Sunday, May 1, 2016

Center for Biologics Evaluation and Research 25th Meeting of: The Transmissible Spongiform Encephalopathies Advisory Committee June 1, 2015 Transcript

FOOD AND DRUG ADMINISTRATION

 

Center for Biologics Evaluation and Research 25th Meeting of: The Transmissible Spongiform Encephalopathies Advisory Committee June 1, 2015 Transcript

 

FDA White Oak Conference Center Building 31, Great Room 10903 New Hampshire Ave. Silver Spring, MD 20993

 

This transcript has not been edited or corrected, but appears as received from the commercial transcribing service. Accordingly, the Food and Drug Administration makes no representation as to its accuracy.

 

snip...

 

Thank you very much.

 

DR. DETWILER: Are there any other members of our public who would like to make a comment?

 

Seeing none, I'll close the public session of the meeting. Thank you very much.

 

Agenda Item: Open Committee Discussion

 

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Now we will proceed to the questions. So this is open to the committee. So the first that the FDA has asked us to consider, please comment on and suggest any modifications to the structure of FDA's vCJD geographic risk assessment model for estimating the contribution of transfusion-transmitted vCJD risk from donors exposed for various periods in different countries.

 

Do we have anyone that wants to make suggestions to the FDA on the model?

 

DR. PRIOLA: I have one question about atypical BSE. I should remember this, but I don't. So this occurs in cattle that are 11 years or older, right, in general. Those cattle don't enter the food chain; is that correct, animals that old?

 

DR. DETWILER: Absolutely. They would go in more on a lean beef type and not your steaks, but it would be more in a ground beef, the older animals.

 

DR. PRIOLA: Okay, that's what I thought. So in considering the model, atypical BSE didn't come up, and I was assuming that's partly because it's considered a sporadic form of BSE and then would be probably consistent across cattle herds in the United States. I mean, did atypical BSE ever enter the discussion when you were modeling import and export numbers for BSE from the UK or other countries? That would be a question for the FDA.

 

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The issue is about atypical BSE and whether that was considered in your risk model.

 

DR. YANG: We did not consider the age. We don't have that kind of information by age of the cattle, no. We don't capture that.

 

DR. PRIOLA: So do you think with some of your other parameters you said that like if the export/import numbers weren't accurate, you assumed that that would have a small impact on your model. Are you also assuming that atypical BSE even though you don't have the numbers, even if you did, that would have a small impact on your model? You can guess. It's okay.

 

DR. YANG: We think it is small, because atypical is much less.

 

DR. ASHER: The issue of atypical BSE and how it arises has not only not been addressed in this particular risk assessment, but it has not been incorporated into the thinking of this at all, and as I mentioned in the introduction this morning, I believe that a precautionary public health policy would be that atypical BSE has to be considered no less dangerous than the other form of BSE, because it is transmissible to animals. Furthermore, and this represents my own thinking, I am not persuaded that we have enough data to conclude that either atypical BSE or sporadic CJD is spontaneously generated and is not an

 

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environmentally-acquired infection.

 

DR. DETWILER: Thank you very much. If you could stay up there, I have another -- can you go over again what inputs were used and where the data came from on the BSE risk to the countries? Again, I know you said Eurostat, but then tell me the difference, because I think that can be significant. The more I was thinking about when different regulations and different movements were into play on that assumption. So can you go over again meat, cattle, where you got the data from cattle and were they combined?

 

DR. YANG: So in our model we include mainly two sources of data. One is reported BSE. So that will represent BSE exposure from domestic beef, and then we also include another source of the data is UK beef. So UK -- so mainly it's these two sources of data, which in our risk assessment we also initially we also consider the meat and bone meal importation from the UK, but we look at the data. We cannot find a direct correlation between the amount of meat, bone meal, and BSE cases, and the model is quite complicated. So at the point we feel like we are not able to use that data to incorporate into the model.

 

DR. DETWILER: So then given that I have a couple of suggestions for the model in that the beef -- and I think you said you had to extrapolate, because you only had Eurostat data up until like 1987, correct? Be careful in

 

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the extrapolations, because the minute the UK reported BSE, countries started to put -- you assumed that it would be the same, but it could have been more, because countries when the UK reported BSE, countries started putting regulations on. So it could have been less actually coming forward, because countries put restrictions on, and then there was a lot of movement within third countries as price dropped. So that's a lot of times economic impact. So if a country puts a regulation on and the price of that product drops because, say, they don't have as much of a market for it, some countries will import that less, that product, but then it will move around more because the price is cheap. When the countries put regulations on what was before actually could have been more, because you start to have regulations on. So I would look at that again and on your assumption that it would have been about the same. That's one. And you keep saying beef, but when we asked the question you said about live cattle. Was that the same thing? You used the numbers. Before and after Eurostat or were live cattle not, because I didn't see anything where it says in your written presentation live cattle.

 

DR. YANG: So actually we check later after the meeting, actually this morning we said we include live cattle, but it's not correct. Actually we did not include

 

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the live cattle, but the live cattle, we look at the data of the live cattle; the number of importation of the live cattle is a very, very small, so compared to the UK beef, so at that time we did not.

 

DR. DETWILER: But live cattle -- again I would suggest at least looking back again, live cattle are going to go with all the high risk tissues coming in, and there was likely countries as the UK's numbers started to climb, countries were putting declines on. So if you looked at the numbers that were after a certain date, they would seem less, but those and prior to in the 1980s would have been more, because there was lack of regulations, and with the live cattle, they would have been increasing dose. So I'm not sure that that would maybe be insignificant. I would think it may be more significant than you think.

 

DR. YANG: At that time we think live cattle is a little bit different from UK, from beef, because beef basically is consumption, human consumption. So live cattle, we don't really understand how they used this live cattle. Are they using it for human consumption, or they use it for other purpose like for breeding or something. So we really have a difficulty to modeling that part. So that is quite complicated, similar to the meat and bone meal. We have the data, but the data is very complicated situation, because you involve in the amplifier of those infectivity

 

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where you have those meat bone meal import into the domestic. So of the different countries.

 

DR. DETWILER: But the live cattle, even if they are for breeding, eventually they get culled into the food chain. So they are either going to go in young for your real good cuts or, in most countries, if they are old or for breeding, then they are going to go in and they will even be more of a risk because --

 

Did you have, Dr. Belay?

 

DR. BELAY: I am just going to echo what you said. If you look at the BSE outbreak in Canada and if you really sat down and analyze it, they can trace it back to live cattle that were imported from the United Kingdom, and that later amplified the outbreak in Canada. So that's not insignificant. It's basically --

 

DR. FORSHEE: This is Rich Forshee. I think that is a good comment, and we will evaluate that after this meeting. If the cattle -- some of that risk could get caught in the BSE risk I believe in the country, but it wouldn't capture the risk of the animals that were slaughtered younger for the steaks.

 

DR. SAFAR: I think that this is going to the table which you presented already in your review, that the mode of prediction compared with the attributed variant CJD cases, because in the UK, Ireland, and France, it fits

 

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basically the prediction, the attributed cases fits the prediction, but if you go down, Spain is a four- or fivefold difference. So that would go to the core of what Linda was trying to sort out, that there are those discrepancies in reporting the beef and cattle positive for BSE.

 

Second source of, I think, the discrepancy could be the way how different countries are providing surveillance for variant CJD. So the reported cases may be reflecting not all the cases which are actually in that country. The surveillance systems differ significantly, even within Europe.

 

So the issue here is that how many cases actually are in reality in those countries, not those which are reported, but how many are in reality? This issue will become more and more significant outside the UK. The UK has very designed the system for surveillance of variant CJD. The farther you go to the countries with lower frequency, the diagnostic precision is becoming lower and lower. We have seen in the case number 4 reported in the morning by Larry, and you saw how difficult it was to actually diagnose it, and without autopsy, it would probably remain very difficult to clearly diagnose it as a variant CJD.

 

We have recovered about 70 percent of CJD in the United States for autopsy; 30 percent is not autopsied, and

 

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the autopsy rate outside our system, our surveillance system, is even lower. So my question is if you would take in account the autopsy rates and increase the frequency of variant CJD in those different countries based on the autopsy rates in those countries and the possible higher numbers of variant CJD, how would it impact the model predictions?

 

DR. HUANG: Can you just briefly repeat your questions in just a couple sentences?

 

DR. SAFAR: The question is very simple. You took the reported cases, which were reported by the public health institutions in different countries. What would happen if you increased those numbers in different countries in Europe, let's say by 30, 50, 60 percent?

 

DR. HUANG: You mean by BSE or vCJD?

 

DR. SAFAR: Variant CJD.

 

DR. HUANG: So based on the -- you mean, the data about vCJD cases, it's maybe underreported?

 

DR. SAFAR: Yes.

 

DR. HUANG: For some European country. Okay, so basically when we do a BSE exposure model, so one of the purpose, as Paul mentioned earlier this morning, is that you also vary the -- if the vCJD case report is actually correct or accurate, so actually based on our analysis for those country, based on the BSE exposure, beef importation,

 

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and the domestic BSE cases and our predictions for those countries, their case rate should be less. I mean, their case reports should be under one case, which is just consistent with what we have seen in those countries. So we believe that the cases may not be significantly underreported based on this BSE model, but of course there is uncertainty associated with this model, but at least from what we validated here I would believe that probably would not be very significant.

 

DR. YANG: Internally, when we do the risk assessment for those countries with reported vCJD, we also check using the case rate imputed based on BSE information. So we actually use these two different case rates to calculate the risk of contribution. So for those three countries, are quite very consistent.

 

DR. SAFAR: I think that I already quoted Spain where it is entirely inconsistent. Your prediction differs from the reality fivefold.

 

DR. ANDERSON: I think one thing we could look at -- I think what the question is could we correlate the autopsy rate in European countries to actually get a better estimate of the vCJD risk. We could do that. Again, it would be -- again, how good can those cases be acquired through that process? So we would have to figure out -- so we would have to use that rate, but then what's the capture

 

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rate of vCJD cases through autopsy, too, is another factor.

 

DR. SAFAR: It will be kind of evaluating the worst-case scenario. That's effectively what I think we should answer.

 

DR. ANDERSON: So can I answer a couple of other questions? So one of the issues about meat and bone meal is we had problems with the model, because we couldn't capture the exact fraction of that meat and bone meal that's imported into a country that actually goes into cattle feed, because it goes into a variety of other different uses, too. So other types of feed, gardening purposes, and so on and so forth.

 

The other thing about live animals going into a country is that I come from -- I also was at the Department of Agriculture. You have to have actually a fairly advanced processing system. So you also have to have a rendering system for the animals for the amplification to occur. If it goes into countries that don't have that type of system, animals either get buried or they get thrown into a pit for other animals to eat. So that's another thing to consider. And the well-developed countries usually do have rendering systems.

 

DR. DETWILER: But, Dr. Anderson, my thing with the live animals wasn't the animal exposure and the amplification. Mine was the direct exposure. You're

 

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bringing not the meat in, but you're bringing the cattle in that eventually are going to go for human consumption, and they are coming in with the SRMs and those countries may have no SRM bans, unlike the country of origin, and I think that's where you --

 

DR. ANDERSON: You are correct on that point. So we didn't consider that in the model.

 

DR. FORSHEE: I just want to respond again to the question about differential surveillance practices. You are right that that is a potential issue in the model. We will do some additional sensitivity analyses after this, but I do want to come back to the point about the underestimate for Spain. We recognize that there are -- it's going to be difficult to get a perfect model for this, and that's one of the reasons that for all of the countries where we had attributed cases we viewed those attributed cases as the best measure for the risk in that case, and we were using the model precisely to get at countries where there hadn't been reported cases but where we thought that there was still risk in those cases. We didn't want to set a risk of zero in those countries that didn't have reported cases, and that's why we were trying to use the model, but where we had cases, we used that in most -- in many of the examples, that was a higher risk than we would have gotten from simply using the

 

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model. But you are correct that there were countries where there was a differential rate of reporting. It could have some impact on our model results, and we will do some additional sensitivity analysis on that.

 

DR. SCHONBERGER: Dr. Detwiler, I was going to confirm what I think you were saying about the importance of the live bovine, and I think the epidemiological evidence for that is that delay in the peak in France versus the peak in the UK. Remember, in my talk I just said that in late 1989 the UK established the SBO ban. That SBO ban wasn't established in France. If it had just been the meat, theoretically they should have had the same peak, but they also shipped considerable amounts of live bovine and what you were postulating is maybe they then later slaughtered those animals without the type of protection that was in the UK and that led to a delay in the peak of the epidemic curve. So I just wanted to bring that point out.

 

DR. DETWILER: Thank you. I think it was Dr. Jackson then on this side.

 

DR. JACKSON: In terms of the model for estimating the contribution of transfusion-transmitted CJD risk from donors exposed in these various countries, I mean, it doesn't -- you know, something is wrong here, because obviously if we heard the UK data, as I mentioned before,

 

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of seven consecutive years, millions of donors, no transmission, and so something is wrong here with either the assumptions regarding infectivity or the threshold for when you have a certain exposure time or period in which you will develop it or you won't, but calculating all these reduction of risk, I mean a 90 percent reduction of zero transmission is still zero. It is hard to see the relevance of the model for this particular estimating this contribution of transfusion-transmitted risk here.

 

You know, in the UK we are talking about millions of donor years of exposure to this potentially contaminated beef or whatever, and if we were to let some of those donors, which would be a small percentage of our blood donor population, I would think the risk would be almost nothing, in addition, since they are not seeing anything at this point. So something is wrong with this model. Just it's not -- it doesn't seem relevant to predicting the risk or reduction of risk in terms of transfusion transmission of CJD.

 

DR. FORSHEE: Thank you very much for those comments. In our model, we were looking at the relative contribution of risk from all of the countries in order to try to come up with a consistent approach for what travel and immigrant deferrals to include. We were not evaluating in this model what the absolute level of risk was. We have

 

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other work where we have tried to evaluate that, and that is very sensitive to which study for the prevalence you use. So for the purpose of this model, we wanted something that was going to help us to focus any donor deferrals that we keep in place that they would be focused on the countries that had the greatest risk for potentially contributing to transfusion-transmitted vCJD cases in the United States.

 

The committee is certainly free to comment on what level of risk management we should follow, and I see Dr. Epstein has some comments.

 

DR. EPSTEIN: Thank you, Madam Chairman. So I think one point that is being overlooked is the issue of latency in tissue. You know, what we have heard from Robert Will and has been published is an estimate of 1 in 2,000 persons in the UK may harbor the infectious prion in tissue, and if that's true, and of course it requires confirmation, the specificity of those analyses, but we believe it's true, then the same should be true of immigrants and travelers who are exposed either in the UK or in other higher risk settings who may also harbor the prion in tissue, and what we are really protecting against is the risk that there might be blood infectivity in such persons and/or the possibility that there might be later waves of disease progression associated with higher levels

 

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of infectivity in the blood.

 

So the fact that we are not seeing current cases is not completely comforting in terms of safety of the blood supply, because there is the underlying concern of risk from latency, and I think that's what drives this, because after all, if the argument is, well, there's no delayed infection, disease, or infectivity in persons who were previously exposed, then you would just say, well, the primary epidemic is virtually over, but what about the fact of tissue latency, and we have a completely unanswered question whether there is infectivity in the blood of individuals who are latently infected, and if there is, the likelihood is that it's low-level exposure that might be associated with very long incubation periods, and we know in other prion diseases, particularly the transmissions from human pituitary-derived growth hormone and also from kuru, that the latency periods could be many decades. I think it was, what, 36 years in the longest case from -- 38.5 years, okay, and up to 50 years in kuru. So that's the reason that we think we need to continue deferrals based on geographic exposure. We have no way to tell who is infected, and the presumption is that there are latent infections in exposed people.

 

DR. JACKSON: If there were latent infection, I mean, wouldn't you think we would at least see one case in

 

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seven years? I mean, if that were the case, I would just --

 

DR. EPSTEIN: I can't answer that question. I don't think -- maybe Dr. Safar can answer that question.

 

PARTICIPANT: And I will speak for the animals, but go ahead, Dr. Safar.

 

DR. SAFAR: I totally concur with Jay Epstein, because I think that our sense of virulence is not really good reason for making decision against it, and the issue here is the fact that we know that subclinical carrier like prion diseases exist. They do exist in animals. There are many experiments like that. We know that the primary target of BSE prions or variant CJD prions is the lymphoreticular(?) system, and even though the infectivity in blood is definitely low, that may translate in very extended incubation time, and the latest reported in kuru is 58 years.

 

But there is a second issue, and that is that many of those carriers may become organ donors and they may become tissue donors, and we know that some tissues which very often are linked to the lymphoreticular system are infectious. So that would generate a secondary problem, and I understand exactly your point. I mean, this is all still hypothetical, but we don't really have evidence now to make a decision for a clearly specified policy which would accept this kind of risk.

 

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DR. DETWILER: I'll just give you an example from the animal world. You said in 7 years would you see it. So we know in North America our exposure to BSE agent from Europe probably ended in 1991 when Canada -- we shut the door in 1989 in the United States, but Canada was a little bit later, and we had infectivity then circulating all along, and each generation of cattle we had it there. We didn't find it until 2003. For 10 years we found no infection, and that's not without looking.

 

Now you can say, well, but we had a systematic way to look at the cattle in both countries and still didn't find the disease for a whole decade. So I think you can miss it on a disease that's not really common on there, but even though it's cycling on there.

 

DR. ROOS: So, Linda, you raised the possibility of concern about live cattle, and are there data involved in the numbers of live cattle to these different European countries?

 

DR. DETWILER: Yeah, there are data. The best would be the European Union did these geographic BSE risk assessments of at least all their members, anybody that submitted. They had a lot of good numbers, and they tried to crosscheck with import the export data from the UK and the import data on there. So that would be another kind of source of information if you can get -- they were all

 

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public on the -- I'm not sure if they are still online, but they were online.

 

DR. LEVIYANG: I just have two suggestions that I think are very -- follow essentially from what previous speakers have said. The first is that in the model, there is no accounting for time in the sense that if someone was exposed or if there was exposure to the BSE 20 years ago in the model that's treated the same as if there was exposure 10 years ago, and I think that's what causes your problem that you can't predict that the UK today will produce less cases than KSA, because you don't, you're not sensitive to when those exposures happened. So I think if you can put that sensitivity, even though we don't know how long latency is and we can't -- just as a hypothetical, you can't declare that after 15 years exposures, if there's no exposure then there's no infection, maybe a model there would be able to help fit the data better.

 

So and then as an example, I think it could profoundly affect your results. So for instance, if I were to hypothesize that after 15 years or after 20 years that the chances of having CJD given that you're exposed drops dramatically, then you could -- your results to KSA would be much higher in terms of its level of risk than UK, right? And that could dramatically change things, and I agree that what probably won't change things is if you

 

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maybe double the number of vCJD that you saw in Spain. That probably doesn't change it very much. But if risk wanes, that could have a profound difference there, and we see in the data that first came UK, then came France. So there seems to be evidence.

 

And the second comment I had just relates to what you had said earlier, that I think there's a need for an assessment of absolute risk, because even we can kind of -- relative risk seems to be hard to get a handle on, but I think everybody would agree that absolute risk seems to be following. So it would be very helpful to have that.

 

DR. YANG: So I just wanted to answer the question about the estimate of the absolute risk. We do think that kind of study for the red blood cell, so the result is basically that risk assessment when we estimate the risk in the United States, we base it on UK's prevalence, and then we incorporate our U.S. donor travel or their compare to countries with the risk for U.S. donor because of the travel, stay in UK and other different countries, based on the relative risks of those countries compared to UK.

 

So the model of primary input is UK prevalence, but the UK prevalence is uncertain. We have two very different prevalence for UK. One is based on epidemiology modeling. That prevalence is lower, much lower, about 100 times lower. Another prevalence is from data from the

 

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tissue surveillance study. That is 100 times higher. So when we do the risk assessment, we don't know which one is true. So we use both prevalence to do the estimate, and then under the low prevalence we estimate in the United States the annual transfusion-transmitted vCJD through red blood cell in 2011. That is the time we conduct that study, in 2011. It's zero under the low prevalence, based on the low prevalence, but under the high prevalence assumption, then we would see 6 infections and 1 clinical cases. So based on currently what we observe, also we use this model; we replace the input data from the UK and France, we try to estimate using this model to estimate transfusion-transmitted cases in the UK and France, and then we find the low prevalence is more reality. So that is what we --

 

DR. DETWILER: Can I ask a follow-up question there? Did you look at the high prevalence data in relationship to the countries that imported UK beef? Did you look at that relationship at all?

 

DR. YANG: Yes, we looked at France. All the countries, the European countries, in the deferral, we looked at those countries.

 

DR. DETWILER: In relationship to the high prevalence levels to the subclinical --

 

DR. YANG: Yes. Basically we all use these two different prevalence, and then we consider each country

 

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risk -- so we calculate the risk of donor-acquired disease on those different countries.

 

DR. DETWILER: So I take it that's not what you presented, though. That was the low prevalence. Do you have confidence interval?

 

DR. YANG: Pretty wide.

 

DR. ANDERSON: So I just wanted to remind the committee, we did present that model. That was the model that Hong is talking about is the model we presented at the March, I think, 2013 TSEAC meeting. So we neglected to bring slides on that model, but that's already been presented here.

 

DR. FORSHEE: And the issue summary on that is available online for anyone to review.

 

DR. YANG: This study also published in Blood Transfusions.

 

DR. FORSHEE: Before we take the next question, I would like to just answer the first part of Dr. Leviyang's question with regard to accounting for time and the potential for the risk to drop after a certain number of years. We actually weren't comfortable making that assumption in the modeling that we were doing, and in part it's because of the potential for a much longer incubation period among certain genetic subtypes. So because of that we weren't comfortable that for everyone who was exposed

 

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that the risk has fallen at this time, and so we thought we needed to include that.

 

In terms of the time we did incorporate that in a couple of ways, the most important of which being that we did an appropriate age shift in the distribution of people who had traveled to the UK and Europe to reflect the fact that many of these individuals have already in a sense aged out of the time period where they are likely to donate blood, and that's going to continue to happen. So since we have an end to the exposure period for UK and the European countries as more and more people who had been exposed to that get to ages where they are much less likely to donate blood, that risk is going to fall in the future.

 

DR. LEVIYANG: So I think in term of absolute risk, absolutely you don't want to underestimate latency because then you are underestimating risk, and that's absolutely I think the right way to go, but in terms of relative risk, if you overestimate latency then you are shifting your risk, your relative risk, which I think could be argued what you've done. You have shifted the relative risk to the UK, and maybe it's right, but that's an assumption.

 

DR. FORSHEE: Thank you. We will give that further consideration.

 

DR. ROOS: I heard that there were -- that part of

 

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the rationale for opting for the number two option is recovering 100,000 donors, and I wondered whether, where those donors were coming from. Was there particular countries where the majority of these donors, were they spread out to all of the European countries besides -- were they France in later years?

 

DR. FORSHEE: I believe that -- and Hong can follow up if there's something I don't get perfectly right, but I believe that most of the donors are going to be coming from people who visited some of the other countries in Europe that were at lower risk. I don't know if we parsed out the people who had traveled to France after 2001 or not. Hong, do we have a sense of what those numbers are?

 

DR. HUANG: So you talk about donor travel to France after 2001?

 

DR. ROOS: My question was there were 100,000 donors that were going to be accessible if one chooses option two. Where are they from? Are they from Europe and not UK? Are they spread out in all of those countries?

 

DR. HUANG: So they are basically from the -- because we are relaxing the donors from other countries. So now we only defer the top three countries, and that's the donor basically from the other countries rather than the top three countries, yes.

 

DR. BELAY: I have concern about the risk that's

 

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attributed to Saudi. I understand about adjusting for differential surveillance in European countries, but in Saudi they don't even have a surveillance system. In the three cases happened to be diagnosed because the tissues were sent outside of Saudi or they were residents of the United States in one case and Canada in the other one. So the risk in Saudi clearly has to be adjusted but I don't have an answer on how to do it, because they don't even have surveillance, but clearly the three cases do not in my mind reflect what's true in Saudi Arabia, but you said you were going to adjust the rate potentially or the cases for other European countries. I don't know how you plan to do it, but Saudi would be very critical for me.

 

DR. FORSHEE: I would just agree that that is something that will require a lot of internal discussion about how to manage that. I do want to remind the committee that we did use the three attributed cases to KSA for the purpose of the risk assessment that we presented today. So we are not using, we are not potentially underestimating on the basis of our modeling, but again, if there is underreporting because of poor surveillance in the country, we have not made an adjustment for that yet. Based on the feedback from the committee, we are going to give some consideration to that.

 

DR. BELAY: It's my understanding you used the

 

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import data, UK beef import data, to estimate the number of cases in Saudi?

 

DR. FORSHEE: Well, we produced that estimate, but for the calculation of risk reduction we used the attributed cases, the actual attributed cases whenever that was available for a country. So in the case of Saudi Arabia, we had, I believe it was a 0.05 estimate from the model, but because we had three cases attributed to KSA, that was what was used in the calculation of the vCJD case rate for KSA.

 

DR. BELAY: Right, but clearly the import data, it's not good, at least for Saudi, because it gave you .05 when we know there are three cases.

 

DR. FORSHEE: Again, if that's clearly an outlier in our modeling and we could speculate as to what the causes of that are, but we do recognize that their attributed cases were much higher than what would have been predicted by the model.

 

DR. ROOS: The other concern here is that I don't know whether it was true of all three cases, but at least two cases were I guess diagnosed outside Saudi, maybe all three.

 

DR. BELAY: All three of them were diagnosed outside of Saudi. One of them was in Saudi, but the tissue was sent to the United States for diagnosis. The other two

 

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resided here.

 

DR. ROOS: So it underlines and emphasizes the problem with surveillance of variant Creutzfeldt in particular countries, the fact that in a sense there were no cases diagnosed in Saudi.

 

DR. DETWILER: Relative to other countries' import of beef, where did Saudi line up with other countries? Were there countries that didn't have cases of BSE that had more imports of UK beef? And the reason that I'm bringing this up is because it would really concern me with the model, but also in just reality of countries that have no BSE surveillance, and that there are a number of those in the world still, and then have no vCJD surveillance; they may be much more of a risk than -- and if it's only the UK beef imports that you're going on, like you said, Saudi popped up because they had the cases, but there might be countries that those cases wouldn't get sent to another country.

 

DR. BELAY: That basically in my mind shows the limitations of the UK import data. If you believe what happened in the United Kingdom, which is for us to see the 177 cases that they have in the UK, they had millions of exposure in the population, each case of variant CJD indicates that there are thousands and probably hundreds of thousands of exposures in the population. So for Saudi to have three cases of variant CJD, there must be a lot of

 

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exposure that's happening in the population. Where it's coming from, I don't know.

 

DR. HUANG: So I think previous question, if I understand correctly, you were talking about more risk from BSE or from the UK beef?

 

DR. DETWILER: Which countries had more beef -- that didn't report BSE but had more UK beef than Saudi? Do you remember any offhand?

 

DR. HUANG: Had more imported beef than Saudi. I think the beef importation from UK to Saudi is not a lot, so a lot more countries actually from the data we have it's more than Saudi actually.

 

DR. LEVIYANG: I have a question about the extension of -- from the deferral that's going from 1980 to present and 1980 to 2001. So in the model you assume, you consider your person-year exposure as only up to 2001 for those individuals. So I'm just having trouble; the model doesn't really capture that contraction of the deferral rate or it doesn't -- it's just, that's the complete assumption that that has no cost in terms of risk, right? Or can you help understand that?

 

DR. FORSHEE: I believe that that is correct. That is correct that that's the assumption in the model. That is based on what we know about the implementation of protective measures in the EU that -- and perhaps David can

 

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follow up on this, that it is believed that the risk to individuals in those countries did end after these measures were introduced in 2001.

 

DR. ASHER: That is correct. The reasoning was that we accepted the end -- based on information provided by the United Kingdom, we accepted the end of 1996, because of their food and feed protections, as the end of the period of concern, recognizing that the risk didn't entirely disappear but that it had been reduced to a level that we were willing to accept. We were unwilling to do that until recently for other countries, because we at least through the year 2000 and a little later, we were concerned about cross-border travel, importations across cross-borders, but on reexamining the situation, it appeared to us that because the European Union had implemented in the original 15 countries UK-type food and feed protections by the end of 2001, that it was not consistent to accept assurances from the UK and not accept similar assurances from the European Union. So that was the reason.

 

DR. DETWILER: We have kind of crossed into 2, so I will just read it in case there's other comments that you would like to add. Number 2 is please comment on and suggest any modifications to the assumptions or the inputs used in the FDA risk assessment referenced in question 1.

 

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So we have been doing that as well here on both the structure of the model and whatnot.

 

DR. KRANITZ: I can't really speak to the studies, because they are a little above me, but I do want to speak a little bit more about the human risk. We are dealing with a disease that in humans has changed significantly. There are new forms of it that are being discovered, and as Dr. Safar said, with the latency we don't really know exactly what we are dealing with. If we had a clear picture and we knew what was causing it or what risks we were exposing our population to, it would be really more comfortable to say, okay, let's start relaxing some of our restrictions.

 

Having seen this disease and knowing what it looks like and especially in children, this is very unpleasant and so I don't know that I have seen anything that reassures me that we can make changes.

 

DR. DETWILER: Thank you.

 

Any other comments for the committee, suggestions to the FDA on the model itself or inputs?

 

DR. BELAY: One of the adjustments, when you are deriving variant CJD risk based on BSE cases, I think the basic assumption you used was 185,000 BSE cases in the United Kingdom, and I think that data is based on what was detected by the existing surveillance in the United Kingdom, but the actual number of BSE cases far exceeds

 

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185,000. So what happens if you actually use the estimated exact number of BSE cases?

 

DR. FORSHEE: You are absolutely right with that observation. We don't think that that causes a serious threat to the model because we are using the observed BSE cases in each country, and so we are making reasonable comparisons. Now again to the point that has been raised a number of times, if there are differences in the effectiveness of BSE surveillance in the different countries then applying what we observed in the UK to the other countries does have some risk, does present a potential issue for the modeling, and we will explore that some more, but if the unobserved cases of BSE are similar across the countries, that would not affect our model. If it's differential across the model, then that is more of an issue for our modeling.

 

DR. BELAY: But what it potentially affects is not just the number of cases of BSE but the relative efficiency of the control measures that have been put in place in the different countries at different times. Does that make sense? Because the BSE cases, having BSE cases, if you have very good control measure does not mean that you will have variant CJD.

 

DR. FORSHEE: Yes, and when we were applying this conversion it was during periods when we believed that

 

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there were not effective control measures in place. After the effective control measures were in place in a country we assumed the transmission was essentially zero.

 

DR. DETWILER: Just two suggestions for when you're going back to look at BSE surveillance, take into consideration when new member states joined the EU, because the EU had a very structured surveillance system, and when the members joined, then they had to do -- they had case definitions, et cetera, and certain tests that they had to use, and you will see that as members joined, then they found BSE because of the surveillance of the EU, and then I would also suggest looking at the OIE, the world organization for animal health, their classification for countries and the undetermined risk countries are the ones that there's -- usually there are flaws in their surveillance and control measures.

 

DR. FORSHEE: Thank you. I think that's very helpful.

 

DR. DETWILER: If there are no other comments or questions on there, I guess we are at time for a vote here. So I will read the question to the committee. All the slides are up here, too, so you can see. Does the committee agree that it is reasonable to move to revised geographic vCJD deferral as described in option 2, table 3, the UK greater than 3 months, 1980 to 1996, France and Ireland

 

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greater than 5 years, 1980 to 2001, and you have in front of you the clickers.

 

DR. LEVIYANG: Could I ask a question. So what I don't -- for instance, I have a concern about KSA. So this seems fine, but I mean are we voting that this is exactly and only what would be done, or that this would be done and then potentially others? What does a yes or no mean?

 

DR. DETWILER: The way I understand it -- and please, because that's a very, very important -- that this would be the recommendation by the committee there, but then there is an option too that there are other vCJD risk mitigation strategies the FDA should consider at this time. So that is the fourth question that Dave asked us to consider and comment, and that would be, I would think -- Dr. Epstein, Dr. Forshee, did I interpret that incorrectly or --

 

DR. EPSTEIN: Yes, I agree. We are in the fourth question opening the issue to any other suggestions from the committee, and that could include adding countries to the deferral list.

 

DR. DETWILER: So it is important before we vote; does everybody have an understanding how --

 

MR. EMERY: I am just going to tell the committee that these pucks that look like calculators, basically the top three, the very first one will be yes, the second

 

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button across will be no, and the third one will be abstain, and from the last time we used these, what we learned is you have to push it pretty hard when you make that decision, but only push one button when we do that.

 

DR. DETWILER: And then before you vote, too, when we are done voting, we are going to go around and we would like to have -- the FDA has asked that they would like you to tell why you voted one way or the other, okay, so they have those comments, they can capture those comments, as well.

 

All right, so we are all good. Okay, so you can vote now.

 

(Members vote.)

 

MR. EMERY: What we'll do is I will go through each one one at a time, and when that person is not showing, I'll ask that person to tell how they voted. In a moment -- he's going to bring up one name at a time, and I will read off on the record the votes that each person individually --

 

Dr. Blumberg voted 1, which is yes.

 

DR. BLUMBERG: I voted yes because I do not think the current guidelines for donor screening provide any greater benefit than the proposed ones and they will label fewer healthy individuals as potentially carrying a fatal disease, which is a burden for the donor.

 

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MR. EMERY: Florence Kranitz voted no. I just have to read on the record how everybody votes, that's all.

 

David Huskie voted no. You can give a reason now or we can wait until the end and go around in a round robin after I get all the votes in.

 

DR. HUSKIE: The reason I voted no is I really didn't have confidence in the risk assessment versus how many individuals that would actually be -- how many units would be given versus the risk to the population in general.

 

DR. EMERY: Dr. Priola voted no.

 

DR. PRIOLA: I voted no because of some concern -- I actually like option 2, but I'm a little bit concerned about countries like KSA not being included and the fact that even with our current surveillance, we would have missed 50 percent -- that wouldn't have caught 50 percent of the cases of vCJD that were diagnosed here in the United States.

 

DR. EMERY: Dr. Leviyang voted no as well.

 

DR. LEVIYANG: I also like option 2, and I also think that they should consider KSA and similar countries. So that's why.

 

DR. EMERY: Dr. Roos voted no.

 

DR. ROOS: I hope I voted correctly here, which was against choosing option 2, because I like the idea of

 

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the model, but I had concern about the data. I had concern about the BSE surveillance because of issues raised about live cattle, and I had concern about variant Creutzfeldt-Jakob surveillance because of the KSA data that we have. So I like the idea of a model; I just don't think we have the data that I feel secure enough to act on that model to change the present surveillance system.

 

MR. EMERY: Dr. Belay voted 1, yes.

 

DR. BELAY: Yes, I voted for option 2, because it simplifies the donor questionnaire and it also affords the same level of protection as the current policy, but simplifying the donor questionnaire and bringing in additional 100,000 donors I thought was good.

 

MR. EMERY: Dr. Detwiler voted no, as well.

 

DR. DETWILER: So I was all set to vote yes until we had some of the discussion, and so I have a lot of concerns about the model itself and that maybe we are missing more riskier countries and some of the others, and then the UK, the 1996, the assumption that it was a total break after that and given that Dr. Will said that there are some of the appendix positive findings that were actually after that. So that was another concern of mine.

 

MR. EMERY: Dr. Schexneider voted yes.

 

DR. SCHEXNEIDER: I feel that option 2 gives us really equivalent risk, which is very low and opens up the

 

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donor pool, which is critically important for us in the military and, I think, nationwide in the United States.

 

MR. EMERY: Dr. Sigurdson voted yes.

 

DR. SIGURDSON: I voted yes with the option that we could revise option 2 in the next question. So maybe I didn't do this correctly, because I would really also like to see KSA as well as Portugal, Spain, Netherlands, and Italy included as well, because they contributed 2.4 of the risk and I think in those countries there may be latent subclinical infections with CJD from patients that have the codon 129 MV.

 

MR. EMERY: Dr. Kascsak voted yes.

 

DR. KASCSAK: I also voted yes but also under the same assumptions. We know that there were nine countries where vCJD cases were identified, and I thought that we could modify this list where now we have only excluded France and Ireland and might able to include other countries as well.

 

MR. EMERY: Dr. Safar, okay, yours didn't read. How did you vote?

 

DR. SAFAR: I voted no, because the uneven quality of the input data into the model related to the BSE surveillance distribution and CJD, variant CJD surveillance data. Second reason is the appendix and tonsillectomy studies in the UK and subclinical variant CJD.

 

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MR. EMERY: Dr. Jackson is no.

 

DR. JACKSON: I voted no mainly because I really don't like either option, 1 or 2, and think the risk is relatively minimal and wonder whether if we used universal leukoreduction like in England we would have zero cases in the last 7 years as well.

 

MR. EMERY: For the record, we had 5 yesses, 8 noes, and 0 abstentions, and I would like to hear from Dr. Doug Lee if he has anything to say from representing industry.

 

DR. LEE: The only thing that I'm a little concerned of is that -- and it only became clear as we were kind of going around the table here is really what was what the question we were asking as part of it, because you're really talking about a minor -- what I perceive as a relatively minor edit to the geographical exclusions, only around the big three countries that we were really dealing with, and it really just narrowed the timeframe down.

 

I don't think in my mind it precluded any of the other edits that we were talking about down the road, or potentially down the road. So that's my only concern with the way we have kind of circled around is that really you are only narrowing the timeframe that you would be included or that was being edited in to reduce, to allow for more donors post that timeframe. Right now it's open-ended. It

 

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will go in perpetuity it seems as though. So that was -- to me I liked the idea of putting the boundaries on it, to open up and get more donors in, and I didn't see a big risk to it.

 

I understand the concerns with the risk assessment. I think they are valid. But I am not so sure that it really has a big impact by the question as it's currently phrased. That's my perception of it.

 

DR. DETWILER: I think the question was because of the -- what's reasonable and not. I think that was but the FDA, by the comments, does that help you out on -- Dr. Epstein?

 

DR. EPSTEIN: I am little confused because two members who voted yes commented that they actually thought other European countries should be retained in the deferral, and that should have triggered no votes. In other words, the whole concept of limiting it to UK, France, Ireland was that we could cease deferring for other European countries that are currently listed. So I'm a little confused by the voting. I'm not as confused by the comments. I understand all the comments, and I do think the comments are very helpful.

 

DR. KASCSAK: For people who voted yes sort of with an option, I mean, there are nine countries where variant CJD has been identified, and I think even the

 

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people who voted yes are concerned about blood donations from those countries. So if those countries were included, I think that would ease fears from many people, even though we voted yes.

 

DR. EPSTEIN: Well, I think it would be important to perhaps entertain a vote or at least a discussion whether we should continue deferrals for countries with reported vCJD, because I think that's what's bothering some of the members, but again as far as question 1 was concerned, we were really asking, recognizing that there is risk in other European countries and considering the effort to look at relative risk, was it reasonable to narrow to just France, Ireland and UK, and I think the confusion that we are hearing is it's not clear what the sense of the committee really is about other countries of Europe that are reporting vCJD.

 

DR. DETWILER: I think it was Dr. Sigurdson and Dr. Kascsak, you two, that said you would like at least some other European countries on there. Is that correct?

 

DR. SIGURDSON: That is right. So if this question was strictly on option 2, then I would vote no.

 

DR. EPSTEIN: The question was strictly on option 2.

 

DR. KASCSAK: I think some of us assumed that on further votes we would be able to add some of those other

 

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countries where variant CJD has been identified.

 

DR. EPSTEIN: Well, I mean, the committee can recommend whatever it thinks is right, but what FDA was trying to ask was whether based on the quantitative risk assessment it is reasonable or not to eliminate all the questions about countries other than UK, France, and Ireland. So I think it's important to have a discussion among the members about other European countries where vCJD has been reported.

 

DR. DETWILER: Let me try to see if we can get a clarity. So I think everyone that voted no would still vote no. Is that correct? Okay. For the folks that voted yes, would you switch to no if it was narrow, if the question was this question would not have you --

 

(Power loss.)

 

(Note: The Committee continued the discussion for about 20 minutes and voted on question 3A. Not able to record the proceedings until the power was restored.)

 

(Power back on.)

 

DR. DETWILER: So the FDA has asked us if we could make it official and then do a vote for the leukoreduction, all right? So if we can ask you again, even if you cut your paper in half or whatnot, if you can just write your name on it. Yes would be you would support a measure, a recommendation to the FDA for universal leukoreduction, no,

 

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or abstain.

 

MR. EMERY: For the record, the committee is voting on universal leukoreduction, and the first vote I have is yes from Dr. Kascsak.

 

DR. KASCSAK: For the reasons I gave before, that I think we already have 95 percent reduction and the addition of the additional 5 would serve as further protection for the elimination of variant CJD. MR. EMERY: Yes for Dr. Blumberg.

 

DR. BLUMBERG: Pretty much what was just said, and I've probably said enough, but I think this provides an additional level of protection against this disease and other additional benefits.

 

MR. EMERY: Yes for Florence Kranitz.

 

DR. KRANITZ: I agree with everything that's been said. Even if you get one more small percentage point towards safety we should be doing that.

 

MR. EMERY: Yes for David Huskie.

 

DR. HUSKIE: For the same reasons. The safer the better as far as the blood supply goes.

 

MR. EMERY: Yes for Dr. Priola.

 

DR. PRIOLA: I agree with Dr. Blumberg said.

 

MR. EMERY: Dr. Leviyang will abstain from this vote.

 

Dr. Raymond Roos is yes.

 

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Dr. Ermias is yes.

 

DR. BELAY: In my judgment it will probably do more protection against variant CJD than the geographic deferral. The geographic deferral would not have removed two out of the four cases in the United States, but leukoreduction would have afforded additional protection.

 

MR. EMERY: Dr. Detwiler is yes.

 

DR. DETWILER: I echo what everyone else is saying.

 

MR. EMERY: Dr. Safar is yes.

 

DR. SAFAR: So it's the, I think, rich experimental data reducing showing the reduced risk, plus other cumulative benefits.

 

MR. EMERY: Dr. Jackson is yes.

 

DR. JACKSON: Yes, I think it will provide greater risk protection that may more than offset any increased risk by relaxing these donor areas. I think this is probably the most important thing.

 

MR. EMERY: Dr. Sigurdson is yes.

 

DR. SIGURDSON: I agree with the prior comments on the benefits of universal leukoreduction.

 

MR. EMERY: And Dr. Schexneider is yes.

 

DR. SCHEXNEIDER: I agree with the comments made around the table.

 

MR. EMERY: So in total the committee has voted a

 

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majority, 12 yes, 1 abstention, 0 noes.

 

DR. DETWILER: Thank you very much to the committee for that vote and the message to the FDA. I don't know if there's any, then the last question here, are there any other vCJD risk mitigation strategies that FDA should consider at this time? So I guess we would open that up again, risk mitigation strategies.

 

Dr. Epstein, did you --

 

DR. EPSTEIN: It is not clear that the committee really answered question 3B. I would be interested to hear committee members. We heard some individual opinions, and it would be good to go around the table.

 

DR. DETWILER: So we will --

 

DR. LEE: (Off mic.)

 

DR. JACKSON: I think that there's minimal risk of keeping these geographically -- doing away with these geographical donor deferral in terms of the time spent in these countries.

 

DR. SAFAR: I think the idea in the case should go for the quality control of those assumptions and I think that the indicator is that there is pretty well established expected incidence of sporadic CJD. So if sporadic CJD is a measure of the recoverable prion disease in the human population, it should be a good measure of the quality of the surveillance system in each country.

 

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And the second is just the autopsy rate itself. So those two measures should be considered in evaluating different geographical risks of variant CJD and reported or not reported cases of variant CJD.

 

DR. KASCSAK: I think there should be more studies on genetic susceptibility. We know that methionine-methionine is a genetic risk factor, but there must be also other genetic factors that preclude all methionine-methionine individuals from being susceptible, and also I think we have to look at the latency as was mentioned before, the latency of this disease and how genetic factors influence that latency. We know in animal models that genetic factors have a great control over latency of agent, and whether that should be a concern for this disease, whether 20 or 30 years from now people that were infected in the 1990s may begin to show symptoms. So I think the more we know about genetic susceptibility relative to the variant CJD the better off we'll be.

 

DR. SIGURDSON: I similarly have concerns about the genetics of this disease and that half the cases that were -- half of those 16 cases that were reported with PrP scrapie in the appendix were MV. So this really may indicate a latent subclinical population of infected individuals, and that's why I suggested adding the four additional European countries, because they have had cases

 

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of variant CJD, and it may be an indicator of high exposure of the population.

 

DR. SCHEXNEIDER: No comments to add.

 

DR. BELAY: I feel a little bit more comfortable about the variant CJD surveillance in Europe, in most European countries, for two reasons. One, it requires thousands of BSE cases before you see variant CJD, and you would be unlikely to miss those numbers of BSE cases in Europe, one, and two, there is good sporadic CJD surveillance as we were saying in most European countries, which could be used as a surrogate whether or not that system would pick up variant CJD. Having said that, I'm not at the same level of comfort for Saudi Arabia. So in my mind, keeping the top three countries as FDA suggested with the addition of Saudi Arabia would be okay with me.

 

DR. ROOS: I would like to see some more specific data for the individual European countries and then make some decisions, perhaps country by country, perhaps in the same way that countries are approved with respect to BSE surveillance and so forth, that there are individual numbers and credits given depending on how significant that surveillance is. So I would like to see those details.

 

And I think that some revision of our present policy in order. I'm not quite sure I understand why

 

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certain countries are -- donors are limited for five years up until the present time. That didn't seem to me that -- it seems to me that the time has to be adjusted appropriately. So I think revisiting this with a little bit more data would be very valuable.

 

The issue of latency concerns me, and I think probably we need to keep our hands on that pulse. The problems with prion diseases have been that unexpected things happen, and there are hugely long incubation periods, and my suspicion is that if those individuals live long enough, there very likely may be some aspects of prion disease. So I am concerned about that. It would be very good to have some kind of model in which one could study this, but I'm not sure we are there at present.

 

DR. LEVIYANG: As I said before, I think option 2 is a good option, but I have concerns about KSA. It's kind of statistically an outlier and maybe it's trying to tell us something about the epidemic. So I think it warrants further consideration.

 

DR. PRIOLA: As I said earlier, I also actually I like the simplified option number 2 and had recommended earlier adding KSA. I understand from past meetings that the FDA has often been reluctant to get into this sort of pattern of adding country by country as data changes, but this vote on the leukoreduction, I think Dr. Belay said it

 

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very well: this is a downstream check now on possible contamination of the blood supply with variant CJD. So in the UK they have 0 out of 25 cases of transfusion-transmitted variant CJD from people who got leukoreduced blood. So that's a strong indicator that leukoreduction was very helpful there, and so if the FDA is able to recommend 100 percent leukoreduction, and I understand there are reasons that may not be possible, that gives much less weight to determining which country has the highest risk and which country has the lowest risk of variant CJD. So I guess I would just say option 2 is okay with me. If you can't add KSA but can do the 100 percent leukoreduction, I think that would be the best for me of all possible worlds.

 

DR. HUSKIE: I have nothing to add at this time.

 

DR. KRANITZ: I agree with Dr. Priola, and I think adding KSA, considering that, would be very, very important.

 

DR. BLUMBERG: I don't think I have anything to add really.

 

DR. DETWILER: Thank you, Dr. Blumberg. So I will just add my comments. So I am going to take a little different path here, but I think one of the most important things with the latent cases in the UK but even worldwide

 

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as people move around is that it's really important not only on prevention and whatnot but to monitor what's happening in the world.

 

So I would suggest -- and I know this is not really FDA's purview; it's CDC's purview -- but it's really, really important for FDA to support within HHS continual monitoring of neurologic diseases and other conditions in the United States, right, to see if there is any to go along, and that goes along with the work that Dr. Safar is doing, and to look for those outliers, to look for these different emerging things that have been done.

 

So I would say that my thing would be it's really, really important for us, and when we test -- I know this from the animal world -- when we test not just for the prion protein, but I think it's also good for infectivity, because those are the things that sometimes when they change the manifestation, we sometimes don't see that the same way, or there are different forms that you have to really sort out.

 

DR. SAFAR: I would like to thank you for what you said. I think that it's the best prevention is to get solid precise data, and that is what we provide, and we are looking at the human diseases, and there are not only variant CJD, but there are those other potential zoonoses like CWD, chronic wasting disease, which is constantly

 

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spreading. We don't know yet if it is a real threat or just potential threat.

 

So I think that this is the best defense for what we were discussing today, to get real solid surveillance data. I have, if I may, one aspect which is beyond the scope of this committee, but I think that it came out from the USDA presentation and there are, I think, really important issues related to the atypical BSE and the fact that we are screening for atypical BSE without really validated tests. They have only validated for the classical BSE. So that's one of the concerns I have, because we know very little about it, and we don't know how danger it is, if it is transmissible to -- if it is another kind of zoonosis, and related to it is the specified risk materials. There were definitely incidents in the past which showed that the system, control system and control measures, do not work very well and I don't know how to address it from this committee, because it is effectively USDA jurisdiction, but I'm really concerned about it, because the atypical BSE is another zoonosis.

 

DR. DETWILER: Maybe I will have a suggestion on how to pose it for the FDA. So I think the way I look at it, if you prevent -- well, the best is to prevent the disease in cattle. So it's important for -- and the FDA does regulate feed. So it's important to maintain those,

 

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especially if atypical would be a spontaneous disease, to maintain the feed ban. So that is under another CVM at FDA. So that would be important.

 

And then to prevent the initial foodborne, which is what you mentioned with the SRMs. So we would tell -- it's part of FDA -- CFSAN has some jurisdiction there. So that would all part and parcel, and if you prevent those, then the initial foodborne cases -- there is going to be pressure from the industry, I can you, ag industry already, as the cases of both diseases go down to start to relax those, and I think it's important for the government to at least until we really get a good handle, to maintain those. At least that would be my opinion. So did I capture what you were? Yes, okay.

 

So we covered number 3B. Number 4, and we are going to go around again. So if you have any -- if you don't have anything, you can just say, but any additional things, I just want to make sure that everyone -- this will be your chance to say anything else that you would like in your opinion. So are there any other vCJD risk mitigation strategies that FDA should consider at this time?

 

So we'll start, Dr. Blumberg, we'll start at your end this time.

 

DR. BLUMBERG: I don't think I have the expertise to comment.

 

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DR. DETWILER: Dr. Priola?

 

DR. PRIOLA: No.

 

DR. LEVIYANG: No.

 

DR. ROOS: Talking about surveillance, it I think would be beneficial although not without difficulties to look at the appendices in the United States and get some idea of whether there is latent disease here.

 

DR. DETWILER: So, Dr. Asher, did you want to make a comment, Dr. Asher?

 

DR. ASHER: Yeah, we made a back of the envelope assessment of what it would cost to do a similar survey in the United States, and it was beyond anything that we could conceive of. It ended up being millions and millions of dollars. One has to get the paraffin blocks from the hospitals, get the sections cut, find the people with the expertise to read them, at least at the beginning from the UK. None of this is free, and it soon became clear that we simply couldn't conceive of finding the funding to do that. Those of you who are interested in doing it, maybe NIH would entertain a contract or an RO1 grant, but FDA, it was beyond the capability of the FDA. We agree that it would be very interesting, but it just wasn't feasible.

 

DR. DETWILER: You should let us vets do it. In the United States now we are doing about almost 100,000 between sheep and cattle samples.

 

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DR. BELAY: Just reiterating what was already said, it doesn't make sense to have the different policy for the rest of the European countries other than the UK open-ended. For the UK it ends in 1996. There's general agreement in the European Union that the risk probably ended in 2001. So leaving it open-ended doesn't make sense.

 

DR. DETWILER: Thank you.

 

DR. SCHEXNEIDER: Nothing to add.

 

DR. SIGURDSON: Nothing to add.

 

DR. KASCSAK: I just want to reiterate, I think we need to know more about genetic susceptibility. The methionine-methionine obviously is a tremendous risk factor, but there may be other genetic factors in humans that we just don't understand at this point that control susceptibility. So I think that would be something to look at down the road.

 

DR. SAFAR: Nothing to add.

 

DR. JACKSON: Just to say that I understand the concern about latency and certainly would support studies to look at that, but in terms of the clinical relevancy from the data presented, you know, this curve of the 229 cases, you know, practically going to zero with most latent diseases, if it's clinically really a problem it will go down, but flatten out, and whether it's hepatitis C or anything, you know, diseases like that. So the data is

 

232

 

pretty reassuring that clinically it doesn't look like that this is a problem at this point, but obviously we need to get more data.

 

DR. DETWILER: Thank you. Dr. Lee?

 

DR. LEE: Nothing else to add.

 

DR. ASHER: I just wanted to comment about Dr. Kascsak's feeling that genetic susceptibility should be -- of latency -- should be better understood. I think it may have escaped you this morning in the way it was phrased, but there has been in the United Kingdom a clinically typical case of variant CJD in a person who had -- who was heterozygous at codon 129 of the prion protein encoding gene. Dr. Will commented that it couldn't be confirmed. That was not because histopathology was negative. It was because there was no biopsy and the family would not allow an autopsy.

 

But there was no reason, as I understand it, to doubt that that person had a clinically typical case, right age, right clinical findings. So my comment, and I think that Dr. Safar's suggestion to adjust for the autopsy rate is interesting. I would caution, though, that there are certain problems. You can't, in my view, correct for the overall autopsy rate for the country, because the autopsy rate in a young person with a progressive dementing disease would probably be higher, just as it is in the United

 

233

 

States.

 

Dr. Safar believes that we are getting, what, 70 percent of the patients with sporadic or iatrogenic or familial CJD come to autopsy, whereas our overall autopsy rate is probably closer to 10 percent, and below it. So you would have to take into consideration the fact that young patients with this kind of disease are much -- particularly if they have a motivated neurologist -- are much more likely to come to autopsy, and there are some other things that are perhaps a little more complicated to address than simply looking at national rates.

 

We saw, for instance, for Saudi Arabia, that dietary consumption is not uniform over the country. A fraction of the population eats almost all the beef, and the rest of the country doesn't eat much beef. So these -- I'm just trying to make the point that these are sometimes more complex to break down to plug into a risk assessment than it would initially appear, but I would like to thank you for the interesting suggestions, and what I take away from this is that you don't like the three top country model as presented. You have some doubts about some of the assumptions going into the risk assessment, but that you don't like the current policy either. You do like leukoreduction.

 

DR. DETWILER: Thank you. FDA, anybody, is there

 

234

 

anything else that you want the committee to consider, or if not, we are getting --

 

DR. EPSTEIN: No. We are grateful for the advice.

 

DR. DETWILER: Thank you.

 

Then as chair I would like to thank the committee very, very much for all your participation and comments to the FDA. Thank you to the FDA speakers, and thank you to the audience, and so the meeting will be adjourned.

 

MR. EMERY: I want to thank the audience, the FDA, and the committee, and I'm sure we will be in touch.

 

(Whereupon, at 5:09 p.m., the meeting was adjourned.)

 


 


 

***DR. DETWILER: Yeah, there are data. The best would be the European Union did these geographic BSE risk assessments of at least all their members, anybody that submitted. They had a lot of good numbers, and they tried to crosscheck with import the export data from the UK and the import data on there. So that would be another kind of source of information if you can get -- public on the -- I'm not sure if they are still online, but they were online.

 

it’s called the BSE Inquiry Dr. Detwiler, however, at this point in time, it would be more prudent, to be much more concerned, with what North America is exporting around the globe, imo. ...terry

 

UK EXPORTS OF MBM TO WORLD

 


 


 


 

OTHERS

 

BEEF AND VEAL

 


 


 


 

LIVE CATTLE

 


 

FATS

 


 

EMBRYOS

 


 

GELATIN ETC

 


 

SEMEN

 


 

MEAT

 


 

*DR. ASHER: The issue of atypical BSE and how it arises has not only not been addressed in this particular risk assessment, but it has not been incorporated into the thinking of this at all, and as I mentioned in the introduction this morning, I believe that a precautionary public health policy would be that atypical BSE has to be considered no less dangerous than the other form of BSE, because it is transmissible to animals. Furthermore, and this represents my own thinking, I am not persuaded that we have enough data to conclude that either atypical BSE or sporadic CJD is spontaneously generated and is not an environmentally-acquired infection...182

 

THANK YOU DR. ASHER Sir!

 

I strenuously once again urge the FDA and its industry constituents, to make it MANDATORY that all ruminant feed be banned to all ruminants, and this should include all cervids as soon as possible for the following reasons...

 

======

 

In the USA, under the Food and Drug Administrations BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system.

 

***However, this recommendation is guidance and not a requirement by law.

 

======

 

31 Jan 2015 at 20:14 GMT

 

*** Ruminant feed ban for cervids in the United States? ***

 

31 Jan 2015 at 20:14 GMT

 

see Singeltary comment ;

 


 

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;

 


 

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

 

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.

 

*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

 

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

 

see page 176 of 201 pages...tss

 


 

***atypical spontaneous BSE in France LOL***

 

FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many spontaneous events of mad cow disease $$$

 

***so 20 cases of atypical BSE in France, compared to the remaining 40 cases in the remaining 12 Countries, divided by the remaining 12 Countries, about 3+ cases per country, besides Frances 20 cases. you cannot explain this away with any spontaneous BSe. ...TSS

 

Sunday, October 5, 2014

 

France stops BSE testing for Mad Cow Disease

 


 

Thursday, March 24, 2016

 

FRANCE CONFIRMS BOVINE SPONGIFORM ENCEPHALOPATHY BSE MAD COW (ESB) chez une vache dans les Ardennes

 


 

***atypical spontaneous BSE in France LOL***

 

FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many spontaneous events of mad cow disease $$$

 

If you Compare France to other Countries with atypical BSE, in my opinion, you cannot explain this with ‘spontaneous’.

 

Table 1: Number of Atypical BSE cases reported by EU Member States in the period 2001–2014 by country and by type (L- and H-BSE) (extracted from EU BSE databases on 1 July 2014). By 2015, these data might be more comprehensive following a request from the European Commission to Member States for re-testing and retrospective classification of all positive bovine isolates in the EU in the years 2003–2009

 

BSE type

 

Country 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013(a) 2014(a) Total

 

H-BSE Austria 1 1

 

France(b) 1 2 3 1 2 2 2 2 15

 

Germany 1 1 2

 

Ireland 1 1 2 1 5

 

The Netherlands 1 1

 

Poland 1 1 2

 

Portugal 1 1

 

Spain 1 1 2

 

Sweden 1 1

 

United Kingdom 1 1 1 1 1 5

 

Total 2 3 3 1 1 2 2 2 4 4 5 1 4 1 35

 

L-BSE Austria 1 1 2

 

Denmark 1 1

 

France(b) 1 1 1 1 2 1 3 2 1 1 14

 

Germany 1 1 2

 

Italy 1 1 1 1 1 5

 

The Netherlands 1 1 1 3

 

Poland 1 2 2 1 2 1 2 1 12

 

Spain 2 2

 

United Kingdom 1 1 1 1 4

 

Total 0 5 3 4 3 3 6 3 3 4 3 6 1 1 45

 

Total Atypical cases (H + L)

 

2 8 6 5 4 5 8 5 7 8 8 7 5 2 80

 

(a): Data for 2013-2014 are incomplete and may not include all cases/countries reported.

 

(b): France has performed extensive retrospective testing to classify BSE cases, which is probably the explanation for the higher number of Atypical BSE cases reported in this country.

 

The number of Atypical BSE cases detected in countries that have already identified them seems to be similar from year to year. In France, a retrospective study of all TSE-positive cattle identified through the compulsory EU surveillance between 2001 and 2007 indicated that the prevalence of H-BSE and L-BSE was 0.35 and 0.41 cases per million adult cattle tested, respectively, which increased to 1.9 and 1.7 cases per million, respectively, in tested animals over eight years old (Biacabe et al., 2008). No comprehensive study on the prevalence of Atypical BSE cases has yet been carried out in other EU Member States. All cases of Atypical BSE reported in the EU BSE databases have been identified by active surveillance testing (59 % in fallen stock, 38 % in healthy slaughtered cattle and 4 % in emergency slaughtered cattle). Cases were reported in animals over eight years of age, with the exception of two cases (one H-BSE and one L-BSE) detected in Spain in 2011/2012. One additional case of H-BSE was detected in Switzerland in 2012 in a cow born in Germany in 2005 (Guldimann et al., 2012).

 


 


 

Wednesday, July 15, 2015

 

Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?

 


 

***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.

 

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

 

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

 

Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT

 


 

SEE THE DRASTIC REDUCTION OF CONFIRMED BSE CASES IN THE UK ONCE THE FEED BAN TOOK HOLD FROM THE TOP YEAR DOWN TO THE FIRST ZERO YEAR ;

 

1992 36680 SLAUGHTERED SUSPECTS IN WHICH BSE CONFIRMED

 

2013 0 0 0 0 0 0 0 0

 


 


 


 


 


 

10 years post mad cow feed ban August 1997

 

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

 

Date: March 21, 2007 at 2:27 pm PST

 

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

 

PRODUCT

 

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

 

CODE

 

Cattle feed delivered between 01/12/2007 and 01/26/2007

 

RECALLING FIRM/MANUFACTURER

 

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

 

Firm initiated recall is ongoing.

 

REASON

 

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

 

VOLUME OF PRODUCT IN COMMERCE

 

42,090 lbs.

 

DISTRIBUTION

 

WI

 

___________________________________

 

PRODUCT

 

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

 

CODE

 

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

 

RECALLING FIRM/MANUFACTURER

 

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

 

REASON

 

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

 

VOLUME OF PRODUCT IN COMMERCE

 

9,997,976 lbs.

 

DISTRIBUTION

 

ID and NV

 

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

 


 

16 years post mad cow feed ban August 1997

 

2013

 

Sunday, December 15, 2013

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE

 


 

17 years post mad cow feed ban August 1997

 

Monday, October 26, 2015

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015

 


 

Tuesday, December 23, 2014

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION

 


 

Thursday, April 07, 2016

 

What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016

 

Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008).

 

***In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research, however, suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008). It is apparent, though, that CWD is affecting wild and farmed cervid populations in endemic areas with some deer populations decreasing as a result.

 

snip...

 

For the purpose of the qualitative risk assessment developed here it is necessary to estimate the probability that a 30-ml bottle of lure contains urine from an infected deer. This requires an estimate of the proportion of deer herds in the USA which are infected with CWD together with the within herd prevalence.

 

The distribution map of CWD in US shows it is present mainly in central states (Figure 1). However, Virginia in the east of the country has recorded seven recent cases of CWD (Anon 2015a). Some US manufacturers claim to take steps to prevent urine being taken from infected animals eg by sourcing from farms where the deer are randomly tested for CWD (Anon 2015a). However, if disease is already present and testing is not carried out regularly, captive populations are not necessarily disease free (Strausser 2014). Urine-based deer lures have been known to be collected from domestic white-tailed deer herds and therefore there is a recognised risk. This is reflected by 6 US States which have

 

14

 

banned the use of natural deer urine for lures, as the deer urine may be sourced from CWD-endemic areas in the USA as well as from areas free of CWD. For example, the US State of Virginia is banning the use of urine-based deer lures on July 2015 and Vermont from 2016 due to the risk of spread of CWD. Alaska banned their use in 2012 (Anon 2015a). Pennsylvania Game Commission has banned urine-based deer lures and acknowledged that there is no way to detect their use (Strausser 2014). On the basis of unpublished data (J. Manson, Pers. Comm.) it appears that up to 50% of deer herds can be infected with 80-90% of animals infected within some herds.

 

*** It is therefore assumed that probability that a 30-ml bottle of deer urine lure imported from the USA is sources from an infected deer is medium.

 

SNIP...

 

In the USA, under the Food and Drug Administration’s BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. ***For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. ***However, this recommendation is guidance and not a requirement by law.

 

***Animals considered at high risk for CWD include:

 

***1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and

 

***2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.

 

***Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants. The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB cannot be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the very low tonnage of non-fish origin processed animal proteins that were imported from US into GB.

 

*** Overall, therefore, it is considered there is a greater than negligible risk that (non-ruminant) animal feed and pet food containing deer and/or elk protein is imported into GB. There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.

 

SNIP...

 


 

Summary and MORE HERE ;

 

What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016

 


 

Tuesday, April 12, 2016

 

*** The first detection of Chronic Wasting Disease (CWD) in Europe

 


 

 Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission Greetings again FDA and Mr. Pritchett et al, I would kindly like to comment on ; Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission #158 Guidance for Industry Use of Material from Deer and Elk in Animal Feed This version of the guidance replaces the version made available September15, 2003. This document has been revised to update the docket number, contact information, and standard disclosures. Submit comments on this guidance at any time. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the Docket No. FDA-2003-D-0432 (formerly 03D-0186). For further information regarding this guidance, contact Burt Pritchett, Center for Veterinary Medicine (HFV-222), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 240-402-6276, E-mail: burt.pritchett@fda.hhs.gov. Additional copies of this guidance document may be requested from the Policy and Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, and may be viewed on the Internet at either http://www.fda.gov/AnimalVeterinary/default.htm or http://www.regulations.gov. U.S. Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine March 2016 Contains Nonbinding Recommendations 2 Guidance for Industry Use of Material from Deer and Elk in Animal Feed This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title page. I. Introduction Under FDA’s BSE feed regulation (21 CFR 589.2000) most material from deer and elk is prohibited for use in feed for ruminant animals. This guidance document describes FDA’s recommendations regarding the use in all animal feed of all material from deer and elk that are positive for Chronic Wasting Disease (CWD) or are considered at high risk for CWD. The potential risks from CWD to humans or non-cervid animals such as poultry and swine are not well understood. However, because of recent recognition that CWD is spreading rapidly in white-tailed deer, and because CWD’s route of transmission is poorly understood, FDA is making recommendations regarding the use in animal feed of rendered materials from deer and elk that are CWD-positive or that are at high risk for CWD. In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required. II. Background CWD is a neurological (brain) disease of farmed and wild deer and elk that belong in the animal family cervidae (cervids). Only deer and elk are known to be susceptible to CWD by natural transmission. The disease has been found in farmed and wild mule deer, white-tailed deer, North American elk, and in farmed black-tailed deer. CWD belongs to a family of animal and human diseases called transmissible spongiform encephalopathies (TSEs). These include bovine spongiform encephalopathy (BSE or “mad cow” disease) in cattle; scrapie in sheep and goats; and classical and variant Creutzfeldt-Jakob diseases (CJD and vCJD) in humans. There is no known treatment for these diseases, and there is no vaccine to prevent them. In addition, although validated postmortem diagnostic tests are available, there are no validated diagnostic tests for CWD that can be used to test for the disease in live animals. Contains Nonbinding Recommendations III. Use in animal feed of material from CWD-positive deer and elk Material from CWD-positive animals may not be used in any animal feed or feed ingredients. Pursuant to Sec. 402(a)(5) of the Federal Food, Drug, and Cosmetic Act, animal feed and feed ingredients containing material from a CWD-positive animal would be considered adulterated. FDA recommends that any such adulterated feed or feed ingredients be recalled or otherwise removed from the marketplace. IV. Use in animal feed of material from deer and elk considered at high risk for CWD Deer and elk considered at high risk for CWD include: (1) animals from areas declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and (2) deer and elk that at some time during the 60-month period immediately before the time of slaughter were in a captive herd that contained a CWD-positive animal. FDA recommends that materials from deer and elk considered at high risk for CWD no longer be entered into the animal feed system. Under present circumstances, FDA is not recommending that feed made from deer and elk from a non-endemic area be recalled if a State later declares the area endemic for CWD or a CWD eradication zone. In addition, at this time, FDA is not recommending that feed made from deer and elk believed to be from a captive herd that contained no CWD-positive animals be recalled if that herd is subsequently found to contain a CWD-positive animal. V. Use in animal feed of material from deer and elk NOT considered at high risk for CWD FDA continues to consider materials from deer and elk NOT considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal feeds in accordance with current agency regulations, 21 CFR 589.2000. Deer and elk not considered at high risk include: (1) deer and elk from areas not declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and (2) deer and elk that were not at some time during the 60-month period immediately before the time of slaughter in a captive herd that contained a CWD-positive animal. 3 http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052506.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission Greetings again FDA and Mr. Pritchett et al, MY comments and source reference of sound science on this very important issue are as follows ; Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission I kindly wish to once again submit to Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed. Thank you kindly for allowing me to comment again, ...and again...and again, on a topic so important, why it is ‘NON-BINDING’ is beyond me. this should have been finalized and made ‘BINDING’ or MANDATORY OVER A DECADE AGO. but here lay the problem, once made ‘BINDING’ or ‘MANDATORY’, it is still nothing but ink on paper. we have had a mad cow feed ban in place since August 1997, and since then, literally 100s of millions of pounds BANNED MAD COW FEED has been sent out to commerce and fed out (see reference materials). ENFORCEMENT OF SAID BINDING REGULATIONS HAS FAILED US TOO MANY TIMES. so, in my opinion, any non-binding or voluntary regulations will not work, and to state further, ‘BINDING’ or MANDATORY regulations will not work unless enforced. with that said, we know that Chronic Wasting Disease CWD TSE Prion easily transmits to other cervid through the oral route. the old transmission studies of BSE TSE floored scientist once they figured out what they had, and please don’t forget about those mink that were fed 95%+ dead stock downer cow, that all came down with TME. please see ; It is clear that the designing scientists must also have shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection. http://web.archive.org/web/20061003022720/http://www.bseinquiry.gov.uk/files/ws/s145d.pdf

 

it is clear that the designing scientists must have also shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection.

 


 

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

 

snip...

 

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

 


 

*** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN ***

 

Sunday, March 20, 2016 Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary Submission

 


 

disease.blogspot.com/2016/03/docket-no-fda-2003-d-0432-formerly-03d.html

 

Sunday, March 20, 2016

 

UPDATED MARCH 2016 URGENT Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission

 


 

Tuesday, April 19, 2016

 

Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission

 


 

Saturday, April 16, 2016

 

APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission

 


 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

 

22

 

Visits to Colorado State University, College of Veterinary Medicine and the Wyoming Game and Fish Department, Sybille Wildlife Research and Conservation Education Unit.

 

The main objective here was to obtain some understanding of CWD. A visit was made to the University of wyoming Game and Fish Department, Sybille wildlife Research and Conservation Education Unit where most of the cases of CWD have occurred. The Sybille Wildlife facility is situated some 50 miles northeast of Laramie, Wyoming through the Laramie Mountains. Here most of the hoofed big game species of North America; Hule Deer (odocoileus hemionus), Whitetail Deer (Odocoileus virginianus), Elk (Cervis canadensis) Mountain Goat (Oreamnos americana), Bighorn Sheep (0vis canadensis} and Pronghorn (Antilocapra americana) and some other wildlife species are kept in small numbers for experimental use in the investigation of wildlife diseases.

 

A colony of the blackfooted ferret (Hustela nigripes) has been established because of its imminent extinction. At present there are only 35 but it is proposed to breed up to 200 and then, probably in 1991, re-introduce them into the wild in a nation wide operation. Blackfooted ferret diet is mainly Prairie Dog (Cynoms spp.) and it is thought that the elimination of this species from large areas by poisoning campaigns in the past has been responsible for the precipitous ferret decline.

 

The buildings and pens at the facility are entirely of wooden/log construction with heavy duty wire mesh fences. Pen floors are bare earth. A long race connecting many different areas within the facility enables movement of deer and antelope between pens when necessary. There is provision for holding deer of different sizes in a custom built crush for bleeding and treatments.

 

23

 

The educational role of the unit includes school visits to provide instruction in the work of the department and to promote conservation. I was accompanied on this visit by Stuart Young and Beth Williams. on arrival I was introduced to Hughie Dawson who has managed the facility for some 20 years.

 

CWD occurred principally in two locations, this one at Sybille and in a similar facility at Fort Collins, Colorado, some 120 miles southwest. It was estimated that in total probably 60-10 cases of CWD have occurred.

 

It was difficult to gain a clear account of incidence and temporal sequence of events ( - this presumably is data awaiting publication - see below) but during the period 1981-84, 10-15 cases occurred at the Sybille facility. Recollections as to the relative total numbers of cases at each facility were confusing. Beth Williams recalled that more cases had occurred in the Colorado facility.

 

The morbidity amongst mule deer in the facilities ie. those of the natural potentially exposed group has been about 90% with 100% mortality. the age distribution of affected deer was very similar to that in ESE. The clinical duration of cases was 6-8 weeks. Mortality in CWD cases was greatest in winter months which can be very cold.

 

When the problem was fully appreciated both the Sybille and the Colorado facilities were depopulated. All cervids were culled but Pronghorn, Bighorn Sheep and Mountain goat, where present simultaneously in the facility, were retained. There have been no cases of CWD in these non cervid species.

 

A few cases continue to occur at Sybille, the last was 4 months ago.

 

24

 

An account of the occurrence of CWD at the Colorado facility was obtained from Terry spraker, Diagnostic Laboratory, CSU College of Veterinary Medicine, Fort Collins. He examined tissues from cases of CWD at the Colorado facility some time prior to Beth Williams's involvement and examination of brains which resulted in the initial diagnosis. The deer holding facilities in Colorado comprise the Colorado Division of Wildlife Research Pen, established 10 years ago and some older deer pens at the Foot Hills Campus of CSU, close to Fort Collins. Originally there were just 1-2 cases CWD/year and a total of 24 over several years. In contrast to Beth Williams recollection Terry Spraker thought more cases had‘ occurred at Sybille than in Colorado. The cull at the Colorado facility involved 20-30 clinically normal deer. Early lesions in dorsal nucleus of the vagus and olfactory cortex were found in (some) of these deer. At the time of the cull here Pronghorn was the only other hoofed species present. Bighorn sheep and Mountain Goat were introduced only one year after the cull and occupied ground where CWD had occurred. Immediately after depopulation the ground was ploughed and disinfection was carried out using ?1% NaOH. The buildings/pens were not changed. There has been no recurrence of disease at the Colorado facility since the cull.

 

25

 

Transmission Studies

 

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases (‘’first passage by this route’’ MARKED OUT...TSS) resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. one control animal became affected, it is J believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in all of these species with the shortest incubation period in the ferret.

 

Mouse and hamster transmissions were attempted at Wyoming State Diagnostic Laboratory, Laramie and at CSU Fort Collins but were unsuccessful.

 

Also at the Wyoming State Diagnostic Laboratory, Laramie, transmission to goats was attempted. In 1984 three goats were inoculated intracerebrally with a 10% CWD brain suspension. one goat, untreated, was placed in contact with the CWD inoculated goats and three controls, housed separately, received saline intracerebrally. To date these animals remain healthy.

 

Epidemiology of CWD

 

Descriptive epidemiological data has been collected from the two wildlife facilities and a publication is in preparation.

 

The occurrence of CWD must be viewed against the context of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province! Thus

 

26

 

there have been no specific epidemiological studies, other than information gained from noting the occurrence of cases. Because of the relatively short term nature of the programmed research at the facilities it has not been possible to keep Mule Deer under the appropriate experimental circumstances or for sufficient periods to establish horizontal or maternal transmission. Beth Williams is of the view that the occurrence of CWD at Sybille is entirely related to propagative spread by contagion. Investigations have failed to identify any common source of infection and the incident has presented a protracted time course with sporadic cases throughout. There is no evidence that wild born deer were responsible for introduction of the disease to the facility.

 

I asked Hughie Dawson about the nutritional aspects of the deer kept at Sybille. Mule Deer calves are reared on condensed milk and homogenised or pasteurised domestic cow's milk from birth to 1 month or to 6 months. some would be given "Lamb milk replacer" which has a higher butter fat content than either of the former products, but is derived also from domestic cow's milk. It was thought that at the Colorado facility calves would receive only "evaporated milk". Calves are weaned on to a pelletted feed containing corn, wheat bran and linseed meal with no crude mineral suppliment. Salt licks ("sulphur blocks") which have a specific mineral composition are supplied.

 

CWD has occurred or is suspected to have occurred in establishments supplied with Mule Deer from the Colorado facility. In some cases evidence for this is tenuous. For example, it is understood that Denver zoo state that "they have not had cases of CWD" and yet they have had cases of Mule Deer succumbing to a chronic wasting disorder which was not diagnosed. A case of CWD occurred in a Mule Deer in Toronto zoo in 1976. The animal in

 

27

 

question came from Denver zoo but was originally from the Colorado wildlife facility.

 

Pathology of CWD

 

A paper (Williams et al) is in preparation on the distribution of brain lesions in CWD. Vacuolar changes occur predominantly in the dorsal nucleus of the vagus nerve (this nucleus is invariably affected), the hypothalamus and the olfactory cortex with occasional vacuolation of the olfactory tract white matter.

 

Cerebellar lesions are sometimes present but there are very few changes in the spinal cord which probably accounts for the rarity of ataxia clinically. As in sheep scrapie the hypothalamic lesions correlate with the common clinical occurrence of polydipsia. Beth Williams is aware of occasional neuronal vacuoles occurring in the red nucleus of clinically normal deer! Spraker has added that he has experienced vacuoles in neurons of Gasserian ganglia and at the level of the obex in normal deer.

 

It has never been reported but Pat Merz carried out SAF detection on CWD brain material. Work may be undertaken with NIH on the immunohistological demonstration of PrP in sections but to date there has been no PrP work.

 

Does CWD occur in free-living cervids?

 

There is some, mostly circumstantial, evidence that CWD occurs in free-living cervids but to what extent, if at all, this represents an established reservoir of infection in the wild is not known.

 

At Sybille two Mule Deer orphans (wild caught) and a White—tail Deer (Odocoileus virginianus) hybrid developed clinical signs when only 2 1/2 years of age.

 

28

 

An Elk (Cervus canadensis) wild caught as an adult, presumed 2 years old, developed signs when 3-4 years old.

 

Another group of elk, wild caught 400 miles from the facility, with an age range 2-8 years, old subsequently developed the disease in the facility (?period of captivity). The location of capture relative to the facility did not apparently rule out that they may have at some time had fence-line nose contact with animals in the facility!

 

Cases have also occurred in Mule Deer that were obtained from the wild within one hour of birth but these were never kept completely isolated through to maturity.

 

Also at Sybille there has been one case of CWD diagnosed in a free ranging Elk. It was killed in Sybille Canyon 3 miles from the facility. It could have had fence-line contact with captive Mule Deer in the facility.

 

Similar incidents had occurred in Colorado. In 1985 a free-ranging affected Elk was caught in the Rocky Mountain National Park within a 2 mile radius of the Colorado Division of Wildlife Research Pen. In 1986 and again in 1987 a single affected Mule Deer on each occasion was caught within a 5 mile radius of the Pen. These latter cases occurred within 2 years of the -cervid cull at the Pen (?1985). Brain tissue from the free—ranging Elk brain was inoculated into mice but for some reason these were kept for only 6 months and then the experiment was abandoned.

 

A specific exercise has been carried out by Beth Williams with the Wyoming State Diagnostic Laboratory and Fish Department to sample the brains of healthy wild Mule Deer for histological examination. On two separate occasions the first in 1985 and again in 1987 a total of 150 Mule Deer

 

29

 

brains were collected from areas of, and ajacent to, Sybille Canyon. These deer would have been shot under a game permit by local hunters. As they were brought down from the hills to the Game station for the mandatory registration of the kill the heads were removed and ages estimated. Most were 2-5 year old with a few 6 year old. For obvious reasons hunters were reluctant to give up stag heads. Thus, but for 15-20 brains from stags, examinations were on brains from females. No evidence of CWD lesions was found in any of these brains. However, it was considered that sporadic cases of CWD, should they occur in the wild population, would soon become separated from the herd and fall prey to coyotes (Canis latrans).

 

The possibility of any reservoir of infection in wild cervids originating from scrapie in domestic sheep flocks seems remote. Scrapie has been recorded in only three flocks in Wyoming since 1947 and Beth Williams could recall only one previous occurrence in 1966. This had involved a Suffolk flock close to the border with Nebraska. However, there has been one new confirmed and a suspected affected flock this year in Wyoming. In the latter a ewe bought—in from an Illinois flock is incriminated.

 

Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr Bob Davis. At or about that time, allegedly, some" scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. Whether they were scrapie infected sheep or not is unclear. There were domestic sheep and goats present in the facility also in the 1960's but there is no evidence that these animals developed scrapie. During the 60's hybridization studies between the Bighorn and domestic sheep were carried

 

30

 

out, again, without evidence of scrapie. Domestic goats were also kept at Sybille in the 1960's.

 

Spraker considers that the nasal route is responsible for transmission of CWD through nose to nose contact, which may well occur also between captive and free—living individuals.

 

In domestic cattle of which about 15-20 adults were necropsied per year at the Diagnostic Laboratory, CSU., Spraker had not encountered any lesions suggesting BSE. Polioencephalomalacia (PEM) and Encephalic Listeriosis were the most common morphologic neuropathological diagnoses. No bovine rabies was seen.

 

31

 

Appendix I

 

VISIT TO USA - OR A E WRATHALL — INFO ON BSE AND SCRAPIE

 

Dr Clark lately of the Scrapie Research Unit, Mission Texas has I successfully transmitted ovine and caprine Scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is:-

 

Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a 2nd Suffolk scrapie passage:- i/c 1ml; i/m, 5ml; s/c 5ml; oral 30ml.

 

1/6 went down after 48 months with a scrapie/BS2-like disease.

 

Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus 2/6 went down similarly after 36 months.

 

Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.

 

Diagnosis in A, B, C was by histopath. No reports on SAF were given.

 

2. Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally— (and naturally) infected sheep by ET. He had found difficulty in obtaining embryos from naturally infected sheep (cf SPA).

 

3. Prof. A Robertson gave a brief accout of BSE. The us approach was to

 

32

 

accord it a very low profile indeed. Dr A Thiermann showed the picture in the "Independent" with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in USA.

 

4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.

 

5. Scrapie agent was reported to have been isolated from a solitary fetus.

 

6. A western blotting diagnostic technique (? on PrP) shows some promise.

 

7. Results of a questionnaire sent to 33 states on" the subject of the national sheep scrapie programme survey indicated

 

17/33 wished to drop it

 

6/33 wished to develop it

 

8/33 had few sheep and were neutral

 

Information obtained from Dr Wrathall‘s notes of a meeting of the U.S. Animal Health Association at Little Rock, Arkansas Nov. 1988.

 

33

 

snip...see full text ;

 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

 

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...

 


 

CHRONIC WASTING DISEASE CWD TSE PRION ROUNDUP USA 2016 UPDATE

 

Friday, April 22, 2016

 

*** COLORADO CHRONIC WASTING DISEASE CWD TSE PRION SURVEILLANCE AND TESTING PROGRAM IS MINIMAL AND LIMITED ***

 


 

Monday, April 25, 2016

 

Arkansas AGFC Phase 2 sampling reveals CWD positive deer in Madison and Pope counties

 


 

Tuesday, April 19, 2016

 

Arkansas First Phase of CWD sampling reveals 23 percent prevalence rate in focal area With 82 Confirmed to Date

 


 

Saturday, April 02, 2016

 

TEXAS TAHC BREAKS IT'S SILENCE WITH TWO MORE CASES CWD CAPTIVE DEER BRINGING TOTAL TO 10 CAPTIVES REPORTED TO DATE

 


 

Friday, February 26, 2016

 

TEXAS Hartley County Mule Deer Tests Positive for Chronic Wasting Disease CWD TSE Prion

 


 

Friday, February 05, 2016

 

TEXAS NEW CHRONIC WASTING DISEASE CWD CASE DISCOVERD AT CAPTIVE DEER RELEASE SITE

 


 

Wednesday, April 20, 2016

 

TVMDL hosts legislative representatives, discusses CWD

 


 

Monday, April 25, 2016

 

TEXAS Nilgai Exotic Antelope Let Loose for Trophy Hunts Blamed for Spreading Cattle Tick Fever, and what about CWD TSE Prion Disease ?

 


 

Friday, April 22, 2016

 

Missouri MDC finds seven new cases of ChronicWasting Disease CWD during past‐season testing

 


 

Wednesday, April 20, 2016

 

UTAH CHRONIC WASTING DISEASE CWD TSE PRION SURVEILLANCE AND TESTING PROGRAM 70 mule deer and two elk have tested positive

 


 

WISCONSIN CWD CASES OUT OF CONTROL

 

Wednesday, March 16, 2016 Wisconsin CWD sample survey 2015 confirms 290 cases of Chronic Wasting Disease TSE Prion

 


 

Wednesday, February 10, 2016

 

Wisconsin Two deer that escaped farm had chronic wasting disease CWD

 


 

Friday, June 01, 2012

 

*** TEXAS DEER CZAR TO WISCONSIN ASK TO EXPLAIN COMMENTS

 


 

Tuesday, July 10, 2012

 

Dr. James C. Kroll Texas deer czar final report on Wisconsin

 


 

KANSAS CWD CASES ALARMING

 

Wednesday, March 02, 2016 Kansas Chronic Wasting Disease CWD TSE Prion 52 cases 2015 updated report 'ALARMING'

 


 

Tuesday, February 02, 2016

 

Illinois six out of 19 deer samples tested positive for CWD in the Oswego zone of Kendall County

 


 

Thursday, March 31, 2016

 

*** Chronic Wasting Disease CWD TSE Prion Roundup USA 2016 ***

 


 

Comment from Terry S. Singeltary Sr. Return to Docket Folder Summary This is a Comment on the Food and Drug Administration (FDA) Notice: Risk Assessment of Foodborne Illness Associated With Pathogens From Produce Grown in Fields Amended With Untreated Biological Soil Amendments of Animal Origin; Request for Scientific Data, Information, and Comments

 

For related information, Open Docket Folder Docket folder icon

 

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Show agency attachment(s) AttachmentsView All (0)

 

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Comment View document:Greetings FDA et al, I kindly would like to make comment submission to ;

 

Docket No. FDA-2016-N-0321 Risk Assessment of Foodborne Illness Associated with Pathogens from Produce Grown in Fields Amended with Untreated Biological Soil Amendments of Animal Origin; Request for Comments, Scientific Data, and Information

 

A Notice by the Food and Drug Administration on 03/04/2016

 

MY comment as follows,

 

There has been proven documented risk for Untreated Biological Soil Amendments of Animal Origin and risk of transmitting Transmissible Spongiform Encephalopathy TSE Prion disease aka mad cow type disease such as the typical and atypical Bovine Spongiform Encephalopathy strains, typical and atypical Scrapie strains, typical and atypical Chronic Wasting Disease CWD strains, and even the Transmissible Mink Encephalopathy TME Prion disease.

 

Science has shown that infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces thereby leading to transmission by direct contact and environmental contamination.

 

Ingestion of prion contaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate.

 

Plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves) [please see data from Soto et al Prion2015 Conference below in Science reference data].

 

Also, Detection of protease-resistant cervid prion protein in water from a CWD-endemic area is very concerning.

 

Science has shown that soil plays a role in the spreading and transmission of the CWD and Scrapie TSE prion agent.

 

For these reason and more (see reference materials) I urge the FDA to stop this practice of Untreated Biological Soil Amendments of Animal Origin, including blood, for use on our produce grown in fields, for the following reasons,

 

please see attachments and updated TSE Prion science on these very important matters here (I do not advertise or make money the science is there for educational use for Transmissible Spongiform Encephalopathy TSE Prion disease.

 

just made a promise to mom dod 12/14/97 confirmed Heidenhain Variant Creutzfeldt Jakob Disease, hvCJD. ... AttachmentsView All (1) Comment from Terry S Singeltary Sr View Attachment:

 


 


 

Tuesday, March 15, 2016

 

Docket No. FDA-2016-N-0321 Risk Assessment of Foodborne Illness Associated with Pathogens from Produce Grown in Fields Amended with Untreated Biological Soil Amendments of Animal Origin; Request for Comments, Scientific Data, and Information Singeltary Submission

 


 

 

 

Comment from Terry Singeltary

 

Comment Period Closed

 

Jun 3 2015, at 11:59 PM ET

 

This is a Comment on the Food and Drug Administration (FDA) Notice: Draft Guidance for Industry on Ensuring Safety of Animal Feed Maintained and Fed On-Farm; Availability

 


 

Comment from Terry S Singletary

 

Comment Period Closed

 

Nov 24 2006, at 11:59 PM ET

 

This is a Comment on the Animal and Plant Health Inspection Service (APHIS) Proposed Rule: Bovine Spongiform Encephalopathy; Minimal-Risk Regions, Identification of Ruminants and Processing and Importation of Commodities

 


 

 

 

***These results suggest that cattle experimentally inoculated with CWD may have some limited amount of prion infectivity outside of the brain and spinal cord that may represent a previously unrecognized risk for transmission. This information could have an impact on regulatory officials developing plans to reduce or eliminate TSEs and farmers with concerns about ranging cattle on areas where CWD may be present.***

 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

Title: Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle Authors

 

item Haley, Nicholas - item Siepker, Christopher - item Greenlee, Justin item Richt, Jürgen -

 

Submitted to: Journal of General Virology Publication

 

Type: Peer Reviewed Journal Publication Acceptance

 

Date: March 30, 2016 Publication Date: N/A Interpretive

 

Summary: Chronic Wasting Disease (CWD), a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Cattle could be exposed to chronic wasting disease (CWD) by contact with infected farmed or free-ranging cervids. The purpose of this study was to use an in vitro amplification method called real time quaking induced conversion (RT-QuIC) to assess tissues from cattle inoculated with CWD for low levels of prions not detected by traditional diagnostic methods such as western blot and immunohistochemistry. This study reports that prions were identified by RT-QuIC only in cattle that were confirmed positive by traditional methods. However, prions were rarely identified in some peripheral tissues such as mesenteric lymph node, tonsil, or nasal turbinate that were not considered positive by traditional methods. These results suggest that cattle experimentally inoculated with CWD may have some limited amount of prion infectivity outside of the brain and spinal cord that may represent a previously unrecognized risk for transmission. This information could have an impact on regulatory officials developing plans to reduce or eliminate TSEs and farmers with concerns about ranging cattle on areas where CWD may be present.

 

Technical Abstract: Chronic wasting disease (CWD) is a fatal neurodegenerative disease, classified as a prion disease or transmissible spongiform encephalopathy (TSE) similar to bovine spongiform encephalopathy (BSE). Cervids affected by CWD accumulate an abnormal protease resistant prion protein throughout the central nervous system (CNS), as well as in both lymphatic and excretory tissues – an aspect of prion disease pathogenesis not observed in cattle with BSE. Using seeded amplification through real time quaking induced conversion (RT-QuIC), we investigated whether the bovine host or prion agent was responsible for this aspect of TSE pathogenesis. We blindly examined numerous central and peripheral tissues from cattle inoculated with CWD for prion seeding activity. Seeded amplification was readily detected in the CNS, though rarely observed in peripheral tissues, with a limited distribution similar to that of BSE prions in cattle. This seems to indicate that prion peripheralization in cattle is a host-driven characteristic of TSE infection.

 


 

These results suggest that cattle experimentally inoculated with CWD may have some limited amount of prion infectivity outside of the brain and spinal cord that may represent a previously unrecognized risk for transmission. This information could have an impact on regulatory officials developing plans to reduce or eliminate TSEs and farmers with concerns about ranging cattle on areas where CWD may be present.

 

Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease - (Abstract Only) - (12-Aug-15) Transmission of chronic wasting disease to sentinel reindeer (Rangifer tarandus tarandus) - (Abstract Only) - (12-Aug-15) Transmission of scrapie prions to primate after an extended silent incubation period - (Peer Reviewed Journal) Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573. Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles - (Abstract Only) Greenlee, J., Moore, S.J., Smith, J.., West Greenlee, M.H., Kunkle, R. 2015. Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum. Prion 2015. p. S62.

 

Monday, April 04, 2016

 

Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle

 


 

LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ *** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249 PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS *** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE *** O18 Zoonotic Potential of CWD Prions Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA *** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection. ================== ***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.*** ================== P.105: RT-QuIC models trans-species prion transmission Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD. ***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated. ================ ***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.*** ================ https://prion2015.files.wordpress.com/2015/05/programguide1.pdf *** PRICE OF CWD TSE PRION POKER GOES UP 2014 *** Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014 *** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein. *** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype. http://wwwnc.cdc.gov/eid/article/20/1/13-0858_article.htm http://chronic-wasting-disease.blogspot.com/2014/01/molecular-barriers-to-zoonotic.html *** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249 *** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies. http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf Chronic Wasting Disease and Potential Transmission to Humans Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,† Michael W. Miller,‡ Pierluigi Gambetti,§ and Lawrence B. Schonberger* Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWDassociated prions has been demonstrated in an in vitro cellfree experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions. Conclusions The lack of evidence of a link between CWD transmission and unusual cases of CJD, despite several epidemiologic investigations, and the absence of an increase in CJD incidence in Colorado and Wyoming suggest that the risk, if any, of transmission of CWD to humans is low. Although the in vitro studies indicating inefficient conversion of human prion protein by CWD-associated prions raise the possibility of low-level transmission of CWD to humans, no human cases of prion disease with strong evidence of a link with CWD have been identified. However, the transmission of BSE to humans and the resulting vCJD indicate that, provided sufficient exposure, the species barrier may not completely protect humans from animal prion diseases. Because CWD has occurred in a limited geographic area for decades, an adequate number of people may not have been exposed to the CWD agent to result in a clinically recognizable human disease. The level and frequency of human exposure to the CWD agent may increase with the spread of CWD in the United States. Because the number of studies seeking evidence for CWD transmission to humans is limited, more epidemiologic and laboratory studies should be conducted to monitor the possibility of such transmissions. Studies involving transgenic mice expressing human and cervid prion protein are in progress to further assess the potential for the CWD agent to cause human disease. Epidemiologic studies have also been initiated to identify human cases of prion disease among persons with an increased risk for exposure to potentially CWD-infected deer or elk meat (47). If such cases are identified, laboratory data showing similarities of the etiologic agent to that of the CWD agent would strengthen the conclusion for a causal link. Surveillance for human prion diseases, particularly in areas where CWD has been detected, remains important to effectively monitor the possible transmission of CWD to humans. Because of the long incubation period associated with prion diseases, convincing negative results from epidemiologic and experimental laboratory studies would likely require years of follow-up. In the meantime, to minimize the risk for exposure to the CWD agent, hunters should consult with their state wildlife agencies to identify areas where CWD occurs and continue to follow advice provided by public health and wildlife agencies. Hunters should avoid eating meat from deer and elk that look sick or test positive for CWD. They should wear gloves when field-dressing carcasses, boneout the meat from the animal, and minimize handling of brain and spinal cord tissues. As a precaution, hunters should avoid eating deer and elk tissues known to harbor the CWD agent (e.g., brain, spinal cord, eyes, spleen, tonsils, lymph nodes) from areas where CWD has been identified. https://cpw.state.co.us/Documents/Hunting/BigGame/CWD/PDF/ResearchArticles/EID_CDWPotTrans.pdf now, let’s see what the authors said about this casual link, personal communications years ago. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans” From: TSS (216-119-163-189.ipset45.wt.net) Subject: CWD aka MAD DEER/ELK TO HUMANS ??? Date: September 30, 2002 at 7:06 am PST From: "Belay, Ermias" To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias" Sent: Monday, September 30, 2002 9:22 AM Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated. Ermias Belay, M.D. Centers for Disease Control and Prevention -----Original Message----- From: Sent: Sunday, September 29, 2002 10:15 AM To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS Thursday, April 03, 2008 A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ. snip... *** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***, snip... full text ; http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html CJD is so rare in people under age 30, one case in a billion (leaving out medical mishaps), that four cases under 30 is "very high," says Colorado neurologist Bosque. "Then, if you add these other two from Wisconsin [cases in the newspaper], six cases of CJD in people associated with venison is very, very high." Only now, with Mary Riley, there are at least seven, and possibly eight, with Steve, her dining companion. "It's not critical mass that matters," however, Belay says. "One case would do it for me." The chance that two people who know each other would both contact CJD, like the two Wisconsin sportsmen, is so unlikely, experts say, it would happen only once in 140 years. Given the incubation period for TSEs in humans, it may require another generation to write the final chapter on CWD in Wisconsin. "Does chronic wasting disease pass into humans? We'll be able to answer that in 2022," says Race. Meanwhile, the state has become part of an immense experiment. https://www.organicconsumers.org/old_articles/madcow/killer123103.php I urge everyone to watch this video closely...terry *** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans *** http://zoomify.uzh.ch:8080/zoomify/videos/video-004/video-004.html Envt.07: Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease ***The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans. http://www.landesbioscience.com/journals/prion/Prion5-Supp-PrionEnvironment.pdf?nocache=1333529975 Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Rachel C. Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡, Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ snip... Abstract The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure. http://www.sciencemag.org/content/311/5764/1117.long ***********CJD REPORT 1994 increased risk for consumption of veal and venison and lamb*********** CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994 Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ... Table 9 presents the results of an analysis of these data. There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01). Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal. There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51). The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02). The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08). snip... It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05). snip... In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ... snip... In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS) snip...see full report ; http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf CJD9/10022 October 1994 Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ Dear Mr Elmhirst, CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published. The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication. The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department. The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme. I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all. http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf *** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249 O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. *** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, ***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), ***is the third potentially zoonotic PD (with BSE and L-type BSE), ***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. =============== ***thus questioning the origin of human sporadic cases*** =============== ***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. ============== https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Title: Transmission of scrapie prions to primate after an extended silent incubation period Authors item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe - Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573. Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans. Technical Abstract: Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. *** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. *** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. *** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160 why do we not want to do TSE transmission studies on chimpanzees $ 5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis. snip... R. BRADLEY http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

 

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

 

Taylor & Francis

 

Prion 2016 Animal Prion Disease Workshop Abstracts

 

WS-01: Prion diseases in animals and zoonotic potential

 

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

 

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

 

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

 

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

 

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

 

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

 

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 


 

Saturday, April 23, 2016

 

*** SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016 ***

 

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

 


 

Sunday, November 23, 2014

 

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European

 

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas

 

Updated: October 7, 2014

 

CDC and the Texas Department of State Health Services (DSHS) have completed the investigation of the recently reported fourth vCJD case in the United States. It confirmed that the case was in a US citizen born outside the Americas and indicated that the patient's exposure to the BSE/vCJD agent most likely occurred before he moved to the United States; the patient had resided in Kuwait, Russia and Lebanon. The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia.

 

***The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.

 


 

2015 PRION CONFERENCE

 

*** RE-P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

 

***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. ***

 

P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

 

Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA

 

Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’ infections in UK residents emphasize the continued need for information about disease risk in humans. A large study of blood component infectivity in a non-human primate model has now been completed and analyzed. Among 1 GSS, 4 sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6 year surveillance period. A transmission study in recipients of multiple whole blood transfusions during the incubation and clinical stages of sCJD and vCJD in ic-infected donor animals was uniformly negative. These results, together with other laboratory studies in rodents and nonhuman primates and epidemiological observations in humans, suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. The issue of decades-long incubation periods in ‘silent’ vCJD carriers remains open.

 


 

ran across an old paper from 1984 ;

 

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent. ***

 


 

From: Terry S. Singeltary Sr.

 

Sent: Saturday, November 15, 2014 9:29 PM

 

To: Terry S. Singeltary Sr.

 

Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984

 

THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE

 

R. G. WILL

 

1984

 

snip...

 


 

THE BAXTER STUDY...SEE MORE HERE ;

 


 


 

Saturday, May 30, 2015

 

PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS

 


 

Wednesday, December 11, 2013

 

*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***

 


 

THE BAXTER STUDY...SEE MORE HERE ;

 


 

Thursday, September 10, 2015

 

25th Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015

 


 


 


 


 

Saturday, April 23, 2016

 

*** v-CJD prion distribution in the tissues of patients at preclinical and clinical stage of the disease ***

 


 

Thursday, April 14, 2016

 

*** Arizona 22 year old diagnosed with Creutzfeldt Jakob Disease CJD ***

 


 

Sunday, November 23, 2014

 

*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European ***

 


 

*** IATROGENIC vpspr-sgss-sffi-tse-prion what if ? ***

 


 

Thursday, September 10, 2015

 

25th Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015

 


 

Tuesday, April 21, 2015

 

Transmissible Spongiform Encephalopathy Advisory Committee TSEAC MEETING SCHEDULED FOR June 1, 2015

 


 

TSE Prion and blood transfusion: will there be additional cases? this should be the concern. ...TSS

 

Thursday, March 26, 2015

 

Variant CJD and blood transfusion: are there additional cases?

 

Vox Sanguinis (2014) 107, 220–225 ORIGINAL PAPER © 2014 International Society of Blood Transfusion DOI: 10.1111/vox.12161

 


 

Tuesday, December 30, 2014

 

TSEAC USA Reason For Recalls Blood products, collected from a donors considered to be at increased risk for Creutzfeldt-Jakob Disease (CJD), were distributed END OF YEAR REPORT 2014

 


 

Sunday, March 09, 2014

 

A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease

 

FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES

 


 

Sunday, June 9, 2013

 

TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory Committee Meeting Webcast

 


 

Wednesday, June 29, 2011

 

TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

 


 

Wednesday, June 29, 2011 TSEAC JUNE 2, 1999 Welcome to the FDA traveling road show From: TSS

 

Subject: TSEAC JUNE 2, 1999 Welcome to the FDA traveling road show

 

Date: October 15, 2007 at 3:18 pm PST

 

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE MEETING Thursday, June 2, 1999

 


 

Wednesday, March 2, 2011

 

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript Posted: 3/2/2011 Posted: 3/2/2011

 

October 28, 2010

 

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript Posted: 3/2/2011

 


 

Monday, February 7, 2011

 

FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

 


 

October 28, 2010:

 

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript

 


 

October 29, 2010

 

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript Posted: 3/2/2011

 


 

Monday, October 18, 2010

 

TSEAC Transmissible Spongiform Encephalopathies Advisory Committee Draft Agenda and Meeting Materials,

 

Posted: 10/18/2010

 

Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Center Date Time Location

 


 

Tuesday, September 14, 2010

 

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

 


 

Saturday, September 5, 2009

 

TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS

 


 

Sunday, May 10, 2009

 

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)

 

TO : william.freas@fda.hhs.gov

 

May 8, 2009

 

Greetings again Dr. Freas, TSEAC et al,

 

I would kindly, once again, wish to comment at this meeting about the urgent actions that need to be taken asap, to the Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009. Due to my disability from my neck injury, I will not be attending this meeting either, however I hope for my submission to be read and submitted. ...

 

IN reply to ;

 


 

snip...see full text ;

 

Sunday, May 10, 2009

 

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)

 

TO : william.freas@fda.hhs.gov

 


 

Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website:

 


 

Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary. This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

 


 

From: Terry S. Singeltary Sr.

 

To: FREAS@CBER.FDA.GOV

 

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

 

Sent: Friday, December 01, 2006 2:59 PM

 

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION

 

snip...

 

ONE FINAL COMMENT PLEASE, (i know this is long Dr. Freas but please bear with me)

 

THE USA is in a most unique situation, one of unknown circumstances with human and animal TSE. THE USA has the most documented TSE in different species to date, with substrains growing in those species (BSE/BASE in cattle and CWD in deer and elk, there is evidence here with different strains), and we know that sheep scrapie has over 20 strains of the typical scrapie with atypical scrapie documented and also BSE is very likely to have passed to sheep. all of which have been rendered and fed back to animals for human and animal consumption, a frightening scenario. WE do not know the outcome, and to play with human life around the globe with the very likely TSE tainted blood from the USA, in my opinion is like playing Russian roulette, of long duration, with potential long and enduring consequences, of which once done, cannot be undone.

 

These are the facts as i have come to know through daily and extensive research of TSE over 9 years, since 12/14/97. I do not pretend to have all the answers, but i do know to continue to believe in the ukbsenvcjd only theory of transmission to humans of only this one strain from only this one TSE from only this one part of the globe, will only lead to further failures, and needless exposure to humans from all strains of TSE, and possibly many more needless deaths from TSE via a multitude of proven routes and sources via many studies with primates and rodents and other species. ...

 

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

 

snip... 48 pages...

 


 


 

Wednesday, October 17, 2007

 

TSEAC MEETINGS

 

----- Original Message -----

 

From: Terry S. Singeltary Sr.

 

To: FREAS@CBER.FDA.GOV

 

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

 

Sent: Wednesday, November 29, 2006 1:24 PM

 

Subject: TSE advisory committee for the meeting December 15, 2006 [TSSSUBMISSION]November 29, 2006

 

Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,

 

a kind and warm Holiday Greetings to you all.i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derivedantihemophilic factor (FVIII) productsmanufactured from U.S. plasma donors and related communication material ;

 


 

i see the media picked up on this as a 'low risk', from what the gov. agency perceived to be to them;

 


 

 Unofficial Summary

 

for the

 

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

ADVISORY COMMITTEE Meeting on

 

December 15, 2006

 


 

 

 

There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

 

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.

 

 

 


 


 

 

 

 [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle

 


 

 [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

 


 

 

 

2001 Docket Singeltary Submission ;

 


 

however, i seem to disagree. from my primitive ciphering, i see it another way. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, wha tabout the mixed genotypes/mixed susceptibility?

 

what about the silent carriers that donated tainted blood?

 

what about the sporadic CJDs of UNKNOWN strain or phenotype?

 

this risk assessment is just more BSe to me. just another in a long line of industry fed crap. i pray that my assessment is the one that is wrong. but it is THEY who roll the dice with your life. it is THEY who refuse to regulate an industry that has run amok. just from are call aspect of potentially tainted blood, and these are just recent recalls ; ...SNIP...END...TSS

 

*** IATROGENIC vpspr-sgss-sffi-tse-prion what if ? ***

 


 

Saturday, September 21, 2013

 

CJD CONFIRMED in patient at New Hampshire Department of Health and Human Services (DHHS), Catholic Medical Center (CMC), and the Manchester Health Department (MHD)

 


 

Tuesday, May 26, 2015

 

Minimise transmission risk of CJD and vCJD in healthcare settings Last updated 15 May 2015

 


 

Miss Storms, Olympus et al stated ;

 

>>> As duodenoscopes do not contact tissue at high risk associated with CJD, ...snip...end <<<

 

BUT, duodenoscopes DO contact medium to low dose TSE prion infections tissues, if the person being scoped is silently harboring a CJD TSE prion, thus exposing everyone after that to the CJD TSE prion disease. I am very well aware of the old study by Gibbs et al, and those brain electrodes ;

 

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

 

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

 


 

regardless of how many lives endoscopy equipment saves ever year, I strongly, strenuously, urge Olympus to warn their product users, and consumers, that there is NO KNOWN way to date, that will completely clean and decontaminate the endoscopy equipment from the CJD TSE prion disease, and they risk exposure to this agent when exposed to endoscopy equipment. anything less than that would be criminal in my opinion, with the documented science to date. these atypical strains of TSE prion disease are mutating, and as they mutate, they can, and have, become more virulent.

 

with the emergence of atypical strains of TSE prion in animals and humans, we cannot wait to prove a negative, while exposing millions waiting on that negative to come. the science to date, in my opinion, has shown us that this negative has not, and is not coming, thus, exposure, and friendly fire, i.e. iatrogenic, is the key to the 85%+ of all human TSE, i.e. sporadic CJD, and once the science is finally peeled all the way back, biomarkers of some sorts are discovered, and trace back of iatrogenic events are finally able to be documented and traced back to source, I believe that companies like Olympus, that chose to continue to expose millions, regardless of these facts, will be left for much litigation.

 

I strongly urge Olympus et al to state plainly these risk factors of their equipment to the CJD TSE prion like disease, for all to know and see, ASAP. ...

 

thank you, with kind regards, terry

 

Saturday, January 16, 2010

 

*** Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al ***

 

Evidence For CJD/TSE Transmission Via Endoscopes

 

From Terry S. Singletary, Sr flounder@wt.net 1-24-3

 

Terry S. Singeltary Sr., P.O. BOX 42, Bacliff, Texas 77518 USA

 


 

Professor Michael Farthing wrote:

 

Louise Send this to Bramble (author) for a comment before we post. Michael

 

snip...

 

Evidence For CJD/TSE Transmission Via Endoscopes

 

From Terry S. Singletary, Sr flounder@wt.net 1-24-3

 

I have researched human/animal TSEs now for over 5 years due to the death of my Mother from the Heidenhain Variant Creutzfeldt Jakob disease, one of six - known - variants of the infamous 'sporadic' CJD.

 

I did a little survey several years ago about CJD and ENDOSCOPY in 2001, and then went there again when another article was released recently. However, they seemed to only be concerned with the vCJD strain and risk from endoscopy equipment.

 

My concerns are if vCJD can be transmitted by blood, and there are now 6 variants of the infamous sporadic CJDs that they are documenting to date, how do they know that none of these 6 variants will not transmit the agent (prion) via blood?...especially since the sporadic CJDs are the only ones documented to date to transmit via the surgical arena and now that the CWD is spreading more and more, who knows about the cattle?

 

I would always read this study and it would bring me back to reality as to how serious/dangerous this agent is in the surgical/medical arena. You might want to read this short abstract from the late, great Dr. Gibbs twice, and let it really sink in. And please remember while reading some of these transmission studies, that most all, if not ALL these agents transmit freely to primates. Humans, of course, are primates.

 

Regarding claims that:

 

'Well, it has never been documented to transmit to humans."

 

There are two critical factors to think about:

 

A. CJD/TSEs in the USA are NOT reportable in most states and there is NO CJD/TSE questionnaire for most victims and their families, and the one they are now issuing asks absolutely nothing about route and source of the (prion) agent, only how the disease was diagnosed. Furthermore, the elderly are only very rarely autopsied, ie looking for Alzheimer's or 'FAST Alzheimer's' OR prion disease-related factors and phenomena, such as heart failure caused by disease.

 

B. It is unethical and against the law to do transmission studies of TSEs to humans, they are 100% FATAL.

 

I suggest you read these case studies about medical arena CJD transmission very carefully:

 

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

 

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

 

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

 


 

PLEASE REMEMBER, IN 55 YEARS AND OLDER, THE RATE OF DOCUMENTED CJD JUMPS TO ONE IN 9,000. but officials don’t tell you that either. carry on...

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

 

Terry S. Singeltary, Sr Bacliff, Tex

 

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

 


 

26 March 2003

 

Terry S. Singeltary, retired (medically) CJD WATCH

 

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

 


 

2 January 2000

 

British Medical Journal

 

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

 


 

The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

 

Tracking spongiform encephalopathies in North America

 

Original

 

Xavier Bosch

 

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt—Jakob ...

 


 

Terry S. Singeltary Sr. Declares a DECLARATION OF EXTRAORDINARY EMERGENCY DUE TO A FOREIGN ANIMAL DISEASE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION CHRONIC WASTING DISEASE CWD IN THE UNITED STATES AND NORTH AMERICA.

 

Monday, April 11, 2016

 

DECLARATION OF EXTRAORDINARY EMERGENCY DUE TO A FOREIGN ANIMAL DISEASE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION CHRONIC WASTING DISEASE CWD IN THE UNITED STATES AND NORTH AMERICA ?

 


 

IN A NUT SHELL ;

 

(Adopted by the International Committee of the OIE on 23 May 2006)

 

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,

 


 

I have seen and proven that the USDA et al will do fraudulent deeds with regards to the TSE Prion aka mad cow type disease, all one has to do is read my FOIA reports on the mad sheep of mad river valley. I do not trust the USDA et al at all for this reason, and others...

 

Monday, April 11, 2016

 

*** DECLARATION OF EXTRAORDINARY EMERGENCY DUE TO A FOREIGN ANIMAL DISEASE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION CHRONIC WASTING DISEASE CWD IN THE UNITED STATES AND NORTH AMERICA ?

 


 

or, how the USDA et al employees out BSE TSE Prion testing, and this is not the first time either ;

 

Wednesday, March 2, 2016

 

*** RANCHO He did not know that they were placing healthy cow heads next to suspect carcasses BSE TSE Prion ***

 


 

or what Dr. Paul Brown of NIH said;

 

"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that." Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive.

 

USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general.

 

"Everything they did on the Texas cow makes everything they did before 2005 suspect," Brown said.

 


 

or former Ag Secretary Ann Veneman;

 

Thursday, October 22, 2015

 

*** Former Ag Secretary Ann Veneman talks women in agriculture and we talk mad cow disease USDA and what really happened ***

 


 

Thursday, January 14, 2016

 

*** EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address Future Risks Report to the Chairman, Committee on Energy and Commerce, House of Representatives December 2015 GAO-16-132

 

GAO

 


 

 

 

 

Greetings again Prion World,

 

well, Since I can’t gain access this year to Prion 2016 Japan Congressional Poster and Oral Abstracts and such (1st time ever, moratorium still holding on me for any access at all to Prion 2016, thanks to Taylor $ Francis et al). I guess I have reduced myself to getting excited over the titles to the abstracts. it does not take much to excite me at this age now I guess. I guess family and friends of victims of CJD TSE Prion disease, or anyone interested, are reduced again to secrecy from corporate science, reduced to guessing of what the TSE Prion science is doing, or not doing. rather disgusting imo, and after reading some of the title to these abstracts, I see why Corporate TSE Prion science DOES NOT WANT YOU TO READ THIS CJD TSE PRION 2016 cjd family...imo///

 

Prion 2016

 


 

Prion 2016

 

Purchase options Price * Issue Purchase USD 198.00

 


 

‘’IN CONFIDENCE’’ flounder9@verizon.net

 

 

2001

 


 

 

Saturday, April 16, 2016

 

APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission

 


 

 

 Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net