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.
230
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.
231
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
http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052506.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery
http://chronic-wasting-
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
--------------------------------------------------------------------------------
Show agency attachment(s) AttachmentsView All (0)
--------------------------------------------------------------------------------
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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
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
