Thursday, January 26, 2012

Facilitated Cross-Species Transmission of Prions in Extraneural Tissue

Science 27 January 2012:
Vol. 335 no. 6067 pp. 472-475
DOI: 10.1126/science.1215659

  • Report

Facilitated Cross-Species Transmission of Prions in Extraneural Tissue

+ Author Affiliations

  1. 1Institut National de la Recherche Agronomique (INRA), UR892, Virologie Immunologie Moléculaires, Bâtiment 440, F-78350 Jouy-en-Josas, France.
  2. 2INRA, UMR1313, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.

  1. *To whom correspondence should be addressed. E-mail: (V.B.); (H.L.)

  1. These authors contributed equally to this work.


Prions are infectious pathogens essentially composed of PrPSc, an abnormally folded form of the host-encoded prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity and to control cross-species transmission into other host populations, including humans. We compared the ability of brain and lymphoid tissues from ovine and human PrP transgenic mice to replicate foreign, inefficiently transmitted prions. Lymphoid tissue was consistently more permissive than the brain to prions such as those causing chronic wasting disease and bovine spongiform encephalopathy. Furthermore, when the transmission barrier was overcome through strain shifting in the brain, a distinct agent propagated in the spleen, which retained the ability to infect the original host. Thus, prion cross-species transmission efficacy can exhibit a marked tissue dependence.

Mammalian prions are proteinaceous infectious agents responsible for fatal neurodegenerative disorders in farmed animals and humans. They are primarily composed of macromolecular assemblies of PrPSc, a misfolded form of the ubiquitously expressed, host-encoded prion protein PrPC. Upon infection, PrPSc assemblies are thought to self-perpetuate the conformational conversion from PrPC to PrPSc, leading to PrPSc deposition in the brain and sometimes in the lymphoid tissue (1, 2). Multiple prion strains can self-propagate in the same host and exhibit distinct, heritable phenotypic traits, presumably through the existence of stable, structurally distinct PrPSc conformers (3, 4).

Prions can transmit between species presenting a zoonotic risk, as exemplified by the emergence of variant Creutzfeldt-Jakob disease (vCJD) in the human population after exposure to bovine spongiform encephalopathy (BSE) prions (2). However, such events are restricted by the so-called transmission barrier (5, 6), the strength of which depends on interactions between host PrPC and the infecting prion strain type(s). The transmission barrier is routinely gauged by the appearance of disease-specific, clinical signs and/or PrPSc in the brain of the new host. Their concomitant absence (79) would usually suggest a resistance to infection or a disease incubation time exceeding the exposed host life span. Prion interspecies transmission can be associated with the acquisition of new biological strain properties (1014). To accommodate these observations, the conformational-selection model proposes that prion interspecies transmission is essentially constrained by the degree of steric compatibility between the incoming PrPSc and the spectrum of conformations the exposed host PrPC primary structure can adopt in the PrPSc state (6). It is not clear whether different cellular environments or PrPC isoform variation among brain and extraneural tissues is involved in prion cross-species transmission. A number of prion strains can replicate in the lymphoid tissue, which can be targeted after infection, whatever the entry route (5, 15).

We examined the tissue-dependence of prion cross-species transmission efficacy in three different mouse models in which primary transmission seemed to be particularly inefficient, based on the absence of clear neurological signs and of proteinase K–resistant PrPSc (PrPres) in the brains of most inoculated animals at end of life. In each model, mice were inoculated intracerebrally and euthanized at end of their life span or in triplicate at regular intervals postexposure, so as to consider any age-related immune system dysfunction (16). Mice culled because of intercurrent disease were also analyzed whenever possible. The presence of PrPres in brain and spleen tissues was assessed by immunoblotting (17).

The first model consisted of ovine PrP transgenic mice (VRQ allele, tg338 line) (18) inoculated with prions responsible for chronic wasting disease (CWD) in cervids, an expanding epidemic in northern America. As expected (19), no clinical disease was observed upon inoculation with one elk CWD field isolate, despite efficient transmission to murine PrP transgenic mice (tga20) (fig. S1). PrPres was observed in only 2 of 29 (2/29) tg338 brains at the end of life (507 and 793 days). In marked contrast, significant levels of PrPres were detected in the spleens of all but one mouse analyzed from ~380 days onward (n = 18 mice) (Fig. 1, A and B, and fig. S2). Quantifying the leakiness of the transmission barrier as the proportion of PrPres-positive mice in the brain and spleen yielded large differences from 9% in the brain to 94% in the spleen (Table 1). Because interspecies transmission of prions can occur in the absence of detectable PrPres in the brain (20), a second passage was performed with PrPres-negative brain and PrPres-positive spleen material from an asymptomatic mouse euthanized at 545 days postinfection. None of the six mice inoculated with the brain material demonstrated neurological signs or accumulated PrPres in brain and spleen, even at a very late stage (range of survival time: 616 to 973 days), whereas three out of five mice inoculated with spleen material accumulated PrPres in brain and spleen tissue (749, 836, and 947 days) (Fig. 1B and fig. S3). Thus CWD prions propagate much more easily in the spleen than in the brain on primary passage in “ovinized” mice.

Fig. 1
View larger version:
Fig. 1
Time course of PrPres accumulation in the brain and spleen tissue of ovine and human PrP mice inoculated with CWD, Sc237, and BSE prions. PrPres extracted from spleen (Sp, red) and brain (Br, blue) tissues was detected by immunoblot (B, D, F) and quantified (A, C, E) as a percentage of that found at maximum in the spleens (logarithmic scale). The positive threshold is indicated by the horizontal dotted line (17). Tissue samples in which no PrPres was detected are symbolized by open circles. (A and B) Ovine PrP tg338 mice inoculated with elk CWD prions. (A) Data resulting from two independent primary transmission experiments have been pooled (see Table 1 and fig. S2 for more detailed data). (B) Secondary passage was made using either brain or spleen homogenates (fig. S3), as indicated. (C and D) tg338 mice inoculated with different infectious sources of closely related hamster (Ha) prions (Sc237 and 263K; see text) (see Table 1 and fig. S2 for more detailed data). (D) The second and third passages were made with brain homogenates from tg338 mice inoculated with hamster Sc237 prions. (E and F) Human PrP tg650 mice inoculated with various cattle BSE isolates or with BSE prions serially passaged in bovine PrP transgenic mice (tgBov) (see Table 1 and fig. S2 for more detailed results). (F) The electrophoretic pattern of variant CJD in tg650 mouse spleen is shown for comparison. Variant CJD PrPres levels in spleen would attain ~100% on (E) at terminal stage of disease.

Table 1
Leakiness of the transmission barrier, depending on whether PrPres detection is performed on brain or spleen tissue. exp, experiment; Fr, French, It, Italy. tgHa and tgBov are prions passaged in hamster (Ha) or bovine (Bov) PrP transgenic (tg) mice.

We next examined whether a similarly facilitated lymphoid replication might also occur upon interspecies transmission of prions known to be essentially neurotropic. Hamster prion (15, 21) from three different sources [cloned Sc237 and 263K propagated in hamster and Sc237 serially passaged and recloned in hamster PrP transgenic tg7 mouse (22)] was inoculated into tg338 mice. None of the mice developed clinical signs. Only 8/40 brains analyzed were PrPres-positive, all at the end of the mouse life span (from ~570 to 875 days). However, the proportion of PrPres-positive spleens was substantially higher overall (18/30), and the protein was detected earlier, inconsistently from 380 days onward but in every mouse after 500 days (Fig. 1C, fig. S2, and Table 1). Spleen and brain also differed in the PrPres electrophoretic type, which was stably maintained on serial passage (Figs. 1D and 2B). In the spleen, the unglycosylated PrPres core consistently retained an apparent molecular mass of ~21 kD (n = 29), as in the original inocula, whereas a shift to 19 kD was observed in all PrPres-positive tg338 brains (n = 20). The possibility that distinct agents were preferentially amplified in brain and spleen tissues was formally examined by transmitting collected tissue materials from the same tg338 mice (at third and fourth passage) to reporter tg338 and tg7 mice (Fig. 2A). In tg338 mice, the prion phenotypic features largely overlapped, whether spleen or brain extract was inoculated. Yet the presence of an additional 21-kD PrPres pattern (Fig. 2B) and of numerous plaquelike PrPres deposits (Fig. 2C), specifically after spleen extract inoculation, suggested that the 21- and 19-kD components coexisted in this tissue, with the 21-kD component in higher proportion. The tissue-specific differences were even greater upon transmission to tg7 mice. Tg338 spleen extracts were able to reinfect all tg7 mice in ~350 days (Fig. 2A) and to induce PrPres accumulation in their brain (Fig. 2, B and C), whereas the tg338 brain extracts repeatedly failed to do so (Fig. 2). Thus, the selection and/or mutational constraints imposed onto Sc237 prions by the cross-species barrier differ radically between the brain and spleen, allowing the component preferentially amplified in the spleen to reinfect the donor species efficiently, despite iterated passage in the new host.

Fig. 2
Retrotransmission to hamster PrP mice of Sc237 prions serially passaged in the spleen and brain tissue of ovine PrP mice. (A) Summary of the transmissions of hamster Sc237 prions to ovine PrP tg338 mice (white mice) and hamster PrP tg7 mice (gray mice). Transmissions with brain and spleen extracts are indicated with blue and red lines, respectively. The number of affected/inoculated mice (mice with neurological signs or positive for PrPres by immunoblot) and the mean survival time in days ± SEM are indicated for each inoculated group. As tg338-passaged brain extracts were unable to induce disease upon retrotransmission to hamster tg7 mice, an additional round of inoculation was performed with individual or pool brain extracts as inocula, which proved also negative. For these transmissions, the range of survival time is reported. (B) Representative immunoblot showing the presence and electrophoretic pattern of Sc237 PrPres in spleen and brain in ovine PrP tg338 mice and on retrotransmission to hamster PrP tg7 mice [two successive passages (p)], depending on whether tg338-passaged brain (Ov Br) or spleen (Ov Sp) material (at third passage) is used for inoculation. (C) Representative histoblots in two different anteroposterior sections showing the presence and distribution of Sc237 PrPres deposits in the brains of ovine tg338 PrP and hamster PrP tg7 transgenic mice inoculated with tg338-passaged brain or spleen extracts (at third passage). After spleen extract inoculation, note the presence of numerous plaquelike PrPres deposits in the tg338 brain (arrowheads), particularly in the corpus callosum (inset squares). Scale bars, 1 mm.

To see whether our observations could extend to another mouse model, we compared the susceptibility of lymphoid and brain tissue from human PrP transgenic mice (Met allele, tg650 line) (12) to epizootic BSE prions. The two primary BSE isolates and the bovine PrP mouse-passaged BSE and goat BSE isolates used here have been previously described (11, 2325); they all exhibited similarly high infectivity levels in bovine PrP mice. Their transmission to tg650 mice appeared inefficient on primary passage, as shown by the absence of clear neurological signs and the detection of PrPres in 3/44 brains analyzed, all beyond 600 days postinfection (Fig. 1E and fig. S2) (24, 25). The pathological protein was not detectable in the brains of healthy mice euthanized before that time point (n = 24) (Fig. 1E and fig. S2). PrPres-negative brains appeared 250- to 1000-fold less infectious than PrPres-positive brains (table S1). Out of 41 spleens analyzed, 26 were PrPres-positive, the first as early as at 230 days postinfection (detection not assayed before) (Fig. 1, E and F). This provides a transmission barrier that is more than sevenfold leakier in the spleen than in the brain (Table 1). The spleen PrPres electrophoretic signature was identical to that found after vCJD transmission to tg650 mice (12), and most positive spleens had PrPres levels that did not differ by more than threefold (Fig. 1, E and F). In contrast, vCJD inoculation led to accumulation of PrPres in the brain of all infected mice (12). Thus, again these data argue for a markedly higher permissiveness of the spleen over the brain tissue to foreign prions.

Here, we have demonstrated that prion cross-species transmission efficacy can exhibit a dramatic tissue-dependence in the same host. In three distinct mouse models, lymphoid tissue appeared markedly more permissive than nervous tissue, despite an intracerebral infection route. This phenomenon was observed with both natural and experimental prions and did not seem to rely on a pronounced, preexisting lymphotropism. The PrP transgenic models used here faithfully reproduce the most relevant disease features in the natural host, including prion strain-dependant (in)ability to replicate in lymphoid tissue (12, 18, 23). Furthermore, the spleen-to-brain PrPC level ratios (~1:20) in all of the transgenic lines used are comparable to that in conventional models (fig. S4A). The strongest PrPC staining was associated with the follicular dendritic cells network (fig. S5), as documented in nontransgenic species (16, 26). The PrPC level in the spleen of the overexpressing lines stayed below its physiological level in the brain (fig. S4B). Thus, our findings are unlikely to be caused by an aberrant qualitative or quantitative expression of the PrP transgene in the spleen. Despite strong selective pressure, active prion replication in a nonneuronal tissue on minimal passage in a foreign host clearly constitutes a possible way to extend prion host range. This questions the long established notion of absolute species barriers (27). Chronic inflammation induces the formation of secondary lymphoid follicles, thus expanding extraneural prion replication to otherwise refractory organs (28). It has been proposed that prions could exist as quasi-species (6, 29) and may thus be endowed with organ-specific subvariants, as observed repeatedly with viral pathogens (30, 31). Alternatively, or in combination, tissue-specific host factors may differentially regulate prion replication dynamics under selection pressure. This could involve PrPC itself, due to some isoform variation between the spleen and brain tissues, or ancillary factors that would create a more favorable environment, including, for instance, a prolonged residence of the incoming prions in lymphoid tissues.

Our data call for closer examination of extraneural PrPres in humanized or primate models when assessing any zoonotic potential of animal prions. The human species barrier to BSE prions may be dramatically lower than previously anticipated, according to brain PrPres detection only (10, 24, 25, 32). Because the oral route is known to target lymphoid tissue, albeit less well than the intracerebral route used here (15), our data reinforce the legitimacy of the current investigations aimed at evaluating the proportion of silent carriers (26, 33, 34) in the BSE-exposed UK population (35). To provide a reliable assessment of people at risk and determining the probability of vCJD onward transmission via surgery or donated blood or organs, it may be necessary to pursue such screening policy on a long-term basis, because, as shown here, prions could persist silently for nearly a third of a host’s life span before being detectable extraneurally by conventional diagnostic methods. Finally, including prion detection in the lymphoid tissue whenever possible might be considered for the surveillance of people exposed to CWD-infected tissue.

Supporting Online Material

Materials and Methods
Figs. S1 to S5
Table 1
References (3642)

  • Received for publication 24 October 2011.
  • Accepted for publication 30 November 2011.

References and Notes

  1. Materials and methods are available as supporting material on Science Online.
  2. Acknowledgments: We thank the animal facility staff (Infectiologie Expérimentale Rongeurs Poissons, Jouy-en-Josas, France) for excellent animal care; S. Mouillet-Richard, O. Andréoletti, and H. Rezaei for critical reading of the manuscript; R. Young (INRA-Jouy, France) and M. Farrow (University College London, UK) for English style editing; A. Gröner (Commonwealth Serum Laboratories Behring, Marburg, Germany) for tg7 mice; and C. Laude for mouse drawings in graphics. This work was partly supported by the Alliance Biosecure Foundation and INRA-Transfert.


“which may prompt a reevaluation of the effectiveness of species barriers”

Nature | News

Prion diseases hide out in the spleen

UK population could harbour thousands of silent infections.

The prion proteins that can cause variant Creutzfeldt–Jakob disease in humans could be lurking undetected in our lymphatic system.
Prion diseases such as bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease (vCJD) are able to jump species much more easily than previously thought. A study published in Science today shows that in mice, prions introduced from other species can replicate in the spleen without necessarily affecting the brain1.

The study reinforces the concern that thousands of people in the United Kingdom might be silent carriers of prion infection, potentially able to pass a lethal form of the disease to others through surgery or blood transfusions.

Prions are infectious pathogens, primarily composed of the misfolded form of a protein called PrP. Normal PrP molecules that are converted into the misshapen type then aggregate in the brain to form hard, insoluble clumps — with fatal consequences.

Previous studies have judged the ease of cross-species transmission by looking for clinical symptoms as well as the presence of prions in infected animals’ brains. Results from these studies suggested that in many cases there is an effective 'species barrier', with most inoculated animals seemingly free of prions at the end of their lives.

Breaking barriers

But prions don’t just replicate in the brain — they also affect lymphoid tissue, such as the spleen, tonsils and appendix. So Vincent Béringue, a prion researcher at the French National Institute for Agricultural Research in Jouy-en-Josas, France, and his colleagues used mice that had been genetically engineered to express either the sheep or human version of PrP to look beyond the brain.

As expected, few of the mice had detectable prions in their brains. When those expressing human PrP were inoculated with the BSE prion, only 3 out of 43 had detectable prions in their brains at the end of their lives. But in lymphoid tissue it was a different story, with 26 of 41 spleens testing positive for prions, even though the mice showed no clinical symptoms of BSE.

The research shows that prions jump species into lymphoid tissue much more easily than into brain tissue, says Béringue. “If you extrapolate that to the human situation, you can imagine that there are more people infected subclinically in lymphoid tissues such as the spleen, who may never develop the disease.”

That’s a concern because these carriers could infect others, for example by blood transfusion, organ donation or contaminated surgical instruments. Once passed human to human, the infection could in theory then affect the brain and cause lethal vCJD, says John Collinge, director of the Medical Research Council Prion Unit at University College London, who wrote an analysis to accompany the Béringue paper2. “The main adaptation — that the incoming BSE proteins have triggered the formation of human prions — has occurred,” he says.

An epidemic of BSE among cows, dubbed 'mad cow disease', in Britain in the 1980s, led to stringent controls on meat production and the use of surgical and dental instruments. Human cases of the disease, vCJD, were first seen in the mid-1990s. That sparked fears of a devastating human epidemic, but only around 200 people have died from the disease since then, and cases have been tailing off.

But two recent surveys of tissue samples from removed appendixes suggest that as many as 1 in 4,000 people in the United Kingdom could be carriers3, 4.

Béringue’s findings could help to explain these results, says Collinge. “These estimates suggest there may be 15 to 20,000 people in the United Kingdom incubating the disease,” he says. “Maybe they predominantly have an infection restricted to the lymphoreticular system.”

Collinge warns that “all efforts should be made” to assess the prevalence of prion infection in the United Kingdom by analysing surgical and autopsy tissues, and to investigate whether blood tests for vCJD can detect the infection in silent carriers. “Maybe they will never develop the disease themselves,” he says. “But it’s precisely those people who present a risk to others.”

Journal name:

Thursday, January 26, 2012

The Risk of Prion Zoonoses

Science 27 January 2012: Vol. 335 no. 6067 pp. 411-413 DOI: 10.1126/science.1218167

Sunday, January 22, 2012

Chronic Wasting Disease CWD cervids interspecies transmission

Wednesday, January 18, 2012


February 1, 2012

Saturday, December 3, 2011

Isolation of Prion with BSE Properties from Farmed Goat

Volume 17, Number 12—December 2011

Wednesday, January 18, 2012

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:

February 2012 - Volume 71 - Issue 2 - p 140–147
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)


Increased Atypical Scrapie Detections

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.

J Vet Diagn Invest 21:454-463 (2009)

Nor98 scrapie identified in the United States

Christie M. Loiacono,' Bruce V. Thomsen, S. Mark Hall, Matti Kiupe!, Diane Sutton, Katherine O'Rourke, Bradd Barr, Lucy Anthenill, Deiwyn Keane


A distinct strain of scrapic identified in sheep of Norway in 1998 has since been identified in numerous countries throughout Europe. The disease is known as Nor98 or Not-98-like scrapic. among other names. Distinctions between classic scrapie and Nor98 scrapie are made based on histopathologv and immunodiagnostic results. There are also differences in the epidemiology, typical signalment, and likelihood of clinical signs being observed. In addition, sheep that have genotypes associated with resistance to classic scrapie are not spared from Nor98 disease. The various differences between classic and Nor98 scrapie have been consistently reported in the vast majority of cases described across Europe. The current study describes in detail the patholo gic changes and diagnostic results of the first 6 cases of' Nor98 scrapic disease diagnosed in sheep of the United States.

Key words: Hisiopathology: Nor98: PrP imniunolabeling; scrapie: sheep.



Case I

The first case identified as consistent with Nor98 scrapie had nonclassic PrP distribution in brain tissue, no PrPSC in lymph tissue, and nonclassic migration of protein bands on a Western blot test. The animal was an aged, mottled-faced ewe that was traced back to a commercial flock in Wyoming. ...

Case 2

The second case was a clinically normal 8-year-old Suffolk ewe that had been in a quarantined flock for 5 years at a USDA facility in Iowa.

Case 3

A 16-year-old, white-faced, cross-bred wether was born to a black-faced ewe. He lived his entire life as a pet on a farm in California.

Case 4

The fourth case of Nor98 scrapie was identified in an approximately 8-year-old Dorset ewe that was born into a flock of approximately 20 ewes in Indiana.

Case 5

The fifth case was a clinically normal, approximately 3-year-old, white-faced, cross-bred ewe from an approximately 400 head commercial flock in Minnesota.

Case 6

The sixth case of Nor98 scrapie was identified in a 4-year-old, white-faced ewe that was purchased and added to a commercial flock in Pennsylvania


see full text ;

Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

Monday, October 10, 2011

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


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


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 ;

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


Friday, December 30, 2011; ;

Feds back Quebec R+D for SRM removal equipment Canada

Friday, January 6, 2012

OIE 2012 Training Manual on Wildlife Diseases and Surveillance and TSE Prion disease

Monday, January 2, 2012

EFSA Minutes of the 6th Meeting of the EFSA Scientific Network on BSE-TSE Brussels, 29-30 November 2011


Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.



R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (; 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.


A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

Monday, December 1, 2008

When Atypical Scrapie cross species barriers


Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.


Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

why do we not want to do TSE transmission studies on chimpanzees $


5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.












Tuesday, November 17, 2009



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


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


page 9 of 14 ;

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

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

snip... see full text

Wednesday, July 28, 2010

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



Tuesday, November 02, 2010

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

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

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"

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

Friday, December 23, 2011

Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

Volume 18, Number 1—January 2012 Dispatch

Saturday, November 19, 2011

Novel Prion Protein in BSE-affected Cattle, Switzerland

Owens, Julie

From: Terry S. Singeltary Sr. []

Sent: Monday, July 24, 2006 1:09 PM

To: FSIS RegulationsComments

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

Page 1 of 98


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

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

Saturday, June 19, 2010


Friday, August 20, 2010

USDA: Animal Disease Traceability August 2010

Friday, November 18, 2011

country-of-origin labeling law (COOL) violates U.S. obligations under WTO rules WT/DS384/R WT/DS386/R

Saturday, July 23, 2011


Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU


Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR>

Prion disease update 2010 (11) PRION DISEASE UPDATE 2010 (11)

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.


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





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.



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).

Wednesday, February 16, 2011




Sunday, April 18, 2010


Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

Sunday, March 28, 2010

Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?

Monday, November 30, 2009


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

Wednesday, January 18, 2012

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

Journal of Neuropathology & Experimental Neurology:

February 2012 - Volume 71 - Issue 2 - p 140–147

Thursday, July 14, 2011

Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

Wednesday, January 5, 2011


David W. Colby1,* and Stanley B. Prusiner1,2

+ Author Affiliations

1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence:



I believe the statement and quote below is incorrect ;

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

Please see ;

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

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

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

kindest regards,

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

MARCH 1, 2011


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

From: David Colby


Cc: stanley@XXXXXXXX

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

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

Dear Terry Singeltary,

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

Warm Regards, David Colby


David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware




Wednesday, September 08, 2010


Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies Location: Virus and Prion Diseases of Livestock



Hamir, Amirali Kunkle, Robert Cutlip, Randall - ARS RETIRED Miller, Janice - ARS RETIRED Williams, Elizabeth - UNIVERSITY OF WYOMING Richt, Juergen

Submitted to: European Society of Veterinary Pathology Publication Type: Abstract Publication Acceptance Date: June 5, 2006 Publication Date: August 31, 2006 Citation: Hamir, A., Kunkle, R., Cutlip, R., Miller, J., Williams, E., Richt, J. 2006.

Transmission of chronic wasting disease agent of mule deer (CWD**md) to Suffolk sheep by intracerebral route

[abstract]. European Society of Veterinary Pathology 24th Annual Meeting. Paper No. P63. p. 171-172.

Technical Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that has been identified in captive and free-ranging cervids in the U.S. since 1967. To determine the transmissibility of CWD to sheep, 8 Suffolk lambs [4 QQ and 4 QR at codon 171 of prion protein (PRNP) gene] were inoculated intracerebrally with a pooled brain suspension from 28 mule deer naturally affected with CWD (CWD**md). Two other lambs (1 QQ and 1 QR at codon 171 of the PRNP gene) were kept as non-inoculated controls. Within 36 months post inoculation (MPI), 2 animals became sick and were euthanized. Only 1 sheep (euthanized at 35 MPI) showed clinical signs that were consistent with those described for scrapie. Microscopic lesions of spongiform encephalopathy (SE) were only seen in the sheep with the clinical signs of TSE and its tissues were positive for the abnormal prion protein (PrP**res) by immunohistochemistry and Western blot. Between 36 and 60 MPI, 3 other sheep were euthanized because of conditions unrelated to TSE. The remaining 3 sheep remained non-clinical at the termination of the study (72 MPI) and were euthanized at that time. One of the 3 animals revealed SE and its tissues were positive for PrP**res. Both sheep positive for PrP**res were homozygous QQ at codon 171. Retrospective examination of the PRNP genotype of the 2 TSE-positive animals revealed that the sheep with clinical prion disease (euthanized at 35 MPI) was heterozygous (AV) and the sheep with the sub-clinical disease (euthanized at 72 MPI) was homozygous (AA) at codon 136 of the PRNP. These findings demonstrate that transmission of the CWD**md agent to sheep via the intracerebral route is possible. Interestingly, the host genotype may play a significant part in successful transmission and incubation period of CWD**md.

Transmission of chronic wasting disease of mule deer to Suffolk sheep following intracerebral inoculation

Amir N. Hamir,1 Robert A. Kunkle, Randall C. Cutlip, Janice M. Miller, Elizabeth S. Williams, Juergen A. Richt

Abstract. To determine the transmissibility of chronic wasting disease (CWD) to sheep, 8 Suffolk lambs of various prion protein genotypes (4 ARQ/ARR, 3 ARQ/ARQ, 1 ARQ/VRQ at codons 136, 154, and 171, respectively) were inoculated intracerebrally with brain suspension from mule deer with CWD (CWDmd). Two other lambs were kept as noninoculated controls. Within 36 months postinoculation (MPI), 2 inoculated animals became sick and were euthanized. Only 1 sheep (euthanized at 35 MPI) showed clinical signs that were consistent with those described for scrapie. Microscopic lesions of spongiform encephalopathy (SE) were only seen in this sheep, and its tissues were determined to be positive for the abnormal prion protein (PrPres) by immunohistochemistry and Western blot. Three other inoculated sheep were euthanized (36 to 60 MPI) because of conditions unrelated to TSE. The 3 remaining inoculated sheep and the 2 control sheep did not have clinical signs of disease at the termination of the study (72 MPI) and were euthanized. Of the 3 remaining inoculated sheep, 1 was found to have SE, and its tissues were positive for PrPres. The sheep with clinical prion disease (euthanized at 35 MPI) was of the heterozygous genotype (ARQ/VRQ), and the sheep with subclinical disease (euthanized at 72 MPH) was of the homozygous ARQ/ARQ genotype. These findings demonstrate that transmission of the CWDmd agent to sheep via the intracerebral route is possible. Interestingly, the host genotype may play a notable part in successful transmission and incubation period of CWDmd.


Thus far, among domestic animals, CWDmd has been transmitted by the intracerebral route to a goat18 and cattle.5–7 The present findings demonstrate that it is also possible to transmit CWDmd agent to sheep via the intracerebral route. However, the only sheep to develop clinical TSE within 35 MPI was genotypically AV at PRNP codon 136, suggesting that host genotype may play a notable part in successful transmission of the disease in this species. Although in Suffolk sheep the AV variant at codon 136 is very rare,17 selective breeding of Suffolk sheep with this codon has begun in the hope of testing this differential susceptibility hypothesis in a future study of CWDmd transmission to sheep.

Key words: Chronic wasting disease; immunohistochemistry; intracerebral transmission; prion protein; sheep; spongiform encephalopathy.

Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies Location: Virus and Prion Diseases of Livestock



Hamir, Amirali Kunkle, Robert Miller, Janice - ARS RETIRED Greenlee, Justin Richt, Juergen

Submitted to: Journal of Comparative Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: July 25, 2005 Publication Date: January 1, 2006 Citation: Hamir, A.N., Kunkle, R.A., Miller, J.M., Greenlee, J.J., Richt, J.A. 2006. Experimental second passage of chronic wasting disease (CWD(mule deer)) agent to cattle. Journal of Comparative Pathology. 134(1):63-69.

Interpretive Summary: To compare the findings of experimental first and second passage of chronic wasting disease (CWD) in cattle, 6 calves were inoculated into the brain with CWD-mule deer agent previously (first) passaged in cattle. Two other uninoculated calves served as controls. Beginning 10-12 months post inoculation (PI), all inoculates lost appetite and weight. Five animals subsequently developed clinical signs of central nervous system (CNS) abnormality. By 16.5 months PI, all cattle had been euthanized because of poor prognosis. None of the animals showed microscopic lesions of spongiform encephalopathy (SE) but the CWD agent was detected in their CNS tissues by 2 laboratory techniques (IHC and WB). These findings demonstrate that inoculated cattle amplify CWD agent but also develop clinical CNS signs without manifestation of microscopic lesions of SE. This situation has also been shown to occur following inoculation of cattle with another TSE agent, namely, sheep scrapie. The current study confirms previous work that indicates that the diagnostic tests currently used for confirmation of bovine spongiform encephalopathy (BSE) in the U.S. would detect CWD in cattle, should it occur naturally. Furthermore, it raises the possibility of distinguishing CWD from BSE in cattle due to the absence of microscopic lesions and a unique multifocal distribution of PrPres, as demonstrated by IHC, which in this study, appears to be more sensitive than the WB. Technical Abstract: To compare clinicopathological findings of first and second passage of chronic wasting disease (CWD) in cattle, a group of calves (n=6) were intracerebrally inoculated with CWD-mule deer agent previously (first) passaged in cattle. Two other uninoculated calves served as controls. Beginning 10-12 months post inoculation (PI), all inoculates lost appetite and lost weight. Five animals subsequently developed clinical signs of central nervous system (CNS) abnormality. By 16.5 months PI, all cattle had been euthanized because of poor prognosis. None of the animals showed microscopic lesions of spongiform encephalopathy (SE) but PrPres was detected in their CNS tissues by immunohistochemistry (IHC) and Western blot (WB) techniques. These findings demonstrate that intracerebrally inoculated cattle not only amplify CWD PrPres but also develop clinical CNS signs without manifestation of morphologic lesions of SE. This situation has also been shown to occur following inoculation of cattle with another TSE agent, scrapie. The current study confirms previous work that indicates the diagnostic techniques currently used for confirmation of bovine spongiform encephalopathy (BSE) in the U.S. would detect CWD in cattle, should it occur naturally. Furthermore, it raises the possibility of distinguishing CWD from BSE in cattle due to the absence of neuropathologic lesions and a unique multifocal distribution of PrPres, as demonstrated by IHC, which in this study, appears to be more sensitive than the WB.

Wednesday, September 21, 2011

Evidence for distinct CWD strains in experimental CWD in ferrets

Wednesday, October 12, 2011

White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation

Wednesday, July 06, 2011

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation

see incredible infection rate at one of these game farms Wisconsin shut down and bought out. 86% infection rate...

Monday, January 16, 2012


Tuesday, December 20, 2011



Sunday, January 22, 2012

Chronic Wasting Disease CWD cervids interspecies transmission

*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.

Chronic Wasting Disease Susceptibility of Four North American Rodents

Chad J. Johnson1*, Jay R. Schneider2, Christopher J. Johnson2, Natalie A. Mickelsen2, Julia A. Langenberg3, Philip N. Bochsler4, Delwyn P. Keane4, Daniel J. Barr4, and Dennis M. Heisey2 1University of Wisconsin School of Veterinary Medicine, Department of Comparative Biosciences, 1656 Linden Drive, Madison WI 53706, USA 2US Geological Survey, National Wildlife Health Center, 6006 Schroeder Road, Madison WI 53711, USA 3Wisconsin Department of Natural Resources, 101 South Webster Street, Madison WI 53703, USA 4Wisconsin Veterinary Diagnostic Lab, 445 Easterday Lane, Madison WI 53706, USA *Corresponding author email:

We intracerebrally challenged four species of native North American rodents that inhabit locations undergoing cervid chronic wasting disease (CWD) epidemics. The species were: deer mice (Peromyscus maniculatus), white-footed mice (P. leucopus), meadow voles (Microtus pennsylvanicus), and red-backed voles (Myodes gapperi). The inocula were prepared from the brains of hunter-harvested white-tailed deer from Wisconsin that tested positive for CWD. Meadow voles proved to be most susceptible, with a median incubation period of 272 days. Immunoblotting and immunohistochemistry confirmed the presence of PrPd in the brains of all challenged meadow voles. Subsequent passages in meadow voles lead to a significant reduction in incubation period. The disease progression in red-backed voles, which are very closely related to the European bank vole (M. glareolus) which have been demonstrated to be sensitive to a number of TSEs, was slower than in meadow voles with a median incubation period of 351 days. We sequenced the meadow vole and red-backed vole Prnp genes and found three amino acid (AA) differences outside of the signal and GPI anchor sequences. Of these differences (T56-, G90S, S170N; read-backed vole:meadow vole), S170N is particularly intriguing due its postulated involvement in "rigid loop" structure and CWD susceptibility. Deer mice did not exhibit disease signs until nearly 1.5 years post-inoculation, but appear to be exhibiting a high degree of disease penetrance. White-footed mice have an even longer incubation period but are also showing high penetrance. Second passage experiments show significant shortening of incubation periods. Meadow voles in particular appear to be interesting lab models for CWD. These rodents scavenge carrion, and are an important food source for many predator species. Furthermore, these rodents enter human and domestic livestock food chains by accidental inclusion in grain and forage. Further investigation of these species as potential hosts, bridge species, and reservoirs of CWD is required.

please see ;

Oral.29: Susceptibility of Domestic Cats to CWD Infection

Amy Nalls, Nicholas J. Haley, Jeanette Hayes-Klug, Kelly Anderson, Davis M. Seelig, Dan S. Bucy, Susan L. Kraft, Edward A. Hoover and Candace K. Mathiason† Colorado State University; Fort Collins, CO USA†Presenting author; Email:

Domestic and non-domestic cats have been shown to be susceptible to one prion disease, feline spongiform encephalopathy (FSE), thought to be transmitted through consumption of bovine spongiform encephalopathy (BSE) contaminated meat. Because domestic and free ranging felids scavenge cervid carcasses, including those in CWD affected areas, we evaluated the susceptibility of domestic cats to CWD infection experimentally. Groups of n = 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD deer brain homogenate. Between 40–43 months following IC inoculation, two cats developed mild but progressive symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors and ataxia—ultimately mandating euthanasia. Magnetic resonance imaging (MRI) on the brain of one of these animals (vs. two age-matched controls) performed just before euthanasia revealed increased ventricular system volume, more prominent sulci, and T2 hyperintensity deep in the white matter of the frontal hemisphere and in cortical grey distributed through the brain, likely representing inflammation or gliosis. PrPRES and widely distributed peri-neuronal vacuoles were demonstrated in the brains of both animals by immunodetection assays. No clinical signs of TSE have been detected in the remaining primary passage cats after 80 months pi. Feline-adapted CWD was sub-passaged into groups (n=4 or 5) of cats by IC, PO, and IP/SQ routes. Currently, at 22 months pi, all five IC inoculated cats are demonstrating abnormal behavior including increasing aggressiveness, pacing, and hyper responsiveness. Two of these cats have developed rear limb ataxia. Although the limited data from this ongoing study must be considered preliminary, they raise the potential for cervid-to-feline transmission in nature. Prion

see more recent science abstracts from the Prion 2011 on CWD here ;


Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculam (?saline).

Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in all of these species with the shortest incubation period in the ferret.

Generation of a New Form of Human PrPScin Vitro by Interspecies Transmission from Cervid Prions*

Marcelo A. Barria‡, Glenn C. Telling§, Pierluigi Gambetti¶, James A. Mastrianni‖ and Claudio Soto‡,1

+ Author Affiliations

From the ‡Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, Houston, Texas 77030,

the §Departments of Microbiology, Immunology, and Molecular Genetics and Neurology, Sanders Brown Center on Aging, University of Kentucky Medical Center, Lexington, Kentucky 40506,

the ¶Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, and

the ‖Department of Neurology, The University of Chicago, Chicago, Illinois 60637

1 To whom correspondence should be addressed: University of Texas Medical School at Houston, 6431 Fannin St., Houston, TX 77030. Tel.: 713-500-7086; Fax: 713-500-0667; E-mail:


Prion diseases are infectious neurodegenerative disorders that affect humans and animals and that result from the conversion of normal prion protein (PrPC) into the misfolded prion protein (PrPSc). Chronic wasting disease (CWD) is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. Determining the risk of transmission of CWD to humans is of utmost importance, considering that people can be infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the misfolded form by CWD PrPSc, we performed experiments using the protein misfolding cyclic amplification technique, which mimics in vitro the process of prion replication. Our results show that cervid PrPSc can induce the conversion of human PrPC but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, the newly generated human PrPSc exhibits a distinct biochemical pattern that differs from that of any of the currently known forms of human PrPSc. Our results also have profound implications for understanding the mechanisms of the prion species barrier and indicate that the transmission barrier is a dynamic process that depends on the strain and moreover the degree of adaptation of the strain. If our findings are corroborated by infectivity assays, they will imply that CWD prions have the potential to infect humans and that this ability progressively increases with CWD spreading.


Interestingly, when the Western blot profile of this newly generated form of human PrPSc (termed CWD-huPrPSc) was compared with known strains of human prions, it was clear that CWD-huPrPSc exhibited a different pattern (Fig. 4A). The electrophoretic migration of this protein after PK-digestion is similar to the type 1 strain of sCJD, but its glycosylation profile is clearly different, showing a highly predominant diglycosylated form (Fig. 4A and B). This result suggests that CWD hu-PrPSc corresponds to a new human prion strain. Interestingly, a detailed previous study from Gambetti’s group comparing the biochemical characteristics of PrPSc from cervids and humans showed that CWD PrPSc is similar to sCJDMM1 in terms of electrophoretic mobility (6). However, the misfolded protein associated with CWD is predominantly di-glycosylated, whereas PrPSc from type 1 sCJD is mostly monoglycosylated (6). Based on the fact that transmission of BSE prions to humans resulted in a new form of PrPSc very similar to the one in cattle (6;27), these authors predicted that if humans were infected by CWD it is likely that PrPSc would be of type 1 and with a predominance of the diglycosylated isoform (6). Our results agree with that prediction and suggest that the newly generated CWD-huPrPSc acquires the biochemical properties of the cervid infectious material (Fig. 4A and B).


Our results have far-reaching implications for human health, since they indicate that cervid PrPSc can trigger the conversion of human PrPC into PrPSc, suggesting that CWD might be infectious to humans. Interestingly our findings suggest that unstable strains from CWD affected animals might not be a problem for humans, but upon strain stabilization by successive passages in the wild, this disease might become progressively more transmissible to man.

Reference List


please see full text and many thanks to the Professor Soto and the other Authors of this study AND to The Journal Of Biological Chemistry for the free full text !!!

Amyloid Neurodegeneration Neurological Diseases Prions Protein Conformation Prion Diseases

see full text and more here ;


there are now two documented strains of CWD, and science is showing that indeed CWD could transmit to humans via transmission studies ;



Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5

The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.


Prion Transmission from Cervids to Humans is Strain-dependent

Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

Key words: CWD, strain, human transmission

Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.


Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.


Biochemical and Biophysical Characterization of Different CWD Isolates

Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany

Key words: CWD, strains, FT-IR, AFM

Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of disease-associated prion protein PrPTSE. Limited proteolysis with different concentrations of proteinase K and/or after exposure of PrPTSE to different pH-values or concentrations of Guanidinium hydrochloride resulted in distinct isolate-specific digestion patterns. Our CWD isolates were also examined in protein misfolding cyclic amplification studies. This showed different conversion activities for those isolates that had displayed significantly different sensitivities to limited proteolysis by PK in the biochemical experiments described above. We further applied Fourier transform infrared spectroscopy in combination with atomic force microscopy. This confirmed structural differences in the PrPTSE of at least two disinct CWD isolates. The data presented here substantiate and expand previous reports on the existence of different CWD strains.

Saturday, November 12, 2011

Human Prion Disease and Relative Risk Associated with Chronic Wasting Disease

Fri, 22 Sep 2006 09:05:59 –0500

Tuesday, May 31, 2011

Chronic Wasting Disease

DOI: 10.1007/128_2011_159 # Springer-Verlag Berlin Heidelberg 2011

Top Curr Chem (2011) DOI: 10.1007/128_2011_159 # Springer-Verlag Berlin Heidelberg 2011

Chronic Wasting Disease

Sabine Gilch, Nandini Chitoor, Yuzuru Taguchi, Melissa Stuart, Jean E. Jewell, and Hermann M. Schatzl


Chronic wasting disease (CWD) is a prion disease of free-ranging and farmed ungulates (deer, elk, and moose) in North America and South Korea. First described by the late E.S. Williams and colleagues in northern Colorado and southern Wyoming in the 1970s, CWD has increased tremendously both in numerical and geographical distribution, reaching prevalence rates as high as 50% in freeranging and >90% in captive deer herds in certain areas of USA and Canada. CWD is certainly the most contagious prion infection, with significant horizontal transmission of infectious prions by, e.g., urine, feces, and saliva. Dissemination and persistence of infectivity in the environment combined with the appearance in wildliving and migrating animals make CWD presently uncontrollable, and pose extreme challenges to wild-life disease management. Whereas CWD is extremely transmissible among cervids, its trans-species transmission seems to be restricted, although the possible involvement of rodent and carnivore species in environmental transmission has not been fully evaluated. Whether or not CWD has zoonotic potential as had Bovine spongiform encephalopathy (BSE) has yet to be answered. Of note, variant Creutzfeldt–Jakob disease (vCJD) was only detected because clinical presentation and age of patients were significantly different from classical CJD. Along with further understanding of the molecular biology and pathology of CWD, its transmissibility and species restrictions and development of methods for preclinical diagnosis and intervention will be crucial for effective containment of this highly contagious prion disease.


8 Zoonotic Potential Deer hunting is a popular sport in the USA; venison is usually consumed by hunters and their families, and this raises reasonable concerns about the transmissibility of CWD to humans, as exemplified by the zoonotic transmission of BSE. Epidemiological studies have not revealed an increased incidence of CJD in CWD endemic areas. Suspicious case reports about persons having consumed venison and succumbed to neurological disorders turned out to be classical or familial CJD and a causal link to the consumption of contaminated meat could not be proven [109]. In vitro conversion assays were performed to assess the convertibility of human PrPc into PK resistant PrP using CWD derived from elk, mule deer, and white-tailed deer as a template. Only a very low conversion rate could be demonstrated, indicative of a considerable species barrier [110]. In a very recent study employing protein misfolding cyclic amplification (PMCA), a highly sensitive method for in vitro amplification conversion of human PrPc was successful, albeit with the restriction that CWD prions had to be adapted by PMCA or in vivo passage through cervidized tg mice. Passaged CWD template gave rise to a new form of human PrPSc, and its infectivity is currently under investigation. Of note, when field isolates of CWD Chronic Wasting Disease brains were used as a template, no conversion of human PrPc was achieved, which again questions the relevance of the in vitro data [111]. Studies using humanized tg mouse inoculated with CWD furthermore argue against transmissibility to humans since mice did not develop prion disease [112–114]. The best possible animal models to study transmission of animal prion diseases to humans probably are non-human primates. For instance, inoculation of BSE prions into Cynomolgus macaques provided the first hints that BSE might be transmissible to humans [115]. However, oral or i.c. challenge with CWD of macaques did not cause disease [116]. On the other hand, squirrel monkeys (Saimiri sciureus) were susceptible to i.c. inoculation with CWD prions [116, 117], and after oral exposure PrPSc was detectable in brain, spleen, and lymph nodes of 2/15 squirrel monkeys [116]. This shows that CWD can be transmitted to certain non-human primates, although results in Cynomolgus macaques might be of higher relevance since they are evolutionary closer relatives of humans than squirrel monkeys. Overall, there is no compelling evidence that CWD can be transmitted to humans with high efficiency.


Monday, June 27, 2011

Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates


October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,


Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.


Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;

Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH , Lawrence B. Schonberger, MD , Ermias D. Belay, MD

Accepted 15 November 2010. Abstract Full Text PDF References .


The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission.

"These findings indicate that a high percentage of the United States population engages in hunting and/or venison consumption. If CWD continues to spread to more areas across the country, a substantial number of people could potentially be exposed to the infectious agent."

Potential Venison Exposure Among FoodNet Population Survey Respondents, 2006-2007

Ryan A. Maddox1*, Joseph Y. Abrams1, Robert C. Holman1, Lawrence B. Schonberger1, Ermias D. Belay1 Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA *Corresponding author e-mail:

The foodborne transmission of bovine spongiform encephalopathy to humans, resulting in variant Creutzfeldt-Jakob disease, indicates that humans can be susceptible to animal prion diseases. However, it is not known whether foodborne exposure to the agent causing chronic wasting disease (CWD) in cervids can cause human disease. The United States Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for foodborne diseases through an extensive survey administered to respondents in selected states. To describe the frequency of deer and elk hunting and venison consumption, five questions were included in the 2006-2007 FoodNet survey. This survey included 17,372 respondents in ten states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. Of these respondents, 3,220 (18.5%) reported ever hunting deer or elk, with 217 (1.3%) reporting hunting in a CWD-endemic area (northeastern Colorado, southeastern Wyoming, and southwestern Nebraska). Of the 217 CWD-endemic area hunters, 74 (34.1%) were residents of Colorado. Respondents reporting hunting were significantly more likely to be male than female (prevalence ratio: 3.3, 95% confidence interval: 3.1-3.6) and, in general, older respondents were significantly more likely to report hunting than younger respondents. Venison consumption was reported by more than half (67.4%) of the study population, and most venison consumers (94.1%) reported that at least half of their venison came from the wild. However, more than half (59.1%) of the consumers reported eating venison only one to five times in their life or only once or twice a year. These findings indicate that a high percentage of the United States population engages in hunting and/or venison consumption. If CWD continues to spread to more areas across the country, a substantial number of people could potentially be exposed to the infectious agent.

now, let’s see what the authors said about this casual link, personal communications years ago. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ????

“Our conclusion stating that we found no strong evidence of CWD transmission to humans”

From: TSS (


Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"


Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM


Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.

That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

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


Sent: Sunday, September 29, 2002 10:15 AM

To:;; ebb8@CDC.GOV


Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease

2008 1: Vet Res. 2008 Apr 3;39(4):41

A prion disease of cervids: Chronic wasting disease

Sigurdson CJ.


*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,


full text ;

Monday, November 14, 2011

WYOMING Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011

Wednesday, November 16, 2011

Wisconsin Creutzfeldt Jakob Disease, CWD, TSE, PRION REPORTING 2011

Sunday, November 13, 2011


Monday, May 23, 2011 CDC

Assesses Potential Human Exposure to Prion Diseases Travel Warning

Public release date: 23-May-2011

Contact: Francesca Costanzo 215-239-3249 Elsevier Health Sciences

CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association Philadelphia, PA, May 23, 2011 – Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular – bovine spongiform encephalopathy (BSE or "Mad Cow Disease"), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) – were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association.

"While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases," commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta."But it's also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents."

Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak.

CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York.

Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild.

The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents.

The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWD-endemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses.

According to Abrams, "The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health."


The article is "Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet population survey" by Joseph Y. Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger, MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic Association, Volume 111, Issue 6 (June 2011) published by Elsevier.

In an accompanying podcast CDC's Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at

Thursday, December 29, 2011

Aerosols An underestimated vehicle for transmission of prion diseases?

please see more on Aerosols and TSE prion disease here ;

Sunday, July 27, 2008

DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability

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

Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability

Date: Fri, 16 May 2003 11:47:37 -0500

From: "Terry S. Singeltary Sr."


Greetings FDA,

i would kindly like to comment on;

Docket 03D-0186

FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability

Several factors on this apparent voluntary proposal disturbs me greatly, please allow me to point them out;

1. MY first point is the failure of the partial ruminant-to-ruminant feed ban of 8/4/97. this partial and voluntary feed ban of some ruminant materials being fed back to cattle is terribly flawed. without the _total_ and _mandatory_ ban of all ruminant materials being fed back to ruminants including cattle, sheep, goat, deer, elk and mink, chickens, fish (all farmed animals for human/animal consumption), this half ass measure will fail terribly, as in the past decades...

2. WHAT about sub-clinical TSE in deer and elk? with the recent findings of deer fawns being infected with CWD, how many could possibly be sub-clinically infected. until we have a rapid TSE test to assure us that all deer/elk are free of disease (clinical and sub-clinical), we must ban not only documented CWD infected deer/elk, but healthy ones as well. it this is not done, they system will fail...

3. WE must ban not only CNS (SRMs specified risk materials), but ALL tissues. recent new and old findings support infectivity in the rump or ass muscle. wether it be low or high, accumulation will play a crucial role in TSEs.

4. THERE are and have been for some time many TSEs in the USA. TME in mink, Scrapie in Sheep and Goats, and unidentified TSE in USA cattle. all this has been proven, but the TSE in USA cattle has been totally ignored for decades. i will document this data below in my references.

5. UNTIL we ban all ruminant by-products from being fed back to ALL ruminants, until we rapid TSE test (not only deer/elk) but cattle in sufficient numbers to find (1 million rapid TSE test in USA cattle annually for 5 years), any partial measures such as the ones proposed while ignoring sub-clinical TSEs and not rapid TSE testing cattle, not closing down feed mills that continue to violate the FDA's BSE feed regulation (21 CFR 589.2000) and not making freely available those violations, will only continue to spread these TSE mad cow agents in the USA. I am curious what we will call a phenotype in a species that is mixed with who knows how many strains of scrapie, who knows what strain or how many strains of TSE in USA cattle, and the CWD in deer and elk (no telling how many strains there), but all of this has been rendered for animal feeds in the USA for decades. it will get interesting once someone starts looking in all species, including humans here in the USA, but this has yet to happen...

6. IT is paramount that CJD be made reportable in every state (especially ''sporadic'' cjd), and that a CJD Questionnaire must be issued to every family of a victim of TSE. only checking death certificates will not be sufficient. this has been proven as well (see below HISTORY OF CJD -- CJD QUESTIONNAIRE)

7. WE must learn from our past mistakes, not continue to make the same mistakes...


Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus ) Christina J. Sigurdson1, Elizabeth S. Williams2, Michael W. Miller3, Terry R. Spraker1,4, Katherine I. O'Rourke5 and Edward A. Hoover1

Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523- 1671, USA1 Department of Veterinary Sciences, University of Wyoming, 1174 Snowy Range Road, University of Wyoming, Laramie, WY 82070, USA 2 Colorado Division of Wildlife, Wildlife Research Center, 317 West Prospect Road, Fort Collins, CO 80526-2097, USA3 Colorado State University Veterinary Diagnostic Laboratory, 300 West Drake Road, Fort Collins, CO 80523-1671, USA4 Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, 337 Bustad Hall, Washington State University, Pullman, WA 99164-7030, USA5

Author for correspondence: Edward Hoover.Fax +1 970 491 0523. e-mail

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrP res, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.


These results indicate that mule deer fawns develop detectable PrP res after oral exposure to an inoculum containing CWD prions. In the earliest post-exposure period, CWD PrPres was traced to the lymphoid tissues draining the oral and intestinal mucosa (i.e. the retropharyngeal lymph nodes, tonsil, ileal Peyer's patches and ileocaecal lymph nodes), which probably received the highest initial exposure to the inoculum. Hadlow et al. (1982) demonstrated scrapie agent in the tonsil, retropharyngeal and mesenteric lymph nodes, ileum and spleen in a 10-month-old naturally infected lamb by mouse bioassay. Eight of nine sheep had infectivity in the retropharyngeal lymph node. He concluded that the tissue distribution suggested primary infection via the gastrointestinal tract. The tissue distribution of PrPres in the early stages of infection in the fawns is strikingly similar to that seen in naturally infected sheep with scrapie. These findings support oral exposure as a natural route of CWD infection in deer and support oral inoculation as a reasonable exposure route for experimental studies of CWD.


snip...see full text ;

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

Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability

Date: Fri, 16 May 2003 11:47:37 -0500

From: "Terry S. Singeltary Sr."


Greetings FDA,

i would kindly like to comment on;

Docket 03D-0186

FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability


Experimental oral transmission of chronic wasting disease to red deer

(Cervus elaphus elaphus): Early detection and late stage distribution

of protease-resistant prion protein

Aru Balachandran, Noel P. Harrington, James Algire, Andrei Soutyrine, Terry R. Spraker,

Martin Jeffrey, Lorenzo González, Katherine I. O'Rourke

Abstract - Chronic wasting disease (CWD), an important emerging prion disease of cervids, is readily transmitted by intracerebral or oral inoculation from deer-to-deer and elk-to-elk, suggesting the latter is a natural route of exposure. Studies of host range susceptibility to oral infection, particularly of those species found in habitats where CWD currently exists are imperative. This report describes the experimental transmission of CWD to red deer following oral inoculation with infectious CWD material of elk origin. At 18 to 20 months post-inoculation, mild to moderate neurological signs and weight loss were observed and animals were euthanized and tested using 3 conventional immunological assays. The data indicate that red deer are susceptible to oral challenge and that tissues currently used for CWD diagnosis show strong abnormal prion (PrPCWD) accumulation. Widespread peripheral PrPCWD deposition involves lymphoreticular tissues, endocrine tissues, and cardiac muscle and suggests a potential source of prion infectivity, a means of horizontal transmission and carrier state.


There is a strong correlation between the presence of PrPTSE and infectivity in prion diseases. Although the epidemiologic evidence strongly suggests that CWD is not transmissible to humans, this study and others suggest caution in this regard. The finding of PrPCWD in various organs, albeit in clinical CWD, suggests that humans who consume or handle meat from CWD-infected red deer may be at risk of exposure to CWD prions. This study found that red deer tissues other than nervous and lymphoid tissue can support CWD prion replication and accumulation. As a result, the consumption or handling of meat from CWD-infected red deer will put humans at risk of exposure to CWD prions. In spite of a well-documented species barrier, a cautious approach would involve preventing such tissues from entering the animal and human food chains. Future studies will require sensitive and quantitative techniques such as bioassays in transgenic mice that assess tissue infectivity and quantitative immunoassays adapted to PrPCWD detection in peripheral tissues.


The exact mode of transmission of CWD in nature remains unclear but is believed to involve direct animal-to-animal contact or environmental contamination. As TSE agents are extremely resistant in the environment (39), oral exposure is the most plausible pathway by which the CWD prion may be introduced to deer in nature and represents a significant obstacle to eradication of CWD from either farmed or free-ranging cervid populations. The distribution of PrPCWD in gut-associated lymphoid tissues, salivary glands, and nasal mucosa in the red deer of this study suggests potential routes of PrPCWD shedding into the environment via fluids such as saliva or feces. However, this study did not identify the point at which an animal may become infectious during the course of infection. An improved understanding of the mechanisms of shedding and transmission will be important in the future management of CWD.


In summary, this study demonstrates the potential for oral transmission of CWD to red deer and describes the pattern of PrPCWD accumulation for this species. The current surveillance testing regime for cervids would be expected to identify CWD-infected red deer should it occur in North America. These results confirm the usefulness of rapid tests such as ELISA but with generally slightly lower sensitivity when compared with IHC when testing tissues with patchy or sporadic PrPCWD deposition. The finding of PrPCWD in several extraneural tissues including cardiac muscle and the endocrine system suggests that further investigation and monitoring of the potential transmissibility to other species including humans is warranted.


(Traduit par Isabelle Vallières)

Can Vet J 2010;51:169-178

Ottawa Laboratory - Fallowfield, Canadian Food Inspection Agency, Ottawa, Ontario (Balachandran, Harrington, Algire,

Soutyrine); Veterinary Diagnostic Laboratory, Colorado State University, Fort Collins, Colorado, USA (Spraker); Veterinary

Laboratory Agency, Department for the Environment, Food & Rural Affairs, Lasswade, Midlothian, Scotland, United Kingdom

(Jeffrey, González); Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman,

Washington, USA (O'Rourke).

Address all correspondence to Dr. Aru Balachandran; e-mail:

Wednesday, January 18, 2012


February 1, 2012

Friday, January 6, 2012

OIE 2012 Training Manual on Wildlife Diseases and Surveillance and TSE Prion disease

Tuesday, January 17, 2012

Annual report of the Scientific Network on BSE-TSE EFSA-Q-2011-01110 Issued: 20 December 2011

Monday, June 27, 2011

Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

2011 Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

Tuesday, November 08, 2011

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008

Vol. 37, No. 3-4, 2011 Original Paper Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis

full text with source references ;

Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD


CJD Deaths Reported by CJDSS1, 1994-20112 As of January 31, 2011

3. Final classification of 49 cases from 2009, 2010, 2011 is pending.


USA 2011


National Prion Disease Pathology Surveillance Center

Cases Examined1

(November 1, 2010)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 51 33 28 5 0 0

1997 114 68 59 9 0 0

1998 87 51 43 7 1 0

1999 121 73 65 8 0 0

2000 146 103 89 14 0 0

2001 209 119 109 10 0 0

2002 248 149 125 22 2 0

2003 274 176 137 39 0 0

2004 325 186 164 21 0 13

2005 344 194 157 36 1 0

2006 383 197 166 29 0 24

2007 377 214 187 27 0 0

2008 394 231 205 25 0 0

2009 425 258 215 43 0 0

2010 333 213 158 33 0 0

TOTAL 38315 22656 1907 328 4 3

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

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

3 Disease acquired in the United Kingdom;

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

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

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

Please notice where sporadic CJD cases in 1996 went from 28 cases, to 215 cases in 2009, the highest recorded year to date. sporadic CJD is on a steady rise, and has been since 1996.

I also urge you to again notice these disturbing factors in lines 5 and 6 ;

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

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.


Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

THE steady rise of sporadic CJD cases in Canada AND USA, with many unusual cases of ''PENDING CLASSIFICATIONS" which have been pending now FOR 3 YEARS. HOW long can this cover-up continue $$$

The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.


Saturday, March 5, 2011



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