, eggs, milk, to the ever more dangerous sprouts. So in answer to some of the questions of what additional information should NARMS collect and report? Inclusion of FDA regulated products as well as sampling of surface and groundwater for antibiotic resistant bacteria could be considered. (Slide) KAW supports other identified improvements to the NARMS program as described in the Strategic Plan but believes the emphasis must be on improving sampling. Under Goal 4, objective 4.2, to work more closely with international partners to harmonize antimicrobial resistance testing and reporting and to facilitate data sharing. KAW would also like to see that harmonization also includes harmonization of sampling strategies. (Slide) It is important, however, that we simply cannot hide behind the excuse of data limitations before we take action. Where is the threshold before important changes are made? How Audio Associates 301/577-5882 209 many people, cases, must contract antibiotic resistant illnesses before important changes are prioritized? How many stories from STOP would it take -- make sense for us to share to make a difference? Looking at HealthyPeople 2020 goals for antimicrobial resistance, the broadly stated goal is to prevent an increase in the proportion of nontyphoidal salmonella and Campylobacter jejuni isolates from humans that are resistant to antimicrobial drugs. I would encourage in this goal we should reflect an aim towards progress. Simply preventing an increase is not ambitious enough, we much take action to reduce illnesses. (Slide) I think we can all agree that NARMS is a public health program. So in conclusion, NARMS being a vital public health program that needs certain improvements to achieve its main purpose which still may need to be better defined based on today’s conversations, the focus of improvement should be on creating a statistically valid sampling program as this is the core activity of NARMS. Next steps should make clear that improved sampling is the key priority. In addition, future plans must include incorporating antimicrobial drug use data into the NARMS system as well as data on disease outbreaks and recalls. KAW appreciates the work and effort that the three Audio Associates 301/577-5882 210 agencies have put into the NARMS program in the past and hopes to see a much strong NARMS in the future as we all work to combat the public health problem of antibiotic resistance. (Slide) Thank you for the time allotted me to deliver comments today. I would like to acknowledge those who have been working tirelessly on this issue at KAW for many years and who could not be in attendance with me here today particularly Mardi Mellon, David Wallinga, Ben Cohen, Rich Wood and especially Steven Roach. Their combined work has helped bring the issue to the forefront of concern for policymakers and consumers alike. I am honored and privileged to work with them. I would like to leave everyone with a final thought. I recognize that some of the changes that we are asking for and considering today from the leadership from industry and government will be costly but we cannot let the economic health of a business or industry become more important than the actual health of the public. When it does, we have lost our moral compass. Thank you. (Applause) DR. TATE: Thank you. Are there any others who had any prepared comments? Comments from the National Pork Producers Council by Liz Wagstrom, DVM Audio Associates 301/577-5882 211 DR. WAGSTROM: Hi, I am Liz Wagstrom from the National Pork Producers Council. I was late in requesting getting time for prepared comments so I appreciate the ability to come forward with these comments. The National Pork Producers Council and the pork industry has been a very staunch supporter of NARMS and have understood the value of a strong rigorous NARMS system for many years. NPPC has gone to the hill and fought for budget for NARMS through many very tough budget battles and we will continue to support and fight for budget for NARMS. We do however want to stress the importance of equality across budget for all arms of NARMS and arms of NARMS will probably be kind of a Dr. Seuss type thing you will hear me say over and over again. But we looked at the budget this morning that was presented and saw quite a bit of inequality between those different arms. Now we understand that some FoodNet support comes out of the CDC branch and there are supplies that come out of the FDA branch but what we heard in the sampling discussions throughout the day is that there is starting to be a lot of cost to try and get animal samples. And we are looking at cutting out sampling of certain products because you have to sample too many to get positive results. And so in my mind back from Epi 101, when we took classes in epidemiology, if you are looking to get prevalence Audio Associates 301/577-5882 212 data the lower the prevalence the more samples you need to take. And so to that end we would encourage that funding be shifted to look at some of those low prevalence but highly informative samples such as whole meat cuts where you might be getting very low numbers of isolates but they might have very important information about either prevalence or trends. The other thing that we were really encouraged to hear about today -- well the whole discussion today was very encouraging. It is encouraging that this process of trying to look at how to strengthen the sampling of NARMS and the frankness, openness, the discussion was very encouraging. But I thought it was really encouraging for everybody here that has talked about how do we define what the goal of NARMS sampling is. And I would challenge that if your goal is to determine what are public health outcomes of the isolates, the resistance that we find, then we need to really look at refining what it is we are sampling. We do know that with the meat sampling, you need to not only look at quantity going through a packing plant but also the form in which a meat product may be consumed by the public. So with pork and whole muscle cuts, well they may be a really low yield for the number of Salmonella isolates you will get from them, and almost no Campylobacter that you will get out of pork, those are the cuts that end up on the dinner plate, end up in a person’s refrigerator, get handled Audio Associates 301/577-5882 213 barehanded at home and have the opportunity to have a negative public health outcome. When you look at raw products such as ground pork and trim in a packing plant that will then go on to further processing which often includes a lethality step, the likelihood of isolates from those products contributing to a public health outcome is greatly diminished and will give you very little information on potential public health impacts. So while we were very encouraged to hear FSIS say that they are having trouble finding bacteria on whole muscle cuts, we would say that what you probably need to do is increase sampling rather than stop sampling. So how do you do that? You know it is real easy to look at other people’s budgets and make suggestions but it appears to me that there are dollars, there are real dollars involved with collecting samples for meat whether it is at retail or whether you are going into the packing plants. I am a little more naive about the actual samples, the dollars of what it costs to get samples from sick people. When I worked at a FoodNet site, as I understood it, sick people went to a doctor, the doctor eventually asked for a stool specimen, if you got an isolate that isolate was submitted to a FoodNet site and the cost to NARMS would be the postage to get that isolate from the FoodNet site to a laboratory and to get it characterized. So in my mind there Audio Associates 301/577-5882 214 are more dollars needed for sample collection in retail meats, on-farm and the animal samples than for the dollars that need to go into collecting the samples from outbreaks and sick people. Again like I said it is real easy for me to look at somebody else’s budget and make suggestions but that is one thought we would ask the NARMS steering committee to consider. And we will end up with just a total little change here and shift into looking at communication and interpretation. We know that NARMS suffers from what I am calling small number syndrome so that we often have a small number of isolates that we are trying to over interpret. And I think the committee did or the sampling experts here did a really good job of saying if we wanted big enough numbers of isolates, what would we have to sample? But we would challenge those branches to look at interpretation of their results. If you have small numbers, can you actually make any interpretation? And I know coming from NPPC and having the sound bites that I sometimes have to have in public talks, I have probably over-interpreted that data as well. But I really believe that until we get big enough sample sizes we really run the risk of over- interpreting that data. And then I will follow up -- or the final thing I Audio Associates 301/577-5882 215 would say is to keep encouraging the open communication we have between many of the arms of NARMS with the various stakeholders. It is encouraging to see what I think is an improved working relationship in the years I have been an outsider looking into NARMS, between the branches or arms of NARMS. And I would encourage that that communication needs to continue to be open, to be frank, and to improve. And as well we need to keep all arms of NARMS communicating with the stakeholders, either provide data or use the data. I want to applaud the improved timeliness of reports but would encourage them to become even closer to real-time. It will help us to have better data to make better decisions with. Thank you. (Applause) DR. TATE: Were there any others? (No response) DR. TATE: Okay, I think we can move on to the last bit of today and we will start with some comments from Dr. Bruce Wagner who is with APHIS. Comments from APHIS by Bruce Wagner, MS, MA, PhD DR. WAGNER: Thanks for the opportunity. I am kind of jealous of Mr. Yancy who had half a day to prepare his comments; I have had a half hour. My name is Bruce Wagner. I am the Director for the Audio Associates 301/577-5882 216 National Animal Health Monitoring Systems. We are part of USDA/APHIS veterinary services. We are located out in Ft. Collins, Colorado. We have been around for probably 21 or 22 years now and have been doing quite a bit of work along some of the lines that you all are talking about. Our primary focus is animal health although we look at the interactions of animal health with production, with environment, with product wholesomeness and that would be the food safety aspects, and animal welfare. We are probably best known for our national studies that we do on a periodic basis. It is probably about a five to six year cycle. It used to be every five years but as we have become more well known, more commodities have asked for us to do a survey so it has stretched out to more like six or seven years between studies now. We do a wide variety of different species, beef cattle, dairy, swine, sheep, equine, poultry, catfish, goats, and other things as they come along. We do the rotational basis mostly because it is resource limited. We work really closely with the National Agricultural Statistics Service and for those of you who do not know them, they are the ones who basically count the number of farms in the United States, they maintain a list frame of farms, and they are actively always updating that. Any time you have a list like that, it would be outdated the Audio Associates 301/577-5882 217 next day but they do as good a job as anybody of keeping a list. So we contract with them to sample off of their list. Typically we try to represent between 70 percent of the farms and 70 percent of the animals on those farms in our sampling. So we do not go to all 50 states for our studies but we will probably go to 20 to 24 states. Typically we will end up representing more like 80 to 90 percent of the farms in our sampling. So in doing that, in doing a stratified random sample, that we are able to make inference to the national population and I think that has kind of come a little bit here and there. But for these national studies they are statistically based, they are probability based, we use specialized software and specialized statistical processes to be able to estimate to the national population. One of the issues that has arisen is that we do these statistical -- we will go out to maybe 5000 farms and do the questionnaires and then we will go back and do a second part where we do the biological sampling. And because of resource limitations we do not necessarily go to all of those farms; we just cannot afford all of the testing and we work really closely with Paula to be able to do that. So what happens instead of taking samples on a thousand farms, we will take samples on 100 or 150 farms so in that sense we get a Audio Associates 301/577-5882 218 little bit away from our design that is so statistically based because we are having such a small subsample of our original sample and that does cause us a little bit of trouble. It would be nicer to take samples on more operations, we are already there, the veterinarians from Veterinary Services are doing the collections, we just have not been able to do that. We have been working on antibiotic use and resistance for probably 16 to 17 years now in varying degrees. We have been tracking resistance patterns with Paula for a number of years now. This last year we worked with the swine industry to try to estimate total usage; we had not done that before. Not only where it was used but how it was used so that is a new idea for us. We had looked at the different ways it had been used but never the total use. And we are trying to build that into our next study, the feedlot study, which will kick off here in August actually where we will try to estimate again total use in the industry if we can and build that into other studies as we go forward. So that is just kind of a nutshell of who we are. (Applause) Focused Discussion Moderated by Heather Tate, MS, PhD DR. TATE: So I think there have been a lot of things that have been discussed today and one of the things that we have heard over and over again is that we need to Audio Associates 301/577-5882 219 better define our mission. And I know that Pat initially you mentioned what our mission was and what we were going to move forward with in today’s objectives so I would like for you to restate that so we can kind of go from there. DR. McDERMOTT: I shall try. I think we are suffering a little bit from semantic problems but let me take another stab at it. And this is a little bit risky because I may just wade into a quagmire here but I am going to give it a shot. In my mind then, if I was listening closely enough, is that the Randy Singer’s and Morgan Scott’s and the epidemiologists say to me when I hear them speaking, what is the purpose of the program, tell me what the purpose of the program is and I will tell you how to sample it. And then I hear from the industry side and those who clearly have justified concerned about how the data might be used in a negative way against them are asking what is the purpose of the program using that in a different way. In other words, how is the data going to be used relative to policy versus what are you trying to measure relative to a sampling design. And I think that has led to some of the confusion; I could be wrong. So I am going to try if I can to speak as a bacteriologist hearing that question to try again to reframe the context and I am open to the possibility that I have not Audio Associates 301/577-5882 220 considered some things and need to rethink this in order to answer the confusion that seems to be swirling about today. (Slide) But the public health issue is how does the use of antimicrobials in food animals and animal production affect resistance among foodborne pathogens and commensals. Now I can see -- and secondarily what is the impact on public health. So that is the issue that NARMS was put together to try to answer. NARMS was put together as a post-approval monitoring system designed for human public health purposes. Okay, so that is why it is there and it is part of, as I mentioned, a multi-component process. Now I think one of the concerns that has been raised is the risk assessment part and it has been a confusing day. We have heard that really we should do more risk assessment, it should be quantitative; we shouldn’t do any risk assessment, not even the qualitative, because of the data. So there is a lot to digest today but I will come back to that in a moment. (Slide) Now one issue and I think the issue that has caused concern on one of the aisle if you will is how is it going to be used in 152; Tom mentioned that was a valid purpose for the data is in the 152 process, also to inform prudent use. So this is a sort of information gathering for action. And I Audio Associates 301/577-5882 221 think it is the “for action” part that has led some people to raise the question of the purpose. And then lastly for research purposes. So I will not satisfy a lot of people when I tell you that the reason we met today and the function we serve within CVM is to provide the data. I cannot help answer your question about how that will be used to inform policy or whether that will be used to establish policy and the regulatory side of the center does that. I know that is not a satisfactory answer but I would be speaking out of ignorance if I tried to tell you how it would be used in every case to either inform policy or make a decision on the approval of a product. So I cannot give you a better answer than that. If the question is to the epidemiologists and the statistician side, is what is the purpose of the program? The purpose of the program is to monitor trends in antibiotic resistance in bacteria derived from foods, in this case retail meats. I appreciate the comments about non-meat sources but we are not approving antibiotics in CVM for non-animal sources I don’t think. EPA has the environmental side, the pet side is a valid question but again -- and I think CVM has seriously recognized that as a valid question but that is not part of NARMS now and whether it will be in the future or not I do not know. (Slide) Audio Associates 301/577-5882 222 So to me it seems fairly clear. The data can be used for a lot of different purposes but the reason we are here, the goal of the program, is to monitor trends in antibiotic resistance. The data, like I said, how it will be used is another question and a valid question. So we look to these goals again. To monitor these trends, that means to do it in a scientifically valid way with the same methods in the different labs which we are doing with the proper quality control, all the things that are necessary for valid scientifically controlled[sic] data generation; that is the first part making sure the laboratory side is right. To provide this information so it can be used. I mean it can be used -- we heard it mentioned by the producer representatives up here that they are interested in that information so they can use that information as well. We want to do something with it whether it is to revise prudent use guidelines for example or to do something in response to something that has risen very rapidly in one commodity or another. That is a challenging issue as well and again a bit outside our purview but I think we are all interested in that as a common objective. Conduct research to better understand the emergence of resistance and spread of resistance. I do not mind telling you it has been a day of candid speech so I will be candid too. I disagree wholeheartedly with those who say we do not Audio Associates 301/577-5882 223 need the research component of NARMS. I am trying to reconcile in my mind the call for more science-based decision making with the call to stop doing research. I think the research part of it is absolutely essential. I am sure everybody would want to know that DT104 when it blew through the food animal systems, what it looked like and how it was resistant and the fact that it was a stable chromosomal element that was a part of the normal genomics of that organism and it was not directly from drug use. You would only know that from research. Or whether it was on a plasmid that was being harbored by E. coli and jumped around much more easily than these genomic islands did. You need to know that, that is part of understanding the magnitude of the problem that is before us. MRSA is another one. If somebody came and said we found MRSA in meat, do something, do something, and you did not do the research to show that these strains are not epidemiologically linked to community-acquired infections in humans, you would have made the wrong decision. I could go on and on. Morgan showed us a slide about a study at Harvard where they found all sorts of cryptic resistance genes. Somebody would say, oh my gosh this is what is coming down the pike, well maybe not; you need research to answer those questions. You need to know if they are -- I could go on. This is something I am fairly passionate about; Audio Associates 301/577-5882 224 I could go on about this all day. (Laughter) DR. McDERMOTT: You need research to supplement the monitoring program. And then the last one again, assist FDA making decisions. I can see where this might need to be reworded. Really technically what we do is we provide the data to the regulatory side of CVM; that is what we do. We do not really directly get involved in how that data is used very often, extremely rare. So perhaps that one needs to be reworded. So I think there -- it has been a complex day. We have heard a lot of interesting opinions about what we ought to do and how the goals ought to be expressed and how they affect different stakeholders and believe me I appreciate it. I think I understand the concerns that are present on this issue from the different perspectives. I am sorry I cannot give satisfactory answers to some of them. And we are probably going to go from here trying to chew on some of the contradictory advice and work through the information that we have been given but we certainly have had a lot of really good information brought to the fore today. I just want to say I really appreciate everybody who has participated and their candid comments as we discuss this really complex issue, obviously very complex issue. But just to reiterate, our goal and the goal of the Audio Associates 301/577-5882 225 program and the reason we are here to talk about sampling is directed toward a program, a scheme if you will, that will best allow us to detect changes in resistance over time in these commodities. DR. TAKE: I just wanted to say that so yes we came here wanting to give you examples or at least demonstrate to you how our sampling program is laid out whether it be retail or the animal sampling. And we have shown you how we are, at least with the --- animal sampling, how we are also considering moving on-farm, or not even considering, we actually are moving on-farm. And I think we just wanted your thoughts as to now that we have this program where we have on- farm, we have slaughter, we have retail, and of course we have the human component, is this sufficient? Is it too much? Should we just be focusing on either abattoir or on-farm? So I think we are kind of looking for something that may be a little more concrete than what we have been given which is we need to redefine our mission. So are there any suggestions or comments from any of you? DR. McEWEN: Maybe I, sitting in the back of the room, didn’t hear it quite the same way. I mean I did not hear a lot of criticisms about lack of mission or mission creep and all that sort of thing. To me it was more of a question of balancing priorities. I guess because among the goals and objectives that are listed, there are competing Audio Associates 301/577-5882 226 issues there that need to be sort of balanced and optimized. For example, the sampling and sample size and some of the issues for monitoring need to be considered in the light of how much of the resources are going for Number 3 for population-level studies to test hypotheses and better understand resistance emergence. So that was my sort of take on it. I heard Paul Sundberg ask questions about surveillance and I think to some extent some of us are using monitoring and surveillance as kind of synonyms when in fact you were using that technically correct version and that is that surveillance implies some kind of action based on the outcome. And I think NARMS is largely still a monitoring program with the exception of the Goal Number 4 and that is providing data, results I guess, to inform decision-making by the authority which seems appropriate. I had a more upbeat feel about the discussion about goals and objectives and so on; maybe that is just me. DR. TATE: Anyone else? DR. SCOTT: Yes, I guess I will second Scott’s words; I felt pretty positive about the discussions. I guess, after what you just said Heather about it is moving into on- farm sampling, monitoring, I guess if I were to stand up here and say well if you had a fixed number of dollars and you were going to take money from slaughter sampling and redirect it Audio Associates 301/577-5882 227 into on-farm, I would probably stand here and say unless you could do it more efficiently and get more for each dollar I would not do it personally. I will stand here and say that because I think you are drifting away from your public health mission if you do that. If you tell me though that this is a 1 million dollar sustained infusion or 1.1 million dollars, then I would say yes, maybe if it is mission creep or if it is an opportunity to take it back and start answering those questions that you say are there that relate to use and resistance, then presumably you are going to have to leave the slaughter plant to start addressing some of those. So maybe that is why you are getting conflicting answers is -- I mean I saw that 1.1 million dollars in an otherwise 10-year flat budget but it is not clear to me that you know you are going to keep going this way. And if you move out of slaughter when there is an infrastructure, when there are apparently samples available and not just from the Eastern Lab, and the possibility -- and yes there is sample deterioration but the possibility of examining a more sample- based, that is my bias, approach even if it still is focused on isolates in the end, personally I would stay there rather than drifting too far upstream. But if you have this infusion then maybe that is okay. DR. McDERMOTT: I might make a couple comments about Audio Associates 301/577-5882 228 that because I think Scott said right at the start of his comments that the animals are coming to you at the abattoir, you know, that is the most effective use of resources and I personally agree with that. I have always thought that going out to the farm and getting samples would be just prohibitively expensive and Paula has done those numbers too with her CAS* program. So I don’t think I said that before, but that has always been my bias. Since we are kind of wrapping up here, I guess I will reveal that now. There was a push within the agency, as many or all of you know, is how do we get antibiotic use information? We get aggregate sales data right now, it is all the authority CVM FDA has to collect that data. Then we have some individual estimates from different producer groups and they fight with the estimates from another group. And so the agency is still grappling with how do we get good use data; can NARMS get that data? And I think that is a very difficult challenge for NARMS to play a role in that process. But if we got isolates on-farm we might be able to at least get use information that went with a sub-set of isolates even though it was not a nationally representative set of strains. And so there was a push within the agency, there was a pressure there within the agency. And from my perspective, when I turn around and look at FSIS and say well okay the animals are showing up here, Audio Associates 301/577-5882 229 maybe our sample unit is the truck as I said and not the animal. Can we get samples before they have gone through all the selection -- keep I mind this is my microbiologist speaking again. These multi-drug resistant plasmids that have ceftiofur resistance and nine other resistances, have resistance to cetylpyridinium chloride on them which is a selective agent used to decontaminate carcasses. So I do not want to call those animal isolates after these carcasses have been sprayed in the abattoir. Those are not animal isolates to me anymore, those are retail meat isolates that have not been bagged and shipped. Where is the best place along this line from the expense of getting out to the farm to in-plant treatments which skew the results which we are capturing with the retail meat anyway? Where do we move in that area to make the best use of resources? I always wish we could get animals off the trucks, I mean, like I said please correct me if I am all wet here but that to me seems like the best trade-off. We cannot afford to go on-farm and be nationally representative. We may be nationally representative but in sampling trucks instead of individual animals; but we certainly are not, getting carcasses that have been treated with something that these organisms already have high-level genetic resistance to so that is how I have been thinking about it. Audio Associates 301/577-5882 230 DR. WAGSTROM: Liz Wagstrom, National Pork Producers Council. I will reveal my biases. I pretty much think the abattoir is about the worst place you can get to represent anything on-farm. I understand your thought on trucks but we have enough producers who either congregate groups of animals going on to a truck, who backhaul on trucks that may not have been washed and cleaned between who knows where else they have been. And well we have large systems, we have dedicated trucks, that is not the only sample you would get and I think you would have a really confounded picture of what you would get coming off the truck. You also have a lot more likelihood of shedding so it is going to be a higher yield sample but we also know that those stressed animals are shedding things that they may not be shedding and seen on-farm. DR. McDERMOTT: And if I could answer, I am aware of that and I agree with all of that so like I said these are always trade-offs. So that has to become part of the description of your monitoring system. An acknowledgement of what happens during transport, how it influences the data because somebody else in another country -- it was brought up harmonization of sampling; I do not see that ever happening. I mean maybe in a few lifetimes from now. I just do not see it happens because people eat different animals, they distribute things differently. So everybody has to explain what they are doing in detail. Here is exactly what we are Audio Associates 301/577-5882 231 doing, we are sampling here, here are the consequences of it, here is the trade-off, and it is almost an art form sort of to say what is the best set of trade-offs to make here but they are all trade-offs in my mind. MS. VAUGHN GROOTERS: So if we are thinking about on-farm sampling and we are thinking about ideal and we want to get at public health impacts, what about farm workers? What about people who are in those plants and people who are those farms who are contracting antibiotic resistant infections and then taking them home to their families? So I think there is ideally a place for on-farm sampling and I recognize that there are limitations to budgets but I think that the conversation should continue. DR. NICKELL: Jason Nickel, Research and Development with Bayer Animal Health. And just to try and maybe tie some of these points together. They are all very good points but we use the term on-farm in my mind, and maybe I am coming from a very ignorant perspective, but using it relatively loosely and it feels like we need to have a very defined definition of what on-farm means to be able to answer some of those questions and some of the issues that Morgan rose as well. And so across species, to be able to define what on the farm means would actually be able to begin to clarify how some of that sampling could begin to be laid out. DR. McDERMOTT: Good point, thanks Jason. Audio Associates 301/577-5882 232 DR. SHRYOCK: I will wear the AHI hat for this one. The way I am thinking about the goals up there, the trends, we talked about the sampling with retail meats as well as post- slaughter and it strikes me that, no disrespect intended here, that is almost a turn-key operation. You go out and routinely collect, culture, do your susceptibilities report, it does not involve a whole lot more than that once you get the program started. So you know I kind of look at that as kind of the core activity-base if you will that does not take a whole lot from NARMS. When it comes to the on-farm piece, following up on what Jason said, that is really unique and really complicated. It is fraught with all the issues we have heard all day long. And that is why we were thinking that separating that out from that turn-key type of approach for the rest of NARMS would make some degree of sense. To give the latitude to go and do on those sentinel sites what needs to be done to collect appropriate context information, whether that is environmental sampling, antibiotic use data, disease outcome data, the whole nine yards; that is probably going to take a heck of a lot more money and independent research that can be hooked up in some way. Sure it can still fall under a blanket of NARMS but it is different, it is different than retail meats, it is different than the CDC collections and somehow that, I think, Audio Associates 301/577-5882 233 is really the crux of the issue. How do you get that control back to the folks that can get on to the live production phase premises, get the data that is needed, and move it forward because it is not just a turn-key thing. And once you get that data, you have to analyze it; it is a little different. And then taking all those isolates, whether they come from on-farm, the retail, et cetera to do the characterizations that you were mentioning about MRSA and all the rest, sure that can be done in any number of the appropriate laboratories and that certainly is a research component but that is taking those isolates and doing something with them once you have them. So I do not know if that helps but that is kind of where we are coming from with some of the remarks that were made earlier. DR. McDERMOTT: Then maybe Tom I could ask you a question about that. So it brings up the next trade-off. So Liz mentioned the trade-offs with getting post-shipment samples. So the trade-off here is you will not probably have nationally representative data, is that trade-off worth making? DR. SHRYOCK: Well I would say let’s do another approach and that is where the NAHMS program has a very important role. Do we need to have the yearly on-farm data or can NAHMS, whether it is 5, 6, 7 years or whatever, is there Audio Associates 301/577-5882 234 an opportunity to fold that in to provide that national on- farm prevalence on a commodity basis? And if the answer to that is yes we need that, then maybe 7 years is too long; maybe it is something else. Maybe there is more priority that should be placed against that. So I do not think they are mutually exclusive, I think it is just going to take another paradigm shift. DR. McDERMOTT: Could we still address the first -- if we do that can we still monitor trends? Can we trend that data if we are sampling a commodity every 5 years or whatever? Will we really be able to say this has changed, something has changed? DR. SHRYOCK: Even though I stayed at the Holiday Inn, I am not an epidemiologist. (Laughter) DR. TATE: And then I also wanted to, before we leave, also touch on the retail sampling. We spent a lot of time talking about animal sampling but are there any suggestions on -- Emily had posed some questions earlier about adding additional organisms to -- well actually that would be to the NARMS program in general but also should we add other commodities in our retail sampling and if so which ones? And what should our selection criteria be for inclusion of additional states? Does anyone have any additional thoughts on that? Audio Associates 301/577-5882 235 (No response) DR. TATE: Okay. DR. MOLLA: Maybe one of the issues which needs to be considered by NARMS in regard to retail meat is MRSA which we discussed even though we know that the public health -- I mean the food safety implications of MRSA is not well understood. It is an important public health pathogen and would be important to investigate at the retail level and some related also food animal production systems like swine; that is what I have in mind. Thank you. DR. McDERMOTT: Well we are under no obligation to go up against any special dial on the clock so I think it has been a pretty long grueling day and if everybody is satisfied with what we have tried to accomplish, we can adjourn. I think we have a lot to chew on, no pun intended, and a lot of really -- I really appreciate all the thoughtful comments. I think people are really earnest about what we are trying to accomplish here and I appreciate everybody’s candor and as I said contribution. I expect we will be following up with another meeting in the not too distant future. Tom, comments on the Strategic Plan, we will make those available. I do not see any problem with that. And we will get to work on revising it based on the comments we have gotten and including comments from this meeting. Do not forget that you have 30 days after Audio Associates 301/577-5882 236 today to go ahead and add comments to the docket on this meeting. We will read and consider them all of course and we will keep working away. I mean we would like to realize some improvement to the program before 2012’s testing year is up; that would be a nice goal to have so that is one of our goals. And having your contributions to the discussion is going to help us meet that goal so thank you everybody very much and safe travels. (Where upon the meeting was adjourned at 4:08 p.m.) Audio Associates 301/577-5882
"IN THE CIRCUIT COURT FOR ANNE ARUNDEL COUNTY "