DR. VOGEL: For the first issue, is the current sampling process by FSIS adequate and effective for Salmonella surveillance? Well, first I need to start -- I don’t know that I can answer that question without knowing what the objective of the sampling of the FSIS sampling is.

So I will start there. So, without knowing what the specific objective is, I cannot judge whether it is adequate and effective. Now, if the objective is to determine changes over time in the percent resistant of Salmonella isolated for slaughter and processing, well, then I think the sampling process is currently adequate to do that.

As explained, it is not a national representative sample, so we cannot make predictions of what the percent resistance is in slaughter samples. But, we can examine what the changes are over time. You know, we can look at trend data.

I do have a caveat. I am not sure whether the numbers are currently adequate to do everything that we want to do with those Salmonella slaughter isolates. If we want to quickly identify emergence of infection of resistance, well, then I am not sure if the numbers are adequate to be able to identify that quickly. Especially, if we are looking at rare serotypes and strains of those serotypes.

If the objective of this surveillance is to help FDA regulate on-farm drug usage through the approval, disapproval, or withdrawal of drugs, then this system is not adequate. And it is not effective. What we need is an on-farm surveillance system that can record resistance on-farm in Salmonella and tie that with the epidemiological data, such as drug usage on those farms. So in that aspect, I guess I would be supportive of a program such as the CAHFSE, the Collaboration for Animal Health, Food Safety, and Epidemiology. An expansion of that program, if the objective of NARMS is to help FDA regulate drug usage.

That is it. Thank you.

DR. YOUNGMAN: Well, if I can press on that point. You have spoken in favor of on-farm sampling and also trying to monitor drug usage.

DR. VOGEL: Right.

DR. YOUNGMAN: Do you have a proposal for how to go about that?

DR. VOGEL: I mentioned CAHFSE, Collaboration for Animal Health, Food Safety, and Epidemiology. And as I understand, that program will do that. It will take samples on-farm, it will follow those samples to the slaughter plant to determine if there is a change in serotypes, as well as resistance, between the farm and the slaughter plant and the processing plants. And the intent is also to record what drugs are used on those farms.

DR. YOUNGMAN: Just if I can press on that further, one of the things we have really been trying to achieve in NARMS is to be able to look at temporal trends. And, possibly, even further to detect problems where they are, year-by-year. One of the concerns if we use the CAHFSE structure is that -- as my understanding about that is -- is that one particular species wouldn’t be gone back to until five years’ time.

DR. VOGEL: No.

DR. YOUNGMAN: So you wouldn’t really be able to look easily at temporal trends.

DR. VOGEL: No, I think you are thinking of NAHMS, the National Animal Health Monitoring System, which does surveys on a five-year basis. CAHFSEs would be a yearly project.

DR. YOUNGMAN: Okay. Did you want to speak to the sampling for campylobacter? That was a part of the first question.

DR. VOGEL: Okay, are these samples adequate and effective for campylobacter? Well, I think some of the same comments I made for Salmonella apply here. You know, what is the objective for sampling for campylobacter. If it is to examine trends, changes over time, it is probably adequate. If we are looking at trends of resistant campylobacter from poultry rinsates since 2001. If the objective is to look at all campylobacter, well then no, it is not adequate. We need to get sampling from other products, such as pork. Do you want me to go on with the others then?

DR. YOUNGMAN: Sure.

DR. VOGEL: What other pathogens should or should not be isolated in susceptibility tested from the poultry rinsates? I don’t see any additional that need to be added. If we come down to prioritization and need to start cutting testing, I would suggest looking at testing of cutting Enterococci testing. I am not convinced that that has given us a lot of useful information about human illness related to resistant Enterococci. And, I guess, I would also maybe just do minimal E. coli testing from those rinsates.

DR. YOUNGMAN: Okay. Are there things you think we should stop doing in addition to those?

DR. VOGEL: No.

DR. YOUNGMAN: Okay. Thank you very much. Can I go to Awa next.

DR. AIDARA-KANE: Yes, thank you. For the first part of the question, I think that, although not adequate to estimate national surveillance, the sampling can provide descriptive data on trends over time of antimicrobial susceptibility for Salmonella. And I think that it would be useful to monitor antimicrobial use at farm level. Can you hear me at the back?

DR. YOUNGMAN: If you move the microphone maybe a little.

MS. : If you speak into the mics and a little louder, that would be great for us in the back. Thank you.

DR. AIDARA-KANE: Okay. So I think that the sampling process is not adequate for effective Salmonella samples, but it can give an idea of trends over time on antimicrobial susceptibility testing. It would be also useful to monitor use of antimicrobials at farm level and try to link antimicrobial resistance to antimicrobial use.

I think that there is selection bias, because the plants that do not meet the regulatory performance standards can be over represented. So I think that this can lead to a bias. And the fact that there are more frequent sampling during the first six months of the year can also lead to a bias on representativeness all over.

Concerning campylobacter, I think that campylobacter are fragile organisms and the fact that the isolation is delayed and the samples are delayed, may lower the number of positive samples. But still, it can give an idea of antimicrobial resistant campylobacter.

Concerning other bacteria of interest, I think that if we have to add one bacteria, it should be E. coli as indicator micro-organism. And I don’t think that testing Enterococcis is of interest.

If less funding is available, I think that one way to lower the cost should be to avoid taking multiple samples from the same source. That is all.

DR. YOUNGMAN: Thank you very much. We appreciate your comments. Thank you. Scott.

DR. MCEWEN: Well, thanks very much and I appreciate being asked to come and comment. I always find this very informative and enjoyable. When I was preparing my comments, there was a number of issues that cut across and all the questions are maybe sort of broader than the questions. So I have got some notes on that and ask you if you want those --

DR. YOUNGMAN: Maybe after we address each specific question, we can open it for more general comments. Would that be okay?

DR. MCEWEN: Yes, as long as we have time for that.

DR. YOUNGMAN: Okay.

DR. MCEWEN: With respect to the first question, I agree with what previous panel members have said. So it all depends on what the objective is, I guess. I also didn’t see, and would encourage you to undertake a formal revisit of the design issues and undertake a specific design; including sample size estimates in order to see whether the available samples -- how they fit with -- how you would design a program to fulfill the objectives.

Based on what we heard in the short time there has been to sort of look at it, it seems to me that the baseline samples are probably most ideally suited to identifying prevalence in slaughter animals. I think with respect to information from the other isolates, I would like to see some epidemiologists and statisticians turned loose to identify how some verification samples can be used in a meaningful way. I have got some of the same concerns that were raised yesterday and today about their representativeness. And inferences that can be drawn from those.

We will be talking later about budget, but I guess in the face of at least short-term budget issues, you kind of have to work with other partners and leverage other efforts. But I think you can try to do that in a sort of more meaningful way; perhaps, by sampling some of the available isolates in a more strategic fashion.

With respect to other pathogens, I think it is important to prioritize. Dr. Sundlof said, and for that, the major foodborne pathogens are top priority, and Salmonella and campylobacter, obviously. But I, certainly, wouldn’t want to see the commensals cut from the program. I think we could maybe be strategic and --

DR. YOUNGMAN: The Enterococcus and E. coli.

DR. MCEWEN: As representatives of gram negative, gram positive populations that -- Enterococcis has been sort of walking the line between a pathogen and an indicator species, and so we have heard a bit about its role in both camps. But, I think, it is important to have a representative species for sort of both major groups. And I am not sure that we need to have thousands of isolates, but at least a bit more strategic there.

And whether they come from poultry rinsates or whatever source, whatever works out the best, but I agree that we need other species represented there as well.

In terms of the concerns about campylobacter isolation from the rinsates, I guess there is an issue of survival, and then that affects prevalence, so we have to be careful about making -- but unless it results in a differential loss based on resistance, I think we can still make inferences about prevalence of resistance among cultured organisms. Maybe not prevalence of resistance at the carcass level if there is going to be loss of campylobacter.

What should we stop doing? I guess I have kind of addressed that in terms of being more strategic in sampling. With respect to identifying other areas that need to be sampled, such as farm, and so on, I think I will leave that for the funding issue, because I think it is tied in with that.

DR. YOUNGMAN: Okay. Thank you very much. Thank you. Marissa.

DR. MILLER: Thank you for the invitation to be here. It has been very gratifying to see how this program has grown and matured in all the different areas now. You know, you are conquering the world, and I like that concept.

I just have a few thoughts. I am kind of echoing what Dr. Vogel and McEwen have already touched on, that I think you do need to go back and re-evaluate the original mission goals and objectives, along with your stakeholders. Because there may have been a bit of a mission creep in what has gone on over the years.

And, I guess, to start with the animal, the FSIS sampling for Salmonella and other pathogens, I really think at this stage of the game, what is needed is more than descriptive data; which was in the original kind of mission statement. I think that I would strongly encourage the agencies collaborating here to move towards a nationally representative sample of slaughter isolates, if at all possible.

Not to say what has been done in the past hasn’t been useful, it has. But I think you are bumping up to a point where if you want to use these data in making policy, being able to go forward into litigation and other areas, and be able to say what the data represent, they need to be based on a nationally representative sample.

And Sean suggested in something he said, and I don’t know if this is just a thought or in the plans or not, that FSIS may move back to the baseline sampling strategy. Kind of pre-HACCP, which was a nationally representative sampling scheme.

If that is possible, that would be wonderful. I think that there are other options if you had some good statisticians working with you to look at the type “A” facility sampling and how to do that. You could probably get there as well from that direction. And as I said, I think this is a critical element at this time.

Now, that having been said, I also have some concerns about possible overlap between what the data will be telling you from the slaughter samples and the retail meat arm. So I think that what you should do in the near future is do a side-by-side comparison of those data and that information and see, actually, the nuances and what is most useful for the missions of the different agencies.

In case the slaughter isolates are actually telling you what you are already seeing in the retail. That may or may not be true, I don’t know, and there needs to be some studies looking at that.

I think that what Dr. Vogel was saying about the following from the farm, including the drug use into the slaughter facilities is extremely elegant.

And I don’t know if that would be tied into the surveillance system, or that would be an off-shoot study that could be done, or done on an ongoing basis. But that is very compelling and would answer some of the really basic questions we have been asking for so long about causality.

Let’s see, I have rambled now for awhile. As far as campylobacter, I think more thought is needed here, from what I have heard. Because of the issues related to losing the very sensitive organisms. And I pose a question, I don’t know the answer, but could sampling earlier in the slaughter process be more productive as far as getting a more reasonable estimate of the prevalence of campylobacter?

And also, on the other side, are the retail meat samples actually giving you more information, or more useful information? So, just some questions to consider as you move forward in that area.

There weren’t any other pathogens that I could think of that need to be looked at at this time. I think you have a very comprehensive spectrum. I guess I would agree with the other presenter, or the comments made, that if you want to focus down, the commensals are less relevant if you have to make cuts, then the pathogens. And I guess I will stop there.

DR. YOUNGMAN: Okay, thank you very much. Sue.

DR. KOTARSKI: Yes, I want to first say thank you for inviting me here and I just want to say I am just so impressed with all the information you have collected over these many years and the expertise that you have accumulated. It is an honor for me to be here and I feel like you should be telling me about the answers to these questions, quite frankly. I think you can do a great job on that.

But, since I am asked, I would like to echo, actually, many of the sentiments that have already been expressed by the panel members. The first question I would have is, in response to the question, is the current sampling process by FSIS adequate and effective for Salmonella surveillance? Again, surveillance of what and what is the objective of the surveillance program.

There can be many surveillance objectives. One, to understand the temporal trends on a national basis. A second can be a surveillance system constructed with emphasis to provide an early warning program of resistance emergence. It can be set up as a portion of a program in risk assessment and in support of our Guidance 152 platform within that framework, within that framework, for our drug approval process.

And I am sure that members of the group, as well as this panel, can provide other objectives as well.

So given that, it is difficult to answer the question. The system is it is designed to obtain Salmonella from the HACCP Program includes the A and B and C sets. I do question, based on the presentations yesterday as to whether or not the B set and the C set are needed in terms of providing national representation because of the bias.

Or, if you are going to consider continuing to provide resistance information about B and C set, please provide the public information about that bias, and to the extent to which it is a component of that data-set that you are providing. It helps everyone as you provide this public data to understand that bias and to go forward.

With regard to the campylobacter, is that adequate and effective? Yesterday’s comments about the implications of isolating campylobacter from the rinsate materials brought questions to my mind as to what biases that actually introduced if that is significant for the purposes of resistance monitoring. How does that bias the campylobacter set that we do obtain as to the percentage resistance?

I would ask the group to consider that bias, and if they do identify a bias, then to provide that in the information that they provide in their published documents, in the commentary.

What other pathogens should or should not be isolated in susceptibility tested from the poultry rinsates? I would like to comment on the E. coli and the Enterococcus, only from the interest of focus. My understanding is is that by the time we get through the six questions, we will say what should we emphasize and what shouldn’t we emphasize.

My understanding is is that the E. coli and Enterococcus isolates are a component of the program, or future program, as a sentinel indicator of resistance emergence. If that is the case, I would like to know the database we have, or the database we intend to generate to allow us to say, yes, by monitoring E. coli in these isolates, we are predicting the likelihood of certain types of resistance plasmas, or whatever.

In other words, there is a lot of resources expended in getting those isolates, and if you are going to go for that for the purposes of sentinel, try to generate that database to help you decide that, in fact, you will be meeting objectives of having sentinel organisms on resistance emergence.

Or, possibly, just focus on your campylobacter and Salmonella. Take resources, expend them on understanding -- getting more campylobacter and more Salmonella isolates so you can fulfill your primary goals if, indeed, that is what they are.

If additional sampling is suggested, please consider what we should stop doing on NARMS, since no additional funding is available. I wouldn’t suggest to do additional sampling, per se, but I wanted to emphasize that as we look at the slaughter isolates, if we are going to use that as an indicator of healthy foods, from my standpoint, it seems that the slaughter isolates represent contamination of Salmonella and/or campylobacter due to the animal as it came into the plant.

It also represents that contamination that occurred as a result of commingling of the animals before they entered the plant, the contamination that occurred at the truck, the contamination that occurs at the slaughter plant.

So, as a representation of resistances occurring on-farm, it provides the information collectively about the contamination. So I don’t know, it is an indirect indicator of resistance that occurs on-farm. And if we look within the nom-sampling for a particular year, for a particular commodity, versus what we see for resistance in the slaughter plants for that same commodity, I am not sure that we would see the same numbers.

And I would ask the group to think in terms of making those comparisons between a broad national base where you have resistance information on-farm, versus what you see in the HACCP Program; particularly, just the A sets and say, are they the same, are they representative, do I have the information to go forward and say this is what I have for resistance on-farm. Does it adequately represent, or is it predictive, of what is on-farm. If the answer is no, or you need information to address that, then try to find out if you can do that. I guess I have said enough.

DR. YOUNGMAN: Okay. Thank you very much. All right, Sean.

DR. ALTEKRUSE: I just wanted to thank you for the conference, it really shows how far things have come in the last 10 years. I think that everything that has been done, and that was talked about, has been worthwhile. It is just we are in a slightly different environment now.

I am confident that after we go through this particular cycle, the program will be stronger. And, in fact, it is kind of useful to assess where we are with what we know now. And, you know, adapt accordingly.

In terms of is the current sampling process for the FSIS isolates adequate and effective, that sounds like a yes/no type of questions. But really, there are a variety of issues there. First of all, those are regulatory isolates and, therefore, they are of a lot value to FSIS.

Secondly, we are at a crossroads in terms of how we are doing our HACCP verification testing. And, in the past, it wasn’t an absolutely perfect representative sample, but it was pretty good. And I think it worked. But, as we move towards risk-based verification, we are going to be sampling more frequently in establishments where we think there is evidence of Salmonella problem. And it will become less representative.

So, it may be worthwhile considering adding a carefully designed, nationally representative sample of slaughter isolates to this activity. So if I can jump ahead to if additional sampling is recommended, what should be done since no additional funding is available, perhaps, this could be done as part of CAHFSE. So, additional funding could be identified for this purpose.

And, secondly, if we really are forced to cut, I might suggest that the emphasis be placed on serotypes that appear to cause human illness. Because I think the objective of NARMS is related to human illness, and we are not so interested in serotypes that occur with a high frequency in veterinary isolates, but aren’t particularly common in people. Just a thought there.

In terms of are the samples adequate for campylobacter, Dr. Walker mentioned yesterday -- or, he had some question about the 24-hour shipment at four degrees Celsius, and whether we were getting survival -- or, perhaps, some viable, but non-culturable campylobacter as a consequence of that. And I think that could be addressed very easily by taking rinses and doing same-day plating and 24-hour plating to see if there is a substantial difference in counts, or in prevalence.

In fact, my guess is the answer is likely to be no. I think that the coccoid state for campylobacter starts to come into effect at about 48 hours. But there is an inherent issue with campylobacter that will be difficult to address, and that is injured cells and detecting of them.

What pathogens should also be considered? Dr. White presented some data about campylobacter coli yesterday, showing macrolide resistance. And campylobacter coli isn’t found with high frequency in poultry isolates, to the best of my awareness. So my question is, what would be the reservoir of that in people? That type of infection? Two possibilities are turkey and pork.

Now, the ground turkey isolate, the ground turkey samples at retail are not, particularly, ideal for campylobacter because they have been through the grinder, literally. And you don’t find very high rates of campylobacter in those samples. So, I don’t know, perhaps, some of our turkey sponge samples could be added to this activity and, perhaps, some swine samples as well, just to see if we are finding C. coli. and if they are macrolide resistant. It is just a thought.

In terms of the baseline concept, I think in this sampling for other pathogens, maybe that would be a good time to do a little pilot study beforehand to see if there are differences in prevalence and enumeration, depending on the media and the atmospheres that are used. And that might be done before FSIS starts its 2006 Campy baseline. Sometime in the next budget year. I think that is all I have got. Thanks.

DR. YOUNGMAN: Okay. Thank you very much for your comments.