Volume 17, Number 12—December 2011
Research
Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies
Pedro Piccardo , Larisa Cervenakova, Irina Vasilyeva, Oksana Yakovleva, Igor Bacik, Juraj Cervenak, Carroll McKenzie, Lubica Kurillova, Luisa Gregori, Kitty Pomeroy, and David M. Asher
Author affiliations: University of Edinburgh, Easter Bush, UK, (P. Piccardo); Food and Drug Administration, Kensington, Maryland, USA (P. Piccardo, I. Bacik, J. Cervenak, L. Kurillova, L. Gregori, K. Pomeroy, D.M. Asher); Holland Laboratory American Red Cross, Rockville, Maryland, USA (L. Cervenakova, I. Vasilyeva, O. Yakovleva, C. McKenzie)
Abstract
Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue–derived medical products, human blood components, and animal vaccines. The objective of this study was to determine the potential susceptibility to infection of 5 cell lines used or proposed for manufacture of biological products, as well as other lines. Cell lines were exposed to the infectious agents of sporadic and variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE). Exposed cultures were tested for TSE-associated prion protein (PrPTSE) and TSE infectivity by assay in rodents and nonhuman primates. No PrPTSE or infectivity has been detected in any exposed cell line under study so far. Animals inoculated with BSE brain homogenate developed typical spongiform encephalopathy. In contrast, animals inoculated with cells exposed to the BSE agent remained asymptomatic. All cell lines we studied resisted infection with 3 TSE agents, including the BSE agent.
Transmissible spongiform encephalopathies (TSEs or prion diseases) are a heterogeneous group of fatal neurodegenerative diseases that affect animals and humans. TSEs can be sporadic, transmitted iatrogenically, or expressed as familial disorders. TSEs include scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease in cervid ruminants, and mink encephalopathy. In humans the most common TSEs are sporadic, familial, and variant Creutzfeldt-Jakob disease (sCJD, fCJD, and vCJD, respectively). TSEs are characterized by the accumulation in the central nervous system and, less often, in lymphoid tissues of TSE-associated prion protein (PrPTSE), a conformational variant of a normal host cellular prion protein (PrPC). PrPC is a nonessential protein but, at least in mice and cows, must be expressed by animals susceptible to TSE infection. There is compelling evidence that the BSE agent has infected humans, causing vCJD. Most cases of vCJD are attributed to exposure to contaminated beef products (1–3). In addition, vCJD infections have been transmitted by transfusions of nonleukoreduced erythrocyte concentrates and by a human-derived coagulation factor (factor VIII) (4–6).
The conclusion that PrPTSE is central to the pathogenesis of TSE is based o
n the temporal and anatomic correlations between accumulation of PrPTSE and the development of pathologic changes in tissues of the central nervous system (1). However, TSEs can develop in the absence of detectable PrPTSE and, conversely, PrPTSE might accumulate without causing either clinical illness or the neuropathologic alterations typical of TSEs (i.e., a progressive fatal illness with spongiform degeneration of the brain) (7,8). In short, the molecular basis of TSE infection and the role of PrPTSE (unquestionably important in pathogenesis of TSEs) are not yet entirely clear, and both remain key issues in TSE research (9,10). The standard assay for detecting a TSE agent remains bioassay in susceptible animals.
Many investigators once believed that TSE agents infected mainly, if not exclusively, cells of neuronal and lymphoid lineages. It has become clear, however, that the susceptibility of cells to infection with TSE agents cannot be reliably predicted either from their tissue of origin or level of expression of PrPC (11,12). Studies showing that murine fibroblast cell lines are susceptible to infection with mouse-adapted scrapie agent (11,12) increased concern that nonneuronal cell substrates used to propagate viruses for vaccine production might become infected with a TSE agent contaminating some component of culture medium, especially bovine serum (13). The theoretical risk of contaminating vaccines or other biologic products prepared in culture cells with TSE agents from animal-derived materials in media has been considered low. However, 1) as noted above, the blood of asymptomatic humans has transmitted vCJD, and 2) in a variety of experimentally TSE-infected animals, TSE agent has been detected in blood, mainly in nucleated cells and plasma (4–6,14–17). Fortunately, no human vaccine has ever been implicated as a source of iatrogenic TSE. However, 2 animal tissue–derived vaccines have caused outbreaks of scrapie in sheep, and 2 medical products of human origin—dura mater allograft and human cadaveric pituitary hormones (no longer marketed in the United States)—have transmitted hundreds of cases of CJD; corneal grafts have transmitted a few cases as well (2,18). Since 1993, the US Food and Drug Administration has recommended against the use in the manufacture of biological products of bovine-derived materials from countries identified by the US Department of Agriculture (USDA) as having BSE or being at increased risk for BSE in native cattle (19).
The recognition of >20 BSE cases in North America since 2003 (most in Canada) has increased the need to determine whether cell substrates that might be accidentally exposed to the BSE agent are capable of acquiring and propagating the infectious agent and potentially transmitting infections to vaccine recipients (20). To address these issues, we investigated the susceptibility of cell lines used or proposed for manufacture of biologics and controls to propagate TSE agents, especially the BSE agent, under simulated worst-case conditions.
snip...
Results
TSE in TgBo Mice and Primates Inoculated with BSE agent
Neuropathologic characterization of TgBo mice inoculated with BSE agent showed spongiform degeneration in the cerebrum with variable amounts of fine-punctate, coarse, and, in some cases, plaque-like deposits in the cerebrum, cerebellum, and brain stem. Mice inoculated with the bacteria-free filtrate of 1% BSE-infected brain suspension used to expose cells also developed signs of TSE, and PrPTSE was detected in brains, demonstrating that the inoculum used to expose cell cultures contained a TSE agent transmissible to mice (Figure 1).
Figure 2
Histopathologic analysis of squirrel monkey inoculated with bovine spongiform encephalopathy agent (A, B). Spongiform degeneration in the cerebral cortex (A), adjacent section showing abundant prion protein (PrP) immunopositivity (B). Squirrel monkey...
Squirrel monkeys were inoculated with serial dilutions of the same material used to inoculate TgBo mice. At the time this report was written, 6 monkeys have already developed neurologic signs typical of TSE. Three animals inoculated with 10–1 (10%) unfiltered low-speed clarified BSE reference material became ill and were euthanized ≈3.2 years after inoculation; 2 primates inoculated with 10–2 unfiltered, low speed–clarified BSE suspension were euthanized 3.7 years after inoculation; and 1 primate inoculated with the 0.45-μm filtered bacteria-free 10–2 (1%) BSE-infected brain suspension used to expose cells also developed signs of TSE and was euthanized 3.3 years after inoculation. Brain extracts from each of these monkeys contained PrPTSE demonstrated by WB. Preliminary neuropathologic studies of formalin-fixed paraffin-embedded brain sections of each of the 6 animals showed severe spongiform degeneration of the cerebrum, cerebellum, and brainstem. Immunohistochemical studies showed widespread accumulations of PrP-immunopositive deposits throughout the brain of each monkey (Figure 2). Control brains from 4 other squirrel monkeys dying of nonneurologic diseases, including 1 housed with monkeys used to titrate BSE agent, showed no evidence of TSE (Figure 2). A detailed neuropathologic report of all monkeys is in press (22).
Attempts to Infect Actual or Candidate Cell Substrates
Analysis of Cell Cultures and Bioassay in Rodents
Figure 3
Western blot of recombinant prion protein (PrP) 5 ng (lane 1), CHO cells (lanes 2–5) and Vero cell (lanes 6–9). Cells exposed to normal bovine brain and passaged 30 times (lanes...
No PrPTSE was detected in cells exposed to normal brain extracts (controls) or after passage 5 in any of the cell substrates or control TSE-resistant cells exposed to brain extracts containing TSE agents. PrPTSE was detected in some samples of cells collected 96 h after inoculation (passage 0), suggesting the probable presence of residual inoculum. The consistent failure to detect PrPTSE in any cell line exposed to TSE agents after >5 passages suggests that proteinase K–resistant PrP was not generated de novo under these experimental conditions. WB analyses of cells collected after 30 serial passages showed no detectable PrPTSE in any cell line (Figure 3). Samples of each cell line exposed to human TSE agents (sCJD, vCJD) and BSE agent were expanded after 30 passages for bioassay in TgHu and TgBo mice. At the time of this report, no mice inoculated with cells exposed to TSE agent have evidence of TSE illness during their expected lifespan (Table 2, Table 3). WB with extracts of brain tissue from all culled animals showed no PrPTSE. Neuropathologic analyses of selected mouse brains found no spongiform encephalopathy or accumulations of PrP (data not shown). The results confirm that no cell substrate propagated infectivity detectable by mouse bioassay, even when mice were observed for their expected lifespan.
Nonhuman Primate Bioassay
Lysates of Vero, CHO, WI-38, and R9ab cells exposed to BSE agent and passaged 30 times were inoculated into squirrel monkeys in May 2006. Lysates of MDCK and HEK-293 cells exposed to BSE agent and passaged 30 times were inoculated into squirrel monkeys in August 2007. No monkey inoculated with those cells had neurologic signs. One monkey inoculated with Vero cells exposed to the BSE agent was attacked by a cage mate; the wound became infected, suppuration increased despite treatment with antimicrobial drugs, and the injured monkey was euthanized several days later without ever showing any sign of neurologic disease. The brain showed no neuropathologic changes of TSE or PrPTSE by WB (data not shown). In contrast, as noted above, primates inoculated with Swiss Reference BSE brain extracts at 10–1 and 10–2 dilutions developed typical TSE confirmed by neuropathologic results (Figure 2) and by WB (not shown). These results indicate that 1) squirrel monkeys are susceptible to infection with the BSE agent, and 2) BSE infectivity was present in the bacteria-free filtrate used to expose cell substrates.
Murine Fibroblast Cell lines Generate PrPTSE after Exposure to Mouse-adapted Scrapie Agent
Figure 4
Western blot of brain extract from C57/Bl mouse inoculated with 22L mouse-adapted scrapie agent (lanes 1, 2); NIH-3T3 cells exposed to normal mouse brain and passaged 30 times (lane 3); NIH-3T3...
Several murine tissue cultures have been successfully infected with TSE agents, providing a promising alternative to assays of TSE agents by time-consuming and expensive bioassays in animals (9,11,12,23–28). Previous studies reported that several commonly used mouse fibroblast cell lines can be efficiently infected with the scrapie agent and support formation of PrPTSE (11). We studied 2 such cell lines as a positive control to confirm that our protocol would have detected an infected cell line and that our failures to find PrPTSE or infectivity by bioassay in cell substrates exposed to the BSE agent were more likely to have resulted from an intrinsic resistance of the cells to infection rather than to some technical problem. We exposed monolayers of NIH-3T3 and L929 murine fibroblast cells to the mouse-adapted 22L strain of scrapie agent and observed the formation of readily detectable PrPTSE that persisted through 30 passages (Figure 4). We are performing bioassays of the PrPTSE-positive cells in C57/BL6 mice to determine amounts of infectivity. Several mice inoculated with samples of NIH-3T3 and L929 fibroblasts collected 30 passages after exposure to 22L mouse-adapted scrapie agent have already developed spongiform encephalopathy, confirming that the agent was successfully propagated in vitro (unpub. data).
Discussion
Candidate cell substrates used to produce biologics were not infected by a simulated worst-case exposure to BSE agent. Similar more limited studies exposing the same cultures to vCJD and sCJD agents also gave negative results.
The finding of PrPTSE in several cell culture samples collected at passages 0–4 probably resulted from small amounts of residual inoculum. This conclusion is reinforced by our consistent failure to detect PrPTSE in any cell sample at or after passage 5. However, we cannot rule out the possibility of a transient de novo generation of PrPTSE in the earliest passages of the cultures. Other investigators (23) have shown some immediate (acute) formation of new PrPTSE in infection-resistant cell cultures exposed to scrapie agent; the new PrP formed did not depend upon the strain of TSE agent used or cell type involved and was not associated with infectivity (23). Whether the failure of infectivity to persist after transient formation of PrPTSE resulted from death of the infected cells or the dilution of a small amount of TSE agent is unknown. We recognized no overt cytotoxicity in any cell line inoculated with a TSE-infected brain suspension. Thus, our data so far suggest that several cell substrates actually or potentially used to produce biologics were not susceptible to the propagation of TSE agents under the experimental conditions we used. In agreement with these results, others showed that MDCK cells were refractory to infection with human and mouse TSE agents (24). MRC5 human diploid cells also failed to support the replication of a TSE agent (25).
Because bioassays are time-consuming and expensive, a few lines of cells susceptible to infection with certain strains of TSE agent have been derived (9,11,12,26–30). However, for unknown reasons, most cell lines have resisted TSE infections. In addition, most cell lines infectable with TSE agents have been highly heterogeneous and not stable, requiring repeated subcloning of susceptible cells, and they have been successfully infected with only a few strains of TSE agent (27). Thus, it was vital to verify that the protocol we chose as a simulated worst-case model would successfully infect previously characterized cell lines with a TSE agent to which they were known to be susceptible. We demonstrated that the protocol we used was valid by persistently infecting 2 murine fibroblast cell lines with a mouse-adapted scrapie agent. However, we must caution that even cell lines susceptible to infection have shown widely different responses when exposed to various TSE agent strains (27). Furthermore, the emergence of atypical forms of BSE raises a new concern, i.e., that cell substrates resistant to infection with the original classic BSE agent (31) might not resist infection with newer strains of BSE agent (if new strains are implicated in atypical BSE).
Although BSE has been transmitted to many animal species, the efficiency of transmission between species has been difficult to predict. Low transmission rates and long incubation periods are often observed when TSEs are transmitted to a new species—commonly known as a species barrier (32)—but experience with squirrel monkeys (sensitive to almost all TSE agents affecting humans and to several animal TSEs as well) suggests that they are an especially useful model species (33). To that end we initiated titration experiments of the BSE agent and found at the time of writing this report that squirrel monkeys develop TSE when inoculated with BSE brain suspensions at high concentration 10–1 and 10–2 dilutions (work in progress). Given the long incubation time (years) needed to elicit disease in this primate model, we will continue the observation of monkeys inoculated with cell cultures exposed to the BSE agent in an attempt to determine whether low infectivity could potentially be detected in this model.
Because few cell lines used as substrates for biologics are of bovine origin, it is tempting to speculate that the potential for contaminating biologics with the BSE agent is low. However, an observation that cells derived from a pheochromocytoma of the rat adrenal medulla (PC12 cells) could be infected with a mouse-adapted scrapie agent and murine hypothalamic cells with a human TSE agent demonstrates that cross-species transmissions of TSE agents in cells in culture are possible (29). Recent studies showed that passage of TSE agents through different animal species altered key characteristics of the agent, sometimes producing variants with increased virulence or broader host range, as happened when BSE agent was passaged through sheep (34). Thus, further experiments are needed to evaluate the potential susceptibility of various cultured cell lines to infection with new emerging TSE strains.
Dr Piccardo is Senior Investigator in the Laboratory of Bacterial and TSE Agents, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, and professor in the Neuropathogenesis Division, The Roslin Institute, University of Edinburgh, UK. His research interest is in the pathogenesis of TSE and other neurodegenerative diseases.
snip...
see full text ;
http://wwwnc.cdc.gov/eid/article/17/12/11-0607_article.htm
PPo3-9: Potential of Cell Substrates used for Production of Biologics to Propagate Transmissible Spongiform Encephalopathy (TSE) Agents: 5-year Update
P. Piccardo,1,* L. Cervenakova,2 I. Vasilyeva,2 O. Yakovleva,2 I. Bacik,1 J. Cervenak,1 L. Gregori,1 K. Pomeroy,1 L. Kurillova,1 C. McKenzie2 and D.M. Asher1
1Laboratory of Bacterial and TSE Agents; CBER; FDA; USA; 2J. Holland Laboratory; American Red Cross; USA
*Presenting Author
Key words: cell culture, animal models, biologics, prion, TSE-agent
Background. TSE agents have contaminated human-tissue-derived therapeutics and animal vaccines. Many biologics are prepared in cell cultures. Although most cultures studied resisted infection with TSE agents, a few were susceptible.
Objectives. We are investigating susceptibility of several cell lines to infection with TSE agents.
Results. We studied Vero, CHO, MDCK, HEK-393 and WI-38 cells. We also studied SH-SY5Y cells overexpressing wild-type PrP and mutant PrPs. Cells exposed to TSE agents were serially propagated for 30 passages and samples tested for TSE-associated PrP (PrPTSE) and infectivity by intracerebral inoculation into transgenic mice and squirrel monkeys (BSE-exposed cells only). No exposed cell substrate has transmitted TSE to mice or monkeys to date. No PrPTSE was found in any exposed cells after 30 passages. Known susceptible murine cells exposed to mouse-adapted scrapie agent as positive controls accumulated PrPTSE. Three monkeys inoculated with BSE reference material have developed TSE to date.
Discussion. To date, no candidate cell substrate exposed to 3 TSE agents accumulated PrPTSE or propagated a TSE agent. Squirrel monkeys provide a new model to study BSE pathogenesis.
Methods. We inoculated brain suspensions containing agents of bovine spongiform encephalopathy (BSE), variant Creutzfeldt-Jakob disease (vCJD) or sporadic CJD into several cell lines important in manufacture of biologics. Serial dilutions of the BSE reference material used as inoculum were also inoculated into mice and squirrel monkeys.
The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Administration determination or policy.
Acknowledgements
Support. NIAID-NIH AI-4893-02/FDA 224-05-1307
International Prion Congress: From agent to disease
September 8–11, 2010
Salzburg, Austria
PRION
Volume4 Issue3July/August/September 2010
www.landesbioscience.com/journals/prion
http://www.prion2010.org/online/page.php?P=34
Tuesday, February 8, 2011
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
I was lucky enough to sit in on this BSE conference call today and even managed to ask a question. that is when the trouble started.
I submitted a version of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so.
"They tell me it is a closed meeting and they will release whatever information they deem fit. Rather infuriating."
and i would have been doing just fine, until i asked my question. i was surprised my time to ask a question so quick.
(understand, these are taken from my notes for now. the spelling of names and such could be off.)
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
from this point, i was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;
[unknown woman] what group are you with?
[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?
at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference.
IF i were another Country, I would take heed to my notes, BUT PLEASE do not depend on them. ask for transcript from;
RBARNS@ORA.FDA.GOV 301-827-6906
he would be glad to give you one ;-)
Rockville Maryland, Richard Barns Host
BSE issues in the U.S., How they were labelling ruminant feed? Revising issues.
The conference opened up with the explaining of the U.K. BSE epidemic winding down with about 30 cases a week.
although new cases in other countries were now appearing.
Look at Germany whom said NO BSE and now have BSE.
BSE increasing across Europe.
Because of Temporary Ban on certain rendered product, heightened interest in U.S.
A recent statement in Washington Post, said the New Administration (old GW) has a list of issues. BSE is one of the issues.
BSE Risk is still low, minimal in U.S. with a greater interest in MBM not to enter U.S.
HOWEVER, if BSE were to enter the U.S. it would be economically disastrous to the render, feed, cattle, industries, and for human health.
(human health-they just threw that in cause i was listening. I will now jot down some figures in which they told you, 'no need to write them down'. just hope i have them correct. hmmm, maybe i hope i don't ???)
80% inspection of rendering
*Problem-Complete coverage of rendering HAS NOT occurred.
sizeable number of 1st time FAILED INITIAL INSPECTION, have not been reinspected (70% to 80%).
Compliance critical, Compliance poor in U.K. and other European Firms.
Gloria Dunason Major Assignment 1998 goal TOTAL compliance. This _did not_ occur. Mixed level of compliance, depending on firm.
Rendering FDA license and NON FDA license
system in place for home rendering & feed 76% in compliance 79% cross contamination 21% DID NOT have system 92% record keeping less than 60% total compliance
279 inspectors 185 handling prohibited materials
Renderer at top of pyramid, significant part of compliance. 84% compliance
failed to have caution statement render 72% compliance & cross contamination caution statement on feed, 'DO NOT FEED TO CATTLE'
56 FIRMS NEVER INSPECTED
1240 FDA license feed mills 846 inspected
"close to 400 feed mills have not been inspected"
80% compliance for feed.
10% don't have system.
NON-FDA licensed mills There is NO inventory on non licensed mills. approximately 6000 to 8000 Firms ??? 4,344 ever inspected. "FDA does not have a lot of experience with"
40% do NOT have caution statement 'DO NOT FEED'.
74% Commingling compliance
"This industry needs a lot of work and only half gotten to"
"700 Firms that were falitive, and need to be re-inspected, in addition to the 8,000 Firms."
Quote to do BSE inspection in 19 states by end of January or 30 days, and other states 60 days. to change feed status??? Contract check and ask questions and pass info.
At this time, we will take questions.
[I was about the third or fourth to ask question. then all B.S.eee broke loose, and i lost my train of thought for a few minutes. picked back up here]
someone asking about nutritional supplements and sourcing, did not get name. something about inspectors not knowing of BSE risk??? the conference person assuring that Steve Follum? and the TSE advisory Committee were handling that.
Some other Dr. Vet, whom were asking questions that did not know what to do???
[Dennis Wilson] California Food Agr. Imports, are they looking at imports?
[Conference person] they are looking at imports, FDA issued imports Bulletin.
[Linda Singeltary ??? this was a another phone in question, not related i don't think] Why do we have non-licensed facilities?
(conference person) other feed mills do not handle as potent drugs???
Dennis Blank, Ken Jackson licensed 400 non FDA 4400 inspected of a total of 6000 to 8000, (they really don't know how many non licensed Firms in U.S. they guess 6000 to 8000??? TSS)
Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not'
Warren-Maryland Dept. Agr. Prudent to re-inspect after 3 years. concerned of Firms that have changed owners.
THE END
TSS
############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
snip...see full text and more here on tissue donor herds and the TSE Prion disease ;
http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
page 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org/
please see full text ;
http://transmissiblespongiformencephalopathy.blogspot.com/
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
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
snip...
http://www.neuroprion.org/en/np-neuroprion.html
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Saturday, December 3, 2011
Isolation of Prion with BSE Properties from Farmed Goat
Volume 17, Number 12—December 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/isolation-of-prion-with-bse-properties.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
http://transmissiblespongiformencephalopathy.blogspot.com/
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
TIP740203/l 0424 CONFIDENTIAL
http://www.mad-cow.org/00/may00_news.html#aaa
TWA LITTLE minute
2. We have identified one problem over where we are unable to act and this is the use of gonadotrophins in embryo transfer work. Some veterinary surgeons are quite legally using this exemption from the Medicines Act contained in Section 9(2) to prepare gonadotrophins from pituitary glands from various species, including cattle. These hormones are used to stimulate superovulation in donor cows.
http://collections.europarchive.org/tna/20080102164806/http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
http://collections.europarchive.org/tna/20080102164811/http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf
http://collections.europarchive.org/tna/20080103031215/http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf
COMMERCIAL IN CONFIDENCE
3.2 Minute 5.3 - 5.4 Bovine Spongiform Encephalopathy
It was reported that some replies had been received from Companies using pituitary glands in their products. Copies of the BSE document had also been sent to DHSS and NIBSC.
and then another 3 + pages of blank space. ...TSS
http://collections.europarchive.org/tna/20080102164813/http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf
COMMERCIAL IN CONFIDENCE
BSE - CURRENT POSITION WITH VETERINARY LICENCED PRODUCTS (MA.1968)
There are three areas of particular concern, vaccines (including emergency vaccines), pharmaceuticals which are covered by MA licences and unlicenses hormonal products produced under exemptions claimed under (Section 9(2) Medicines Act).
1) Vaccines
http://collections.europarchive.org/tna/20080103033809/http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf
NOT FOR PUBLICATION
another 6 pages of blank space. ...TSS
http://collections.europarchive.org/tna/20080103032658/http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf
http://collections.europarchive.org/tna/20080103032631/http://www.bseinquiry.gov.uk/files/yb/1988/11/04003001.pdf
http://collections.europarchive.org/tna/20080103033926/http://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdf
COMMERCIAL IN CONFIDENCE
http://collections.europarchive.org/tna/20080103034137/http://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdf
COMMERCIAL IN CONFIDENCE
Medicines Act - Veterinary Products Committee
http://collections.europarchive.org/tna/20080103034140/http://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdf
COMMERCIAL IN CONFIDENCE
http://collections.europarchive.org/tna/20080102164744/http://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdf
MANAGEMENT IN CONFIDENCE
CERTIFIED BSE-FREE HERDS FOR SOURCE OF MATERIAL FOR BIOLOGICAL PRODUCTS
http://collections.europarchive.org/tna/20080102184729/http://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdf
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
http://collections.europarchive.org/tna/20080102185137/http://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdf
http://web.archive.org/web/20030515185220/http://www.bseinquiry.gov.uk/files/yb/1989/01/30001001.pdf
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
http://web.archive.org/web/20030704202503/http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...
http://collections.europarchive.org/tna/20090114045856/http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf
more on the 1968 medicine act, they forgot to follow i.e. no Scrapie-like disease. ...TSS
http://web.archive.org/web/20030526124448/http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
Draft cover letter to product licence holders (considered by Human and Vet Medicines including deer)
CONCERN ABOUT BSE IN HUMAN MEDICINE
http://collections.europarchive.org/tna/20080103002832/http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://collections.europarchive.org/tna/20081105201818/http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
(It was noted with concern that hormone extracts could be manufactured by a veterinary surgeon for administration to animals under his care without any Medicines Act Control.)
http://collections.europarchive.org/tna/20080102164725/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
http://collections.europarchive.org/tna/20090505223756/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
COMMERCIAL IN CONFIDENCE
http://collections.europarchive.org/tna/20080102164736/http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf
TWA LITTLE STATEMENT 331
http://collections.europarchive.org/tna/20080102163939/http://www.bseinquiry.gov.uk/files/ws/s331.pdf
snip...
http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm
http://collections.europarchive.org/tna/20080103032631/http://www.bseinquiry.gov.uk/files/yb/1988/11/04003001.pdf
8. The Secretary of State has a number of licences. We understand that the inactivated polio vaccine is no longer being used. There is a stock of smallpox vaccine. We have not been able to determine the source material. (Made in sheep very unlikely to contain bovine ingredients).
CONFIDENTIAL
http://collections.europarchive.org/tna/20080102164642/http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdf
From: TSS
Subject: How many NHS patients as having received blood from a donor who later developed vCJD were people with haemophilia
Date: December 21, 2006 at 9:13 am PST
Health: vCJD Lord Morris of Manchester asked Her Majesty's Government:
How many NHS patients identified by the National Blood Service as having received blood from a donor who later developed vCJD were people with haemophilia. [HL750]
19 Dec 2006 : Column WA291
The Minister of State, Department of Health (Lord Warner): No patient with haemophilia or other bleeding disorders have been identified as having received blood from a blood donor who subsequently developed vCJD, nor have there been any reported cases of vCJD associated with receipt of plasma products.
However, all haemophilia patients who received plasma products between 1980 and 2001 sourced from UK donor plasma have been designated as "at risk of vCJD for public purposes". All plasma products are now sourced from non-UK plasma. The United Kingdom Haemophilia Centre Doctors' Organisation is collecting data that will provide an estimate of the number of haemophilia patients who have been exposed to plasma products which may be implicated with vCJD.
Lord Morris of Manchester asked Her Majesty's Government:
What is their response to the findings of Professor John Collinge in the December 2006 edition of the Lancet on the transmission by infected blood of variant CJD; and what action they are planning to take. [HL751]
Lord Warner: The Lancet article refers to the third known case of vCJD transmission via blood transfusion from a vCJD-infected donor. This case was originally notified to the department in January 2006 and announced by the Health Protection Agency in a press release on 9 February 2006, a copy of which has been placed in the Library.
There are 24 living patients in a group of people who had received blood components from donors subsequently known to have developed vCJD. They were all notified in 2005 or earlier, through their GPs, of their risk status and have been provided with information and support. The Health Protection Agency contacted the GPs earlier in the year to notify them of this third case and the agency has ensured that the GPs are fully informed and briefed about the subsequent Lancet publication.
The department has implemented a series of measures to reduce the risk of vCJD being transmitted through the blood supply. Shortly after vCJD was first identified in 1996, the possibility of human-to-human transmission through blood was considered, and the department implemented precautionary measures to reduce what was, at that time, a theoretical risk. These measures have been strengthened since evidence of transmission via blood began to emerge from animal studies, and following the first case of transfusion-associated transmission in humans, reported in December 2003. An important additional step, introduced in March 2004, was to exclude from blood donation those people who had themselves received a blood transfusion since January 1980. Other precautionary measures include:
from December 1997, blood components, plasma products or tissues obtained from any individual who later develops vCJD, were withdrawn/recalled;
19 Dec 2006 : Column WA292
in July 1998, it was announced that plasma for the manufacture of blood products, such as clotting factors, would be obtained from non-UK sources;from November 1999, white blood cells, which may carry a significant risk of transmitting vCJD, were removed from all blood used for transfusion;in August 2002, it was announced that fresh frozen plasma for treating babies and young children born on or after 1 January 1996 would be obtained from the USA; in July 2004, the exclusion criteria for blood donation were extended to include previously transfused platelet donors, and donors who were unsure if they had previously had a blood transfusion;in September 2004, the department announced further precautionary measures for patients who had received certain batches of plasma products;in July 2005, the use of USA-sourced fresh frozen plasma was extended to all children up to the age of 16;in July 2005, the department announced further precautionary measures for those patients who donated blood to three people who later developed vCJD. The department continues to keep all the evidence in relation to transmission of vCJD by blood under close review.
http://www.publications.parliament.uk/pa/ld200607/ldhansrd/text/61219w0004.htm#06121940000034
http://www.whale.to/v/singeltary7.html
Subject: Re: VACCINES/CHILDREN/TSE'S -- 'CONFIDENTIAL'
Date: Wed, 6 Sep 2000 18:20:09 -0800
From: tom
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de References: 1
######### Bovine Spongiform Encephalopathy #########
Just when I was thinking the Internet had reached a terminal condition of shallow pages and broken links, some young people come along and invent a really effective Internet search engine: http://www.google.com/ This works quite well to search the entire http://www.mad-cow.org site (or find 393 web sites such as GenBank that link to it, or 936 sites that cite it in text) back to 1996 as well as the BSE Inquiry http://www.bse.org.uk/
Thus for louping ill (unnecessary cites suppressed):
http://www.bse.org.uk/witness/htm/stat537.htm
Witness Statements 537 - Coulthard
29.Pituitary FSH from pigs has been used in the USA prior to its use in the UK and much more extensively there and Canada.... 30.Thousands of embryos were exported from this country to the USA prior to the ban being imposed... 42. No cow pituitaries were used in the preparation of FSH [follicular stimulating hormone] products compared with the case of louping ill vaccine for scrapie.
http://www.mad-cow.org/~tom/fda_late.html#ill
In the 1930's: 18,000 UK sheep were inoculated against louping ill, a brain inflammatory illness spread by ticks. Despite formalin-treatment of the inoculated agent, the procedure gave rise to 1,500 cases of scrapie. Louping is a Scottish word for fleeing or leaping, related to loping. In humans, louping ill is called Russian spring-summer encephalitis, a meningo-encephalitis with muscular tremors and spasms followed by varying degrees of paralysis.... [John Lanchester 2 Dec 96 New Yorker]
http://www.foodsafety.org/consumer/ht/ht294.htm
In what the story calls a grand historical irony, this landmark series of experiments was being confirmed at the same time in England as a result of an outbreak of scrapie in several hundred sheep that had been immunized against louping ill with a vaccine prepared from tissue from the brain, spinal cord, and spleen of sheep that were belatedly discovered to have been exposed to natural scrapie infection.[6.Gordon WS. Advances in veterinary research. Vet Rec 1946; 58: 516-520] The transmissible nature of the scrapie agent was thus established beyond any doubt. [P Brown, 1755 and All That: A Historical Primer of TSE.
We need to look at the full text of the article and its cites to see how they actually made the vaccine, whether they exported vaccine-infected sheep to Canada and the US, and what became of the vaccinated flocks. Perhaps there is still sample available, Moredun Institute is still around.
Gordon WS. Advances in veterinary research. Vet Rec 1946; 58: 516-520 (not covered by Medline) Gordon, Bronlee and Wilson 1939 [full cite is available only in a letter we don't have)
Terry was reading Draft Factual Account 17
http://www.bse.org.uk/dfa/dfa17.htm
http://bseinquiry.blogspot.com/2008/05/bse-inquiry-draft-factual-account-dfa.html
236. Mrs Alderman replied on 3 June 1988, listing products containing bovine insulin and noting there were two rabies vaccines listed but the species used in manufacture was not shown.[282] 237. On 6 June 1988 Mr Lawrence wrote to Sir Richard Southwood and enclosed some brief answers to the questions that had been tabled at the meeting on 19 May.[283] In relation to Q6, which asked OWhat is meat and other material from scrapie infected sheep used for - does it include pet food and material for biological products?¹ Part of the answer stated: ...
There has been one instance of inadvertant [sic] transmission of the scrapie agent to sheep through louping ill vaccine (Gordon, Bronlee and Wilson 1939). One of the three batches of vaccine made in 1935 at the Moredun Institute contained the scrapie agent resulting in 7% of the recipients of the 18, 000 doses in the batch developing scrapie. This vaccine was made from formalin-inactivated sheep brain, and brought to the attention of research workers that formalin, at a concentration of 0.35% for at least 3 months, which inactivated conventional viruses, did not totally inactivate the scrapie agent.
----------------------------
4. Questions we might want to have answered are: the highest risk would be from parenterals prepared from brain (eg rabies vaccine). Any species in which transmissible spongiform encephalopathies have been described would be suspect ("natural" infections in sheep, goats, cattle, deer, mink, but can be transmitted to hamster, mouse, guinea-pig etc). Are sterilisation processes adequate for the most resistant strain of scrapie agent or for CJD agent? Should companies be asked to include investigation for inclusion of scrapie agent (eg mouse innoculation [sic]) in at least some batches? If BSE behaves like scrapie, then we might expect other nervous tissue, spleen, lymph nodes and placenta to be contaminated. Infection has been described in other tissues too, eg gut wall, and we can not [sic] be sure blood is free. Do we know what bovine materials are used in which products, both as the active ingredient and in production? Bovine active ingredients in human products include insulin, vasopressin, bone, immune globulins, fibrin, dermal collagen, albumin. Bovine serum albumin and fetal calf serum must be used in preparation of very many products. For each of these products would any "BSE agent" be destroyed or eliminated in processing? If not, and the product is administered parenterally or topically into an open wound, might there be a risk? [For oral products, there would only be a trivially increased load on top of that taken in food in omnivores/carnivores including man. But for some herbivores, this might allow the agent to be introduced into yet another species].
--------------------------
Medicines and medical devises;
Subject: 2 known incidents of iatrogenic scrapie
Date: Thu, 7 Sep 2000 09:51:14 -0800
From: tom
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de References: 1
######### Bovine Spongiform Encephalopathy #########
One really has to wonder what went on in veterinary products produced during the peak BSE years. At this point, there are only 2 known incidents, both involving sheep brain vaccines.
I found a better source for needed references for iatrogenic scrapie in a nice review by Ray Bradley at http://www.iica.org.ar/Bse/6-%20Bradley.html. Disclosure has been meagre on the 1998 vaccine incident in Italy. Note 3 of the 5 references are totally off Medline and the other 2 fail to have abstracts or links, due to journal ineptness, burial in conference proceedings, and age of article.
If anyone has the first 3, I would appreciate a fax 542-484-0669 US.
tom
GORDON , W.S., 1959. Scrapie panel. In: Proceedings of 63rd Annual Meeting of the US Livestock Sanitary Association, 63, 286-294. [no medline record]
GORDON, W.S., 1946. Advances in Veterinary Research: Louping ill, tick-borne fever and scrapie. Veterinary Record, 58, 516-525. [no medline record]
GORDON , W.S., BROWNLEE, A.& WILSON, D.R., 1939. Studies in louping-ill, tick-borne fever and scrapie. 3rd International Congress for microbiology, 362-363. [no medline record]
-=-=--=
CAPUCCHIO, M.T., GUARDA,F., ISAIA,M.C., CARACAPPÀ, S. & DiMARCO,V., 1998. Natural occurrence of scrapie in goats in Italy. Veterinary Record, 143, 452-453. [title only]
AGRIMI, U., GLUSOPPE, R.U., CARDONE, F., POCCHIARI, M. & CARAMELLI, M., 1999. Epidemic transmissible spongiform encephalopathy in sheep and goats in Italy. Lancet, 353, 560-561. [title only]
IATROGENIC DISEASE IN ANIMALS
http://www.iica.org.ar/Bse/6-%20Bradley.html
Ray Bradley Private BSE Consultant Veterinary Laboratories Agency, United Kingdom
There have been two reported incidents of iatrogenic disease in animals, both involving scrapie. One was in Great Britain (Gordon, Brownlee and Wilson, 1939, Gordon 1946, 1959) the other in Italy (Capucchio et al, 1998, Agrimi et al, 1999). Both resulted from infection being introduced into vaccines, louping ill vaccine in Great Britain, Mycoplasma agalactiae vaccine in Italy. Each of these vaccines was prepared from tissues that included sheep brain. In both episodes it seems most likely that natural scrapie infection was present unknowingly in some brains used for the purpose. Once prepared and having passed all the conventional vaccine tests large numbers of sheep in Great Britain, and goats and some sheep in Italy were inoculated. After the necessary incubation period large numbers (> 1,000 in each case) of inoculated animals came down with scrapie. In the meantime some inoculated clinically healthy goats and sheep may have entered food and feed chains or have been used for other purposes. In the British outbreak there appears to have been no consequence for humans who may have consumed infected sheep. It is too early to say what may be the consequences in Italy but measures have been taken to reduce any risk there may have been. .........end
Louping-ill vaccine documents from November 23rd, 1946 FULL TEXT
THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946
NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND
ANNUAL CONGRESS, 1946
The annual Congress, 1946, was held at the Royal Veterinary College, Royal College Street, London, N.W.I. from September 22nd to September 27th.
Opening Meeting
[skip to scrapie vaccine issue...tss]
Papers Presented to Congress
SNIP...FULL TEXT ;
http://www.whale.to/v/singeltary7.html
although 176 products do _not_ conform to the CSM/VPC guidelines.
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
http://web.archive.org/web/20030704202503/http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
8. The Secretary of State has a number of licences. We understand that the inactivated polio vaccine is no longer being used. There is a stock of smallpox vaccine. We have not been able to determine the source material. (Made in sheep very unlikely to contain bovine ingredients).
CONFIDENTIAL
http://collections.europarchive.org/tna/20080102164642/http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdf
CONFIDENTIAL
http://collections.europarchive.org/tna/20080103002544/http://www.bseinquiry.gov.uk/files/yb/1989/02/14011001.pdf
more on the 1968 medicine act, they forgot to follow
http://web.archive.org/web/20030526124448/http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
Draft cover letter to product licence holders (considered by Human and Vet Medicines including deer)
http://collections.europarchive.org/tna/20080103002832/http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://collections.europarchive.org/tna/20080102155758/http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
2.3.Iatrogenic exposure
Iatrogenic exposure of scrapie has probably occurred twice. The first report determined that the vehicle was a louping ill vaccine prepared from sheep tissues and this infected a large number of sheep sheep (Gordon, 1946, Greig, 1950). The second was more recent and in this case a vaccine against Mycoplasma agalactiae prepared from sheep tissues was incriminated (Agrimi et al 1999, Capucchio, 1998) but not all outbreaks could be linked to the use of the vaccine. In this episode goats were predominantly affected10.
http://ec.europa.eu/food/fs/sc/ssc/out170_en.pdf
http://ec.europa.eu/food/fs/sc/ssc/out247_en.pdf
5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products for injection or surgical implantation which are prepared from bovine tissues, or which utilise bovine serum albumin or similar agents in their manufacture, might also be capable of transmitting infectious agents. All medicinal products are licensed under the Medicines Act by the Licensing Authority following guidance, for example from the Committee on Safety of Medicines (CSM), the Committee on Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing Authority have been alerted to potential concern about BSE in medicinal products and will ensure that scrutiny of source materials and manufacturing processes now takes account of BSE agent.
http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf
BEFORE the BSE Inquiry went online, i was requesting the daily hearings and submissions, and they were sending them to me via air mail. then, when the BSE Inquiry finally went online, i was then able to go back and match up some of what i had with the YB numbers (above), with the official documents. ...TSS
BSE offals used in cosmetics, toiletry and perfume industry Sun, 3 Sep 2000. Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr. of Bacliff, Texas Miss Marion Kelly Cosmetic, Toiletry and Perfumery Association 35 Dover Street London W1X3RA
Department of Trade and Industry 10-18 Victoria Street London SW1H ONN Enquiries 01-215 5000 Telex 8811074 DTHQ G 01 215 3324 1 February 1990
http://www.mad-cow.org/00/sep00_news.html#bbb
40,000 human heart valves a year from BSE herds Sun, 3 Sep 2000. Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr. of Bacliff, Texas
Opinion (webmaster): Below are some shocking documents. Here is a British company preparing 40,000 heart valves a year from bovine pericardium, primarily for export, and they are not required to source this material from BSE-free herds even in peak epidemic years. It is amazing to watch health "authorities" grovelling on their bellies to wring petty concessions from middle management at obscure little companies. The main worry is not the practise of using 800 potentially infected cows a week for human heart transplant material but that the press or recipients will get wind of it, hurting business.
BSE wasn't the problem, it was awkward queries from importing countries like the US. The cows are stunned using brain penetration -- can't do anything about the chunks of bovine brain blasted into the circulatory system, it's the norm. Can't use younger lower-risk animals either, patch would not be big enough. It is fascinating to see the British government worrying about, but doing nothing, with pigs with BSE 10 years ago.
While scrapie was long used as an excuse for continuing with human use of BSE-tainted material, little sheep material was used medically. Bovine transplants, vaccines, insulin doeses, etc. are far more dangerous than dietary material as injections, and are done on a very wide scale. So scrapie was never a valid analogy to BSE, as MAFF knew full well.
The British government deferred to the manufacturer's rep for an opinion on how contaminated pericardium might be, just as this appeared showing that this tissue is extremely dangerous:
http://www.mad-cow.org/00/sep00_news.html#hhh
England worried briefly about infecting other countries 27 Aug 00 confidential correspondence obtained by Terry S. Singeltary Sr.
BSE11/2 020;
SC1337p
DEPARTMENT OF HEALTH AND SOCIAL SECURITY Richmond House, 79 Whitehall, London SWIA 2NS Telephone 01-210 3000 From the Chief Medical Officer Sir Donald Achson KBE DM DSc FRCP FFCM FFOM
Mr K C Meldrum Chief Veterinary Officer Ministry of Agriculture, Fisheries and Food Government Buildings Hook Rise South Tolworth Surbiton Surrey KT6 7NG 3 January 1990
Dear Mr Meldrum
BOVINE SPONGIFORM ENCEPHALOPATHY
You will recall that we have previously discussed the potential risks of BSE occurring in other countries as a result of the continuing export from the UK of meat and bone that may be contaminated by scrapie or possibly BSE.
I remain concerned that we are not being consistent in our attempts to contain the risks of BSE. Having banned the feeding of meat and bone meal to ruminamts in 1988, we should take steps to prevent these UK products being fed to ruminants in other countries. This could be achieved either through a ban on the export of meat and bone meal, or at least by the proper labelling of these products to make it absolutely clear they should not be fed to ruminants [or zoo animals, including rare and endangered primates -- webmaster]. Unless some such action is taken the difficult problems we have faced with BSE may well occur in other countries who import UK meat and bone meal. Surely it is short sighted for us to risk being seen in future as having been responsible for the introduction of BSE to the food chain in other countries.
http://www.mad-cow.org/00/aug00_last_news.html#fff
The documents below were provided by Terry S. Singeltary Sr on 8 May 2000. They are optically character read (scanned into computer) and so may contain typos and unreadable parts.
TIP740203/l 0424 CONFIDENTIAL
Mr Cunningham CMP3 From: D O Hagger MBI Dr Salisbury MED/IMCD3 Mr Burton PD/STB/PG1B B/17/2 Date: 15.02.1989 Mr Dudley PD/AD4
BOVINE SPONGIFORM ENCEPHALOPATHY
http://www.mad-cow.org/00/may00_news.html#aaa
Other US BSE risks: the imported products picture 24 Jul 00 Trade Statistics: UK to US Compiled by Terry S. Singeltary Sr of Bacliff, Texas
[Opinion (webmaster): The US has focused for years on tracing, containing, and eradicating live animal imports from the UK or other countries with acknowledged BSE like Belgium, including some 499 cattle and the Vermont sheep. This strategy does not acknowledge imports of rendered bovine products from England during the BSE period nor secondary products such as surgical catgut, which is to say surgical cowgut, or dairy cattle embryos, vaccines for veterinarian and human medicines. What has become of these?
Mr. Singeltary, who lost his mother to CJD of unexplained origin a few years back and went on to became a well-known TSE activist, has tracked down voluminous pertinent import data through correspondence with UK officials and searches of government web sites. Imports of such products are frequently cited by Europeans in rating BSE risks in the US and in shutting out US exports.
Many people's eyes glaze over when reviewing reams of sometimes older trade statistics. There is no proof that any of the imported products was contaminated with BSE nor if so, any evidence that any BSE product lead to infection in US livestock, surgical patients, or what not. Nonetheless, the data obtained by Mr. Singeltary establish that an appalling variety and tonnage of products that were imported by the US from the UK and othr BSE-affected countries during the peak of the BSE epidemic years.]
10 January 1990 COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
COMMITTEE ON SAFETY OF MEDICINES WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY
SURGICAL CATGUT SUTURES 2.1 At the first meeting of the Working Party on Bovine Spongiform Encephalopathy on 6 September 1989, detailed consideration was given to XXXXX Surgical Catgut. This arose from the Company's response to the Letter to Licence Holders, indicating that the bovine small intestine source material was derived from UK cattle, unlike 8 other licenced catgut sutures. In contrast XXXXX Surgical Catgut was stated to hold over 90% share of the market for catgut sutures, and to constitute approximately 83% of all sutures used in U.K. IMPORTS OF SUTURES FROM THE KNOWN BSE COUNTRY;
http://www.mad-cow.org/00/jul00_dont_eat_sheep.html#hhh
The documents below were provided by Terry S. Singeltary Sr on 8 May 2000. They are optically character read (scanned into computer) and so may contain typos and unreadable parts.
TIP740203/l 0424 CONFIDENTIAL
Mr Cunningham CMP3 From: D O Hagger MBI Dr Salisbury MED/IMCD3 Mr Burton PD/STB/PG1B B/17/2 Date: 15.02.1989 Mr Dudley PD/AD4
BOVINE SPONGIFORM ENCEPHALOPATHY
1. The purpose of this minute is to alert you to recent developments on BSE as they affect medicines and to invite representatives to a meeting in Market Towers on 22 February 1989.
2. The report of the Working Party on Bovine Spongiform Encephalopathy (BSE) was submitted by the CMO to the Secretary of State for Health and Minister for Agriculturer on 9 February.
3. The summary at the end of the report records, inter alia: 'we have drawn the attention of the Licensing Authority to the potential of transfer of BSE agent in human and veterinary medicinal products. In paragraph 7 of his submission (Annex A), the CMO notes:
"I am also putting work urgently in hand to satisfy myself that everything possible has been done to ensure .... that transfer of the BBE agent in human and veterinary medicinal products does not occur."
4. The Veterinary products Committee meets on 16 February and The committee on Safety of Medicines on 23 February when each will be considering a draft of some joint guidelines for manufacturers of medicinal products which use bovine material as an ingredient or an intermediate in the manufacturing process (Annex B).....
6. Although a wide range of medicines may be implicated - and the present proposal is to write to companies for more information - an "instant" telephone survey of manufacturer of vaccines used for children has already been undertaken in response to a request from Dr Harris. The results are in Dr Adams' minute of 14 February (Annex C) - the proviso in his second paragraph, last sentence should be noted. 89/02.15/11.1
89/02.15/11.2 MF580439/1 0584 SOUTHWOOD REPORT: BSE AND MEDICINAL PRODUCTS
1. I attach a list of questions on BSE and medicines compiled with the aim of providing question and answer briefing to DH and MAFF Ministers upon publication of the Southwood Report. I have suggested names of those who may be able to provide answers. All recipients are invited to consider which if any important areas have been missed. Also attached is copy QA briefing being proposed by MAFF. I understand MAFF have produced General QA briefing on the reports as a whole. ..
MF580439/1 0585 Question
1. Which medicines are affected? (person to provide reply) Dr. Jefferys
2. Are the risks greater with some medicines than others? Dr. Jefferys
3. Why are medicines affected? Dr. Jefferys
4. Are some affected products available over the counter from pharmacies or shops? Dr. Purves
5. Are only UK products at risk? Dr. Jefferys
6. Are existing stocks safe? Dr. Jefferys
7. Are pre 1980 stocks available? Mr. Burton
8. Are these alternatives to the use of bovine material? Dr. Purves
9. Why can't we throw away suspect stock and import or manufacture safe medicines? Dr. Jefferys
10. Which patients are at risk? Dr. Jefferys
11. Are some patients particularly vulnerable? Dr Jefferys
12. What risks exist to those who have already used these medicines? Dr. Jefferys
13. HOW might patients be affected? Dr. Jefferys
14. Can BSE be transmitted to patients by medicines? Dr. Jefferys
15. How long will it be before risks are quantified? Dr. Jefferys
100 89/02.17/10.2 MF580439/1 0586
16. What research is going on to find out if medicines can transmit this disease and if any patients have been affected? Dr Jefferys
17. Could recent cases of Creuuzfeld Jacob Disease have been caused by transmission of BSE through medicines? Dr. Jefferys
18. What action is the Licensing Authority taking to ensure proper scrutinising of source materials and manufacturing processes? Dr. Jefferys/Dr. Purves
19. Are the guidelines practical? Dr. Jefferys/Dr. Purves
20. Will the guidelines remove the risk? Dr. Jefferys
21. How will the guidelines be enforced? Dr. Jefferys/Dr. Purves
22. How soon will they come into force? Dr. Jefferys
23. Will the guidelines be published? Mr. Hagger
24. What is being done to reassure patients, parents etc? Mr. Hagger/Dr. Salisbury
25. What advice is being given to doctors, pharmacists etc? Mr. Hagger
26. What advice is the Government giving about its vaccination programme? Dr. Salisbury
27. Is the vaccination programme put at risk because of BSE? Dr. Salisbury
89/02.17/10.3
Q. Will government act on this?
A. Yes - thymus is not used in preparation of baby foods but it is contacting all manufacturers to seek their urgent views on use of kidneys and liver from ruminants. Will consider any necessary measures in the light of their response.
VETERINARY MEDICINES
Q. Can medicines spread BSE to other cattle/animals?
A. The report describes any risks as remote.
Q. How can risks be avoided?
A. In liaison with the DOH the Veterinary Products Committee is examining guidelines for the veterinary pharmaceutical industry which will be issued shortly.
Q. What will Guidelines say?
A. In essence they call for non-bovine sources to be used if possible, including synthetic material of biotechnological origin. Where this is not possible the industry should look for sources which are free of BSE and which are collected in a manner which avoids risk of contamination by the BSE agent.
89/02.17/10.4 MF580439/1 0588
A. Bovine source material is used in [garbled, cannot read...TSS] and some other medicines.
Q. How many medicines are involved?
A. Computer records show that about 300 of the 3,050 veterinary medicines licensed in the U.K. are manufactured directly from bovine source material. However, other medicines may be produced from bovine sources and a letter is going to all license holders so that a comprehensive list can be drawn up.
89/06.19/8.1 BSE3/1 0191 Hr J Maslin (MAFF) Ref: Maslin3g
From: Dr H Pickles Med SEB/B Date: 3 July 1989
CATTLE BY-PRODUCTS AND BSE
I was interested to see the list of by-products sent to the HSE. Those of particular concern included:
* small intestines: sutures (I thought the source was ovine but you are checking this)
* spinal cord: pharmaceuticals
* thymus: pharmaceuticals
Are you able to give me more information on which UK manufacturers use these materials? Our proposed ban on bovine offal for human consumption would not affect these uses, I assume.
Id No. 1934/RD/1 89/08.10/6.1 117A
BOVINE SPONGIFORM ENCEPHALAPATHY MEETING HELD ON 21 AUGUST 1989 AT 2;15 IN ROOM 720 Miss M Duncan (Chairman) Mr W Burton Dr E Hoxey Mrs J Dhell Ms K Turner Dr S Whittle Mr N Weatherhead ... 5. The MCA had sent 2700 questionnaires out, 1,124 had made valid returns; of these 122 use animal material of some kind and there are 582 products involved. ... 6. The MCA/BSE working group will meet on 6th September. Their aim is to review responses from professional officers in MCA who have suggested seven categories of importance (with 1 being the most important} for medical products:
ID 2267/NRE/1 89/08.21/10.1
1. Products with Bovine brain/lymph tissue administered by injection.
2. Products with bovine tissue other than brain/lymph administered by inection.
3. Tissue implants/open wound dressing/surgical materials/dental and ophthlamic products with bovine ingredients.
4. Products with bovine ingredients administered topically.
5. Products with bovine ingredients administered orally.
6. Products with other animal/fish/insect/bird ingredients administered by injection/topically/oral routes.
7. Products with ingredients derived from animal material by chemical processing (eg stearic acid, gelatine, lanolin ext.
The BSE working group will decide which of these are important, and should be examined more closely, and which categories can be eliminated.
The responses by the companies were presented by Ms Turner and were categorised by MCA standards, the products that were discussed were all low volume usage products eg sutures, heart valves.
8. As the responses included some materials of human origin it was decided that more information should be sought about CJD. There had been 2 recent deaths reported associated with human growth hormone. These were being investigated.
9. Re-editing of the Paper on "Incubation of Scrapie-like Agents"
It was suggested that the document could be sent out to companies with the non-standard sterilization Document. The document could have severe implications on the companies whose products have a high risk factor as decided by the MCA working group....
11. The Need for a list of High Priority Implantables The commitee decided that no list is necessary as all implantables, including ones from a human source are of high priority. Concern was shown over Killingbeck who use human material but had not yet responded. The company will be chased for a response. Concern was shown over the fact that there may be other scrapie-like organisms in other animals and further enquiries should be made.
2334q/RD/4 89/08.21/10.7
BOVINE MATERIAL USED IN THE MANUFACTURE OF SURGICAL IMPLANTS AND BLOOD CONTACT MEDICAL DEVICES
Glutaraldehyde, formaldehyde, and ethylene oxide are used in the sterilization of these devices.
However, glutaraldehyde 4,10,12,19 formaldehyde 5,10,11,13,19 and ethylene oxide 19,23 are all reported to be ineffective methods for sterilization of material infected with the agents of CJD or scrapie.
Previous advice and research using the agents of CJD and scrapie, has concentrated on the decontamination of equipment; protection of health care workers from contaminated human material; human growth hormone; and dura mater. The methods developed may not be directly applicable or transferable to material of bovine origin for use in human implantation.
2334q/RD/7 89/08.21/10.10 BSE11/2 020 SC1337
DEPARTMENT OF HEALTH AND SOCIAL SECURITY Richmood House 79 Whitehall, London SW1A 2NS Telephone 01-210-3000 From the Chief Medical Officer Sir Donald Acheson KBE DM DSc FRCP FFCM FFOM
Mr K C Meldrum Chief Veterinary Officer Ministry of Agriculture, Fisheries and Food Government Buildings Hook Rise South Tolworth Surbiton Surrey KT6 7NG
3 January 1990
Dear Mr. Meldrum,
BOVINE SPONGIFORM ENCEPHALOPATHY
You will recall that we have previously discussed the potential risks of BSE occurring in other Countries as a result of the continuing export from the UK of meat and bone that may be contaminated by scrapie or possibly BSE.
I remain concerned that we are not being consistent in our attempts to contain the risks of BSE. Having banned the feeding of meat and bone meal to ruminants in 1988, we should take steps to prevent these UK products being fed to ruminants in other countries. This could be achieved either through a ban on the export of meat and bone meal, or at least by the proper labelling of these products to make it absolutely clear they should not be fed to ruminants. Unless some such action is taken the difficult problems we have faced with BSE may well occur in other countries who import UK meat and bone meal. Surely it is short sighted for us to risk being seen in future as having been responsible for the introduction of BSE to the food chain in other countries.
I would be very interested to hear how you feel this gap in the present prcautionary measures to eliminate BSE should be closed. We should be aiming at the global elimination of this new bovine disease. The export of our meat and bone meal is a continuing risk to other countries.
Signed Sincerely Donald Acheson
Did the US import fetal calf serum and vaccines from BSE-affected countries? 3002.10.0040: FETAL BOVINE SERUM (FBS) U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)
<--- Dec 1998 ---> <--- 1998 YTD ---> Country Quantity Value Quantity Value
=================================================================
WORLD TOTAL . . . . . . . 2,727 233 131,486 8,502 Australia . . . . . . . . --- --- 19,637 2,623 Austria . . . . . . . . . --- --- 2,400 191 Belgium . . . . . . . . . --- --- 17 32 Canada . . . . . . . . . 900 110 30,983 3,220 Costa Rica . . . . . . . 500 20 4,677 169 Federal Rep. of Germany --- --- 105 21 Finland . . . . . . . . . 1 8 9 83 France . . . . . . . . . --- --- 73 7 Guatemala . . . . . . . . --- --- 719 42 Honduras . . . . . . . . --- --- 1,108 88 Israel . . . . . . . . . --- --- 24 165 Netherlands . . . . . . . --- --- 1 5 New Zealand . . . . . . . 26 5 65,953 913 Panama . . . . . . . . . --- --- 1,195 64 Switzerland . . . . . . . 971 8 1,078 23 United Kingdom . . . . . 329 82 743 756 Uruguay . . . . . . . . . --- --- 2,764 98 ------------------------------------------------------------------ 3002.20.0000: VACCINES FOR HUMAN MEDICINE U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)
<--- Dec 1998 ---> <--- 1998 YTD ---> Country Quantity Value Quantity Value
=================================================================
WORLD TOTAL . . . . . . . 25,702 26,150 550,258 378,735 Austria . . . . . . . . . --- --- 45 225 Belgium . . . . . . . . . 14,311 12,029 248,041 199,036 Canada . . . . . . . . . 1,109 1,527 15,798 16,305 Denmark . . . . . . . . . 80 234 246 682 Federal Rep. of Germany 1,064 4,073 12,001 6,329 France . . . . . . . . . 3,902 4,859 87,879 92,845 Ireland . . . . . . . . . --- --- 120 478 Italy . . . . . . . . . . --- --- 2,359 81 Japan . . . . . . . . . . 445 1,903 11,350 11,298 Netherlands . . . . . . . --- --- 94 6 Republic Of South Africa --- --- 2 1 Spain . . . . . . . . . . --- --- 60 30 Switzerland . . . . . . . 716 353 9,303 4,271 United Kingdom . . . . . 4,075 1,172 162,960 47,148 ------------------------------------------------------------------ 3002.30.0000: VACCINES FOR VETRINARY MEDICINE U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)
<--- Dec 1998 ---> <--- 1998 YTD ---> Country Quantity Value Quantity Value =================================================================
WORLD TOTAL . . . . . . . 6,528 237 87,149 2,715 Canada . . . . . . . . . --- --- 2,637 305 Federal Rep. of Germany --- --- 104 5 Netherlands . . . . . . . 138 64 472 192 New Zealand . . . . . . . 6,390 173 83,882 1,895 United Kingdom . . . . . --- --- 54 318
http://www.mad-cow.org/00/may00_news.html
Procedures Manual
Bovine Spongiform Encephalopathy (BSE)
Ongoing Surveillance Plan
Ongoing Surveillance Plan Implementation July 20, 2006
snip...
Personal Safety
If BSE is transmissible to humans in the occupational setting, the most likely routes would be through contact with infective tissues through wounds or open lesions on the skin, contact with mucous membranes (eyes and mouth), or exceptionally, by swallowing. .....snip...end
http://www.aphis.usda.gov/vs/nvsl/PDFs/BSE%20Ongoing%20Surveillance%20SOP%207-20-06.doc
SO, looks like to me the most likely route of transmission of BSE to humans would be through inoculation i.e., the most likely routes would be through contact with infective tissues through wounds or open lesions on the skin, IF you look at all the successful transmission studies in the lab with TSE, inoculations was the most successful route.
BSE-L@LISTS.AEGEE.ORG
Bovine Spongiform Encephalopathy
BSE-L is a discussion forum for scientists who are interested in Bovine Spongiform Encephalopathy (BSE). BSE-L has been created on 20th July, 1994 by Siegfried Schmitt. Impressum: http://www.kaliv.de/impressum.html
LISTS.AEGEE.ORG ( BSE-L: 484 matches (only the first 50 will be shown).. )
https://lists.aegee.org/cgi-bin/wa?S2=BSE-L&X=1D1B9A2D19721D3331&Y=flounder9@verizon.net&q=VACCINES&s=&f=&a=&b
From: TSS (216-119-138-163.ipset18.wt.net)
Subject: Louping-ill vaccine documents from November 23rd, 1946 Date:
September 10, 2000 at 8:57 am PST
Subject: Louping-ill vaccine documents from November 23rd, 1946
Date: Sat, 9 Sep 2000 17:44:57 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946
NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND
ANNUAL CONGRESS, 1946
The annual Congress, 1946, was held at the Royal Veterinary College, Royal College Street, London, N.W.I. from September 22nd to September 27th.
Opening Meeting
[skip to scrapie vaccine issue...tss]
Papers Presented to Congress
The papers presented to this year's Congress had as their general theme the progressive work of the profession during the war years. Their appeal was clearly demonstrated by the large and remarkably uniform attendance in the Grand Hall of the Royal Veterinary College throughout the series; between 200 and 250 members were present and they showed a keen interest in every paper, which was reflected in the expression of some disappointment that the time available for discussion did not permit of the participation of more than a small proportion of would-be contributors.
In this issue we publish (below) the first to be read and discussed, that by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E., "Advances in Veterinary Research." Next week's issue will contain the paper on "Some Recent Advances in Veterinary Medicine and Surgery in Large-Animal Practice" by Mr. T. Norman Gold, M.R.C.V.S. In succeeding numbers of the Record will be reproduced, also with reports of discussions, that by Mr. W. L. Weipers, M.R.C.V.S., D.V.S.M., on the same subject as relating to small-animal practice, and the papers by Mr. J. N. Ritchie, B.SC., M.R.C.V.S., D.V.S.M., and Mr. H.W. Steele-Bodger, M.R.C.V.S., on "War-time Achievements of the British Home Veterinary Services."
The first scientific paper of Congress was read by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E. on Monday, September 23rd, 1946, when Professor J. Basil Buxton, M.A., F.R.C.V.S, D.V.H., Prinicipal of the Royal Veterinary College, presided.
Advances in Veterinary Research
by
W.S. GORDON, PH.D., M.R.C.V.S., F.R.S.E.
Agriculteral Research Council, Field Station, Compton, Berks.
Louping-ill, Tick-borne Fever and Scrapie
In 1930 Pool, Browniee; Wilson recorded that louping-ill was a transmissible disease. Greig et al, (1931) showed that the infective agent was a filter-passing virus with neurotropic characters and Browniee & Wilson (1932) that the essential pathology was that of an encephalomyelitis. Gordon, Browniee, Wilson & MacLeod (1932) and MacLeod & Gordon (1932) confirmed and extended this work. It was shown that on louping-ill farms the virus was present in the blood of many sheep which did not show clinical symptoms indicating involvement of the central nervous system and that for the perpetuation and spread of the disease these subclinical cases were probably of greater importance that the frank clinical cases because, in Nature, the disease was spread by the tick, lxodes ricinus L. More recently Wilson (1945, 1946) has described the cultivation of the virus in a chick embryo medium, the pathogenic properties of this culture virus and the preparation of louping-ill antiserum.
Between 1931 and 1934 I carried out experiments which resulted in the development of an effective vaccine for the prevention of louping-ill.* This vaccine has been in general use since 1935 and in his annual report to the Animal Diseases Research Association this year, Dr. Greig stated that about 227,000 doses of vaccine had been issued from Moredun alone.
Dr. Gordon illustrated this portion of his paper by means of graphs and diagrams projected by the epidiascope.
This investigation, however, did not begin and end with the study of louping-ill; it had, by good fortune, a more romantic turn and less fortunately a final dramatic twist which led almost to catastrophe. After it had been established that a solid immunity to louping-ill could be induced in sheep, a group of immunized and a group of susceptible animals were placed together on the tick-infected pasture of a louping-ill farm. Each day all the animals were gathered and their temperatures were recorded. It was anticipated that febrile reactions with some fatalities would develop in the controls while the louping-ill immunes would remain normal. Contrary to expectation, however, every sheep, both immune and control, developed a febrile reaction. This unexpected result made necessary further investigation which showed that the febrile reaction in the louping-ill immunes was due to a hitherto undescribed infective agent, a Rickettsia-like organism which could be observed in the cytoplasm of the granular leucocytes, especially the neutrophil polymorphs (MacLeod (1932), Gordon, Browniee, Wilson & MacLeod. MacLeod & Gordon (1933). MacLeod (1936). MacLeod collected ticks over many widely separated parts of Scotland and all were found to harbour the infective agent of tick-borne fever, and it is probable that all sheep on tick-infested farms develop this disease, at least on the first occasion that they become infested with ticks. When the infection is passed in series through susceptible adult sheep it causes a sever, febrile reaction, dullness and loss of bodily condition but it rarely, if ever, proves fatal. It is clear, however, that it aggravates the harmful effects of a louping-ill infection and it is a serious additional complication to such infections as pyaemia and the anacrobic infections which beset lambs on the hill farms of Northern Britain.
Studying the epidemiology of louping-ill on hill farms it became obvious that the pyaemic condition of lambs described by M'Fadyean (1894) was very prevalent on tick infested farms Pyaemia is a crippling condition of lambs associated with tick-bite and is often confused with louping-ill. It is caused by infection with Staphylococcus aureus and affected animals may show abscess formation on the skin, in the joints, viscera, meninges and elsewhere in the body. It was thought that tick-borne fever might have been a predisposing factor in this disease and unsuccessful attempts were made by Taylor, Holman & Gordon (1941) to reproduce the condition by infecting lambs subcutaneously with the staphylococcus and concurrently producing infections with tickborne fever and louping-ill in the same lambs. Work on pyaemia was then continued by McDiarmid (1946a, 1946b, 1946c), who succeeded in reproducing a pyaemic disease in mice, guinea-pigs and lambs similar to the naturally occurring condition by intravenous inoculation of Staphylococcus aureus. He also found a bacteraemic form of the disease in which no gross pyaemic lesions were observed. The prevention or treatment of this condition presents a formidable problem. It is unlikely that staphylococcal ???oid will provide an effective immunity and even if penicillin proved to be a successful treatment, the difficulty of applying it in adequate and sustained dosage to young lambs on hill farms would be almost insurmountable.
From 1931 to 1934 field trials to test the immunizing value and harmlessness of the loup-ill vaccine were carried out on a gradually increasing scale. Many thousands of sheep were vaccinated and similar numbers, living under identical conditions were left as controls. The end result showed that an average mortability of about 9 percent in the controls was reduced to less than 1 percent in the vaccinated animals. While the efficiency of the vaccine was obvious after the second year of work, previous bitter experience had shown the wisdom of withholding a biological product from widespread use until it had been successfully produced in bulk, as opposed to small-scale experimental production and until it had been thoroughly tested for immunizing efficiency and freedom from harmful effects. It was thought that after four years testing this stage had been reached in 1935, and in the spring of that year the vaccine was issued for general use. It comprised a 10 percent saline suspension of brain, spinal cord and spleen tissues taken from sheep five days after infection with louping-ill virus by intracerebral inoculation. To this suspension 0-35 percent of formalin was added to inactivate the virus and its safety for use as a vaccine was checked by intracerbral inoculation of mice and sheep and by the inoculation of culture medium. Its protective power was proved by vaccination sheep and later subjecting them, along with controls, to a test dose of living virus.
Vaccine for issue had to be free from detectable, living virus and capable of protecting sheep against a test dose of virus applied subcutaneously. The 1935 vaccine conformed to these standards and was issued for inoculation in March as three separate batches labelled 1, 2, and 3. The tissues of 140 sheep were employed to make batch 1 of which 22,270 doses were used; 114 to make batch 2 of which 18,000 doses were used and 44 to make batch 3 of which 4,360 doses were used. All the sheep tissues incorporated in the vaccine were obtained from yearling sheep. During 1935 and 1936 the vaccine proved highly efficient in the prevention of loup-ill and no user observed an ill-effect in the inoculated animals. In September, 1937, two and a half years after vaccinating the sheep, two owners complained that scrapie, a disease which had not before been observed in the Blackface breed, was appearing in their stock of Blackface sheep and further that it was confined to animals vaccinated with louping-ill vaccine in 1935. At that stage it was difficult to conceive that the occurrence could be associated with the injection of the vaccine but in view of the implications, I visited most of the farms on which sheep had been vaccinated in 1935. It was at this point that the investigation reached its dramatic phase; I shall not forget the profound effect on my emotions when I visited these farms and was warmly welcomed because of the great benefits resulting from the application of louping-ill vaccine, wheras the chief purpose of my visit was to determine if scrapie was appearing in the inoculated sheep. The enquiry made the position clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in a few instances that the owner was associating the occurrence with louping-ill vaccination. The disease was affecting all breeds and it was confined to the animals vaccinated with batch 2. This was clearly demonstrated on a number of farms on which batch 1 had been used to inoculate the hoggs in 1935 and batch 2 to inoculate the ewes. None of the hoggs, which at this time were three- year-old ewes. At this time it was difficult to forecast whether all of the 18,000 sheep which had received batch 2 vaccine would develop scrapie. It was fortunate, however, that the majority of the sheep vaccinated with batch 2 were ewes and therfore all that were four years old and upwards at the time of vaccination had already been disposed of and there only remained the ewes which had been two to three years old at the time of vaccination, consequently no accurate assessment of the incidence of scrapie could be made. On a few farms, however, where vaccination was confined to hoggs, the incidence ranged from 1 percent, to 35 percent, with an average of about 5 percent. Since batch 2 vaccine had been incriminated as a probable source of scrapie infection, an attempt was made to trace the origin of the 112 sheep whose tissues had been included in the vaccine. It was found that they had been supplied by three owners and that all were of the Blackface or Greyface breed with the exception of eight which were Cheviot lambs born in 1935 from ewes which had been in contact with scrapie infection. Some of these contact ewes developed scrapie in 1936-37 and three surviving fellow lambs to the eight included in the batch 2 vaccine of 1935 developed scrapie, one in September, 1936, one in February, 1937, and one in November, 1937. There was, therefore, strong presumptive evidence that the eight Cheviot lambs included in the vaccine although apparently healthy were, in fact, in the incubative stage of a scrapie infection and that in their tissues there was an infective agent which had contaminated the batch 2 vaccine, rendering it liable to set up scrapie. If that assumption was correct then the evidence indicated that:-
(1) the infective agent of scrapie was present in the brain, spinal cord and or spleen of infected sheep: (2) it could withstand a concentration of formalin of 0-35 percent, which inactivated the virus of louping-ill: (3) it could be transmitted by subcutaneous inoculation; (4) it had an incubative period of two years and longer.
Two Frenchmen, Cuille & Chelle (1939) as the result of experiments commenced in 1932, reported the successful infection of sheep by inoculation of emulsions of spinal cord or brain material by the intracerebral, epidural, intraocular and subcutaneous routes The incubation period varied according to the route employed, being one year intracerebrally, 15 months intraocularly and 20 months subcutaneously. They failed to infect rabbits but succeeded in infecting goats. Another important part of their work showed that the infective agent could pass through a chamberland 1.3 filter, thus demonstrating that the infective agent was a filtrable virus. It was a curious coincidence that while they were doing their transmission experiments their work was being confirmed by the unforeseeable infectivity of a formalinized tissue vaccine.
As a result of this experience a large-scale transmission experiment involving the ue of 788 sheep was commenced in 1938 on a farm specially taken for the purpose by the Animal Diseases Research Association with funds provided by the Agricultural Research Council. The experiment was designed to determine the nature of the infective agent and the pathogenesis of the disease. It is only possible here to give a summary of the result which showed that (1) saline suspensions of brain and spinal cord tissue of sheep affected with scrapie were infective to normal sheep when inoculated intracerebrally or subcutaneously; (2) the incubation period after intracerebral inoculation was seven months and upwards and only 60 percent of the inoculated sheep developed scrapie during a period of four and a half years; (3) the incubation period after subcutaneous inoculation was 15 months and upwards and only about 30 percent of the inoculated sheep developed the disease during the four and a half years: (4) the infective agent was of small size and probably a filtrable virus.
The prolonged incubative period of the disease and the remarkable resistance of the causal agent to formalin are features of distinct interest. It still remains to determine if a biological test can be devised to detect infected animals so that they can be killed for food before they develop clinical symptoms and to explore the possibilities of producing an immunity to the disease.
==================================================================
Scrapie Louping-ill Vaccine
‘There has been one instance of inadvertant [sic] transmission of the
scrapie agent to sheep through louping ill vaccine (Gordon, Bronlee and
Wilson 1939). One of the three batches of vaccine made in 1935 at the
Moredun Institute contained the scrapie agent resulting in 7% of the
recipients of the 18, 000 doses in the batch developing scrapie. This
vaccine was made from formalin-inactivated sheep brain, and brought to
the attention of research workers that formalin, at a concentration of
0.35% for at least 3 months, which inactivated conventional viruses, did
not totally inactivate the scrapie agent.
----------------------------
4. Questions we might want to have answered are:
the highest risk would be from parenterals prepared from brain (eg
rabies vaccine). Any species in which transmissible spongiform
encephalopathies have been described would be suspect (“natural”
infections in sheep, goats, cattle, deer, mink, but can be transmitted
to hamster, mouse, guinea-pig etc). Are sterilisation processes
adequate for the most resistant strain of scrapie agent or for CJD
agent? Should companies be asked to include investigation for inclusion
of scrapie agent (eg mouse innoculation [sic]) in at least some batches?
If BSE behaves like scrapie, then we might expect other nervous tissue,
spleen, lymph nodes and placenta to be contaminated. Infection has been
described in other tissues too, eg gut wall, and we can not [sic] be
sure blood is free. Do we know what bovine materials are used in which
products, both as the active ingredient and in production? Bovine active
ingredients in human products include insulin, vasopressin, bone, immune
globulins, fibrin, dermal collagen, albumin. Bovine serum albumin and
fetal calf serum must be used in preparation of very many products. For
each of these products would any “BSE agent” be destroyed or eliminated
in processing? If not, and the product is administered parenterally or
topically into an open wound, might there be a risk? [For oral
products, there would only be a trivially increased load on top of that
taken in food in omnivores/carnivores including man. But for some
herbivores, this might allow the agent to be introduced into yet another
species].
--------------------------
http://www.whale.to/v/singeltary7.html
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html
tss
Saturday, December 3, 2011
Isolation of Prion with BSE Properties from Farmed Goat
Volume 17, Number 12—December 2011
Research
Isolation of Prion with BSE Properties from Farmed Goat
John Spiropoulos , Richard Lockey, Rosemary E. Sallis, Linda A. Terry, Leigh Thorne, Thomas M. Holder, Katy E. Beck, and Marion M. Simmons
Author affiliations: Animal Health and Veterinary Laboratories Agency, Weybridge, Surrey, UK
Abstract
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE) in cattle. Scrapie is not considered a public health risk, but BSE has been linked to variant Creutzfeldt-Jakob disease. Small ruminants are susceptible to BSE, and in 2005 BSE was identified in a farmed goat in France. We confirm another BSE case in a goat in which scrapie was originally diagnosed and retrospectively identified as suspected BSE. The prion strain in this case was further characterized by mouse bioassay after extraction from formaldehyde-fixed brain tissue embedded in paraffin blocks. Our data show that BSE can infect small ruminants under natural conditions and could be misdiagnosed as scrapie. Surveillance should continue so that another outbreak of this zoonotic transmissible spongiform encephalopathy can be prevented and public health safeguarded.
snip...
Discussion
We confirmed that the agent responsible for TSE in a UK goat, which was initially reported as scrapie in 1990 and subsequently as suspected BSE in 2006 (16), was a BSE agent. This conclusion was based on bioassay of nervous tissue in mice demonstrating similarities of histopathologic lesions, PrPSc mapping in the brain, and WB of PrPSc with those of mice inoculated with BSE from various ovine, caprine, and bovine sources.
From a method perspective, the data suggest that AR, IP, and LP are not optimal bioassay parameters for differentiating TSE sources during first passage because they represent mean values derived from a group of animals that have been inoculated with a specific source. Therefore, a substantial number of animals must die of clinical TSE for these parameters to be meaningful. This finding is a limiting factor in instances in which TSE is diagnosed in only a few animals because of low titer, restricted permissiveness of specific TSE strains in certain laboratory animals, or both. These limitations can be overcome by application of IHC and WB to differentiate BSE from scrapie confidently in individual mice on first passage. Use of IHC has shown that different PrPSc deposits can be identified, and the distribution of each deposit in the brain can be mapped (22,28,32). This approach generates high-resolution data that appear to be specific to individual TSE strains.
The data show that the TSE agents in this study were not altered by the adverse conditions applied to them during histologic procedures. However, titer may decrease, suggesting that the effect of histologic processing is quantitative not qualitative. Therefore, bioassay is a valid approach for identifying BSE in archived histologic material when other techniques are not applicable, as in the current study. Regarding the suitability of different mouse lines for confirming BSE, our data show that any mouse line in which the agent can propagate sufficiently is suitable. An additional requirement at a practical level is the ability to characterize the agent on first passage. In this respect, use of PrP-a mice is preferable because in addition to AR, IP, histopathologic analysis, and PrPSc patterning, WB can also be applied to diagnose BSE. In contrast, its application in PrP-b mice is less informative (33).
These methods can also be applied to analyze bioassay data derived from validated transgenic mouse lines that offer the advantage of higher AR and decreased IP, provided that appropriate transgenic lines are selected and the TSE source and the donor species under investigation are taken into consideration. In this particular instance, our first choices would have been the use of a mouse line overexpressing a bovine transgene in combination with 1 that overexpresses a caprine transgene. At initiation of the study, an established bovinised line was not available to us, and the data generated from the wild-type mice were considered sufficient to identify unequivocally the agent strain. Caprine transgenic mouse lines are still under development and not characterized or widely available. Instead, we used tg338 mice although they show <100% AR and extended IP when inoculated with BSE (26,27). Our data show that this ovinized line offers a feasible alternative for detecting and differentiating caprine TSEs.
The 2 cases of naturally occurring BSE in small ruminants—the 1 reported here and the 1 identified in France (15)—occurred in different countries, during different time periods, and before strict BSE control measures were fully implemented. Therefore, the most likely origin of these 2 cases would be exposure to BSE-contaminated food supplements. Although in France goats constitute 14.3% of the small ruminant population, in the United Kingdom they account for only 0.3% of small ruminants. It is intriguing, therefore, that the only naturally occurring BSE cases in small ruminants in France and particularly in the United Kingdom were detected in goats and not in sheep, although they have also been exposed to contaminated food supplements. A possible explanation could be that goats are generally managed more intensively than sheep and thus might have been exposed to higher doses of the infectious agent because of the more frequent use of concentrates in intensive dairy farming. Similar observations have been reported in cattle, in which the incidence of BSE was significantly higher in dairy herds and in which management is much more intensive than in beef herds (34). In the United Kingdom, most of the commercial goat herds are kept for milk production in a typically intensive production system, similar to dairy cattle.
The BSE case we have confirmed was 1 of 26 historic goat samples examined in the United Kingdom collected during 1984–2002 (16,17). Since 1993, scrapie in goats has been a notifiable disease in the United Kingdom, and since 2005, samples from all suspected cases of TSE in small ruminants are required to be tested for BSE-like features by using WB (19). No BSE cases have been identified, although an intermediate case in a goat was reported and is under investigation by bioassay for final resolution (35,36). This screening of brain samples from all small ruminant cases offers reassurance that BSE is not present in the contemporary small ruminant population. However, application of WB to sheep experimentally co-infected with BSE and scrapie detected only the scrapie agent (37). Also, in contrast to BSE, where infectivity is mainly confined to the nervous system, in small ruminants the BSE agent is widely distributed in peripheral tissues and can be transmitted horizontally (11,38). Therefore, feed ban measures alone would be inadequate to control a BSE outbreak in small ruminants. Also, it would be impossible to prevent BSE from entering the human food chain through consumption of food products derived from small ruminants.
Because TSEs in goats are still a problem, particularly in Mediterranean countries, our data suggest that extensive surveillance and breeding schemes must remain in place to prevent a BSE outbreak in small ruminants and to safeguard public health. This report also highlights several issues regarding the use of mouse bioassay to identify TSE strains. As governing bodies seek confirmation of equivocal cases that are identified worldwide, they must be aware of the limitations, cost, and timescale demands of confirming such cases.
Dr Spiropoulos is a veterinary researcher at Veterinary Laboratories Agency with a particular interest in animal pathology. He is the head of the Mouse Bioassay Team that specializes in pathology of experimental animals. His research interests include neurodegenerative disorders and animal diseases of policy relevance, particularly zoonoses.
Acknowledgments
We thank John Sheehan for tissue retrieval from wax-impregnated tissue blocks; Angel Ortiz-Pelaez for epidemiologic assistance; histopathology employees at Veterinary Laboratories Agency for expert technical support in histopathology and immunohistochemistry; and Animal Services Unit employees at Veterinary Laboratories Agency for expert support with animal procedures and care.
This work was supported by a Department of Environment, Food and Rural Affairs grant (project SE1849).
http://wwwnc.cdc.gov/eid/article/17/12/11-0333_article.htm
Sunday, October 3, 2010
Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?
http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep
http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html
http://nor-98.blogspot.com/
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010
http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html
Monday, November 22, 2010
Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control
REVIEW ARTICLES
http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
Wednesday, January 19, 2011
EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally acquired scrapie
http://scrapie-usa.blogspot.com/2011/02/sparse-prp-sc-accumulation-in-placentas.html
Sheep/Goat milk, scrapie-free and or BSE-free ???
Sheep milk, scrapie-free
When consumers perceive a food as unsafe, demand for the food can drop as in the bovine spongiform encephalopathy (BSE) revelations of the 1990s. A European project, Riskscra, has put together comprehensive guidelines for sheep milk producers and the industry as a whole to offer a scrapie-free assurance for ovine milk products.
Sheep milk production is an important part of the dairy products industry in Mediterranean countries. The dairy sheep industry is based on local breeds adapted to the production methods and environment.
Experimental evidence has indicated that BSE is transmissible from cows to sheep through oral and parenteral (other than through the alimentary canal) means. Abnormal prion proteins (PrPs) have been found in the mammary glands of sheep with mastitis and scrapie. The fear is that the scrapie may actually be BSE.
The genetics of scrapie resistance is known inasmuch as the ARQ/ARQ genotype is susceptible to some forms of scrapie and experimental BSE. Presence of the PrP also determines a sheep's resistance or susceptibility to transmissible spongiform encephalopathies (TSE). Genetic selection is used as the main means of scrapie control in the United Kingdom.
Along with initiatives from European institutions to promote TSE resistance in livestock, the EU-funded project Riskscra aimed to develop tools to assess the risk of scrapie in milk. Guidelines and recommendations can be applied by breeders and the dairy industry.
Suitable genetic analysis methods for routine control purposes were researched and drawn up into document form for dairy technicians. 'Guidelines to set up traceability in cheese making factories with associated scrapie risk level' integrates International Advisory Group (IAG) dairy production rules and regulations on PrP allele profile control. Specific training courses were also held for dairy technicians.
To make sure that the results of relevant research reach all levels in the sheep dairy production industry, Riskscra organised cooperation between all players and coordination of national and European policies. Networking of research teams was actively encouraged, particularly by bringing European small and medium-sized enterprises (SMEs) in contact with research centres. The results of this initiative also promise to establish a border-free zone for research and create more jobs in the research sector.
Guidelines developed by Riskscra can be used to implement safety or commercial strategies from scratch as well as to improve existing control systems. The Riskscra control system is particularly relevant to producers, breeder organisations and other institutions interested in controlling the scrapie risk in sheep dairy products. A prime example of appropriate use is its application to the current milk payment criteria based only on non-scrapie–related criteria such as milk quantity and bacterial content.
Improving the quality of dairy products on the market increases the confidence of consumers and constitutes a basis for fair competition among dairy industries across Europe, again with added benefits for consumers. In addition, it enhances European competitiveness on the global market.
Country: ITALY
Information Source: Result from the EU funded FP6-SME programme
Date: 2011-11-25
Contact Details
BONACINA, Cesare (Dr)
ISTITUTO SPERIMENTALE ITALIANO "LAZZARO SPALLANZANI"
Director
MILANO
ITALY
Offer ID: 7435
http://cordis.europa.eu/fetch?CALLER=MSS_IT_OFFR_EN&ACTION=D&DOC=3&CAT=OFFR&QUERY=0133f09c98dd:2ddc:23d0d437&RCN=7435
TO date, and i imphasize 'to date', there has been no documented evidence of transmission of BSE via milk of BSE infected cow to another cow. however, with the limited testing done to date, on just the c-BSE, you cannot rule this out, especially with the atypical BSE L-type i.e. BASE, being much more virulent. Concern has been increasing due to fluids from TSE species i.e. blood, urine, and milk, and the fact that infectivity has been detected. ...tss
Prion infectivity has now been detected in blood, urine and milk.
please see ;
Seven main threats for the future linked to prions
The NeuroPrion network has identified 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
In small ruminants, a new atypical form of scrapie currently represents up to 50% of detected cases and even involves sheep selected for resistance to classical scrapie. The consequences for animal and human health are still unknown and there may be a potential connection with atypical BSE. These atypical scrapie cases constitute a second threat not envisioned previously which could deeply modify the European approach to prion diseases.
Third threat
The species barrier between human and cattle might be weaker than previously expected and the risk of transmission of prion diseases between different species has been notoriously unpredictable. The emergence of new atypical strains in cattle and sheep together with the spread of chronic wasting disease in cervids renders the understanding of the species barrier critical. This constitutes a third threat not properly envisioned previously that could deeply modify the European approach to prion diseases.
Fourth threat
Prion infectivity has now been detected in blood, urine and milk and this has potential consequences on risk assessments for the environment and food as well as for contamination of surfaces including medical instruments. Furthermore the procedures recommended for decontamination of MBM (Meat and Bone Meal), which are based on older methodologies not designed for this purpose, have turned out to be of very limited efficacy and compromise current policies concerning the reuse of these high value protein supplements (cross-contamination of feed circuits are difficult to control). It should be noted that the destruction or very limited use of MBM is estimated to still cost 1 billion euros per year to the European economy,
whereas other countries, including the US,
Brazil, and Argentine do not have these constraints.
However, many uncertainties remain concerning the guarantees that can be reasonably provided for food and feed safety and scientific knowledge about the causative agents (prions) will continue to evolve. This decontamination and environmental issue is a fourth threat that could modify deeply the European approach to prion diseases.
Fifth threat The precise nature of prions remains elusive. Very recent data indicate that abnormal prion protein (PrPTSE) can be generated from the brains of normal animals, and under some conditions (including contaminated waste water) PrPTSE can be destroyed whereas the BSE infectious titre remains almost unchanged, a finding that underlines the possibility of having BSE without any detectable diagnostic marker. These are just two areas of our incomplete knowledge of the fundamental biology of prions which constitute a fifth threat to the European approach to prion diseases.
Sixth threat The absence of common methods and standardisation in the evaluation of multiple in vivo models with different prion strains and different transgenic mice expressing PrP from different species (different genotypes of cattle, sheep, cervids, etc) renders a complete and comprehensive analysis of all the data generated by the different scientific groups almost impossible. This deeply impairs risk assessment. Moreover, the possibility of generating PrPTSE de novo with new powerful techniques has raised serious questions about their appropriateness for use as blood screening tests. The confusion about an incorrect interpretation of positive results obtained by these methods constitutes a sixth threat to European approach to prion diseases.
Seventh Threat The detection of new or re-emerging prion diseases in animals or humans which could lead to a new crisis in consumer confidence over the relaxation of precautionary measures and surveillance programmes constitutes a seventh threat that could modify the European approach to prion diseases.
http://www.neuroprion.org/en/np-neuroprion.html
Goat BSE: Proposal for Improvement of Goat TSE Discriminative Diagnosis and Susceptibility based Assessment of BSE Infectivity in Goat Milk and Meat
Funded by EU, DEFRA This project is run by a consortium of ten research teams in seven EU countries.
In light of the known ability of the BSE agent to cross the animal/human species barrier, recent evidence establishing the presence of BSE in goat is especially alarming, as it represents a new potential risk of food-born contamination to human consumers of goat milk and meat products. The main objective is to determine the tissue distribution of BSE after oral exposure of goats and to do this while simultaneously generating data on genetic susceptibility in the most common used production breeds. This proposal aims at (i) providing data for the evaluation of human risk associated with goat BSE, (ii) providing pathogenesis data and biological material from first and second passage BSE in goats, (iii) evaluating the possibility of BSE self-maintenance in goat herds through maternal or horizontal transmission, (iv) validating and improving our ability to detect caprine BSE and discriminate it from scrapie in goats. Our approach will establish the influence of PrP gene polymorphisms on scrapie and BSE susceptibility so that genetics could potentially be used for the control of field TSE outbreaks in goats. We will also document European field TSE strain variability in goats by recruiting a large number of TSE goat isolates from affected European countries. Already established or specifically created animal models (strain typing) and biochemical tools (PrPSc typing), will be tested for their ability to efficiently discriminate goat BSE/scrapie. Finally, by measuring infectivity in various tissues collected from goats at different stages of BSE infection, we will provide essential data for quantitative risk assessment.
http://www.roslin.ed.ac.uk/wilfred-goldmann/goat-bse:-proposal-for-improvement-of-goat-tse-discriminative-diagnosis-and-susceptibility-based-assessment-of-bse-infectivity-in-goat-milk-and-meat/
Vet. Res. (2010) 41:48 Original article
Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions
Lorenzo González1*, Stuart Martin1, Stephen A.C. Hawkins2, Wilfred Goldmann3, Martin Jeffrey1 and Sílvia Sisó1
1 Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Penicuik, Midlothian EH26 0PZ, United Kingdom 2 VLA-Weybridge, Addlestone, Surrey KT15 3NB, United Kingdom 3 The Roslin Institute and R(D)SVS University of Edinburgh, Roslin, Midlothian EH25 9PS, United Kingdom
* Corresponding author: l.gonzalez@vla.defra.gsi.gov.uk
Received: 13 January 2010 Accepted: 7 April 2010
Abstract
After detection of a high prevalence of scrapie in a large dairy goat herd, 72 infected animals were examined by immunohistochemistry with prion protein (PrP) antibody Bar224 to study the pathogenesis of the infection. Tissues examined included the brain and thoracic spinal cord (TSC), a wide selection of lymphoreticular system (LRS) tissues, the distal ileum and its enteric nervous system (ENS), and other organs, including the mammary gland. The whole open reading frame of the PRNP gene was sequenced and antibodies to caprine arthritis-encephalitis virus (CAEV) infection were determined. Unexpectedly, accumulation of disease-associated PrP (PrPd) in the brain was more frequent in methionine carriers at codon 142 (24/32, 75.0%) than amongst isoleucine homozygotes (14/40, 35.0%). The latter, however, showed significantly greater amounts of brain PrPd than the former (average scores of 9.3 and 3.0, respectively). A significant proportion of the 38 goats that were positive in brain were negative in the ENS (44.7%) or in the TSC (39.5%). These results, together with the early and consistent involvement of the circumventricular organs and the hypothalamus, point towards a significant contribution of the haematogenous route in the process of neuroinvasion. Chronic enteritis was observed in 98 of the 200 goats examined, with no association with either scrapie infection or presence of PrPd in the gut. Lymphoproliferative interstitial mastitis was observed in 13/31 CAEV-positive and scrapie-infected goats; PrPd in the mammary gland was detected in five of those 13 goats, suggesting a possible contribution of CAEV infection in scrapie transmission via milk.
Key words: scrapie / goat / prion neuroinvasion / transmissible spongiform encephalopathy / CAEV
© The British Crown, published by INRA/EDP Sciences, 2010
http://www.vetres.org/index.php?option=com_article&access=standard&Itemid=129&url=/articles/vetres/abs/2010/04/v100001/v100001.html
please see more here ;
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
6 January 2010 - The public “TSEs in goats” website Link:
http://www.goatbse.eu/
Since December 2006 a new EU funded project has started that has been essentially developed from NeuroPrion TSEgoat task group members and their progress: “GoatBSE: Proposal for improvement of goat TSE discriminative diagnosis and susceptibility based assessment of BSE infectivity in goat milk and meat.” (European STREP project FOOD-CT-2006-36353, frame work 6, area Thematic priority: Food quality and safety). In this project the focus of study is about consequences of an infection with BSE in goats for disease transmission and product safety.
http://www.neuroprion.org/en/np-news.html
Sheep with Scrapie and Mastitis Transmit Infectious Prions through the Milk?
Ciriaco Ligios1,†, Maria Giovanna Cancedda1, Antonello Carta2, Cinzia Santucciu1, Caterina Maestrale1, Francesca Demontis1, Mariangela Saba1, Cristiana Patta1, James C. DeMartini3, Adriano Aguzzi4,†,* and Christina J. Sigurdson4,5,6,†,*
+ Author Affiliations
1Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy
2Research Unit of Genetics and Biotechnology, DIRPA, AGRIS Sardinia, Olmedo, Italy
3Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado
4Institute of Neuropathology, UniversitätsSpital Zürich, Zürich, Switzerland
5 Department of Pathology, School of Medicine, University of California, San Diego, California
6Department of Pathology, Microbiology, and Immunology, University of California, Davis, California
Next Section
ABSTRACT
Prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. Prion shedding routes have been shown to be modified by inflammation in excretory organs, such as the kidney. Here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. Thus, lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generations. This study also indicates a risk of prion spread to sheep and potentially to other animals through dietary exposure to pooled sheep milk or milk products.
http://jvi.asm.org/content/85/2/1136.long
Commentary
In vitro amplification of prions from milk in the detection of subclinical infections
Volume 3, Issue 4 October/November/December 2009 Pages 236 - 239 http://dx.doi.org/10.4161/pri.3.4.10425
Kevin C. Gough, Claire A. Baker, Maged Taema and Ben C. Maddison
View affiliations
Prions can be amplified by serial protein misfolding cyclic amplification (sPMCA) from the milk of a high proportion of apparently healthy, scrapie exposed sheep with PRNP genotypes not previously associated with high disease penetrance1. These data strongly suggest the widespread presence of subclinical scrapie infections within scrapie-exposed flocks containing sheep with a range of susceptible PRNP genotypes. These data also lead to the hypothesis that similar subclinical disease states may be common for other animal and human prion diseases. Furthermore, the application of sPMCA to milk provides a method to detect such subclinical disease. Here, we describe the high level amplification of bovine spongiform encephalopathy (BSE) prions from both ovine and bovine origin, a methodology that will facilitate the detection of any prions secreted within bovine and ovine milk during subclinical and clinical BSE disease.
http://www.landesbioscience.com/journals/prion/article/10425/?nocache=543132411
Prion Protein in Milk
Nicola Franscini,1 Ahmed El Gedaily,1 Ulrich Matthey,1 Susanne Franitza,1 Man-Sun Sy,2 Alexander Bürkle,3 Martin Groschup,4 Ueli Braun,5 and Ralph Zahn1
Conclusions/Significance
In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrPC in milk implies the possibility that milk of TSE-infected animals serves as source for PrPSc.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762385/
http://www.allprion.com/Documents/Produkteblatt_PrionProtein.pdf
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Olivier Andréoletti1*, Leonor Orge2, Sylvie L. Benestad3, Vincent Beringue4, Claire Litaise1, Stéphanie Simon5, Annick Le Dur4, Hubert Laude4, Hugh Simmons6, Séverine Lugan1, Fabien Corbière1, Pierrette Costes1, Nathalie Morel5, François Schelcher1, Caroline Lacroux1
Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.
Author Summary
Following the bovine spongiform encephalopathy (BSE) crisis and the identification of its zoonotic properties, a sanitary policy has been implemented based on both eradication of transmissible spongiform encephalopathies (TSE) in food-producing animals and exclusion of known infectious materials from the food chain. Atypical/Nor98 scrapie is a prion disease of small ruminants identified worldwide. Currently it represents a significant part of the TSE cases detected in Europe. The restricted tissue distribution of Atypical/Nor98 scrapie agent in its natural host and the low detected prevalence of secondary cases in affected flocks meant that it is believed to be a poorly transmissible disease. This has led to the view that Atypical/Nor98 scrapie is a spontaneous disorder for which human and animal exposure risk remains low. In this study we demonstrate that in affected individuals, Atypical/Nor98 scrapie agent can disseminate in lymphoid tissues, nerves, and muscles, challenging the idea that it is a brain-restricted infectious agent. Evidence for the deficiencies in the current methods applied for monitoring Atypical/Nor98 scrapie is provided that would indicate an underestimation in the prevalence in the general population and in the affected flocks. These elements challenge the hypothesis on the biology of this recently identified TSE agent.
snip...
Assessing Atypical/Nor98 scrapie transmissibility through oral route in natural host and presence in placenta and in colostrum/milk (which are considered as major sources for TSE transmission between small ruminants) [28], [32] will provide crucial data.
snip...
Citation: Andréoletti O, Orge L, Benestad SL, Beringue V, Litaise C, et al. (2011) Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues. PLoS Pathog 7(2): e1001285. doi:10.1371/journal.ppat.1001285
Editor: David Westaway, University of Alberta, Canada
Received: June 21, 2010; Accepted: January 10, 2011; Published: February 10, 2011
Copyright: © 2011 Andréoletti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The different parts of this work were funded by (i) The Food Standard Agency (UK) M03058, (ii) the FP7 EU project 'Priority' (243950 FP7-KBBE KBBE-2009-1-2-06), and (iii) Programme opérationnel de Coopération territoriale Espagne - France - Andorre 2007-2013 EFA85/08-COTSA. Lymphoid tissue collection in Portuguese sheep was supported by AGROS 558 (PO AGRO 8.1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: o.andreoletti@envt.fr
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001285
Prions in Milk from Ewes Incubating Natural Scrapie
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76
AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE
Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.
One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html
I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
BSE: TIME TO TAKE H.B. PARRY SERIOUSLY
If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html
Case report
Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks
Ana B Rodríguez-Martínez1, Joseba M Garrido1, Sonia Maza1, Leyre Benedicto1, Mariví Geijo1, Nieves Gómez1, Esmeralda Minguijón1, Sylvie L Benestad2 and Ramón A Juste1*
* Corresponding author: Ramón A Juste rjuste@neiker.net
Author Affiliations
1 Department of Animal Health. Neiker-Tecnalia, 48160 Derio. Bizkaia. Spain
2 National Veterinary Institute, Department of Pathology, Postboks 750 Sentrum. 0106 Oslo. Norway
For all author emails, please log on.
BMC Veterinary Research 2010, 6:17 doi:10.1186/1746-6148-6-17
The electronic version of this article is the complete one and can be found online at:
http://www.biomedcentral.com/1746-6148/6/17
Received: 6 November 2009
Accepted: 26 March 2010
Published: 26 March 2010
© 2010 Rodríguez-Martínez et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases with similarities to the previously identified atypical scrapie cases termed Nor98.
Case presentation
Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8), their breed (all Latxa) and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ). All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum.
Conclusions
This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country. Moreover, a new genotype (ALRQ/ALRH) was found associated to atypical scrapie.
SNIP...
Case reports from this study and other case reports from Spain http://www.eeb.es/pags/espana.htm webcite and Portugal [35], indicate a high frequency of atypical cases compared to CS outbreaks in the Iberian Peninsula. It could be speculated that AS/Nor98 is the traditional form of scrapie in the Iberian part of the Basque country, whilst in the French part, the classical form has been predominant [59]. This would point to some unidentified epidemiological features limiting the spread of classical scrapie in the Iberian Peninsula. However, since the analysis of all sheep can not be guaranteed, it is difficult to test this hypothesis. The analysis of all sheep would provide more information about the epidemiology and pathology of this disease. Moreover, it could contribute in assessing whether AS is present in the Basque Country with the same high frequencies as others human TSEs, such as sporadic Creutzfeldt-Jakob disease [60] and Fatal Familiar Insomnia compared to other Spanish autonomous communities (National Epidemiology Centre: http:/ / www.isciii.es/ htdocs/ centros/ epidemiologia/ epidemiologia_listado_ecj.jsp webcite).
SEE FULL TEXT ;
http://www.biomedcentral.com/1746-6148/6/17
Peiffer, J. : Gerstmann-Straussler's disease, atypical multiple sclerosis and carcinomas in a family of sheepbreeders. Acta Neuropath. 56: 87-92, 1982. Peiffer (1982) described a family of sheepbreeders in which a father and 2 sons had GSS. All 3 also had congenital hip dysplasia, as did at least 3 other members of the kindred, all females. Atactic symptoms, dysarthria, and personality changes characterized the clinical course of this disorder, which might be labeled atypical multiple sclerosis. Like CJD , GSS is a form of subacute spongiform encephalopathy. Cases of GSS are clinically similar to the atactic type of CJD. Although there are many neuropathologic similarities, GSS differs from CJD by the presence of kuru-plaques and numerous multicentric, floccular plaques in the cerebral and cerebellar cortex, basal ganglia, and white matter. Whereas only 5 to 15% of CJD cases are familial, most cases of GSS are familial.
http://www.mad-cow.org/Alzheimer_cjd.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
page 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org/
please see full text ;
http://transmissiblespongiformencephalopathy.blogspot.com/
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
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
snip...
http://www.neuroprion.org/en/np-neuroprion.html
Subject: SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 100th meeting held on 25th April 2008
Date: July 13, 2008 at 7:16 pm PST
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 100th meeting held on 25th April 2008
ITEM 2 - APPROVAL OF MINUTES FROM SEAC 99 (SEAC 100/1) 6. The minutes of SEAC 99 were agreed as a correct record with the following amendment: 4 © SEAC 2008 . Paragraph 7, second bullet point, change ".Institute of Animal Health (IAH)." to ".Roslin Institute (RI)." 7. The committee was updated about transmission studies using isolates from a case of Creutzfeldt-Jakob Disease (CJD)1 which had been discussed at SEAC 99. Two lines of transgenic mice expressing the human prion protein gene homozygous for methionine (MM) or valine (VV) at codon 129 and two lines of conventional mice had been inoculated with isolates from the case. Transmission has been more efficient to the humanised mice compared with the conventional mice. The molecular characteristics of the abnormal prion protein (PrPSc) altered on transmission suggesting the patient may have been infected with an unstable TSE strain. Further work was required to characterise the TSE strain. However, it would be difficult to confirm whether this was related to BSE infection unless additional similar cases arose which could be investigated. 8.
snip...
35. Members asked about the spread of chronic wasting disease (CWD) in the USA. Mr Burke replied that CWD was continuing to spread in the cervid population in the USA.
snip...
One sheep in Cyprus, two in the UK and four from France are under investigation for possible BSE infection. Two further BSE cases were identified with unusual transmission properties in a Defra research project (SE1849) and 5 Countries where cases of BSE in cattle were reported in 2007: UK, Austria, Canada, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Poland, Portugal, Slovenia, Slovakia, Spain and The Netherlands. 6 Countries where atypical scrapie in sheep has been reported since 2002: Belgium, Denmark, the Falkland Islands, Finland, France, Germany, Greece, Hungary, Ireland, Italy, The Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, UK and USA. 13 © SEAC 2008 are also subject to further characterisation. BSE has been confirmed in one French goat slaughtered in 2002. A UK goat which was originally diagnosed as a case of scrapie in 1990 is under investigation for possible BSE infection. 37.
snip...
40. Members agreed that the statement should not focus entirely on the risk from BSE. A paragraph should be included to describe the risk that a new zoonotic TSE strain might emerge as a result of the relaxations to TSE controls. The possibility that the transmissibility to humans of such a new strain could be much greater than that of BSE should be acknowledged.
http://www.seac.gov.uk/minutes/final100.pdf
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007
snip...
ITEM 8 - PUBLIC QUESTION AND ANSWER SESSION 40. The Chair explained that the purpose of the question and answer session was to give members of the public an opportunity to ask questions related to the work of SEAC. Mr Terry Singeltary (Texas, USA) had submitted a question prior to the meeting, asking: "With the Nor-98 now documented in five different states so far in the USA in 2007, and with the two atypical BSE H-base cases in Texas and Alabama, with both scrapie and chronic 14 © SEAC 2007 wasting disease (CWD) running rampant in the USA, is there any concern from SEAC with the rise of sporadic CJD in the USA from ''unknown phenotype'', and what concerns if any, in relations to blood donations, surgery, optical, and dental treatment, do you have with these unknown atypical phenotypes in both humans and animals in the USA? Does it concern SEAC, or is it of no concern to SEAC? Should it concern USA animal and human health officials?" 41.
A member considered that this question appeared to be primarily related to possible links between animal and human TSEs in the USA.
There is no evidence that sCJD is increasing in the USA and no evidence of any direct link between TSEs and CJD in the USA. Current evidence does not suggest that CWD is a significant risk to human health. There are unpublished data from a case of human TSE in the USA that are suggestive of an apparently novel form of prion disease with distinct molecular characteristics. However, it is unclear whether the case had been further characterised, if it could be linked to animal TSEs or if other similar cases had been found in the USA or elsewhere. In relation to the possible public health implications of atypical scrapie, H-type BSE and CWD, research was being conducted to investigate possible links and surveillance was in place to detect any changes in human TSEs. Although possible links between these diseases and human TSEs are of concern and require research, there is no evidence to suggest immediate public health action is warranted. The possible human health risks from classical scrapie had been discussed earlier in the meeting. Members noted that there are effective channels of discussion and collaboration on research between USA and European groups. Members agreed it is important to keep a watching brief on new developments on TSEs.
snip...
http://www.seac.gov.uk/minutes/99.pdf
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
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.
snip...
http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1
http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf
see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
http://transmissiblespongiformencephalopathy.blogspot.com/
price of TSE prion poker goes up again $$$
TSS
Research
Isolation of Prion with BSE Properties from Farmed Goat
John Spiropoulos , Richard Lockey, Rosemary E. Sallis, Linda A. Terry, Leigh Thorne, Thomas M. Holder, Katy E. Beck, and Marion M. Simmons
Author affiliations: Animal Health and Veterinary Laboratories Agency, Weybridge, Surrey, UK
Abstract
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE) in cattle. Scrapie is not considered a public health risk, but BSE has been linked to variant Creutzfeldt-Jakob disease. Small ruminants are susceptible to BSE, and in 2005 BSE was identified in a farmed goat in France. We confirm another BSE case in a goat in which scrapie was originally diagnosed and retrospectively identified as suspected BSE. The prion strain in this case was further characterized by mouse bioassay after extraction from formaldehyde-fixed brain tissue embedded in paraffin blocks. Our data show that BSE can infect small ruminants under natural conditions and could be misdiagnosed as scrapie. Surveillance should continue so that another outbreak of this zoonotic transmissible spongiform encephalopathy can be prevented and public health safeguarded.
snip...
Discussion
We confirmed that the agent responsible for TSE in a UK goat, which was initially reported as scrapie in 1990 and subsequently as suspected BSE in 2006 (16), was a BSE agent. This conclusion was based on bioassay of nervous tissue in mice demonstrating similarities of histopathologic lesions, PrPSc mapping in the brain, and WB of PrPSc with those of mice inoculated with BSE from various ovine, caprine, and bovine sources.
From a method perspective, the data suggest that AR, IP, and LP are not optimal bioassay parameters for differentiating TSE sources during first passage because they represent mean values derived from a group of animals that have been inoculated with a specific source. Therefore, a substantial number of animals must die of clinical TSE for these parameters to be meaningful. This finding is a limiting factor in instances in which TSE is diagnosed in only a few animals because of low titer, restricted permissiveness of specific TSE strains in certain laboratory animals, or both. These limitations can be overcome by application of IHC and WB to differentiate BSE from scrapie confidently in individual mice on first passage. Use of IHC has shown that different PrPSc deposits can be identified, and the distribution of each deposit in the brain can be mapped (22,28,32). This approach generates high-resolution data that appear to be specific to individual TSE strains.
The data show that the TSE agents in this study were not altered by the adverse conditions applied to them during histologic procedures. However, titer may decrease, suggesting that the effect of histologic processing is quantitative not qualitative. Therefore, bioassay is a valid approach for identifying BSE in archived histologic material when other techniques are not applicable, as in the current study. Regarding the suitability of different mouse lines for confirming BSE, our data show that any mouse line in which the agent can propagate sufficiently is suitable. An additional requirement at a practical level is the ability to characterize the agent on first passage. In this respect, use of PrP-a mice is preferable because in addition to AR, IP, histopathologic analysis, and PrPSc patterning, WB can also be applied to diagnose BSE. In contrast, its application in PrP-b mice is less informative (33).
These methods can also be applied to analyze bioassay data derived from validated transgenic mouse lines that offer the advantage of higher AR and decreased IP, provided that appropriate transgenic lines are selected and the TSE source and the donor species under investigation are taken into consideration. In this particular instance, our first choices would have been the use of a mouse line overexpressing a bovine transgene in combination with 1 that overexpresses a caprine transgene. At initiation of the study, an established bovinised line was not available to us, and the data generated from the wild-type mice were considered sufficient to identify unequivocally the agent strain. Caprine transgenic mouse lines are still under development and not characterized or widely available. Instead, we used tg338 mice although they show <100% AR and extended IP when inoculated with BSE (26,27). Our data show that this ovinized line offers a feasible alternative for detecting and differentiating caprine TSEs.
The 2 cases of naturally occurring BSE in small ruminants—the 1 reported here and the 1 identified in France (15)—occurred in different countries, during different time periods, and before strict BSE control measures were fully implemented. Therefore, the most likely origin of these 2 cases would be exposure to BSE-contaminated food supplements. Although in France goats constitute 14.3% of the small ruminant population, in the United Kingdom they account for only 0.3% of small ruminants. It is intriguing, therefore, that the only naturally occurring BSE cases in small ruminants in France and particularly in the United Kingdom were detected in goats and not in sheep, although they have also been exposed to contaminated food supplements. A possible explanation could be that goats are generally managed more intensively than sheep and thus might have been exposed to higher doses of the infectious agent because of the more frequent use of concentrates in intensive dairy farming. Similar observations have been reported in cattle, in which the incidence of BSE was significantly higher in dairy herds and in which management is much more intensive than in beef herds (34). In the United Kingdom, most of the commercial goat herds are kept for milk production in a typically intensive production system, similar to dairy cattle.
The BSE case we have confirmed was 1 of 26 historic goat samples examined in the United Kingdom collected during 1984–2002 (16,17). Since 1993, scrapie in goats has been a notifiable disease in the United Kingdom, and since 2005, samples from all suspected cases of TSE in small ruminants are required to be tested for BSE-like features by using WB (19). No BSE cases have been identified, although an intermediate case in a goat was reported and is under investigation by bioassay for final resolution (35,36). This screening of brain samples from all small ruminant cases offers reassurance that BSE is not present in the contemporary small ruminant population. However, application of WB to sheep experimentally co-infected with BSE and scrapie detected only the scrapie agent (37). Also, in contrast to BSE, where infectivity is mainly confined to the nervous system, in small ruminants the BSE agent is widely distributed in peripheral tissues and can be transmitted horizontally (11,38). Therefore, feed ban measures alone would be inadequate to control a BSE outbreak in small ruminants. Also, it would be impossible to prevent BSE from entering the human food chain through consumption of food products derived from small ruminants.
Because TSEs in goats are still a problem, particularly in Mediterranean countries, our data suggest that extensive surveillance and breeding schemes must remain in place to prevent a BSE outbreak in small ruminants and to safeguard public health. This report also highlights several issues regarding the use of mouse bioassay to identify TSE strains. As governing bodies seek confirmation of equivocal cases that are identified worldwide, they must be aware of the limitations, cost, and timescale demands of confirming such cases.
Dr Spiropoulos is a veterinary researcher at Veterinary Laboratories Agency with a particular interest in animal pathology. He is the head of the Mouse Bioassay Team that specializes in pathology of experimental animals. His research interests include neurodegenerative disorders and animal diseases of policy relevance, particularly zoonoses.
Acknowledgments
We thank John Sheehan for tissue retrieval from wax-impregnated tissue blocks; Angel Ortiz-Pelaez for epidemiologic assistance; histopathology employees at Veterinary Laboratories Agency for expert technical support in histopathology and immunohistochemistry; and Animal Services Unit employees at Veterinary Laboratories Agency for expert support with animal procedures and care.
This work was supported by a Department of Environment, Food and Rural Affairs grant (project SE1849).
http://wwwnc.cdc.gov/eid/article/17/12/11-0333_article.htm
Sunday, October 3, 2010
Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?
http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep
http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html
http://nor-98.blogspot.com/
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010
http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html
Monday, November 22, 2010
Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control
REVIEW ARTICLES
http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
Wednesday, January 19, 2011
EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally acquired scrapie
http://scrapie-usa.blogspot.com/2011/02/sparse-prp-sc-accumulation-in-placentas.html
Sheep/Goat milk, scrapie-free and or BSE-free ???
Sheep milk, scrapie-free
When consumers perceive a food as unsafe, demand for the food can drop as in the bovine spongiform encephalopathy (BSE) revelations of the 1990s. A European project, Riskscra, has put together comprehensive guidelines for sheep milk producers and the industry as a whole to offer a scrapie-free assurance for ovine milk products.
Sheep milk production is an important part of the dairy products industry in Mediterranean countries. The dairy sheep industry is based on local breeds adapted to the production methods and environment.
Experimental evidence has indicated that BSE is transmissible from cows to sheep through oral and parenteral (other than through the alimentary canal) means. Abnormal prion proteins (PrPs) have been found in the mammary glands of sheep with mastitis and scrapie. The fear is that the scrapie may actually be BSE.
The genetics of scrapie resistance is known inasmuch as the ARQ/ARQ genotype is susceptible to some forms of scrapie and experimental BSE. Presence of the PrP also determines a sheep's resistance or susceptibility to transmissible spongiform encephalopathies (TSE). Genetic selection is used as the main means of scrapie control in the United Kingdom.
Along with initiatives from European institutions to promote TSE resistance in livestock, the EU-funded project Riskscra aimed to develop tools to assess the risk of scrapie in milk. Guidelines and recommendations can be applied by breeders and the dairy industry.
Suitable genetic analysis methods for routine control purposes were researched and drawn up into document form for dairy technicians. 'Guidelines to set up traceability in cheese making factories with associated scrapie risk level' integrates International Advisory Group (IAG) dairy production rules and regulations on PrP allele profile control. Specific training courses were also held for dairy technicians.
To make sure that the results of relevant research reach all levels in the sheep dairy production industry, Riskscra organised cooperation between all players and coordination of national and European policies. Networking of research teams was actively encouraged, particularly by bringing European small and medium-sized enterprises (SMEs) in contact with research centres. The results of this initiative also promise to establish a border-free zone for research and create more jobs in the research sector.
Guidelines developed by Riskscra can be used to implement safety or commercial strategies from scratch as well as to improve existing control systems. The Riskscra control system is particularly relevant to producers, breeder organisations and other institutions interested in controlling the scrapie risk in sheep dairy products. A prime example of appropriate use is its application to the current milk payment criteria based only on non-scrapie–related criteria such as milk quantity and bacterial content.
Improving the quality of dairy products on the market increases the confidence of consumers and constitutes a basis for fair competition among dairy industries across Europe, again with added benefits for consumers. In addition, it enhances European competitiveness on the global market.
Country: ITALY
Information Source: Result from the EU funded FP6-SME programme
Date: 2011-11-25
Contact Details
BONACINA, Cesare (Dr)
ISTITUTO SPERIMENTALE ITALIANO "LAZZARO SPALLANZANI"
Director
MILANO
ITALY
Offer ID: 7435
http://cordis.europa.eu/fetch?CALLER=MSS_IT_OFFR_EN&ACTION=D&DOC=3&CAT=OFFR&QUERY=0133f09c98dd:2ddc:23d0d437&RCN=7435
TO date, and i imphasize 'to date', there has been no documented evidence of transmission of BSE via milk of BSE infected cow to another cow. however, with the limited testing done to date, on just the c-BSE, you cannot rule this out, especially with the atypical BSE L-type i.e. BASE, being much more virulent. Concern has been increasing due to fluids from TSE species i.e. blood, urine, and milk, and the fact that infectivity has been detected. ...tss
Prion infectivity has now been detected in blood, urine and milk.
please see ;
Seven main threats for the future linked to prions
The NeuroPrion network has identified 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
In small ruminants, a new atypical form of scrapie currently represents up to 50% of detected cases and even involves sheep selected for resistance to classical scrapie. The consequences for animal and human health are still unknown and there may be a potential connection with atypical BSE. These atypical scrapie cases constitute a second threat not envisioned previously which could deeply modify the European approach to prion diseases.
Third threat
The species barrier between human and cattle might be weaker than previously expected and the risk of transmission of prion diseases between different species has been notoriously unpredictable. The emergence of new atypical strains in cattle and sheep together with the spread of chronic wasting disease in cervids renders the understanding of the species barrier critical. This constitutes a third threat not properly envisioned previously that could deeply modify the European approach to prion diseases.
Fourth threat
Prion infectivity has now been detected in blood, urine and milk and this has potential consequences on risk assessments for the environment and food as well as for contamination of surfaces including medical instruments. Furthermore the procedures recommended for decontamination of MBM (Meat and Bone Meal), which are based on older methodologies not designed for this purpose, have turned out to be of very limited efficacy and compromise current policies concerning the reuse of these high value protein supplements (cross-contamination of feed circuits are difficult to control). It should be noted that the destruction or very limited use of MBM is estimated to still cost 1 billion euros per year to the European economy,
whereas other countries, including the US,
Brazil, and Argentine do not have these constraints.
However, many uncertainties remain concerning the guarantees that can be reasonably provided for food and feed safety and scientific knowledge about the causative agents (prions) will continue to evolve. This decontamination and environmental issue is a fourth threat that could modify deeply the European approach to prion diseases.
Fifth threat The precise nature of prions remains elusive. Very recent data indicate that abnormal prion protein (PrPTSE) can be generated from the brains of normal animals, and under some conditions (including contaminated waste water) PrPTSE can be destroyed whereas the BSE infectious titre remains almost unchanged, a finding that underlines the possibility of having BSE without any detectable diagnostic marker. These are just two areas of our incomplete knowledge of the fundamental biology of prions which constitute a fifth threat to the European approach to prion diseases.
Sixth threat The absence of common methods and standardisation in the evaluation of multiple in vivo models with different prion strains and different transgenic mice expressing PrP from different species (different genotypes of cattle, sheep, cervids, etc) renders a complete and comprehensive analysis of all the data generated by the different scientific groups almost impossible. This deeply impairs risk assessment. Moreover, the possibility of generating PrPTSE de novo with new powerful techniques has raised serious questions about their appropriateness for use as blood screening tests. The confusion about an incorrect interpretation of positive results obtained by these methods constitutes a sixth threat to European approach to prion diseases.
Seventh Threat The detection of new or re-emerging prion diseases in animals or humans which could lead to a new crisis in consumer confidence over the relaxation of precautionary measures and surveillance programmes constitutes a seventh threat that could modify the European approach to prion diseases.
http://www.neuroprion.org/en/np-neuroprion.html
Goat BSE: Proposal for Improvement of Goat TSE Discriminative Diagnosis and Susceptibility based Assessment of BSE Infectivity in Goat Milk and Meat
Funded by EU, DEFRA This project is run by a consortium of ten research teams in seven EU countries.
In light of the known ability of the BSE agent to cross the animal/human species barrier, recent evidence establishing the presence of BSE in goat is especially alarming, as it represents a new potential risk of food-born contamination to human consumers of goat milk and meat products. The main objective is to determine the tissue distribution of BSE after oral exposure of goats and to do this while simultaneously generating data on genetic susceptibility in the most common used production breeds. This proposal aims at (i) providing data for the evaluation of human risk associated with goat BSE, (ii) providing pathogenesis data and biological material from first and second passage BSE in goats, (iii) evaluating the possibility of BSE self-maintenance in goat herds through maternal or horizontal transmission, (iv) validating and improving our ability to detect caprine BSE and discriminate it from scrapie in goats. Our approach will establish the influence of PrP gene polymorphisms on scrapie and BSE susceptibility so that genetics could potentially be used for the control of field TSE outbreaks in goats. We will also document European field TSE strain variability in goats by recruiting a large number of TSE goat isolates from affected European countries. Already established or specifically created animal models (strain typing) and biochemical tools (PrPSc typing), will be tested for their ability to efficiently discriminate goat BSE/scrapie. Finally, by measuring infectivity in various tissues collected from goats at different stages of BSE infection, we will provide essential data for quantitative risk assessment.
http://www.roslin.ed.ac.uk/wilfred-goldmann/goat-bse:-proposal-for-improvement-of-goat-tse-discriminative-diagnosis-and-susceptibility-based-assessment-of-bse-infectivity-in-goat-milk-and-meat/
Vet. Res. (2010) 41:48 Original article
Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions
Lorenzo González1*, Stuart Martin1, Stephen A.C. Hawkins2, Wilfred Goldmann3, Martin Jeffrey1 and Sílvia Sisó1
1 Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Penicuik, Midlothian EH26 0PZ, United Kingdom 2 VLA-Weybridge, Addlestone, Surrey KT15 3NB, United Kingdom 3 The Roslin Institute and R(D)SVS University of Edinburgh, Roslin, Midlothian EH25 9PS, United Kingdom
* Corresponding author: l.gonzalez@vla.defra.gsi.gov.uk
Received: 13 January 2010 Accepted: 7 April 2010
Abstract
After detection of a high prevalence of scrapie in a large dairy goat herd, 72 infected animals were examined by immunohistochemistry with prion protein (PrP) antibody Bar224 to study the pathogenesis of the infection. Tissues examined included the brain and thoracic spinal cord (TSC), a wide selection of lymphoreticular system (LRS) tissues, the distal ileum and its enteric nervous system (ENS), and other organs, including the mammary gland. The whole open reading frame of the PRNP gene was sequenced and antibodies to caprine arthritis-encephalitis virus (CAEV) infection were determined. Unexpectedly, accumulation of disease-associated PrP (PrPd) in the brain was more frequent in methionine carriers at codon 142 (24/32, 75.0%) than amongst isoleucine homozygotes (14/40, 35.0%). The latter, however, showed significantly greater amounts of brain PrPd than the former (average scores of 9.3 and 3.0, respectively). A significant proportion of the 38 goats that were positive in brain were negative in the ENS (44.7%) or in the TSC (39.5%). These results, together with the early and consistent involvement of the circumventricular organs and the hypothalamus, point towards a significant contribution of the haematogenous route in the process of neuroinvasion. Chronic enteritis was observed in 98 of the 200 goats examined, with no association with either scrapie infection or presence of PrPd in the gut. Lymphoproliferative interstitial mastitis was observed in 13/31 CAEV-positive and scrapie-infected goats; PrPd in the mammary gland was detected in five of those 13 goats, suggesting a possible contribution of CAEV infection in scrapie transmission via milk.
Key words: scrapie / goat / prion neuroinvasion / transmissible spongiform encephalopathy / CAEV
© The British Crown, published by INRA/EDP Sciences, 2010
http://www.vetres.org/index.php?option=com_article&access=standard&Itemid=129&url=/articles/vetres/abs/2010/04/v100001/v100001.html
please see more here ;
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
6 January 2010 - The public “TSEs in goats” website Link:
http://www.goatbse.eu/
Since December 2006 a new EU funded project has started that has been essentially developed from NeuroPrion TSEgoat task group members and their progress: “GoatBSE: Proposal for improvement of goat TSE discriminative diagnosis and susceptibility based assessment of BSE infectivity in goat milk and meat.” (European STREP project FOOD-CT-2006-36353, frame work 6, area Thematic priority: Food quality and safety). In this project the focus of study is about consequences of an infection with BSE in goats for disease transmission and product safety.
http://www.neuroprion.org/en/np-news.html
Sheep with Scrapie and Mastitis Transmit Infectious Prions through the Milk?
Ciriaco Ligios1,†, Maria Giovanna Cancedda1, Antonello Carta2, Cinzia Santucciu1, Caterina Maestrale1, Francesca Demontis1, Mariangela Saba1, Cristiana Patta1, James C. DeMartini3, Adriano Aguzzi4,†,* and Christina J. Sigurdson4,5,6,†,*
+ Author Affiliations
1Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy
2Research Unit of Genetics and Biotechnology, DIRPA, AGRIS Sardinia, Olmedo, Italy
3Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado
4Institute of Neuropathology, UniversitätsSpital Zürich, Zürich, Switzerland
5 Department of Pathology, School of Medicine, University of California, San Diego, California
6Department of Pathology, Microbiology, and Immunology, University of California, Davis, California
Next Section
ABSTRACT
Prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. Prion shedding routes have been shown to be modified by inflammation in excretory organs, such as the kidney. Here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. Thus, lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generations. This study also indicates a risk of prion spread to sheep and potentially to other animals through dietary exposure to pooled sheep milk or milk products.
http://jvi.asm.org/content/85/2/1136.long
Commentary
In vitro amplification of prions from milk in the detection of subclinical infections
Volume 3, Issue 4 October/November/December 2009 Pages 236 - 239 http://dx.doi.org/10.4161/pri.3.4.10425
Kevin C. Gough, Claire A. Baker, Maged Taema and Ben C. Maddison
View affiliations
Prions can be amplified by serial protein misfolding cyclic amplification (sPMCA) from the milk of a high proportion of apparently healthy, scrapie exposed sheep with PRNP genotypes not previously associated with high disease penetrance1. These data strongly suggest the widespread presence of subclinical scrapie infections within scrapie-exposed flocks containing sheep with a range of susceptible PRNP genotypes. These data also lead to the hypothesis that similar subclinical disease states may be common for other animal and human prion diseases. Furthermore, the application of sPMCA to milk provides a method to detect such subclinical disease. Here, we describe the high level amplification of bovine spongiform encephalopathy (BSE) prions from both ovine and bovine origin, a methodology that will facilitate the detection of any prions secreted within bovine and ovine milk during subclinical and clinical BSE disease.
http://www.landesbioscience.com/journals/prion/article/10425/?nocache=543132411
Prion Protein in Milk
Nicola Franscini,1 Ahmed El Gedaily,1 Ulrich Matthey,1 Susanne Franitza,1 Man-Sun Sy,2 Alexander Bürkle,3 Martin Groschup,4 Ueli Braun,5 and Ralph Zahn1
Conclusions/Significance
In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrPC in milk implies the possibility that milk of TSE-infected animals serves as source for PrPSc.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762385/
http://www.allprion.com/Documents/Produkteblatt_PrionProtein.pdf
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Olivier Andréoletti1*, Leonor Orge2, Sylvie L. Benestad3, Vincent Beringue4, Claire Litaise1, Stéphanie Simon5, Annick Le Dur4, Hubert Laude4, Hugh Simmons6, Séverine Lugan1, Fabien Corbière1, Pierrette Costes1, Nathalie Morel5, François Schelcher1, Caroline Lacroux1
Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.
Author Summary
Following the bovine spongiform encephalopathy (BSE) crisis and the identification of its zoonotic properties, a sanitary policy has been implemented based on both eradication of transmissible spongiform encephalopathies (TSE) in food-producing animals and exclusion of known infectious materials from the food chain. Atypical/Nor98 scrapie is a prion disease of small ruminants identified worldwide. Currently it represents a significant part of the TSE cases detected in Europe. The restricted tissue distribution of Atypical/Nor98 scrapie agent in its natural host and the low detected prevalence of secondary cases in affected flocks meant that it is believed to be a poorly transmissible disease. This has led to the view that Atypical/Nor98 scrapie is a spontaneous disorder for which human and animal exposure risk remains low. In this study we demonstrate that in affected individuals, Atypical/Nor98 scrapie agent can disseminate in lymphoid tissues, nerves, and muscles, challenging the idea that it is a brain-restricted infectious agent. Evidence for the deficiencies in the current methods applied for monitoring Atypical/Nor98 scrapie is provided that would indicate an underestimation in the prevalence in the general population and in the affected flocks. These elements challenge the hypothesis on the biology of this recently identified TSE agent.
snip...
Assessing Atypical/Nor98 scrapie transmissibility through oral route in natural host and presence in placenta and in colostrum/milk (which are considered as major sources for TSE transmission between small ruminants) [28], [32] will provide crucial data.
snip...
Citation: Andréoletti O, Orge L, Benestad SL, Beringue V, Litaise C, et al. (2011) Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues. PLoS Pathog 7(2): e1001285. doi:10.1371/journal.ppat.1001285
Editor: David Westaway, University of Alberta, Canada
Received: June 21, 2010; Accepted: January 10, 2011; Published: February 10, 2011
Copyright: © 2011 Andréoletti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The different parts of this work were funded by (i) The Food Standard Agency (UK) M03058, (ii) the FP7 EU project 'Priority' (243950 FP7-KBBE KBBE-2009-1-2-06), and (iii) Programme opérationnel de Coopération territoriale Espagne - France - Andorre 2007-2013 EFA85/08-COTSA. Lymphoid tissue collection in Portuguese sheep was supported by AGROS 558 (PO AGRO 8.1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: o.andreoletti@envt.fr
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001285
Prions in Milk from Ewes Incubating Natural Scrapie
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76
AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE
Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.
One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html
I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
BSE: TIME TO TAKE H.B. PARRY SERIOUSLY
If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html
Case report
Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks
Ana B Rodríguez-Martínez1, Joseba M Garrido1, Sonia Maza1, Leyre Benedicto1, Mariví Geijo1, Nieves Gómez1, Esmeralda Minguijón1, Sylvie L Benestad2 and Ramón A Juste1*
* Corresponding author: Ramón A Juste rjuste@neiker.net
Author Affiliations
1 Department of Animal Health. Neiker-Tecnalia, 48160 Derio. Bizkaia. Spain
2 National Veterinary Institute, Department of Pathology, Postboks 750 Sentrum. 0106 Oslo. Norway
For all author emails, please log on.
BMC Veterinary Research 2010, 6:17 doi:10.1186/1746-6148-6-17
The electronic version of this article is the complete one and can be found online at:
http://www.biomedcentral.com/1746-6148/6/17
Received: 6 November 2009
Accepted: 26 March 2010
Published: 26 March 2010
© 2010 Rodríguez-Martínez et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases with similarities to the previously identified atypical scrapie cases termed Nor98.
Case presentation
Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8), their breed (all Latxa) and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ). All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum.
Conclusions
This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country. Moreover, a new genotype (ALRQ/ALRH) was found associated to atypical scrapie.
SNIP...
Case reports from this study and other case reports from Spain http://www.eeb.es/pags/espana.htm webcite and Portugal [35], indicate a high frequency of atypical cases compared to CS outbreaks in the Iberian Peninsula. It could be speculated that AS/Nor98 is the traditional form of scrapie in the Iberian part of the Basque country, whilst in the French part, the classical form has been predominant [59]. This would point to some unidentified epidemiological features limiting the spread of classical scrapie in the Iberian Peninsula. However, since the analysis of all sheep can not be guaranteed, it is difficult to test this hypothesis. The analysis of all sheep would provide more information about the epidemiology and pathology of this disease. Moreover, it could contribute in assessing whether AS is present in the Basque Country with the same high frequencies as others human TSEs, such as sporadic Creutzfeldt-Jakob disease [60] and Fatal Familiar Insomnia compared to other Spanish autonomous communities (National Epidemiology Centre: http:/ / www.isciii.es/ htdocs/ centros/ epidemiologia/ epidemiologia_listado_ecj.jsp webcite).
SEE FULL TEXT ;
http://www.biomedcentral.com/1746-6148/6/17
Peiffer, J. : Gerstmann-Straussler's disease, atypical multiple sclerosis and carcinomas in a family of sheepbreeders. Acta Neuropath. 56: 87-92, 1982. Peiffer (1982) described a family of sheepbreeders in which a father and 2 sons had GSS. All 3 also had congenital hip dysplasia, as did at least 3 other members of the kindred, all females. Atactic symptoms, dysarthria, and personality changes characterized the clinical course of this disorder, which might be labeled atypical multiple sclerosis. Like CJD , GSS is a form of subacute spongiform encephalopathy. Cases of GSS are clinically similar to the atactic type of CJD. Although there are many neuropathologic similarities, GSS differs from CJD by the presence of kuru-plaques and numerous multicentric, floccular plaques in the cerebral and cerebellar cortex, basal ganglia, and white matter. Whereas only 5 to 15% of CJD cases are familial, most cases of GSS are familial.
http://www.mad-cow.org/Alzheimer_cjd.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
page 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org/
please see full text ;
http://transmissiblespongiformencephalopathy.blogspot.com/
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
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
snip...
http://www.neuroprion.org/en/np-neuroprion.html
Subject: SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 100th meeting held on 25th April 2008
Date: July 13, 2008 at 7:16 pm PST
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 100th meeting held on 25th April 2008
ITEM 2 - APPROVAL OF MINUTES FROM SEAC 99 (SEAC 100/1) 6. The minutes of SEAC 99 were agreed as a correct record with the following amendment: 4 © SEAC 2008 . Paragraph 7, second bullet point, change ".Institute of Animal Health (IAH)." to ".Roslin Institute (RI)." 7. The committee was updated about transmission studies using isolates from a case of Creutzfeldt-Jakob Disease (CJD)1 which had been discussed at SEAC 99. Two lines of transgenic mice expressing the human prion protein gene homozygous for methionine (MM) or valine (VV) at codon 129 and two lines of conventional mice had been inoculated with isolates from the case. Transmission has been more efficient to the humanised mice compared with the conventional mice. The molecular characteristics of the abnormal prion protein (PrPSc) altered on transmission suggesting the patient may have been infected with an unstable TSE strain. Further work was required to characterise the TSE strain. However, it would be difficult to confirm whether this was related to BSE infection unless additional similar cases arose which could be investigated. 8.
snip...
35. Members asked about the spread of chronic wasting disease (CWD) in the USA. Mr Burke replied that CWD was continuing to spread in the cervid population in the USA.
snip...
One sheep in Cyprus, two in the UK and four from France are under investigation for possible BSE infection. Two further BSE cases were identified with unusual transmission properties in a Defra research project (SE1849) and 5 Countries where cases of BSE in cattle were reported in 2007: UK, Austria, Canada, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Poland, Portugal, Slovenia, Slovakia, Spain and The Netherlands. 6 Countries where atypical scrapie in sheep has been reported since 2002: Belgium, Denmark, the Falkland Islands, Finland, France, Germany, Greece, Hungary, Ireland, Italy, The Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, UK and USA. 13 © SEAC 2008 are also subject to further characterisation. BSE has been confirmed in one French goat slaughtered in 2002. A UK goat which was originally diagnosed as a case of scrapie in 1990 is under investigation for possible BSE infection. 37.
snip...
40. Members agreed that the statement should not focus entirely on the risk from BSE. A paragraph should be included to describe the risk that a new zoonotic TSE strain might emerge as a result of the relaxations to TSE controls. The possibility that the transmissibility to humans of such a new strain could be much greater than that of BSE should be acknowledged.
http://www.seac.gov.uk/minutes/final100.pdf
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007
snip...
ITEM 8 - PUBLIC QUESTION AND ANSWER SESSION 40. The Chair explained that the purpose of the question and answer session was to give members of the public an opportunity to ask questions related to the work of SEAC. Mr Terry Singeltary (Texas, USA) had submitted a question prior to the meeting, asking: "With the Nor-98 now documented in five different states so far in the USA in 2007, and with the two atypical BSE H-base cases in Texas and Alabama, with both scrapie and chronic 14 © SEAC 2007 wasting disease (CWD) running rampant in the USA, is there any concern from SEAC with the rise of sporadic CJD in the USA from ''unknown phenotype'', and what concerns if any, in relations to blood donations, surgery, optical, and dental treatment, do you have with these unknown atypical phenotypes in both humans and animals in the USA? Does it concern SEAC, or is it of no concern to SEAC? Should it concern USA animal and human health officials?" 41.
A member considered that this question appeared to be primarily related to possible links between animal and human TSEs in the USA.
There is no evidence that sCJD is increasing in the USA and no evidence of any direct link between TSEs and CJD in the USA. Current evidence does not suggest that CWD is a significant risk to human health. There are unpublished data from a case of human TSE in the USA that are suggestive of an apparently novel form of prion disease with distinct molecular characteristics. However, it is unclear whether the case had been further characterised, if it could be linked to animal TSEs or if other similar cases had been found in the USA or elsewhere. In relation to the possible public health implications of atypical scrapie, H-type BSE and CWD, research was being conducted to investigate possible links and surveillance was in place to detect any changes in human TSEs. Although possible links between these diseases and human TSEs are of concern and require research, there is no evidence to suggest immediate public health action is warranted. The possible human health risks from classical scrapie had been discussed earlier in the meeting. Members noted that there are effective channels of discussion and collaboration on research between USA and European groups. Members agreed it is important to keep a watching brief on new developments on TSEs.
snip...
http://www.seac.gov.uk/minutes/99.pdf
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
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.
snip...
http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1
http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf
see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;
http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html
Thursday, August 4, 2011
Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
(SEE VIDEO)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
http://transmissiblespongiformencephalopathy.blogspot.com/
price of TSE prion poker goes up again $$$
TSS
Subscribe to:
Posts (Atom)