Thursday, December 25, 2008

Lions and Prions and Deer Demise

Lions and Prions and Deer Demise

Michael W. Miller1*, Heather M. Swanson2, Lisa L. Wolfe1, Fred G. Quartarone1, Sherri L. Huwer1, Charles H. Southwick3, Paul M. Lukacs1

1 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, Colorado, United States of America, 2 City of Boulder Open Space and Mountain Parks, Boulder, Colorado, United States of America, 3 Department of Ecology and Evolutionary Biology, University of Colorado at Boulder, Boulder, Colorado, United States of America

Abstract Background Contagious prion diseases – scrapie of sheep and chronic wasting disease of several species in the deer family – give rise to epidemics that seem capable of compromising host population viability. Despite this prospect, the ecological consequences of prion disease epidemics in natural populations have received little consideration.

Methodology/Principal Findings Using a cohort study design, we found that prion infection dramatically lowered survival of free-ranging adult (>2-year-old) mule deer (Odocoileus hemionus): estimated average life expectancy was 5.2 additional years for uninfected deer but only 1.6 additional years for infected deer. Prion infection also increased nearly fourfold the rate of mountain lions (Puma concolor) preying on deer, suggesting that epidemics may alter predator–prey dynamics by facilitating hunting success. Despite selective predation, about one fourth of the adult deer we sampled were infected. High prevalence and low survival of infected deer provided a plausible explanation for the marked decline in this deer population since the 1980s.

Conclusion Remarkably high infection rates sustained in the face of intense predation show that even seemingly complete ecosystems may offer little resistance to the spread and persistence of contagious prion diseases. Moreover, the depression of infected populations may lead to local imbalances in food webs and nutrient cycling in ecosystems in which deer are important herbivores.

Citation: Miller MW, Swanson HM, Wolfe LL, Quartarone FG, Huwer SL, et al. (2008) Lions and Prions and Deer Demise. PLoS ONE 3(12): e4019. doi:10.1371/journal.pone.0004019

Editor: Matthew Baylis, University of Liverpool, United Kingdom

Received: November 3, 2008; Accepted: November 25, 2008; Published: December 24, 2008

Copyright: © 2008 Miller 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: Our funding came from the Colorado Division of Wildlife, the City of Boulder, and the US Department of Agriculture, Animal&Plant Health Inspection Service, Veterinary Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000094/!


A disturbing study indeed, but even more disturbing, the fact that this very study shows the potential for transmission of the TSE agent into the wild of yet another species in the USA. Science has shown that the feline is most susceptible to the TSE agent. Will CWD be the demise of the mountain lions, cougars and such in the USA? How many have ever been tested in the USA? I recall there is a study taking place ;

Review A prion disease of cervids: Chronic wasting disease Christina J. Sigurdson et al ;

Mountain lion (Puma concolor) susceptibility to experimental feeding of CWD prions is currently under investigation (M. Miller and L. Wolfe, personal communication).

WHAT about multiple strains of CWD ?


North American Cervids Harbor Two Distinct CWD Strains


Angers, R. Seward, T, Napier, D., Browning, S., Miller, M., Balachandran A., McKenzie, D., Hoover, E., Telling, G. 'University of Kentucky; Colorado Division of Wildlife, Canadian Food Inspection Agency; University Of Wisconsin; Colorado State University.


Despite the increasing geographic distribution and host range of CWD, little is known about the prion strain(s) responsible for distinct outbreaks of the disease. To address this we inoculated CWD-susceptible Tg(CerPrP)1536+/· mice with 29 individual prion samples from various geographic locations in North America. Upon serial passage, intrastudy incubation periods consistently diverged and clustered into two main groups with means around 210 and 290 days, with corresponding differences in neuropathology. Prion strain designations were utilized to distinguish between the two groups: Type I CWD mice succumbed to disease in the 200 day range and displayed a symmetrical pattern of vacuolation and PrPSc deposition, whereas Type II CWD mice succumbed to disease near 300 days and displayed a strikingly different pattern characterized by large local accumulations of florid plaques distributed asymmetrically. Type II CWD bears a striking resemblance to unstable parental scrapie strains such as 87A which give rise to stable, short incubation period strains such as ME7 under certain passage conditions. In agreement, the only groups of CWD-inoculated mice with unwavering incubation periods were those with Type I CWD. Additionally, following endpoint titration of a CWD sample, Type I CWD could be recovered only at the lowest dilution tested (10-1), whereas Type II CWD was detected in mice inoculated with all dilutions resulting in disease. Although strain properties are believed to be encoded in the tertiary structure of the infectious prion protein, we found no biochemical differences between Type I and Type II CWD. Our data confirm the co·existence of two distinct prion strains in CWD-infected cervids and suggest that Type II CWD is the parent strain of Type I CWD.

see page 29, and see other CWD studies ;

Sunday, November 23, 2008

PRION October 8th - 10th 2008 Book of Abstracts

Biochim Biophys Acta. Author manuscript; available in PMC 2008 December 9. Published in final edited form as: Biochim Biophys Acta. 2007 June; 1772(6): 681-691. Published online 2006 December 15. doi: 10.1016/j.bbadis.2006.12.006. PMCID: PMC2597801 NIHMSID: NIHMS25810

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The prion strain phenomenon: Molecular basis and unprecedented features

Rodrigo Morales,1,2 Karim Abid,1 and Claudio Soto1# 1 Protein Misfolding Disorders Laboratory, George and Cynthia Mitchell Center for Neurodegenerative diseases, Departments of Neurology, Neuroscience & Cell Biology and Biochemistry & Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555-0646, USA 2 Facultad de Ciencias, Universidad de Chile, Santiago, Chile #To whom correspondence should be addressed at Email: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000094/! The publisher's final edited version of this article is available at Biochim Biophys Acta. See other articles in PMC that cite the published article.


Prions are unconventional infectious agents responsible for transmissible spongiform encephalopathies. Compelling evidences indicate that prions are composed exclusively by a misfolded form of the prion protein (PrPSc) that replicates in the absence of nucleic acids. One of the most challenging problems for the prion hypothesis is the existence of different strains of the infectious agent. Prion strains have been characterized in most of the species. Biochemical characteristics of PrPSc used to identify each strain include glycosylation profile, electrophoretic mobility, protease resistance, and sedimentation. In vivo, prion strains can be differentiated by the clinical signs, incubation period after inoculation and the vacuolation lesion profiles in the brain of affected animals. Sources of prion strain diversity are the inherent conformational flexibility of the prion protein, the presence of PrP polymorphisms and inter-species transmissibility. The existence of the strain phenomenon is not only a scientific challenge, but it also represents a serious risk for public health. The dynamic nature and inter-relations between strains and the potential for the generation of a very large number of new prion strains is the perfect recipe for the emergence of extremely dangerous new infectious agents.


BSE has not only been transmitted to humans. The extensive use of cow-derived material for feeding other animals led to the generation of new diseases in exotic felines such as tiger and cheetah, non human primates, and domestic cats [52,57-60]. As it was mentioned before, the transmission of BSE into these different species could create many new prion strains, each one of them with particular biological and biochemical characteristics and thus a potentially new hazard for human health. Successful transmission of BSE in pigs has been described [61,62] and also in transgenic mice expressing pig PrP (PoPrP) [63]. Porcine derivates are widely consumed and the hypothetic case of "mad pigs" could increase the events of zoonotic transmission of prions to humans. Fortunately, transmission of BSE to pigs is possible only in very drastic conditions, not likely to be occurring naturally [62,63]. More frightening is perhaps the possibility that BSE has been passed into sheep and goats. Studies have already shown that this transmission is possible and actually relatively easy and worrisomely produces a disease clinically similar to scrapie [64]. The cattle origin of this new scrapie makes possible that the new strain may be transmissible to humans. Transmission experiments of BSE infected sheep brain homogenate into human transgenic animal models are currently ongoing in several laboratories. It is very important to note that all materials generated by transmission of BSE in experimental and natural cases show similar biochemical behavior compared to the original inoculum [65], suggesting that all these new generated infectious agents could potentially be hazardous for humans. The origin of BSE is still a mystery. Abundant evidence supports the hypothesis that BSE was produced by cattle feeding with scrapie derivated material [66,67], indicating that bovine PrPSc might be a "conformational intermediary" between ovine PrPSc and human PrPC.

There is currently no mean to predict which will be the conformation of a newly generated strain and how this new PrPSc conformation could affect other species. One interesting new prion disease is CWD, a disease affecting farm and wild species of cervids [68,69]. The origin of CWD and its potential to transmit to humans are currently unknown. This is worrisome, considering that CWD has became endemic in some parts of USA and the number of cases continues to increase [69]. It is presumed that a large number of hunters in the US have been in contact or consumed CWD-infected meat [70]. CWD transmissibility studies have been performed in many species in order to predict how this disease could be spread by consumption of CWD meat [71-73]. In these studies, a special attention has been done to scavenging animals [74], which are presumed to be exposed to high concentration of cervid prions, resulting in the putative generation of many new forms of TSEs. Fortunately negative results were obtained in one experiment done in raccoons infected with CWD [74]. Transmission of CWD to humans cannot be ruled out at present and a similar infective episode to BSE involving CWD could result in catastrophic events, spreading the disease in a very dangerous way through the human population. No clinical evidence linking CWD exposed humans and CJD patients have been found [70], but experimental inoculation of CWD prions into squirrel monkeys propagated the disease [71]. It is important to mention that the species barrier between humans and cervids appears to be greater than with cattle, as judged by experiments with transgenic mice models [75]. Finally, it is important to be aware about CWD transmissibility to other species in which a "conformational intermediary" could be formed, facilitating human infection.


VI. Unique features of prion strains

The biological and infectious characteristics of prions are dramatically different to the conventional infectious agents. These differences are manifested in the prion strains phenomenon in unique and unprecedented features, such as for example strain adaptation and memory, the coexistence and competition of prion strains, among others. In this section, some of these interesting phenomena will be briefly described.

Adaptation of Prion strains

Interspecies transmission of prions could result in the emergence of more than one variety of infectious material. All new collected infectious agents could present particular strain characteristics. That is the case of DY and HY prion strains generation [13,16]. When interspecies transmission of prions occurs, serial passages in the new host are needed in order to stabilize the characteristics of new generated infectious material. In the case of TME transmission in hamsters, at least four serial passages in the new species were required for stabilization [13]. The first passage was characterized by long incubation periods and a dominance of a 19 KDa fragment when newly obtained PrPSc was analyzed after PK digestion. In the three first passages, clinical symptoms were not characteristic of the hamster-adapted HY or DY TME strains. This phenotype was attributed to the combination effects of both strains replicating simultaneously. Thereafter, each of the strains was stabilized in some of the animals and once they are adapted and stabilized, they can be serially propagated in vivo and the characteristics are maintained. It is accepted that both strains present differential conversion kinetics in vitro, with DY being the slowest and HY the fastest [124]. For this reason, in order to select efficiently this prion strain, limit dilutions must be performed [13]. In that way, the most abundant and less convertible DY is favored against the less abundant but fastest HY strain.

Co-existence of prion strains

Related to the above, it has been shown that two or more prion strains can co-exist in natural cases of TSE. Co-existence of prion strains has been found in sporadic cases of CJD [113, 125]. Analyses of several sCJD tissue showed that different biochemical profiles of PrPSc could be found in different brain areas from the same patient [113]. Co-existence of prion strains was mainly observed in patient heterozygous for codon 129 [113]. As many as 50% of these patients present different types of PrPSc in their brains, whereas 9% of MM patients were positive for co-existence of strains. On the other hand, more than one PrPSc type was not observed in VV patients [113].

The biochemical and structural properties of the protein seem to be the major cause of this differential distribution. This observation may explain why sCJD is so heterogeneous in terms of clinical manifestation [34,126,127]. In a recent publication by Bishop et al. [107], vCJD infected transgenic mice expressing human PrPC, present changes in their PrPSc and vacuolation patterns in the brain according to their polymorphic classification for codon 129.

Competition of prion strains

In particular experimental conditions, some prion strains can extend their specific incubation period when co-infected with another strain. Long incubation period prions increase the incubation period of "faster" prions. This phenomenon of "competition of prion strains" has been observed in mice and hamster. In mice, competition between 22A and 22C strains was reported in 1975 by Dickinson et al. [128]. In this study, RIII mice (homozygous for sincs7 allele) were used. 22A and 22C showed long and short incubation period (550 and 230 days), respectively. When 22C strain was intraperitoneally inoculated 100, 200 and 300 days after intraperitoneal administration of the 22A agent, all three experimental groups resulted in Morales et al. Page 8 Biochim Biophys Acta. Author manuscript; available in PMC 2008 December 9. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript incubation periods and lesion patterns matching 22A prions, suggesting that 22C prions were degraded or excreted, in animals previously infected by 22A. Similar results were obtained by Kimberlin and Walker in 1985 [129] using a different strain of sincs7 mice. These authors treated mice using 22A and 22C prion strain. Before inoculation, 22A was treated with different chemical and physical agents in order to see if the "competitor" or "blocking" characteristics of 22A were maintained. From all treatments, 12M urea was shown to almost abolish the blocking properties of 22A agent. This information suggests that infective properties of long incubation period agent are strictly necessary in order to increase the incubation period of faster prions.

In hamster, similar observations were reported using DY and HY [130]. DY prion strain was inoculated 30 and 60 days prior intraperitoneal inoculation of HY at three different doses. When incubation periods of HY inoculated control group were compared with the animals inoculated at 60 days with DY, significant differences in the incubation periods were found, especially when HY prions were administrated in a higher dose [130]. On the other hand no differences were observed in the case of intranerve inoculation, revealing that competition phenomenon occurs only when peripheral inoculation is performed. These results are surprising considering the fact that DY was reported not to be infectious when intraperitoneally inoculated in hamsters [130]. This data suggest that replication of DY is occurring in peripheral tissues but is not able to reach the central nervous system.

In general, the principal variables that need to be observed for a successful competition are the route of infection, the interval between injections and the particular strains and doses of agent used. Prolongation of incubation periods in TSE are therapeutically beneficial and several strategies are under development to reach this aim, including antibodies, beta-sheet breakers, and other chemical agents [131-133]. The experimental evidence described above suggests that prions could be potentially useful for this purpose. In order to prevent spread of prion disease in cattle or humans, prion strains with incubation periods longer than species' lifespan could be used to slowdown the replication of BSE or vCJD prions.

VII. Concluding Remarks

The existence of different strains of an infectious agent composed exclusively of a protein has been one of the most puzzling issues in the prion field. If is already difficult to understand how a protein can adopt two stable and different folded structures and that one of them can transform the other one into itself, it is unthinkable that the misfolded form can in turn adopt multiple conformations with distinct properties. Yet, compelling scientific evidence support the idea that PrP can adopt numerous folding patterns that can faithfully replicate and produce different diseases. The existence of the strain phenomenon is not only a scientific challenge, but it also represents a serious risk for public health. The dynamic nature and inter-relations between strains and the potential for the generation of many new prion strains depending on the polymorphisms and the crossing of species barrier is the perfect recipe for the emergence of extremely dangerous new infectious agents. Although, substantial progress has been made in understanding the prion strains phenomenon, there are many open questions that need urgent answers, including: what are the structural basis of prion strains?; how are the phenomena of strain adaptation and memory enciphered in the conformation of the prion agent?; to what species can a given prion strain be transmissible?; what other cellular factors control the origin and properties of prion strains?.


Friday, December 12, 2008

The prion strain phenomenon: Molecular basis and unprecedented features



How to cite this article: Vet. Res. (2008) 39:41 DOI: 10.1051/vetres:2008018

Review A prion disease of cervids: Chronic wasting disease Christina J. Sigurdson

Department of Pathology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0612, USA

Received 1 November 2007; accepted 31 March 2008; published online 3 April 2008

Abstract - Chronic wasting disease (CWD) is a prion disease of deer, elk, and moose, initially recognized in Colorado mule deer. The discovery of CWD beyond the borders of Colorado and Wyoming, in Canada and as far east as New York, has led to its emergence as a prion disease of international importance. Epidemiological studies indicate that CWD is horizontally transmitted among free-ranging animals, potentially indirectly by prion-containing secreta or excreta contaminating the environment. Experimental CWD transmission attempts to other wild and domestic mammals and to transgenic mice expressing the prion protein of cattle, sheep, and humans have shed light on CWD species barriers. Transgenic mice expressing the cervid prion protein have proven useful for assessing the genetic influences of Prnp polymorphisms on CWD susceptibility. Accumulating evidence of CWD pathogenesis indicates that the misfolded prion protein or prion infectivity seems to be widely disseminated in many nonneural organs and in blood. This review highlights contemporary research findings in this prion disease of free-ranging wildlife.

Key words: CWD / prion / TSE / cervid / amyloid

Corresponding author: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000094/!

© INRA, EDP Sciences 2008


7. Interspecies CWD transmission

Wild predators and scavengers are presumably feeding on CWD-infected carcasses.

Skeletal muscle has been shown to harbor CWD prion infectivity [2], underscoring that other species will almost certainly be exposed to CWD through feeding. However, CWD has not been successfully transmitted by oral inoculation to species outside of the cervid family, suggestive of a strong species barrier for heterologous PrP conversion. Ferrets (family Mustelidae) can be infected with deer CWD after intracerebral (ic) but not oral exposure [5, 80]. Raccoons resisted even ic infection for up to 2 years thus far [24]. Mountain lion (Puma concolor) susceptibility to experimental feeding of CWD prions is currently under investigation (M. Miller and L. Wolfe, personal communication).

Could wild rodents colonizing CWD- or scrapie-infected pastures serve as an environmental reservoir of prion infectivity? Interestingly, bank voles (Clethrionomys glareolus), are readily infected with CWD and sheep scrapie by intracerebral inoculation ([64]; U. Agrimi, unpublished data) and are considered as a potential reservoir for sheep scrapie [64]. Many vole species occur in North America [65, 83] and further research may determine whether voles enhance CWD or scrapie spread through environmental contamination.

Given that environmental contamination with CWD prions likely occurs [55], domestic

ruminants may be exposed to CWD through common grazing areas. However, sheep and

cattle appear to be poorly susceptible to mule deer CWD: ic inoculation with mule deer CWD succeeded to infect only 2 of 8 sheep [28]; likewise cattle have not been infected after cograzing with CWD-infected mule deer, or after a direct oral exposure (over 6 years) (M. Miller, personal communication). Even direct ic inoculation led to CWD infection in only 5 of 13 cattle (38%) after 2-5 years [26]. In contrast, cattle are highly susceptible to white-tailed deer CWD with 12 of 14 animals developing neurologic disease and PrPSc by only 22 months post-ic inoculation (+/-0.5 months) [29]. Further studies are planned to determine whether

cattle are susceptible to white-tailed deer prions after an oral exposure (J. Richt, personal communication). The differential susceptibility of cattle to CWD from mule deer versus whitetailed deer suggests that CWD strains exist, and that CWD may differentially cross species barriers depending on the strain. Nevertheless, to date, natural CWD infections have been detected only in cervids.

Is the converse true, are cervids susceptible to sheep scrapie? Only one study has been performed on cervid susceptibility to sheep scrapie by the ic route, and showed that 3 of 6 elk developed neurologic signs, spongiform encephalopathy and PrPSc in brain [25]. Further experiments to address this question may be interesting since sheep scrapie is considered a possible source for CWD in North America [89, 91].

8. Human susceptibility to CWD

Millions of North Americans hunt deer and elk (U.S. Department of the Interior, Census Bureau), and there is no doubt that people have been exposed to CWD through venison consumption, particularly in light of recent data showing CWD prions in muscle [2]. Human susceptibility to CWD or to other newly emerging animal TSE [9, 14] is still unclear, although we can be somewhat reassured in that there have been no large scale outbreaks of human TSE cases in Colorado and Wyoming, where CWD has existed for decades [51]. Up until approximately 10 years ago, autopsies were not performed on suspect human TSE cases in many states due to biosafety concerns, therefore the diagnosis of potential new TSE strains has been hampered. This indicates that clinical TSE diagnoses in humans were not confirmed, nor was any strain typing done to look for the appearance of potentially subtle or unusual pathological or biochemical phenotypes of a new TSE strain. Fortunately, the

autopsy rate for suspect cases is improving. At the National Prion Disease Pathology

Surveillance Center at Case Western Reserve University (Cleveland, Ohio), Creutzfeldt-Jakob disease (CJD) suspect cases are studied and classified by CJD subtype. Thus far,


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

Surveillance Center***,

however there have been no unusual or novel prion subtypes that might indicate the appearance of a new prion strain [7, 41]. Other indirect studies of human susceptibility to CWD also suggest that the risk is low. In biochemical conversion studies, Raymond et al. [68] showed that the efficiency of CWD to

convert recombinant human PrP into amyloid fibrils was low, but similar to that of both BSE and scrapie fibrils to do the same. These results suggest that there is a molecular incompatibility in the conversion of human PrPC by CWD, sheep scrapie, or BSE, and that cross species infections in humans may be rare events.

To determine whether common PrPSc strain features may link CWD and CJD, histopathology and the PrPSc biochemical characteristics from deer and elk were compared with that of humans with sporadic CJD (sCJD) cases that are methionine homozygous at codon 129 of the Prnp gene by Xie et al. [96], although strain features including histologic profile, target organs, and glycoform patterns will not necessarily remain the same upon crossing species barriers [6, 5, 8, 57]. The PrPSc form is cleaved by proteinase-K (PK) at different sites depending on the conformation of the protein and may aid determination of whether the PrPSc conformation is similar. By western blot (SDS-PAGE) of elk CWD, the unglycosylated

PK-resistant PrPSc migrated at 21 kDa, similar to sCJD (MM1 subtype) and the PK cleavage site was the same, occurring at residues 78 and 82 as assessed by N-terminal sequencing. Conformational stability was evaluated by measuring the PrPSc stability under partially denaturing conditions and also showed no significant difference between elk CWD and sCJD MM1 PrPSc. However, elk CWD and human sCJD MM1 strains exhibited distinct glycoform patterns by two dimensional gel electrophoresis, suggesting that the strains differed. Future studies may utilize luminescent conjugated polymers, which were recently shown to distinguish naturally- and experimentally-derived prion strains [79].

To study elk-human prion species barriers, Kong et al. inoculated elk CWD into transgenic mice expressing either human PrP or elk PrP. Whereas the elk PrP expressing mice developed disease after only 118-142 days post-inoculation, human PrP expressing mice (129M) did not develop any features of TSE after more than 657 or more than 756 days [41].

In accordance with these results, Tamgüney et al. also reported that human PrP

overexpressing mice were not susceptible to 9 CWD isolates from mule deer, white-tailed deer, and elk [84]. However, mice have a limited lifespan and further passages may be necessary to detect low levels of prion infectivity that may be present subclinically. Although indirect evidence is accumulating that there may be a robust species barrier for CWD transmission to humans, one report indicates nonhuman primate susceptibility to CWD. Intracerebral inoculation of squirrel monkeys (Saimiri sciureus) demonstrated a positive CWD transmission [49]. Among non-human primates, however, the Prnp sequence of the new world monkeys are the most distant from humans [72], and therefore may not indicate that human prion conversion would occur by CWD.


HOWEVER, why ignore the old science and transmission studies to date ???

Species Born Onset/Died

Ocelot May 1987 Mar 1994
Ocelot Jul 1980 Oct 1995
Puma 1986 May 1991
Puma 1980 May 1995
Puma 1978 May 1995
Lion Nov 1986 Dec 1998
Tiger 1981 Dec 1995
Tiger Feb 1983 Oct 1998
Ankole 1987 May 1995
Ankole 1986 Feb 1991
Bison 1989/90 Oct 1996

Maff data on 15 May 99

kudu 6
gemsbok 1
nyala 1
oryx 2
eland 6
cheetah 9
puma 3
tiger 2
ocelot 2
bison 1
ankole 2
lion 1

Feline Spongiform Encephalopathy (FSE) FSE was first identified in the UK in 1990. Most cases have been reported in the UK, where the epidemic has been consistent with that of the BSE epidemic. Some other countries (e.g. Norway, Liechtenstein and France) have also reported cases.

Most cases have been reported in domestic cats but there have also been cases in captive exotic cats (e.g. Cheetah, Lion, Asian leopard cat, Ocelot, Puma and Tiger). The disease is characterised by progressive nervous signs, including ataxia, hyper-reactivity and behavioural changes and is fatal.

The chemical and biological properties of the infectious agent are identical to those of the BSE and vCJD agents. These findings support the hypothesis that the FSE epidemic resulted from the consumption of food contaminated with the BSE agent.

The FSE epidemic has declined as a result of tight controls on the disposal of specified risk material and other animal by-products.

References: Leggett, M.M. et al.(1990) A spongiform encephalopathy in a cat. Veterinary Record. 127. 586-588

Synge, B.A. et al. (1991) Spongiform encephalopathy in a Scottish cat. Veterinary Record. 129. 320

Wyatt, J. M. et al. (1991) Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record. 129. 233.

Gruffydd-Jones, T. al.. (1991) Feline spongiform encephalopathy. J. Small Animal Practice. 33. 471-476.

Pearson, G. R. et al. (1992) Feline spongiform encephalopathy: fibril and PrP studies. Veterinary Record. 131. 307-310.

Willoughby, K. et al. (1992) Spongiform encephalopathy in a captive puma (Felis concolor). Veterinary Record. 131. 431-434.

Fraser, H. et al. (1994) Transmission of feline spongiform encephalopathy to mice. Veterinary Record 134. 449.

Bratberg, B. et al. (1995) Feline spongiform encephalopathy in a cat in Norway. Veterinary Record 136. 444

Baron, T. et al. (1997) Spongiform encephalopathy in an imported cheetah in France. Veterinary Record 141. 270-271

Zanusso, G et al. (1998) Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy. Lancet, V352, N9134, OCT 3, Pp 1116-1117.

Ryder, S.J. et al. (2001) Inconsistent detection of PrP in extraneural tissues of cats with feline spongiform encephalopathy. Veterinary Record 146. 437-441

Kelly, D.F. et al. (2005) Neuropathological findings in cats with clinically suspect but histologically unconfirmed feline spongiform encephalopathy. Veterinary Record 156. 472-477.

TSEs in Exotic Ruminants TSEs have been detected in exotic ruminants in UK zoos since 1986. These include antelopes (Eland, Gemsbok, Arabian and Scimitar oryx, Nyala and Kudu), Ankole cattle and Bison. With hindsight the 1986 case in a Nyala was diagnosed before the first case of BSE was identified. The TSE cases in exotic ruminants had a younger onset age and a shorter clinical duration compared to that in cattle with BSE. All the cases appear to be linked to the BSE epidemic via the consumption of feed contaminated with the BSE agent. The epidemic has declined as a result of tight controls on feeding mammalian meat and bone meal to susceptible animals, particularly from August 1996.

References: Jeffrey, M. and Wells, G.A.H, (1988) Spongiform encephalopathy in a nyala (Tragelaphus angasi). Vet.Path. 25. 398-399

Kirkwood, J.K. et al (1990) Spongiform encephalopathy in an Arabian oryx (Oryx leucoryx) and a Greater kudu (Tragelaphus strepsiceros) Veterinary Record 127. 418-429.

Kirkwood, J.K. (1993) Spongiform encephalopathy in a herd of Greater kudu (Tragelaphus strepsiceros): epidemiological observations. Veterinary Record 133. 360-364

Kirkwood, J. K. and Cunningham, A.A. (1994) Epidemiological observations on spongiform encephalopathies in captive wild animals in the British Isles. Veterinary Record. 135. 296-303.

Food and Agriculture Organisation (1998) Manual on Bovine Spongiform Encephalopathy.



J.F. Silva1, J.J. Correia, 1 J. Ribeiro2, S. Carmo2 and L.Orge3

1 Faculdade de Medicina Veterinária (UTL), Lisbon, Portugal 2 Clínica Veterinária Ani+, Queluz, Portugal 3 Laboratório Nacional de Investigação Veterinária, Unidade de BSE, Lisbon, Portugal

Feline spongiform encephalopathy (FSE), affecting domestic and captive feline species, is a prion disease considered to be related to bovine spongiform encephalopathy (BSE). Here we report the first case diagnosed in Portugal, highlighting the neuroapthological findings. In 2004 a 9-year old intact female Siamese cat was referred with chronic progressive behavioural changes, polydipsia, gait abnormalities and episodes of hypersalivation. Clinical signs progressed to tetraparesis and dementia and euthanasia was performed. At necropsy, brain and spinal cord had no significative changes. Tissue samples from brain, cerebellum, brainstem and spinal cord were collected for histopathology and immunohistochemistry for detection of PrPres. Histology revealed neuropil and neuronal perikarion vacuolation in several areas of the central nervous system together with gliosis and cell rarefaction at the granular layer of the cerebellum. Immunohistochemical detection of PrPres showed a strong and widespread PrPres accumulation as granular and linear deposits as well as associated with some neurons. These findings are supportive of FSE. To the authors knowledge this is the first confirmed case of FSE reported in Portugal.


AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.


2005 DEFRA Department for Environment, Food & Rural Affairs

Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail:


Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518

21 November 2001

Dear Mr Singeltary


Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.

As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government’s independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.

Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.

Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less

critical. For more details see- http://www.bseinquiry, .pdf

As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.

Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK

You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.

I hope this is helpful

Yours sincerely 4





b) Fibrillar material closely similar to SAF, found in BSE/Scrapie, was observed in 19 (4.3%) cases, all of which were hounds > 7 years of age. 14/19 of these suspected SAF results correlated with cases in the unresolveable histopathological category.


The following proposals address the hypothesis that the hound survey observations represent a PrP related or scrapie-like disease of dogs in which the pathological response, and possible the spread of infectivity, is neuroanatomically localized. By inference this could also mean that the disorder is clinically silent and non-progressive.


worse still, there is serious risk the media could get to hear of such a meeting…


Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer…

2. The Parliamentary Secretary said that he was concerned about the possibility that countries in which BSE had not yet been detected could be exporting raw meat materials (in particular crushed heads) contaminated with the disease to the UK for use in petfood manufacture…


YOU explained that imported crushed heads were extensively used in the petfood industry…

In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed…

40. When Sir Richard Southwood gave oral evidence to the Agriculture Select Committee, he said:

‘The case of the cat is the first case of spongiform encephalopathy ever in a cat. Well, it appears to be - but if poor moggie got a bit of the staggers, you took it along to the vet and said it was not very happy, it would be put to sleep in the past and no one would have paid £300 to have a post mortem undertaken. So it is just possible that these were occurring before and were in fact caught from moggie being fed scrapie offal from sheep. I cannot say.’[46]

NEXT, ask yourself how many cats and dogs have ever been tested for TSE in the USA ???

DOGS AND CATS are not tested for TSE. THEY ARE RENDERED UP INTO LITTLE PELLETS, WITH ALL THE OTHER ROAD KILL, and fed back to animals for human and animal consumption. it’s an endless cycle of greed,
and disease. ...TSS

Subject: FELINE ALZHEIMER'S OR MAD CAT DISEASE I.E. FSE ???Date: December 6, 2006 at 9:24 am PST

Friday, December 12, 2008

The prion strain phenomenon: Molecular basis and unprecedented features


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