Monday, June 3, 2013

Unsuccessful oral transmission of scrapie from British sheep to cattle

Unsuccessful oral transmission of scrapie from British sheep to cattle

T. Konold, J. Spiropoulos, M. J. Chaplin, M. J. Stack, S. A. C. Hawkins, J. W. Wilesmith, G. A. H. Wells

Following the detection of bovine spongiform encephalopathy (BSE) in the UK, epidemiological studies identified a foodborne source with meat and bone meal (MBM) as the likely vehicle of infection (Wilesmith and others 1988). Subsequent studies demonstrated that the infectious agent is a transmissible spongiform encephalopathy (TSE) strain with uniform neuropathological, molecular and biological properties (Simmons and others 1996, Bruce 2003, Vidal and others 2005, Green and others 2005a, Stack and others 2011a). Furthermore, transmission studies implicated the BSE agent as the cause of variant Creutzfeldt-Jakob disease in human beings (Bruce and others 1997). However, the origin of the agent remains unknown. One hypothesis suggests that it was a strain of sheep scrapie in the UK (Wilesmith and others 1988). Recycling of this agent in MBM, and inclusion of MBM in ruminant feed prior to control measures, would inevitably have resulted in exposure of sheep, raising concerns that the BSE agent may have been established in the sheep population, possibly manifesting in disease indistinguishable from scrapie (Schreuder and Somerville 2003). The present study was initiated in 1997 to determine the susceptibility of cattle to the oral exposure of scrapie-affected brain by using pools of brains from scrapie-affected British sheep sourced during the BSE epidemic.

All procedures were carried out in accordance with the Animal (Scientific Procedures) Act 1986, under licence from the UK Government Home Office.


Within the constraints of the study design, the results do not support the hypothesis of potential pathogenicity of scrapie agents or the BSE agent in British sheep, to cattle by oral exposure. However, this negative finding does not refute the possibility of a sheep origin of the BSE agent. That scrapie strains are pathogenic for cattle by intracerebral inoculation has been shown previously in the USA (Cutlip and others 1994, Clark and others 1995, Robinson and others 1995) and from scrapie brain pools sourced from British sheep culled prior to and during the BSE epidemic (Konold and others 2006). While the cattle in these studies developed a TSE the resulting disease phenotypes did not resemble BSE (Konold and others 2006). Oral dosing of cattle with US isolates of scrapie (raw brain and brain processed to MBM) failed to produce disease in cattle kept up to eight years postdosing (Cutlip and others 2001). Although not addressed in the present study, it is possible, nevertheless, that the rendering processes used previously in the production of MBM in Britain, might have modified a scrapie agent to become pathogenic for cattle by the oral route.


Cattle may be susceptible to other scrapie strains not present in the pools, and these might include atypical scrapie, which has been retrospectively diagnosed in a sheep culled in the UK in 1987 (Webb and others 2009), and is likely to have been present in the British sheep population prior to the discovery of BSE in cattle. As cattle were exposed to a pool of scrapie-affected sheep brains, we also cannot exclude the possibility of interaction between strains, which may prevent the detection of supposedly more pathogenic strains for cattle like the BSE agent, as demonstrated by testing a mix of scrapie and BSE agents by WB (Baron and Biacabé 2001) or wild-type mouse bioassay (Green and others 2005b). Transgenic mice expressing the ovine or bovine prion protein gene, which were not available when the project was initiated, were used successfully to differentiate BSE from scrapie strains in mixed infections of sheep by intracerebral inoculation (Lantier and others 2009), but nothing is known about the potential for interaction of strains following oral exposure to a mixture of agents.

A kind greetings from Bacliff, Texas !

I have often pondered if the whole damn mad cow follies started over here in the USA, and somehow, the USA shipped it over to the UK ?

It happened with S. Korea and CWD, via Canada. see ;

The disease was confirmed only in elk in the Republic of Korea in 2001, 2004 and 2005. Epidemiological investigations showed that CWD was introduced via importation of infected elk from Canada between 1994 and 1997.

but I still am not so sure that the mad cow follies did not start long ago right here in the USA i.e. Richard Marsh and deadstock downer cattle to those mink, and then the USA shipped it to hell and back. just pondering out loud here. ...tss

The exact same recipe for B.S.E. existed in the U.S. for years

and years. In reading over the Qualitative Analysis of BSE

Risk Factors-1, this is a 25 page report by the

USDA:APHIS:VS. It could have been done in one page. The

first page, fourth paragraph says it all;

"Similarities exist in the two countries usage of continuous

rendering technology and the lack of usage of solvents,

however, large differences still remain with other risk factors

which greatly reduce the potential risk at the national level."

Then, the next 24 pages tries to down-play the high risks of

B.S.E. in the U.S., with nothing more than the cattle to sheep

ratio count, and the geographical locations of herds and flocks.

That's all the evidence they can come up with, in the next 24


Something else I find odd, page 16;

"In the United Kingdom there is much concern for a specific

continuous rendering technology which uses lower

temperatures and accounts for 25 percent of total output. This

technology was _originally_ designed and imported from the

United States. However, the specific application in the

production process is _believed_ to be different in the two


A few more factors to consider, page 15;

"Figure 26 compares animal protein production for the two

countries. The calculations are based on slaughter numbers,

fallen stock estimates, and product yield coefficients. This

approach is used due to variation of up to 80 percent from

different reported sources. At 3.6 million tons, the United

States produces 8 times more animal rendered product than

the United Kingdom."

"The risk of introducing the BSE agent through sheep meat and

bone meal is more acute in both relative and absolute terms in

the United Kingdom (Figures 27 and 28). Note that sheep

meat and bone meal accounts for 14 percent, or 61 thousand

tons, in the United Kingdom versus 0.6 percent or 22 thousand

tons in the United States. For sheep greater than 1 year, this is

less than one-tenth of one percent of the United States supply."

"The potential risk of amplification of the BSE agent through

cattle meat and bone meal is much greater in the United States

where it accounts for 59 percent of total product or almost 5

times more than the total amount of rendered product in the

United Kingdom."

Considering, it would only take _one_ scrapie infected sheep

to contaminate the feed. Considering Scrapie has run rampant

in the U.S. for years, as of Aug. 1999, 950 scrapie infected

flocks. Also, Considering only one quarter spoonful of scrapie

infected material is lethal to a cow. Considering all this, the

sheep to cow ration is meaningless. As I said, it's 24 pages of


To be continued...

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


Qualitative Assessment Considering the comparative factors presented, with the exception of some similarities in rendering practices, epidemiologic factors believed conducive to the introduction of BSE in the United Kingdom are significantly different in the United States. This is supported by the following points: Similar changes in the rendering practices have occurred in both countries. Continuous rendering accounts for the vast majority of all product produced. From 1977 to 1982, the portion of United Kingdom product rendered using hydrocarbon solvents dropped from 70 per-cent to 10 percent. Within the United States the decline was at least 5 years earlier with very little if any solvent in current use.

see full text ;

TME in mink was documented in the early 1960s. it was first thought that the TME out break was from scrapie infected sheep, until a investigation was done on feed practices at these mink facilities, and it was later found that the mink had been fed 95%+ dead stock downer cows. and later, the Late Richard Marsh tried to warn the feds of the pending mad cow debacle. they refused to listen. ... some interesting reading on pages 26 to 33


TME originates from feeding mink, scrapie infected materials...

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.


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

Tuesday, July 21, 2009

Transmissible mink encephalopathy - review of the etiology

Folia Neuropathologica 2/2009

full text of the article:

Transmissible mink encephalopathy – review of the etiology

Folia Neuropathol 2009; 47 (2): 195-204


A possible clue was provided during the Stetsonville TME outbreak in which the rancher fed his mink commercial feed (e.g., poultry, fish, cereal) and fresh meat primarily from sick or downer dairy cattle within a 50-mile radius of his ranch [37]. He did not recall including sheep products in his homemade feed ration. Upon reviewing prior TME outbreaks in the U.S. and Canada, in all four cases in which records were available and were not linked to a commercial feed plant, downer cattle were also included in the mink diet. The Stetsonville TME isolate, and subsequently additional TME isolates, were transmitted to cattle by intracerebral inoculation and the Stetsonville TME isolate was the first confirmed case of experimental transmission of a TSE/prion disease to cattle. What was striking was that upon experimental transmission of cattle TME back into mink by the oral and intracerebral routes, the incubation periods were similar to that found for mink passaged TME. Hence, the pathogenicity of the Stetsonville TME agent in mink was not altered upon passage into cattle, suggesting that a previously unrecognized TSE/prion disease in cattle may be the source of TME infection. Additional studies strongly suggest that TME has similarities to L-type BSE in transgenic mice compared to H-type or classical BSE [2]. Since the L-type BSE does not appear to be an infectious form of TSE/prion disease, the proposal by Marsh [35,37] that a rare TSE in cattle may be the source of TME infection seems plausible. This is particularly the case in Wisconsin, which has had the majority of TME in the USA and is a prominent dairy state with aged cattle being a primary source of fresh meat for mink ration. Since mink are a sentinel host it is not surprising that they may have been a key host in amplifying a rare cattle TSE disease. Another possible explanation for the high incidence of TME in Wisconsin is based on the recent identification of a mutation in the prion protein gene in cattle with atypical BSE. There may be cattle breeding stock in Wisconsin that carry a mutation in the prion protein gene that is linked to late onset disease and are also the source of TSE infection for mink TME outbreaks described in the 1960s and 1985.


To this end, mink were shown to be sensitive to scrapie [23,24]. Of interest, following i.c. inoculation with the UK source of scrapie from a Suffolk sheep only a single animal developed the disease. In contrast, American sources B-834 and B-957 from Suffolk sheep readily transmitted to mink. Also, in another outbreak of TME in Stetsonville, Wisconsin, USA, the affected mink were apparently fed with downer cattle but not scrapie-affected sheep [32], and thus TME may result from BSE transmission from cattle to mink [37]. TME is readily transmitted to cattle [26]. The suggestion that TME may result from transmission from infected cattle but not sheep was supported by recent data on phenotypic similarities of TME in cattle and L-type bovine spongiform encephalopathy (BSE) transmitted to ovine transgenic mice (TgOvPrP4) [2]. To this end, L-type of BSE and TME in TgOvPrP4 presented similar molecular mass of all 3 bands of PrPd. Unglycosylated PrPd in L-type BSE, bovine TME and typical BSE has the same molecular mass of approximately 18 kDa in contrast to that of diglycosylated PrPd species which was lower by 0.5-0.8 kDa in L-type BSE and bovine TME as compared to typical BSE. Furthermore, L-type BSE and bovine TME transmitted to TgOvPrP4 mice presented spongiform change of low intensity but PrPd was strongly expressed including amyloid plaques. Mink were also susceptible to BSE [44]. ...


please see full text and more here;

Saturday, December 01, 2007

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

Volume 13, Number 12–December 2007 Research

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

Thierry Baron,* Anna Bencsik,* Anne-Gaëlle Biacabe,* Eric Morignat,* andRichard A. Bessen†*Agence Française de Sécurité Sanitaire des Aliments–Lyon, Lyon, France; and†Montana State University, Bozeman, Montana, USA


Transmissible mink encepholapathy (TME) is a foodborne transmissible spongiform encephalopathy (TSE) of ranch-raised mink; infection with a ruminant TSE has been proposed as the cause, but the precise origin of TME is unknown. To compare the phenotypes of each TSE, bovine-passaged TME isolate and 3 distinct natural bovine spongiform encephalopathy (BSE) agents (typical BSE, H-type BSE, and L-type BSE) were inoculated into an ovine transgenic mouse line (TgOvPrP4). Transgenic mice were susceptible to infection with bovine-passaged TME, typical BSE, and L-type BSE but not to H-type BSE. Based on survival periods, brain lesions profiles, disease-associated prion protein brain distribution, and biochemical properties of protease-resistant prion protein, typical BSE had a distint phenotype in ovine transgenic mice compared to L-type BSE and bovine TME.The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4 mice suggest that L-type BSE is a much more likely candidate for the origin of TME than is typical BSE.



These studies provide experimental evidence that the Stetsonville TME agent is distinct from typical BSE but has phenotypic similarities to L-type BSE in TgOvPrP4 mice. Our conclusion is that L-type BSE is a more likely candidate for a bovine source of TME infection than typical BSE. In the scenario that a ruminant TSE is the source for TME infection in mink, this would be a second example of transmission of a TSE from ruminants to non-ruminants under natural conditions or farming practices in addition to transmission of typical BSE to humans, domestic cats, and exotic zoo animals(37). The potential importance of this finding is relevant to L-type BSE, which based on experimental transmission into humanized PrP transgenic mice and macaques, suggests that L-type BSE is more pathogenic for humans than typical BSE (24,38).

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Sophie Freire,1 Jürgen Richt,2 Justin Greenlee,3 Juan-Maria Torres,4 Paul Brown,1 Bob Hills5 and Jean-Philippe Deslys1

1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Kansas State University; Manhattan, KS USA; 3USDA; Ames, IA USA; 4INIA; Madrid, Spain; 5Health Canada; Ottawa, ON Canada†Presenting author; Email:

The epidemiology of Transmissible mink encephalopathy (TME) indicates an alimentary origin. Several inter-species transmission experiments have not succeeded in establishing with certainty any natural reservoir of this prion strain, although both ovine and bovine sources have been suspected. Cattle exposed to TME develop a spongiform encephalopathy that is distinct from classical Bovine Spongiform Encephalopathy (c-BSE).

Inoculation of c-BSE to cynomolgus macaque provided early evidence of a possible risk to humans, and remains an important model to define the risk of both primary (oral transmission from cattle to primate) and secondary (intravenous intra-species transmission) exposures. We have also evaluated the transmissibility of other cattle prion strains to macaques, including L- and H- atypical forms of BSE, namely BSE-L and BSE-H, and cattle-adapted TME.

BSE-L induced a neurological disease distinct from c-BSE. Peripheral exposures demonstrate the transmissibility of BSE-L by oral, intravenous, and intra-cerebral routes, with incubation periods similar to c-BSE. Cattle-adapted TME also induced a rapid disease in cynomolgus macaque. The clinical features, lesion profile, and biochemical signature of the induced disease was similar to the features observed in animals exposed to BSE-L, suggesting a link between the two prion strains. Secondary transmissions to a common host (transgenic mouse overexpressing bovine PrP) of cattle-TME and BSE-L before or after passage in primates induced diseases with similar incubation periods: like the c-BSE strain, these cattle strains maintained their distinctive features regardless of the donor species and passages.

If the link between TME and BSE-L is confirmed, our results would suggest that BSE-L in North America may have existed for decades, and highlight a possible preferential transmission of animal prion strains to primates after passage in cattle.


link url not available, please see PRION 2011 ;

ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE...

see page 17 here ;

3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle,

*** did not produce the same clinical signs of brain lesions characteristic of BSE. ***

3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345 3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.







Tuesday, November 17, 2009



"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"


''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$


page 9 of 14 ;

30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.

31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...

snip... see full text

Wednesday, July 28, 2010

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report



Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

Thursday, May 02, 2013

Chronic Wasting Disease (CWD) Texas Important Update on OBEX ONLY TEXTING


USDA 2003

We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back. Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS.

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.


Dr. Detwiler: It seems a good idea, but I'm not aware of it. Another important thing to get across to the public is that the negatives do not guarantee absence of infectivity. The animal could be early in the disease and the incubation period. Even sample collection is so important. If you're not collecting the right area of the brain in sheep, or if collecting lymphoreticular tissue, and you don't get a good biopsy, you could miss the area with the PRP in it and come up with a negative test. There's a new, unusual form of Scrapie that's been detected in Norway. We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back.

Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS .

Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.



Completely Edited Version PRION ROUNDTABLE

Accomplished this day, Wednesday, December 11, 2003, Denver, Colorado


snip...see ;

Tuesday, November 02, 2010


The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

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



Appendix I


1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has 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/BSE-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.

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 emhryos from naturally infected sheep (cf SPA).

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. 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.

please see ;

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


see ;


This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies.



Prusiner vs Maff on BSE brains, and delaying science for profits $




Furthermore, we showed that the strain responsible for iCJD is closely related to that of one patient with sCJD, and, more unexpectedly, that these agents were similar to the French scrapie strain studied (but different from the U.S. scrapie strain). This finding requires a cautious interpretation for several reasons, not least because of the inevitably limited number of TSE strains that can be studied by such a cumbersome method as strain typing. Nonetheless, it also prompts reconsideration of the possibility that, in some instances, sheep and human TSEs can share a common origin.


Friday, April 19, 2013

APHIS 2013 Stakeholder Meeting (March 2013) BSE TSE PRION

Thursday, May 30, 2013

World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease

U.S. gets top mad-cow rating from international group and risk further exposing the globe to the TSE prion mad cow type disease

Saturday, December 15, 2012


Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle -- an update 5 December 2012

Thursday, February 14, 2013


The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease

2012 atypical L-type BSE BASE California reports

Saturday, August 4, 2012

*** Final Feed Investigation Summary - California BSE Case - July 2012

atypical L-type BASE BSE California


Summary Report BSE 2012

Executive Summary


Saturday, August 4, 2012


Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation

*** 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.


Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle

Amir N. Hamir, Marcus E. Kehrli, Jr,1 Robert A. Kunkle, Justin J. Greenlee, Eric M. Nicholson, Jürgen A. Richt, Janice M. Miller, Randall C. Cutlip

Journal of Veterinary Diagnostic Investigation 23(3) 407– 420 © 2011 The Author(s) Reprints and permission: DOI: 10.1177/1040638711403404

Abstract. Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. The emergence of BSE and its spread to human beings in the form of variant Creutzfeldt-Jakob disease (vCJD) resulted in interest in susceptibility of cattle to CWD, TME and scrapie. Experimental cross-species transmission of TSE agents provides valuable information for potential host ranges of known TSEs. Some interspecies transmission studies have been conducted by inoculating disease-causing prions intracerebrally (IC) rather than orally; the latter is generally effective in intraspecies transmission studies and is considered a natural route by which animals acquire TSEs. The “species barrier” concept for TSEs resulted from unsuccessful interspecies oral transmission attempts. Oral inoculation of prions mimics the natural disease pathogenesis route whereas IC inoculation is rather artificial; however, it is very efficient since it requires smaller dosage of inoculum, and typically results in higher attack rates and reduces incubation time compared to oral transmission. A species resistant to a TSE by IC inoculation would have negligible potential for successful oral transmission. To date, results indicate that cattle are susceptible to IC inoculation of scrapie, TME, and CWD but it is only when inoculated with TME do they develop spongiform lesions or clinical disease similar to BSE. Importantly, cattle are resistant to oral transmission of scrapie or CWD; susceptibility of cattle to oral transmission of TME is not yet determined.


Atypical bovine spongiform encephalopathy cases: H-type and L-type BSE Bovine spongiform encephalopathies with molecular profiles different from that of C-type BSE have been reported since 2004 by investigators from several countries. To date, 2 molecular types of atypical BSE have been described, and a summary was published on the Internet in 2007 by the Spongiform Encephalopathy Advisory Committee ( htm). One molecular type is the L-type, which has been found in cattle in Italy,20 Japan,117 Germany,16 Belgium,27 and Canada.28 Western blot analysis demonstrates the L-type form to have a lower molecular mass of the unglycosylated PrPd isoform when compared with C-type BSE. The second type of atypical BSE is the H-type, characterized by Western blot analysis to have a higher molecular mass of the unglycosylated isoform. To date, the H-type has been described in cattle from France,11 Germany,16 Japan,101 the Netherlands,55 Poland,55 Switzerland,103 the United Kingdom99 and the United States.86 The unusual molecular phenotype of the H-type BSE cases was characterized by 1) a higher molecular mass of the unglycosylated PrPd isoform, 2) a strong labeling of all 3 PrPd polypeptides (unglycosylated, monoglycosylated and diglycosylated isoforms) with the PrP-specific monoclonal antibodies 6H4 (amino acid epitope consisting of DYEDRYYRE) and P4 (amino acid epitope consisting of GGGWGQGGTHGQWNK), and 3) a glycoform profile with a less prominent diglycosylated PrPd isoform (French and U.S. cases). Some, but not all H-type BSE cases were positive by immunohistochemistry (IHC) because in some cases tissues were not available for immunohistochemical testing. In contrast, L-type cases were characterized by 1) a lower molecular mass of the unglycosylated PrPd isoform, 2) a strong labeling of all 3 PrPd polypeptides with the PrP-specific monoclonal antibody 6H4 but not P4, and 3) a glycoform profile with a monoglycosylated PrPd band at least equally as intense as the diglycosylated PrPd isoform. Epitope mapping with monoclonal antibodies as mentioned above is used as one tool to differentiate TSE strains by IHC57,59 and Western blot.100 Until these recent atypical BSE reports, BSE has been shown to be very consistent and uniform in appearance, even after transmission to other species. There are several hypotheses proposed to explain atypical BSE cases.11 One theory proposes that there are variants of BSE with different molecular features in cattle; a second theory proposes that cattle may have been affected by another TSE (e.g., scrapie or CWD); a third theory proposes that a rare sporadic or genetic form of TSE disease could exist in cattle as described for human TSEs. Recently a new PRNP allele (E211K)85 was reported in a cow with H-type BSE indicating a possible genetic form of BSE that is heritable.77 Research on atypical BSE, first reported in 2004,11 has investigated intra- and interspecies transmissibility, influence of host genotype, PrPd tissue distribution, and incidence rate of atypical BSE.* Both H- and L-type BSE cases have occurred in different breeds and PRNP genotypes. The majority of cases were in older cattle (>10 yrs of age) and very few of the animals had typical clinical signs of C-type BSE. Importantly, experimental transmission of selected H- and L-type BSE cases, into cattle, mice, and nonhuman primates has been reported.7,16,18,23,63,68 Relatively less is known about the histopathological and immunohistochemical characteristics of atypical BSE. Microscopic examination of L-type BSE cases revealed prion deposition in the brain that differed in distribution from C-type BSE cases and included amyloid plaques and increased PrPd immunoreactivity in the olfactory bulbs,19 *References 6, 9, 15, 16, 18, 23, 55, 63, 68, 77, 79, 85, 93 although PrPRes immunoreactivity has been detected by Western blot in olfactory bulbs of cattle with C-type BSE.104 The investigators designated this newly identified disease phenotype “bovine amyloidotic spongiform encephalopathy” or BASE.20 The morphological PrPd deposition of BASE cases differed from that observed in C-type BSE cases: relatively few deposits were found in the obex region but much more occurred in the more rostral structures of the brain, namely in the thalamus and the olfactory bulb. The PrPd-positive deposits were predominantly in the form of amyloid-like plaques.20 The latter has been reported for TSEs in human beings, but not for BSE in cattle. Less is known about the microscopic appearance of H-type BSE, but recent unpublished findings (Chiara Porcario, et al., submitted to BMC Vet Res) comparing the Italian and the U.S. IHC confirmatory methods for BSE differentiated the different phenotypes (C-, H-, and L-type BSE) as each appearing to be characterized by distinctive features of PrPd deposition. Granular and linear tract PrPd deposits were a distinct feature of C-type BSE cases, whereas intraglial and intraneuronal PrPd deposition appeared as the most representative trait of H-type BSE as reported previously,16 and the presence of PrPd deposits organized as plaques was a distinguishing hallmark of L-type BSE (BASE) cases, also as previously reported with a preferential distribution in more rostral brain regions.18,20

Transmissible mink encephalopathy Transmissible mink encephalopathy has been sporadically identified in ranch-raised mink (Neovison vison). It was first documented in Wisconsin in 194729 and the last reported outbreak in the United States was in 1985.70 Like BSE, TME is a food borne disease that has been experimentally transmitted to a variety of animal species, including cattle, sheep, goats, monkeys, hamsters, mink, American sable (pine marten), beech marten, skunks, ferrets, and raccoons. 29,30 Reported histopathological findings in mink with TME indicate detectable lesions limited to the CNS with microvacuolation of the gray matter, reactive astrocytosis in the cerebral cortex, and neuronal degeneration.69 Microscopic lesions were reported as a scrapie-like spongiform encephalopathy, which preceded clinical disease by approximately 6 weeks.69 Weeks before microscopic lesions were visible, ultrastructural alterations were recognized when assessed by electron microscopy and included loss of normal ultrastructure of nerve endings, larger dendritic segments, and variously shaped vesicles and vacuoles in the neuropil. 119 A review of published literature on TME found no descriptions of PrPd distribution patterns in mink as studies in mink were completed prior to development of current diagnostic methods including IHC and Western blotting. Moreover, the lack of natural cases of TME for the past several decades and the advent of the hamster model83 made the mink a less desirable animal model for study. The origin of TME is unknown, but it is speculated to have been derived from sheep scrapie or from an unknown TSE in cattle.70,71

Experimental interspecies transmission of transmissible spongiform encephalopathies into cattle Experimental scrapie transmission to cattle During the 1990s the possibility that U.S. strains of sheep scrapie might cause BSE following transmission to cattle was assessed experimentally through both IC and oral inoculations. Intracerebral inoculations resulted in a 100% transmission of a prion disease to cattle between 14–18 months following inoculation.26 A separate study using multiple simultaneous routes of inoculation (including IC) found only 20–40% transmission depending on the source of inoculum and a longer incubation period of 24–48 months following inoculation.22 Although the affected cattle exhibited anorexia, weight loss, leg and back stiffness, incoordination, and rear leg weakness eventually leading to severe lethargy and ataxia, they did not show signs of hyperactivity, one of the characteristic clinical signs of BSE. To differentiate scrapie in cattle from BSE, there was no microscopic evidence of spongiform changes in the scrapie-affected cattle. Neuropathological changes were not present in the CNS of scrapie-affected cattle whereas spongiform changes are usually observed in clinical BSE cases.91 Immunoreactivity for PrPd in scrapie-affected cattle was observed predominately in neuronal cell bodies with relatively little accumulation in the neuropil,25,26 in contrast to BSE where there is a diffuse distribution of PrPd in the CNS.91 Following oral ingestion of the scrapie agent, cattle did not develop symptoms of neurological disease nor did they develop spongiform lesions nor PrPd deposits in the CNS after eight years post inoculation.24 Such experiments demonstrate that IC inoculation of the U.S. scrapie agent into cattle results in a disease with clinicopathologic hallmarks that differ significantly from cattle with BSE. Whereas oral BSE inoculation into cattle is a highly efficient means of transmission,107 this is not the case for scrapie. 24 Despite the proposed linkage of the BSE epidemic initiation to scrapie,114 scrapie isolates from U.S. sheep could only be transmitted to cattle by IC inoculation, and the pathology and clinical disease differed from both BSE in cattle and scrapie in sheep.25,26 The results were later corroborated by inoculation of cattle with scrapie isolates from the United Kingdom.64 Therefore, current experimental evidence from scrapie transmission studies into cattle does not support the hypothesis that the U.K. BSE epidemic originated from feeding of scrapie PrPd to cattle. However, no experimental transmission studies of atypical scrapie into cattle have been reported to date.

Experimental chronic wasting disease transmission to cattle The recognition of CWD116 in captive and free-ranging cervids in the United States raised questions about the possible transmissibility of such agent to other ruminant species that may contact affected cervids or their carcasses on pasturelands or farms. In 2001, preliminary findings of IC inoculation of cattle with the CWD agent from mule deer tissue were published.37 Although brains of the animals showed no significant histopathologic changes, PrPd was detected by IHC and Western blot, indicating that amplification of the abnormal CWD prion had occurred. In cattle inoculated with CWD, the consistent and sentinel finding of localization of PrPd to multifocal and distinct aggregates confined to glial cells and associated neuropil clearly distinguished this IHC pattern from that seen in scrapie- and BSE-affected cattle, and for that matter, any other TSE. Another distinct feature of the distribution of immunoreactivity for PrPd in CWD of cattle was the infrequent finding of small (≤40 μm) plaques in the cerebrum. Although the characteristic pattern of distinct multifocal aggregates of PrPd predominated, in some white-tailed CWD inoculated cattle labeling in obex and midbrain appeared as coalescing foci. Unlike BSE- and TME-inoculated cattle, PrPd labeling of retina was not present.38,45 On the other hand, in an ongoing study, none of the cattle given the same inoculum orally (50 g of pooled brain/animal) have shown any evidence of prion disease up to 9 years after inoculation.115 In contrast to the current authors’ first study,38 which demonstrated a low attack rate of mule deer CWD upon first passage, subsequent IC inoculation of mule deer CWD passed once in cattle (i.e., cattle-adapted mule deer CWD), showed clinicopathological findings (similar to first passage) in all inoculated cattle within 16.5 months postinoculation. 39 This increased attack rate with shorter incubation periods may indicate adaptation of the mule deer CWD agent to the new cattle host. However, it could also be argued that the inoculum used for the primary passage simply had a lower infectivity titer than that used for the second passage. 37–39 Recent findings of IC inoculation of CWD from white-tailed deer into cattle showed that the white-tailed deer inoculum had a higher attack rate (86%) in cattle than the mule deer CWD inoculum used previously; however, microscopic lesions typical of BSE were still not observed.45 While cattle inoculated with CWD from white-tailed deer and mule deer CWD had similar Western blot molecular profile results, there was no change between first and second passage of mule deer CWD in cattle.39 A recent study (Greenlee JJ, Nicholson EM, Kunkle RA, Hamir AN: 2009, Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from elk. In: Proceedings of the American College of Veterinary Pathologists Annual Meeting, p. 1058) assessing transmissibility of CWD derived from elk to cattle also found a low rate of transmission. Clinical signs of poor appetite, weight loss, circling, and bruxism occurred in 2 out of 16 cattle at 16 and 17 months post-inoculation. No spongiform lesions were detected; however, in the 2 diseased cattle, PrPd was detected and confined to the CNS and was similar in distribution to cattle inoculated with CWD from mule deer with the most prominent immunoreactivity in midbrain, brainstem, and hippocampus with lesser immunoreactivity in the cervical spinal cord. The lack of spongiform lesions in any of the IC CWD-inoculated cattle (first or second passage of mule deer CWD) and no change in PrPd deposition patterns suggests the differences in attack rate between elk CWD, mule deer CWD, and white-tailed deer CWD upon first passage are likely a difference in interspecies transmission susceptibility (i.e., a species barrier), although differences in infectivity titer of each inoculum cannot be excluded. Additional studies are required to fully assess the potential for cattle to develop CWD through a more natural route of exposure, but the cumulative evidence, thus far, of the lack of spongiform lesions and the differences from BSE in PrPd distribution after IC inoculation, along with no evidence of transmission following oral exposure, suggests that risk of transmission through routes other than IC is low.

Experimental transmissible mink encephalopathy transmission to cattle In 1995, 3 different sources of TME were tested in cattle and in all instances the animals developed clinical disease and severe spongiform encephalopathy.88 The spongiform changes and astrocytic responses were considered more pronounced than those of natural BSE, but similar to the pathology observed after experimental IC BSE inoculations. This work confirmed an earlier report of TME transmission to cattle,70 which lent strength to the proposal that TME outbreaks in the United States were caused by contaminations of feed with a TSE agent present in “downer” cows. This hypothesis was also partially supported by subsequent experiments that showed that the BSE agent produced spongiform encephalopathy in mink after oral exposure.87 However, clinical signs and histopathologic lesions were reported to be distinguishable from natural TME.87 Subsequent IC inoculations of cattle with first and second cattle-passaged TME confirmed the earlier findings and also described for the first time the immunohistochemical and Western blot characteristics (lower molecular weight of cattle-adapted TME vs. C-type BSE by Western blot) of the accumulated PrPd, which indicated further similarities between TME and BSE in cattle40 and accentuated their dissimilarities from experimental scrapie and experimental CWD in cattle. A 2007 study lends further to the relationship between TME and L-type BSE, where in an ovinized transgenic mouse model, cattle-passaged TME presented with the same phenotypic characteristics as atypical L-type BSE.5 With TME in cattle, the predominant pattern of immunohistochemical labeling was diffuse, evenly distributed, punctuate and coarse granules that involved most areas of the neuropil. Perineuronal labeling of PrPd was regularly noted, in contrast to its non-presence in scrapie- and CWDinoculated cattle. However, to the authors’ knowledge, experimental studies investigating the oral route of transmission of TME to cattle have as yet not been conducted.

Host species exerts influence over PrPd tissue distribution A consistent finding from the experimental interspecies transmission studies of scrapie, CWD, and TME into cattle is the observation that the PrPd tissue distribution in cattle remains essentially restricted to the CNS and, aside from the distinctions noted above regarding PrPd immunoreactivity distribution within the CNS, it is no more extensive than naturally occurring BSE in cattle.24–26,37,40 Importantly, cattle inoculated with TME,40 scrapie,24–26 and CWD37,38,40 have no evidence of a lymphoid or blood phase of PrPd; which is a distinction from classical scrapie and CWD in their natural hosts. Although detectable PrPd has been reported in the distal ileum following experimental oral BSE challenge in cattle and occasionally in the tonsil, nictitating membrane, or bone marrow,106,109 studies of naturally occurring clinical cases of BSE have found infectivity only in the CNS tissue using conventional mouse bioassays.12 A recent experiment on bone marrow infectivity of cattle orally inoculated with BSE used IC inoculation of cattle as a bioassay with sternal bone marrow collected at 22, 26, 32, and 36 months after exposure and found no evidence of BSE in cattle 70–91 months post inoculation, suggesting that disease-causing BSE material in bone marrow is either a rare event or that it may be consistently present but at levels undetectable by what is perhaps considered the most sensitive bioassay (i.e., IC inoculation of cattle).97 The consistent detectable tissue distribution of PrPd in cattle experimentally inoculated with BSE, TME, CWD, or scrapie is essentially restricted to the bovine nervous system,24–26,37,38,40,42,94 as has been reported in naturally occurring cases of BSE.17 Bovine tissue infectivity studies in transgenic mice that are highly sensitive to BSE have confirmed the essential restriction of infectivity to the nervous system in clinically diseased BSE cattle.17 Collectively, these results indicate that the distribution of PrPd of BSE in cattle is fundamentally different from TSEs in sheep, cervids, or mice.17 In contrast, sheep and cervids appear to have extensive lymphoid tissue involvement with PrPd deposition, regardless of the TSE with which they are inoculated.38,41,44,59 The only exceptions to this paradigm have been studies where lymphoid involvement in elk or European red deer experimentally inoculated with scrapie or BSE, respectively, was not observed.43,44,72 Up to 15% of elk with naturally occurring CWD show PrPd in the CNS and not in the lymphoid tissues.98

It can be concluded that the animal host, especially cattle, exerts considerable influence over the pathogenesis of a prion disease in terms of what tissues are involved and what can be seen in one animal species does not always extrapolate to another. In particular, no evidence exists to suggest that infectivity can be found in the blood of cattle with BSE as tested by bioassay of spleen and/or blood in bovinized transgenic mice,17,34 whereas lines of evidence exist that suggest that infectivity can be found in the blood of cervids with CWD, scrapie in sheep, and vCJD in human beings. Whole blood transfusion studies in sheep using donor sheep with experimental BSE or with natural scrapie have shown that infectivity resides in the blood of sheep.51–54 Similarly, transmissibility by blood transfusion has been reported for deer with experimental CWD.73

Differential diagnosis and conclusions

Over the past 20 years, several interspecies transmissibility studies of various endemic TSEs (scrapie, CWD, and TME) to various livestock hosts have now been completed. A limitation of the published research on experimental

interspecies TSE transmissions to cattle is the possibility that IC inoculation results in the various clinical, histological, and diagnostic test differences observed between scrapie and CWD in cattle versus BSE. However, arguing against those findings being an artifact of the experimental design is the fact that oral challenge studies with both CWD and scrapie into cattle have failed to cause a TSE, and the differences in pathology, IHC, and Western blot that have been observed are in keeping with a species barrier for cattle against these two prion diseases. Moreover, the similarities of experimental BSE transmission to mink by oral or IC challenge support the IC route as a valid experimental approach.87 A brief description of clinical, histopathological, and immunohistochemical findings, and molecular phenotype in cattle is summarized in Table 1. Figure 1 illustrates histological changes in the brain of cattle with the selected TSEs. Figure 2 illustrates the immunohistochemical immunoreactivity differences of cattle from these same studies and Figure 3 illustrates the Western blot molecular profile differences. Although the scrapie and CWD transmission to cattle studies failed to reproduce a prion disease exactly like BSE, they are important in that no reported bovine TSE cases to date appear similar to experimental CWD or scrapie in cattle, thus providing evidence that cattle seem naturally resistant to CWD and scrapie. In contrast to cattle-passaged scrapie and CWD, which are phenotypically distinct from BSE in the natural host, cattle-passaged TME shows intriguing phenotypic similarities with the L-type BSE. It is critical to note these findings give further scientific assurance that the confirmatory histological, immunohistochemical and Western blot tests employed in the current international TSEs surveillance programs are capable of detecting different prion strains in cattle and would implicate their origin, should such a cross-species transmission occur naturally in the future. Finally, these studies provide valuable confirmatory information regarding the range of tissues to include as specified risk material and have established an archive of tissues available to the greater scientific community for prion research.

Key words: Bovine spongiform encephalopathy; cattle; chronic wasting disease, prion diseases; PrP immunohistochemistry; PrP Western blot; spongiform encephalopathy; transmissible mink encephalopathy; variant Creutzfeldt-Jakob disease.

"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."

Please see ;

Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.

"although the infection rate was low (4 of 13 animals [Hamir et al. 2001])."

shouldn't this be corrected, 86% is NOT a low rate. ...

kindest regards,

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


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

From: David Colby


Cc: stanley@XXXXXXXX

Sent: Tuesday, March 01, 2011 8:25 AM

Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations

Dear Terry Singeltary,

Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter.

Warm Regards, David Colby


David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware




Wednesday, September 08, 2010


Tuesday, March 05, 2013

A closer look at prion strains Characterization and important implications Prion

7:2, 99–108; March/April 2013; © 2013 Landes Bioscience

Tuesday, May 28, 2013

Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance

Monday, April 15, 2013


Dr. Stephen B. Thacker Director Centers for Disease Control and Prevention′s Office of Science, Epidemiology and Laboratory Services (OSELS) dies from Creutzfeldt Jakob Disease CJD


Sunday, February 10, 2013

Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection report/CJD

Thursday, January 17, 2013

TSE guidance, surgical, dental, blood risk factors, Part 4 Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings (updated January 2013)

Tuesday, May 21, 2013

CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the International Society of Blood Transfusion, Amsterdam, The Netherlands, June 2-5, 2013

Tuesday, March 5, 2013

Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)

FDA believes current regulation protects the public from BSE but reopens comment period due to new studies



see steady increase of the sporadic CJD’s. ...

The Akron, Ohio-based CJD Foundation said the Center for Disease Control revised that number in October of 2004 to about one in 9,000 CJD cases per year in the population group age 55 and older.

Provider Details

Creutzfeldt-jakob Disease Foundation


CJD is a rare, fatal brain disorder. The statistical incidence of CJD cases in the US has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty five percent of the cases are sporadic, meaning there is no known cause at present.Toll free in state: (800) 659-1991, Main: (330) 665-5590

Service Categories Brain Injury, Dementia/Alzheimer's, Donations, Mental Health

Contact Information: Phone: (330) 665-5590

Last Update Date: 07/23/2010



1990 – 28 cases

(with steady increase in the years from 1990 to 2011. ...tss)

2011 – 90 cases

1 in addition, the NCJDRSU has identified a total of 9 cases of VPSPr.

Thursday, April 4, 2013

Variably protease-sensitive prionopathy in the UK: a retrospective review 1991–2008

Brain (2013) 136 (4): 1102-1115. doi: 10.1093/brain/aws366


PLEASE NOTE, type determination pending Creutzfeldt Jakob Disease (tdpCJD) in Canada is also on a steady increase.

please see ;

> 3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.

CJD Deaths Reported by CJDSS1, 1994-20122

As of May 31, 2012

Deaths of Definite and Probable CJD

Year Sporadic Iatrogenic Familial GSS FFI vCJD Total

1994 2 0 0 1 0 0 3

1995 3 0 0 0 0 0 3

1996 13 0 0 0 0 0 13

1997 16 0 1 1 0 0 18

1998 22 1 0 1 0 0 24

1999 26 2 2 1 0 0 31

2000 32 0 0 3 0 0 35

2001 27 0 2 1 0 0 30

2002 31 0 2 2 0 1 36

2003 27 1 1 0 0 0 29

2004 42 0 1 0 0 0 43

2005 42 0 0 2 0 0 44

2006 39 0 1 3 1 0 44 2007 35 0 0 4 0 0 39

2008 48 0 1 0 0 0 49

2009 48 0 3 2 0 0 53

2010 34 0 3 0 0 0 37

2011 37 0 2 1 0 1 41

2012 1 0 0 0 0 0 1

Total 525 4 19 22 1 2 573

1. CJDSS began in 1998

2. Data before 1998 are retrospective and partial, data from 1998 to 2008 are complete, and data for 2009 - 2012 are provisional

3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.

CJD Deaths Reported by CJDSS1, 1994-20122

As of May 31, 2012


National Prion Disease Pathology Surveillance Center

Cases Examined1

(May 18, 2012)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 50 32 28 4 0 0

1997 114 68 59 9 0 0

1998 88 52 44 7 1 0

1999 123 74 65 8 1 0

2000 145 103 89 14 0 0

2001 210 120 110 10 0 0

2002 248 149 125 22 2 0

2003 266 168 137 31 0 0

2004 326 187 164 22 0 13

2005 344 194 157 36 1 0

2006 382 196 166 28 0 24

2007 377 213 185 28 0 0

2008 396 232 206 26 0 0

2009 423 256 212 43 1 0

2010 413 257 216 41 0 0

2011 410 257 213 43 0 0

2012 153 82 51 15 0 0

TOTAL 44685 26406 2227 387 6 3

1 Listed based on the year of death or, if not available, on year of referral;

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;

5 Includes 14 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded. The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

Rev 5/18/2012

> 6 Includes

> 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded.

> The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

WELL, it seems the USA mad cow strains in humans classified as type determination pending tdpCJD, VPSPr, sFFI, and sCJD) have steadily increased over the years, and the same old song and dance continues with sporadic CJD cases $$$

*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.


OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles

Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA

Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.

Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.

Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.

In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.

Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.

The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

Wednesday, March 28, 2012


*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

EFSA Journal 2011 The European Response to BSE: A Success Story


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.


Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat


Tuesday, March 05, 2013

A closer look at prion strains Characterization and important implications Prion

7:2, 99–108; March/April 2013; © 2013 Landes Bioscience


No comments:

Post a Comment