Chronic wasting disease prions are not transmissible to transgenic mice over-expressing human prion protein
O.K., SO, what does that really tell us ?
WHY is it that the 'GOLD CARD' for determining whether or not a specific Transmissible Spongiform Encephalopathy, in a specific species, will or will not transmit to humans, is based solely on a $ 20,000 dollar tg white mouse that has been scientifically enhanced to be genetically related to whatever species ?
SO what does this really tell us ?
IS it absolute evidence that transmission will never take place in that particular species, from that particular strain of TSE ?
I don't think it is.
IN this study 'Chronic wasting disease prions are not transmissible to transgenic mice over-expressing human prion protein' it is presumed to tell us in the following study, that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. Insinuating that there is a greater species barrier between man and deer, than there was with c-BSE (only).
bbbut, just how robust is the BSE prion transmission barrier to humans, IF, you use all the science to date, and not omit the crucial scientific studies, like the 3 studies explaining that BSE can show up in humans as nvCJD or sporadic CJD ?
HERE we find three studies that show that the BSE agent can propagate as nvCJD prions OR sporadic CJD prions.
WHY does this science not matter $
Published online ahead of print on 7 July 2010 as doi:10.1099/vir.0.024380-0 J Gen Virol (2010), DOI 10.1099/vir.0.024380-0 © 2010 Society for General Microbiology
Chronic wasting disease prions are not transmissible to transgenic mice over-expressing human prion protein
Malin Sandberg1, Huda Al-Doujaily1, Christina Sigurdson2, Markus Glatzel3, Catherine O'Malley1, Caroline Powell1, Emmanuel A Asante1, Jacqueline M Linehan1, Sebastian Brandner1, Jonathan D. F. Wadsworth1,4 and John Collinge1
1 UCL Institute of Neurology; 2 University of California, San Diego; 3 University Medical Center Hamburg-Eppendorf
4 E-mail: firstname.lastname@example.org
Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk, and moose. CWD-infected cervids have been reported in fourteen US states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice over-expressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilised in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains; further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterised.
Received 9 June 2010; accepted 6 July 2010.
Friday, May 14, 2010
Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure
Published Online May 13, 2010 Science DOI: 10.1126/science.1187107 Science Express Index
Thursday, June 03, 2010
Prion Strain Mutation and Selection
Journal of Virology, May 2007, p. 4533-4539, Vol. 81, No. 9 0022-538X/07/$08.00+0 doi:10.1128/JVI.02762-06 Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Resistance to Chronic Wasting Disease in Transgenic Mice Expressing a Naturally Occurring Allelic Variant of Deer Prion Protein
Kimberly Meade-White,1 Brent Race,1 Matthew Trifilo,2 Alex Bossers,3 Cynthia Favara,1 Rachel Lacasse,1 Michael Miller,4 Elizabeth Williams,5 Michael Oldstone,2 Richard Race,1 and Bruce Chesebro1* Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, Hamilton, Montana 59840,1 Viral-Immunobiology Laboratory, Departments of Molecular and Integrative Neurosciences and Infectology, Scripps Research Institute, La Jolla, California,2 Central Institute for Animal Disease Control, Department of Bacteriology and TSEs, P.O. Box 2004, 8203 AA Lelystad, The Netherlands,3 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, Colorado 80526-2097,4 Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming 820705
Received 14 December 2006/ Accepted 14 February 2007
Prion protein (PrP) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. In transgenic mice, expression of prion protein (PrP) from another species often confers susceptibility to prion disease from that donor species. For example, expression of deer or elk PrP in transgenic mice has induced susceptibility to chronic wasting disease (CWD), the prion disease of cervids. In the current experiments, transgenic mice expressing two naturally occurring allelic variants of deer PrP with either glycine (G) or serine (S) at residue 96 were found to differ in susceptibility to CWD infection. G96 mice were highly susceptible to infection, and disease appeared starting as early as 160 days postinfection. In contrast, S96 mice showed no evidence of disease or generation of disease-associated protease-resistant PrP (PrPres) over a 600-day period. At the time of clinical disease, G96 mice showed typical vacuolar pathology and deposition of PrPres in many brain regions, and in some individuals, extensive neuronal loss and apoptosis were noted in the hippocampus and cerebellum. Extraneural accumulation of PrPres was also noted in spleen and intestinal tissue of clinically ill G96 mice. These results demonstrate the importance of deer PrP polymorphisms in susceptibility to CWD infection. Furthermore, this deer PrP transgenic model is the first to demonstrate extraneural accumulation of PrPres in spleen and intestinal tissue and thus may prove useful in studies of CWD pathogenesis and transmission by oral or other natural routes of infection.
Using sensitive biological infectivity assays, the CWD infectious agent was recently found in saliva and blood (26) and skeletal muscle (2) of CWD-infected deer. However, by immunoblotting, which is less sensitive, we failed to detect PrPres in skeletal muscle of CWD-infected Tg mice (Fig. 6). We also failed to detect PrPres in heart tissue of these mice, similar to results with CWD-infected mule deer heart but differing from results with elk heart and white-tailed deer heart (17). Therefore, there are likely to be species differences among cervids and Tg mice which account for these discrepancies. None of the four previous studies of cervid PrP transgenic mice reported on studies of extraneural PrPres. One paper stated that no PrPsen was found in non-brain tissues and ascribed this finding to the use of a modified promoter (7). The finding of PrPres in spleen and intestinal tissue in our line 33 Tg mice indicated that there was sufficient extraneural PrPsen in these tissues to allow PrPres generation. Thus, these mice should prove very useful in studies of peripheral CWD pathogenesis by oral or other possible natural routes of infection.
The most striking discovery from the present studies was the finding that two deer PrP alleles differed in the ability to confer sensitivity to CWD. Previous transgenic mouse studies have analyzed only G96 deer or elk PrP alleles, which were found to confer susceptibility to deer and elk CWD in all studies so far. In contrast, this is the first study testing the S96 deer PrP allele in transgenic mice, and it was surprising to find that this allele failed to confer susceptibility to any of the four CWD pools tested. Of course, it is possible that these mice will develop disease or PrPres at a later time point past the present 600-day observation period.
Our results are similar but not identical to results of naturally occurring CWD in white-tailed deer where S96 homozygous deer appear to be partially resistant to CWD. Nevertheless, at least three such deer have been documented to develop CWD as diagnosed by immunohistochemical PrPres detection in the brain stem (obex) (19, 30).
It is presently unclear exactly how the allelic variation at PrP residue 96 might influence prion disease susceptibility. At a molecular level, deer and elk PrP residue 96 is located in the flexible disordered tail of the N-terminal domain near the globular domain (15). In transgenic mice, expression of PrP constructs with various deletions indicated that the region around residue 96 was important for scrapie susceptibility (13, 34, 37). In addition, molecular PrP conversion studies using N-terminus-deleted PrP showed that the region between residues 94 and 106 influenced the type and amount of PrP conversion (24). However, in other cell-free conversion studies, G96 and S96 deer PrP were found to convert equally well when incubated with CWD from several cervid sources (33). Therefore, in CWD-infected deer, the influence of differing amino acid residues at position 96 probably does not act by alteration of the PrP conversion process.
An alternative explanation of the resistance of S96 PrP Tg mice to CWD infection is that deer expressing G96 or S96 PrP might be preferentially infected by different CWD strains. This selectivity for different strains or isolates has been found in sheep scrapie. Sheep carrying the so-called PrP VRQ allele are more susceptible to VRQ-derived isolates, like SSBP/1, but are more resistant to non-VRQ-derived isolates, like CH1641. In contrast, PrP ARQ carriers or breeds usually resist SSBP/1 but are highly susceptible to CH1641 (14, 16). This selectivity has been further supported by the underlying molecular conversion process in which VRQ and ARQ prion proteins are more rapidly converted by their homologous VRQ or ARQ PrPres molecules (4).
Although no distinct CWD strains have been identified so far, a recent study of CWD infection in cervid PrP Tg mice described a mule deer CWD pool which differed from other pools by its inability to induce vacuolation in the anterior cerebral cortex and olfactory bulb (22). Such regional pathology differences might be due to the existence of a variant CWD strain.
In our experiments, the CWD pools, Deer 2, Deer 3, and Elk, are likely to have come from G96 animals because both mule deer and elk appear to be homozygous for G96 PrP (6, 29). In uninfected white-tailed deer, the S96/S96 homozygous genotype exists naturally at a low frequency (5 to 9%), but its incidence is even lower (0.3 to 3%) in CWD-infected animals (19, 30). Therefore, homozygous S96 PrP deer may not be represented in our Deer 1 pool of CWD-infected white-tailed deer. In future experiments, CWD agent derived from homozygous S96 PrP white-tailed deer will have to be tested in our S96 deer PrP Tg mice to search for a unique CWD strain.
MULE DEER transmission of CWD were by intracerebral inoculation and compared with natural cases
first passage (by this route) [please note that 'first passage (by this route), was marked with a single line through the middle. ...TSS]
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 inoculm (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in all of these species with the shortest incubation period in the ferret.
Mouse and hamster transmissions were attempted at Wyoming State Diagnostic Laboratory, Laramie and at CSU Fort Collins but were unsuccessful. ...
please see ;
Perceptions of unconventional slow virus diseases of animals in the USA
Sunday, April 12, 2009
CWD UPDATE Infection Studies in Two Species of Non-Human Primates and one Environmental reservoir infectivity study and evidence of two strains
CWD Infection Studies in Two Species of Non-Human Primates
Bruce Chesebro Laboratory of Persistent Virus Diseases, Rocky Mountain Laboratories, Hamilton, Montana USA 59840.
CWD is a TSE/prion disease present in wild and domestic cervid populations of North America. CWD from cervids might possibly spread to humans who hunt and eat these species and to domestic animals such as cattle, sheep or horses sharing the same habitat. Therefore, it is important to understand the potential for spread of CWD to other species. Laboratory experiments have shown that CWD does not cause disease in transgenic mice expressing human PrP, suggesting that humans and other primates might be resistant to this infection. However, earlier data from the laboratory of Richard Marsh found that squirrel monkeys could be infected by intracerebral CWD inoculation. We recently followed up this work extending it to studies of two primate species, squirrel monkeys and Cynomolgus macaques. We also compared intracerebral and oral routes of infection. To search for possible CWD variant strains we analyzed 8 different CWD pools obtained from wild or domestic elk, mule deer and white-tailed deer. The results of these experiments will be presented.
Tuesday, August 04, 2009
Susceptibilities of Nonhuman Primates to Chronic Wasting Disease
let's compare PRNP differences from this animal, Macaca fascicularis, to human, elk and deer.
what this means is human, deer, and elk have serine s and asparagine n and arginine at these positions whereas the macaque seq -- at least the seq deposited at GenBank -- has tryptophan, proline and lysine at these positions.
at positions where human, deer, and elk agree but macaque disagrees, the species barrier deer/elk to human cannot be tested with macaque.
see below if everything lines up alright ?
note the region S..N.......N and later R where this monkey is inappropriate model for testing species barrier cervid to human.
Transmission of Elk and Deer Prions to Transgenic Mice
Gu¨ltekin Tamgu¨ney,1 Kurt Giles,1,2 Essia Bouzamondo-Bernstein,3 Patrick J. Bosque,1,2‡ Michael W. Miller,4 Jiri Safar,1,2 Stephen J. DeArmond,1,3 and Stanley B. Prusiner1,2,5* Institute for Neurodegenerative Diseases,1 and Departments of Neurology,2 Pathology,3 and Biochemistry and Biophysics,5 University of California, San Francisco, California, and Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, Colorado4
Received 13 January 2006/Accepted 21 June 2006
Emerg Infect Dis. 2008 December; 14(12): 1898–1901. doi: 10.3201/eid1412.080941. PMCID: PMC2634647
Transmission of Atypical Bovine Prions to Mice Transgenic for Human Prion Protein
Vincent Béringue, Laëtitia Herzog, Fabienne Reine, Annick Le Dur, Cristina Casalone, Jean-Luc Vilotte, and Hubert Laude Institut National de la Recherche Agronomique, Jouy-en-Josas, France (V. Béringue, L. Herzog, F. Reine, A. Le Dur, J.-L. Vilotte, H. Laude) Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Turin, Italy (C. Casalone) Corresponding author. Address for correspondence: Vincent Béringue, Institut National de la Recherche Agronomique, UR892, Virologie Immunologie Moléculaires, F-78350 Jouy-en-Josas, France; email: email@example.com This article has been cited by other articles in PMC. Abstract To assess risk for cattle-to-human transmission of prions that cause uncommon forms of bovine spongiform encephalopathy (BSE), we inoculated mice expressing human PrP Met129 with field isolates. Unlike classical BSE agent, L-type prions appeared to propagate in these mice with no obvious transmission barrier. H-type prions failed to infect the mice.
Keywords: prions, BSE, PrP, strains, transgenic mice, dispatch
The epizootic of bovine spongiform encephalopathy (BSE) is under control in European countries >20 years after the first cases were diagnosed in the United Kingdom. Thus far, BSE is the only animal prion disease known to have been transmitted to humans, leading to a variant form of Creutzfeldt-Jakob disease (vCJD) (1). The large-scale testing of livestock nervous tissues for the presence of protease-resistant prion protein (PrPres) has enabled assessment of BSE prevalence and exclusion of BSE-infected animals from human food (2). This active surveillance has led to the recognition of 2 variant PrPres molecular signatures, termed H-type and L-type BSE. They differ from that of classical BSE by having protease-resistant fragments of a higher (H) or a slightly lower (L) molecular mass, respectively, and different patterns of glycosylation (3–5). Both types have been detected worldwide as rare cases in older animals, at a low prevalence consistent with the possibility of sporadic forms of prion diseases in cattle (6). Their experimental transmission to mice transgenic for bovine PrP demonstrated the infectious nature of such cases and the existence of distinct prion strains in cattle (5,7–9). Like the classical BSE agent, H- and L-type prions can propagate in heterologous species (7–11). Thus, both agents are transmissible to transgenic mice expressing ovine PrP (VRQ allele). Although H-type molecular properties are conserved on these mice (9), L-type prions acquire molecular and neuropathologic phenotypic traits undistinguishable from BSE or BSE-related agents that have followed the same transmission history (7). Similar findings have been reported in wild-type mice (8). An understanding of the transmission properties of these newly recognized prions when confronted with the human PrP sequence is needed. In a previous study, we measured kinetics of PrPres deposition in the brain to show that L-type prions replicate faster than BSE prions in experimentally inoculated mice that express human PrP (7). In a similar mouse model, the L-type agent (alternatively named BASE) was also shown to produce overt disease with an attack rate of ˜30% (12). However, no strict comparison with BSE agent has been attempted. As regards the H-type agent, its potential virulence for mice that express human PrP Met129 remains to be assessed. We now report comparative transmission data for these atypical and classical BSE prions.
We found that atypical L-type bovine prions can propagate in human PrP transgenic mice with no significant transmission barrier. Lack of a barrier is supported by the 100% attack rate, the absence of reduction of incubation time on secondary passage, and the conservation of PrPres electrophoretic profile. In comparison, transmission of classical BSE agent to the same mice showed a substantial barrier. Indeed, 3 passages were necessary to reach a degree of virulence comparable to that of vCJD agent in these mice (13), which likely reflects progressive adaptation of the agent to its new host. At variance with the successful transmission of classical BSE and L-type agents, H-type agent failed to infect tg650 mice. These mice overexpress human PrP and were inoculated intracranially with a low dilution inoculum (10% homogenate). Therefore, this result supports the view that the transmission barrier of BSE-H from cattle to humans might be quite robust. It also illustrates the primacy of the strain over PrP sequence matching for cross-species transmission of prions (15). Extrapolation of our data raises the theoretical possibility that the zoonotic risk associated with BSE-L prions might be higher than that associated with classical BSE, at least for humans carrying the Met129 PrP allele. This information underlines the need for more intensive investigations, in particular regarding the tissue tropism of this agent. Its ability to colonize lymphoid tissues is a potential, key factor for a successful transmission by peripheral route. This issue is currently being explored in the tg650 mice. Although recent data in humanized mice suggested that BSE-L agent is likely to be lymphotropic (12), preliminary observations in our model suggested that its ability to colonize such tissues is comparatively much lower than that of classical BSE agent.
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein
Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth, and John Collinge1 MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1Corresponding author e-mail: firstname.lastname@example.orgReceived August 1, 2002; Revised September 24, 2002; Accepted October 17, 2002. This article has been cited by other articles in PMC. Other Sections?
Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
Keywords: BSE/Creutzfeldt–Jakob disease/prion/transgenic
Originally published in Science Express on 11 November 2004 Science 3 December 2004: Vol. 306. no. 5702, pp. 1793 - 1796 DOI: 10.1126/science.1103932
Reports Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype Jonathan D. F. Wadsworth, Emmanuel A. Asante, Melanie Desbruslais, Jacqueline M. Linehan, Susan Joiner, Ian Gowland, Julie Welch, Lisa Stone, Sarah E. Lloyd, Andrew F. Hill,* Sebastian Brandner, John Collinge
Variant Creutzfeldt-Jakob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)–like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.
Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
* Present address: Department of Biochemistry and Molecular Biology and Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.
To whom correspondence should be addressed. E-mail: email@example.com
Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD
The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype.
Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels.
Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathogical phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission.
Discussion Top In this study we used tg650 mice, a newly developed transgenic line expressing human PrPC, to investigate some aspects of the pathogenesis of vCJD infection. As main findings, we demonstrate that prion strain divergence can occur upon transmission of human, primary vCJD to such mice, and that peripheral challenge leads to an asymptomatic, life-long infection of the lymphoid compartment. A feature of tg650 mice is that following primary intracerebral vCJD challenge they developed a neurological disease with typically 100% attack rate, unlike for previously established PrP129Met, including overexpressing lines , . The mean survival time – typically around 500 days in homozygous mice - did not change notably on subpassaging, implying that vCJD agent might clinically infect the tg650 mice with little or no transmission barrier. This discrepant result may reflect the use of different constructs and genetic backgrounds (Text S1), and the transgene expression levels, although the latter does not seem to greatly differ as far as the tg650+/- and tg45 mice  are concerned.
A surprising result of these studies is the alternate pattern of disease that was induced by one of the inoculated vCJD cases, a WHO reference case here designated vCJD no. 4. Indeed, while vCJD strain features were faithfully propagated in the majority of tg650 mice, almost half of the vCJD 4-inoculated mice were found to propagate a prion replicating faster than vCJD agent, and exhibiting sCJD-like PrPres and neuropathological features. Although strain divergence upon transmission of BSE/vCJD agent to mice was reported to occur in earlier studies , , it was unprecedented within a context of homotypic transmission, i.e. full matching between the donor and receiver PrP sequences. To address the issue of a possible contamination, we performed independent transmission experiments, involving separate inoculum batches of the incriminated case, which all produced consistent results. Therefore, we consider the data inconsistent with contamination of the VCJD no. 4 material by a sCJD infectious source within our laboratory. An alternate possibility, i.e. a cross-contamination of the source material, was judged highly improbable owing to the procedures applied during the collect of the specimen and the preparation of the homogenates ( and P. Minor, personal communication). On the other hand, our observation intriguingly parallels the phenotypic disjunction observed upon transmission of BSE agent to human PrP129Met mice (tg35 line ). Together, these findings lend support to the hypothesis that a minor strain component might be created upon cattle-to-human transmission of BSE agent and could emerge upon subsequent human-to–human transmission. It is also worth mentioning that, while the probability to detect such a variant through mouse bioassay would be expected to depend on the amount - and possibly the regions - of brain tissue taken to establish the source material, the vCJD-4 homogenate was prepared using a larger amount of tissue from the same brain than for the other homogenates analyzed in this study (i.e. 100 mg instead of 1 mg of frontal cortex ).
The above finding has obvious implications in terms of public health as it raises the concern that some humans iatrogenically infected by vCJD agent may develop a clinical disease that would not be recognized as of vCJD origin , . Strikingly however, all vCJD-4-inoculated mice, notwithstanding the strain phenotype divergence propagated bona fide vCJD agent in their spleen, based on the PrPres pattern and the disease phenotype produced by secondary transmission to tg650 mice. This result is of direct relevance to the diagnosis of variant and sporadic CJD. Indeed, looking for peripheral lymphoreticular deposition of abnormal PrP on cases diagnosed as sporadic CJD might reveal a vCJD infection resulting from human-to-human, or cattle-to-human transmission. In this respect, it would be of interest to examine whether BSE-inoculated tg35 mice showing discordant PrPres signatures , or vCJD-challenged PrP129Val transgenic mice producing ‘type 5’ prion in their brain  do accumulate PrPvCJD in their spleens. In any case, our findings provide clear evidence that, as a consequence of strain-related tropism disparities, the same mouse can propagate different prions in different tissues following a single infection event.
Another salient finding emerging from this study was the remarkable ability of vCJD agent to establish asymptomatic infection despite sustained, life-long propagation in extraneural tissues. When challenged peripherally, tg650 mice remained asymptomatic over the whole observation period, and did not accumulate PrPres at detectable levels in their brain before 750 days pi, near the life end-stage. In the spleen of these mice however, PrPres accumulation reached its maximum at an early stage of infection, and remained at stable and substantial levels until death. Plateauing of prion infection in the spleen is consistent with earlier observations, and has been suggested to reflect an exhaustion of target cells (for review ) Importantly, the spleen tissue was highly infectious as it killed 100% of intracerebrally challenged mice within the minimal mean incubation time (~500 days). Altogether these data support the view that the sustained multiplication of the vCJD prion in lymphoid tissues was not accompanied by an efficient neuroinvasion in tg650 mice. Such an extremely delayed neuroinvasion appears to be rare in TSE rodent models, and to our knowledge was only reported for the mouse-adapted strain 87V on IM mice infected intraperitoneally with diluted inoculum . Clearly, while early accumulation of prions in lymphoid tissues may be essential for efficient neuroinvasion , efficient lymphoinvasion does not inevitably lead to rapid neuroinvasion. This finding strengthens the notion that humans infected by vCJD from a human source – including individuals of the MM genotype – might remain clinically asymptomatic for a very prolonged period of time while harboring relatively high levels of prion infectivity in their lymphoid tissues from an early stage of infection on, thereby amplifying the risk of iatrogenic transmission. It also supports the view that the large-scale survey of lymphoreticular tissues  may lead to a reliable assessment of the actual prevalence of vCJD infection in the UK population.
Finally, the human PrP transgenic model described in this study may help to further our understanding of peripheral vCJD pathogenesis, for instance in trying to identify factors that might enhance neuroinvasion efficiency, or modulate the shedding of prion infectivity from the lymphoreticular to the blood compartment. Moreover, preliminary results indicate that the search for abnormal PrP in the spleen of such mice culled at time intervals post infection ,  could allow the detection of low levels of vCJD infectivity within a reasonably short time scale.
Citation: Béringue V, Le Dur A, Tixador P, Reine F, Lepourry L, et al. (2008) Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD. PLoS ONE 3(1): e1419. doi:10.1371/journal.pone.0001419
Academic Editor: Adam Ratner, Columbia University, United States of America
Received: September 20, 2007; Accepted: December 17, 2007; Published: January 9, 2008
Copyright: © 2008 Beringue et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by INRA, Institut de Veille Sanitaire (InVS) and the Ministry of Research, France. The sponsors of this study had no role in study conduct, collection analysis, interpretation of the data, writing of the report or approval of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* To whom correspondence should be addressed. E-mail: firstname.lastname@example.org (HL); email@example.com (VB)
14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)
18.173 page 189
Experimental Challenge of Cattle with H-type and L-type Atypical BSE
A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H. Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany, 2Health Canada, Bureau of Microbial Hazards, Health Products & Food Branch, Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy Secretariat, Ottawa, Canada
Background: After the detection of two novel BSE forms designated H-type and L-type atypical BSE the question of the pathogenesis and the agent distribution of these two types in cattle was fully open. From initial studies of the brain pathology, it was already known that the anatomical distribution of L-type BSE differs from that of the classical type where the obex region in the brainstem always displays the highest PrPSc concentrations. In contrast in L-type BSE cases, the thalamus and frontal cortex regions showed the highest levels of the pathological prion protein, while the obex region was only weakly involved.
Methods:We performed intracranial inoculations of cattle (five and six per group) using 10%brainstemhomogenates of the two German H- and L-type atypical BSE isolates. The animals were inoculated under narcosis and then kept in a free-ranging stable under appropriate biosafety conditions.At least one animal per group was killed and sectioned in the preclinical stage and the remaining animals were kept until they developed clinical symptoms. The animals were examined for behavioural changes every four weeks throughout the experiment following a protocol that had been established during earlier BSE pathogenesis studies with classical BSE.
Results and Discussion: All animals of both groups developed clinical symptoms and had to be euthanized within 16 months. The clinical picture differed from that of classical BSE, as the earliest signs of illness were loss of body weight and depression. However, the animals later developed hind limb ataxia and hyperesthesia predominantly and the head. Analysis of brain samples from these animals confirmed the BSE infection and the atypical Western blot profile was maintained in all animals. Samples from these animals are now being examined in order to be able to describe the pathogenesis and agent distribution for these novel BSE types. Conclusions: A pilot study using a commercially avaialble BSE rapid test ELISA revealed an essential restriction of PrPSc to the central nervous system for both atypical BSE forms. A much more detailed analysis for PrPSc and infectivity is still ongoing.
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
Bacliff, TX, USA
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
12 years independent research of available data
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
International Society for Infectious Diseases Web: http://www.isid.org
PLEASE NOTE, IN 2009 IT WAS FOUND THAT The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype. ...TSS
P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA
Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C. The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
I ask Professor Kong Thursday, December 04, 2008 3:37 PM ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''
Professor Kong reply ;
''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete.
Thanks for your interest.''
Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
DOI: 10.3201/eid1412.080941 Suggested citation for this article: Béringue V, Herzog L, Reine F, Le Dur A, Casalone C, Vilotte J-L, et al.
Transmission of atypical bovine prions to mice transgenic for human prion protein.
Emerg Infect Dis. 2008 Dec; [Epub ahead of print] Transmission of Atypical Bovine Prions to Mice Transgenic for Human Prion Protein Vincent Béringue, Laëtitia Herzog, Fabienne Reine, Annick Le Dur, Cristina Casalone, Jean-Luc Vilotte, and Hubert Laude
Author affiliations: Institut National de la Recherche Agronomique, Jouy-en-Josas, France (V. Béringue, L. Herzog, F. Reine, A. Le Dur, H. Laude, J.-L. Vilotte); and Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Turin, Italy (C. Casalone) To assess risk for cattle-to-human transmission of prions that cause uncommon forms of bovine spongiform encephalopathy (BSE), we inoculated mice expressing human PrP Met129 with field isolates. Unlike classical BSE agent, L-type prions appeared to propagate in these mice with no obvious transmission barrier. H-type prions failed to infect the mice. The epizootic of bovine spongiform encephalopathy (BSE) is under control in European countries >20 years after the first cases were diagnosed in the United Kingdom. Thus far, BSE is the only animal prion disease known to have been transmitted to humans, leading to a variant form of Creutzfeldt-Jakob disease (vCJD) (1). The large-scale testing of livestock nervous tissues for the presence of protease-resistant prion protein (PrPres) has enabled assessment of BSE prevalence and exclusion of BSE-infected animals from human food (2). This active surveillance has led to the recognition of 2 variant PrPres molecular signatures, termed H-type and L-type BSE. They differ from that of classical BSE by having protease-resistant fragments of a higher (H) or a slightly lower (L) molecular mass, respectively, and different patterns of glycosylation (3–5). Both types have been detected worldwide as rare cases in older animals, at a low prevalence consistent with the possibility of sporadic forms of prion diseases in cattle (6).
Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK–resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY TO MICROCEBUS MURINUS, A NON-HUMAN PRIMATE. DEVELOPMENT OF CLINICAL SYMPTOMS AND TISSUE DISTRIBUTION OF PRPRES
Nadine Mestre-Frances1, Anne-Gaelle Biacabe2, Sylvie Rouland1, Thierry Baron2, Jean-Michel Verdier1, 1INSERM U710, Montpellier, France; 2AFSSA, Lyon, France. Contact e-mail: nfrances@univmontp2. fr
Background: Atypical BSE cases have been observed in Europe, Japan and North America. They differ in their PrPres profiles from those found in classical BSE. These atypical cases fall into 2 types, depending on the molecular mass of the unglycosylated PrPres band observed by Western blot: the L-type (lower molecular mass than the typical BSE cases) and H-type (higher molecular mass than the typical BSE cases).
Methods: Height animals (4 males and 4 females) were intracerebrally inoculated with 50 l of a 10% brain homogenates of atypical (L and H-type) French BSE cases.
Results: Only one of the four lemurs challenge with H-type BSE died without clinical signs after 19 months post inoculation (mpi), the 4 animals inoculated with L-type BSE died at 19 mpi (2 males) and 22 mpi (2 females). Three months before their sacrifice, they developed blindness, tremor, abnormal posture, incoordinated movements, balance loss. Symptoms get worse according to the disease progression, until severe ataxia. The brain tissue were biochemically and immunocytochemically investigated for PrPres. For the H-types, spongiform changes without PrPres accumulation were observed in the brainstem. Western blot analysis confirmed that no PrPres was detected into the brain. For the L-types, severe spongiosis was evidenced into the thalamus, the striatum, the mesencephalon, and the brainstem, whereas into the cortex the spongiosis was evidenced, but the vacuolisation was weaker. Strong deposits of PrPres was detected by western blot, PET-blot and immunocytochemistry in the CNS: dense accumulation was observed into the thalamus, the striatum, and the hippocampus whereas in the cerebral cortex, PrPres was prominently accumulated in plaques. Western blot analysis confirmed the presence of protease-resistant prion protein.
Conclusions: L-type infected lemurs showed survival times considerably shorter than for classical BSE strain, indicating that the disease is caused by a very virulent distinct prion strain.
>>> Conclusions: L-type infected lemurs showed survival times considerably shorter than for classical BSE strain, indicating that the disease is caused by a very virulent distinct prion strain. >>>
seems the survival time was the same for the h-type BSE and the l-type BSE i.e. 19 months post inoculation (mpi), interesting. ...TSS
Wednesday, March 31, 2010
Atypical BSE in Cattle / position: Post Doctoral Fellow
Wednesday, February 24, 2010
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
Saturday, June 12, 2010
PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05 Study of Atypical Bse
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
A most interesting case, she was 38 years old, and worked a Tyson meat slaughter house, handling brain and spinal cords ;
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas.She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-
Physician Discharge Summary, Parkland Hospital, Dallas Texas
Admit Date: 12/29/2009 Discharge Date: 1/20/2010 Attending Provider: Greenberg, Benjamin Morris; General Neurology Team: General Neurology Team
Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence.She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers.
The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.
> Up until about 6 years ago, the pt worked at Tyson foods where she
> worked on the assembly line, slaughtering cattle and preparing them for
> packaging. She was exposed to brain and spinal cord matter when she
> would euthanize the cattle.
please see full text ;
Monday, March 29, 2010
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas
Archive Number 20100405.1091 Published Date 05-APR-2010
Subject PRO/AH/EDR> Prion disease update 1010 (04)
[Terry S. Singeltary Sr. has added the following comment
"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.
The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"
3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.
3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345
3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.
3.60 In 1982, Hadlow had studied the infectivity of various tissues from sheep affected with scrapie (see paragraphs 2.162–2.163).346 He determined that after the brain and spinal cord, tissues of the lymphoreticular system (LRS) – including spleen, lymph nodes, intestinal Peyer’s patches and tonsils – were the most infective. It was on this basis that the Specified Bovine Offal (SBO) ban was introduced on 13 November 1989, to exclude tissues from the human food chain that might be most hazardous in terms of potential infectivity. However, a similar study in cattle using the mouse bioassay (see paragraph 1.43 for details on this experimental method) has shown that the spleen, lymph nodes and tonsils from BSE-affected cattle do not transmit disease. Of LRS tissues, only the distal ileum containing Peyer’s patches has proved to be infective in 6-month-old calves.347 However, infectivity has been demonstrated in the spleens of mice into which LRS tissue from BSE cases has been inoculated. Thus, infectivity can be demonstrated after the agent has first been passaged through mice, and the species barrier has been breached.348 Nonetheless, the patterns and extent of tissue infectivity in the two species are quite different.
3.61 Although BSE is a ‘scrapie-like’ disease, once it had emerged in cattle, its characteristics were different, especially in terms of host range and lesion profile. At the very least such differences seem inconsistent with the original proposition that BSE was ‘unmodified scrapie’. It was either modified scrapie, the modification arising from a mutation in sheep, or a new bovine TSE, again arising from a mutation in cattle (see paragraph 3.70); or, less likely, a mutation in some other species. In this regard it is worth noting that carcasses from zoos and bones from overseas were sometimes sent for rendering and could therefore have been a source of MBM in cattle feed.
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
IN CLOSING, I wish to say that if anyone still thinks that 85% to 90% of all sporadic CJD is a spontaneous happening without any route and source of the TSE agent, just a happen stance of bad luck, as some officials still claim today, as with every hospital that has a CJD exposure accident will tell you, if anyone still believes this, they should then go and resign from whatever scientific and or doctors field you practice in, because YOU are then partially responsible for the continued spread of this horrible disease around the Globe. For Pete's sake, if clusters happen with animal TSE, then why not humans? IF all these TSE transmit to many different animal species, both in the field and in the lab, what make's it so hard to believe that it will not transmit to humans? IF all these TSE in all these many different species, with all these many different strains now appearing, both typical and atypical, with over 20 strains in just typical scrapie alone, nor-98 atypical scrapie, with BSE freely transmitting to sheep as well, now 4 BSE strains in cattle i.e. c-BSE, l-BSE, h-BSE, and IBNC (prion gods will have to admit this is a prion TSE disease sooner or later), now 2 strains of CWD documented i.e. CWD-1 and CWD-2, and the TME with the drowsy TME strain and the hyper TME strain, if all this has been fed to humans and to livestock producing animals for human and animal consumption, then what would human TSE there from look like, either from consumption, or 2nd, 3rd, 4th passage via friendly fire i.e. via surgical, dental, blood, medical arenas, from humans exposed by consumption ? NOT to forget all the animal medical by-products there from too? BUT yet, officials will still try and have us believe that 85% to 95% of all human Transmissible Spongiform Encephalopathy TSE i.e. sporadic CJD, is a single strain, that just happens spontaneously, with no route and source from anything. P L E A S E, This is not rocket science. It's 2010, and the UKBSEnvCJD only theory should be put to rest once and for all. Iatrogenic CJD is spreading as we speak, there are many strains, they are becoming more virulent, and they came from some route and some source, and that could be many. North America is home to the most strains of documented natural field TSE in animals. These animals have been fed to both humans and animals for human consumption. The consumer there from are a source of TSE to the medical and surgical arena, and clusters there from are real, they are happening and there is a route and source. CJD and all human TSE prion disease must be made mandatory reportable, with NO age limits, with a CJD Questionnaire asking real questions pertaining to potential routes and sources going to all families of victims of this horrible disease. This must be done Nationally and Internationally immediately. We have floundered too long. ...
PLEASE SEE FULL TEXT WITH SOURCE DATA ON DIFFERENT CJD CLUSTERS AROUND THE GLOBE (i am sure i missed some) ;
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
HOW long can this charade continue $$$
Well, that's too long. ...TSS
Thursday, July 08, 2010
Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518