Friday, January 01, 2016

Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population Monitoring and Capture-Recapture Data

Research Article
 
Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population Monitoring and Capture-Recapture Data
 
Chris Geremia , * E-mail: Chris_Geremia@nps.gov
 
Affiliation: Natural Resource Ecology Laboratory, Department of Ecosystem Science and Sustainability and Graduate Degree Program in Ecology, Colorado State University, Fort Collins, Colorado, United States of America
 
Current Address: Bison Ecology and Management Office, Wildlife and Aquatic Resources Branch, Yellowstone Center for Resources, Yellowstone National Park, National Park Service, Mammoth Hot Springs, WY, United States of America
 
⨯ Michael W. Miller, Affiliation: Wildlife Health Program, Colorado Division of Parks and Wildlife, Fort Collins, Colorado, Colorado, United States of America
 
⨯ Jennifer A. Hoeting, Affiliation: Department of Statistics, Colorado State University, Fort Collins, Colorado, United States of America
 
⨯ Michael F. Antolin, Affiliation: Department of Biology, Colorado State University, Fort Collins, Colorado, United States of America
 
⨯ N. Thompson Hobbs Affiliation: Natural Resource Ecology Laboratory, Department of Ecosystem Science and Sustainability and Graduate Degree Program in Ecology, Colorado State University, Fort Collins, Colorado, United States of America
 
⨯ Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population Monitoring and Capture-Recapture Data Chris Geremia, Michael W. Miller, Jennifer A. Hoeting, Michael F. Antolin, N. Thompson Hobbs PLOS x Published: October 28, 2015 DOI: 10.1371/journal.pone.0140687
 
Abstract
 
Epidemics of chronic wasting disease (CWD) of North American Cervidae have potential to harm ecosystems and economies. We studied a migratory population of mule deer (Odocoileus hemionus) affected by CWD for at least three decades using a Bayesian framework to integrate matrix population and disease models with long-term monitoring data and detailed process-level studies. We hypothesized CWD prevalence would be stable or increase between two observation periods during the late 1990s and after 2010, with higher CWD prevalence making deer population decline more likely. The weight of evidence suggested a reduction in the CWD outbreak over time, perhaps in response to intervening harvest-mediated population reductions. Disease effects on deer population growth under current conditions were subtle with a 72% chance that CWD depressed population growth. With CWD, we forecasted a growth rate near one and largely stable deer population. Disease effects appear to be moderated by timing of infection, prolonged disease course, and locally variable infection. Long-term outcomes will depend heavily on whether current conditions hold and high prevalence remains a localized phenomenon.
 
Discussion
 
The epidemic dynamics of CWD and its consequences for deer populations in northern Colorado and elsewhere will play out over the coming decades, well beyond the duration of any single field campaign or surveillance period. Our 5-year study was too brief to measure temporal trends. Moreover, historical data were incomplete with respect to estimating infection probability. Such challenges are commonly faced by those attempting to understand complex disease or other ecological processes that operate on protracted time scales. In this case, however, our Bayesian hierarchical approach, which integrated a matrix population and disease model with available monitoring data and process level data from contemporary capture-recapture efforts, yielded readily-interpreted estimates of key epidemic parameters despite the collective shortcomings in available data. Our approach allowed for forecasts of population and disease conditions that are far more revealing than simulation models that would traditionally be relied upon to gain such insights.
 
Our approach provides a framework for beginning to assess the effect of CWD on deer populations and yields parameter estimates and short term forecasts that include uncertainty via predictive process distributions. In the areas we studied, CWD did not lower population growth rate to a degree sufficient to precipitate a rapid, catastrophic decline in deer abundance. Instead, the effects on growth appear to have remained subtle despite CWD having been present for decades. Estimated growth rate under the current level of infection centered near one.
 
Prion infection can be thought of as accelerating the time of demise for infected individuals. Disease moves deer into demographic stage equivalent to senescence, characterized by the progressively lower survival and reproduction seen in aged individuals. Moving large numbers of young deer into "disease-related senescence" could have debilitating effects on population growth, as reflected in the dynamics of unchecked CWD epidemics described in captive deer herds [17]. However, under the regimen of natural and prescribed controls operating on herds we studied infection rates were relatively constant between 1.5 and 8.5 years of age. The average life expectancy of CWD-free deer was 5.39 (4.23−6.91) years and most (9 of 15) new infections occurred in deer ≥5.5 years old. Such timing of onset, combined with the slow progression of disease, likely muted the effects of CWD on population growth. Furthermore, infection was spatially localized: annual infection probability varied by an order of magnitude across a relatively short distance, such that overall an insufficient number of deer were becoming infected to cause rapid and widespread population collapse within the timeframe of our study.
 
Regardless of short-term trends and its ultimate fate, the deer population is clearly less robust with CWD. Deer abundance has declined since the 1980s (Fig 2) [27]. We cannot be sure of the ultimate cause of decline, because the deer population has been subject to changing practices to manage population demographics and CWD [27], in the face of other disease outbreaks (such as hemorrhagic disease), habitat fragmentation and a changing climate [1,28–29]. We estimated that the current population (with prevalence near 4%) is stable, and we cannot rule out slow increases or declines in abundance. Declining numbers would be the expected outcome if prevalence levels resembled those measured in this population during the late 1990s. Thus, CWD, under high prevalence, may have been an important contributing cause to the decline observed during the 1980s and 90s (Fig 6).
 
Managers have attempted to promote population growth by essentially ceasing female harvest since 2006 [27]. While the Cherokee Park subpopulation has responded with slow growth, small, if any, increases have been detected in the Red Mountain and Big Hole subpopulations where CWD prevalence exceeds 5%. Management of deer populations throughout the world typically includes some degree of female harvest. Even under low CWD prevalence, CWD appears to affect population growth sufficiently to make annual harvest (of females) an unsustainable management practice.
 
Our mark-recapture study coincided with a period of historically low deer abundance, and thus we expected higher growth rates than observed. Such discrepancy suggests that we may have underestimated CWD’s direct or indirect effects. Average adult survival for susceptible female deer was 0.82 (0.77−0.86), which centered below the range-wide average of 0.85 [20,30]. The difference between susceptible and infected deer survival was therefore less than would be expected if susceptible deer survival was nearer to or above the range-wide average, as might be expected in a low-density population.
 
Population growth rates in the absence of CWD were lowest in Red Mountain and Big Hole, which corresponded to highest local disease prevalence. Apparent competition is an indirect interaction among prey species mediated by a shared predator [31–32]. Mountain lions prey selectively on CWD infected deer [33] and CWD could result in an abundance of vulnerable prey, thereby enhancing mountain lion survival and reproduction [20]. A resulting outcome could be increased predation on uninfected deer and overall depression of the deer population–the inverse relationship between CWD prevalence and survival of uninfected deer supports the possibility of indirect disease effects on population growth.
 
The effect of CWD partly depended on the scale of analysis. When all data were combined, we did not find the remarkably high prevalence observed in two more localized deer populations (< 600 individuals) studied elsewhere. Mule deer in the Table Mesa population in northcentral Colorado exhibited ~20% prevalence among adult females with average annual infection probability of 0.23 [20]. Similarly, 42% of female white-tailed deer developed CWD during a seven year study of the Deer Creek population in central Wyoming [18]. The Table Mesa and Deer Creek populations declined and CWD was implicated as an ultimate or contributing cause [18– 20]. Annual infection probabilities approached such levels only within highly localized portions (< 50 km2) of our study area, and decline was the more likely scenario in associated herd units (Red Mountain and Big Hole). However, those local declines appear to be offset by growth in nearby herd units with lower infection rates. The net outcome becomes largely unchanging overall deer abundance under the conditions currently operating on these different herd units.
 
It follows that the long-term outcomes of CWD may depend heavily on whether high prevalence remains a localized phenomenon. CWD-causing prions appear to persist locally by transmission among individuals and from environmental reservoirs, but spatial spread almost certainly requires transport among spatially-distinct social units [16,34]. Deer show extraordinary fidelity to their female social groups and home ranges established early in life. This may limit prion mobility and thereby afford deer some natural “spatial resistance” against CWD on a larger geographic scale. However, overlap between migrant groups on summer range could bridge these social barriers, as previously suggested for the heavily infected Red Mountain herd unit [34]. Although not studied in depth here, male mule deer have larger home ranges [35], higher infection rates [20,24], and less fidelity to specific social groups [35]. Males could serve as a pathway of infection among bands of females as the males seek mates [34,35].
 
The long-term outcomes of CWD will depend on the extent to which this outbreak increases beyond what we observed. The weight of evidence suggests that the CWD outbreak is less severe today than during the late 1990s (and early 2000s). We cannot be sure that the 1997–2001 and 2010–2014 prevalence estimates are directly comparable. The early data were post mortem tests of harvested or culled deer and the later data were live tests of randomly chosen helicopter captured deer. Ages of sampled deer [36,37], increased vulnerability of infected deer to harvest [38], prion precursor genotype of sampled deer [39], and testing diagnostic method [40] may have influenced prevalence estimates. But, the magnitude of difference in prevalence estimates among time periods is likely greater than would be explained by sampling effects alone.
 
To date, we are unaware of a study that documents a decrease in CWD prevalence over time in mule deer, white-tailed deer or elk. We briefly consider three plausible explanations for our findings: a) that natural oscillations occur in CWD outbreaks; b) that the outbreak has peaked and is declining to a lower endemic level; or c) that previous management actions were more successful at suppressing the outbreak than originally believed.
 
Sharp & Pastor [41] illustrated that CWD outbreaks may play out as a series of reoccurring epidemics characterized by either stable limit cycles or oscillations that may dampen or amplify as a function of deer density. If this is the case, we would expect today’s declining deer population to feedback on conditions–lowering transmission rates leading to reduced CWD effects and a growing population. Increasing abundance would support higher transmission rates, deer decline, and oscillations of CWD prevalence and deer. Alternatively, Almberg et al. [21] (see also [22–24,41,42]) suggested that CWD outbreaks could reach endemic equilibrium characterized by coexistence of a smaller deer population and CWD. Under these scenarios, population prevalence would reach a lower, constant level after a period of high prevalence and deer decline.
 
Although neither of the foregoing scenarios can be dismissed completely, invoking them ignores the extensive management of this deer population that occurred in the years between the two time points we chose as the basis for our analyses. Management aimed to reduce CWD transmission between 2000 and 2005, which included a combination of (crude and unpopular) focal culling and a broader increase in female harvest, decreased overall deer abundance by about 25%. Analyses carried out shortly after suggested that reductions in deer density had made little impact on CWD prevalence [10]. However, our current findings suggest that these management actions may indeed have attenuated the outbreak. Observed dynamics over the last decade closely approximate those predicted from models by Wild et al. [42] that included a substantial amount of selective predation on CWD-infected individuals. That harvest could be a source of selective mortality is supported by an early notion that CWD-infected deer might be more vulnerable to harvest [43], just as infected deer also appear to be more vulnerable to vehicle collisions and predation [20,33,44]. This offers the possibility that hunting could be used as a more tightly controlled substitute for predation in studies of system responses with CWD and perhaps other similar diseases.
 
The protracted time-scale of the CWD outbreak is much longer than the timespan of our research, which limits our ability to identify the true explanation of our findings. Nonetheless, our research suggests that, at least for the foreseeable future (e.g., decades), mule deer populations sharing the overall survival and infection probabilities estimated from our analyses may persist but likely will not thrive where CWD becomes established as an endemic infectious disease.
 
 
 ‘’Nonetheless, our research suggests that, at least for the foreseeable future (e.g., decades), mule deer populations sharing the overall survival and infection probabilities estimated from our analyses may persist but likely will not thrive where CWD becomes established as an endemic infectious disease. ‘’
 
*** Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population Monitoring and Capture-Recapture Data
 
‘’Mountain lions prey selectively on CWD infected deer [33] and CWD could result in an abundance of vulnerable prey, thereby enhancing mountain lion survival and reproduction [20].’’
 
please see  ;
 
‘’preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.’’
 
references on Feline Spongiform Encephalopathy FSE toward the bottom, see ;
 
Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay
 
Tuesday, December 15, 2015
 
Chronic Wasting Disease will cause a Wyoming deer herd to go virtually extinct in 41 years, a five-year study predicts
 
Study: Chronic Wasting Disease kills 19% of deer herd annually
 
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
***Title: Transmission of chronic wasting disease to sentinel reindeer (Rangifer tarandus tarandus)
 
Authors
 
item Moore, S - item Kunkle, Robert item Nicholson, Eric item Richt, Juergen item Hamir, Amirali item Waters, Wade item Greenlee, Justin
 
Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015 Publication Date: N/A
 
Technical Abstract: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of North American cervids. Reindeer (Rangifer tarandus tarandus) are susceptible to CWD following oral challenge, but CWD has not been reported in free-ranging caribou (Rangifer tarandus caribou) or farmed reindeer. Potential contact between CWD-affected cervids and Rangifer species that are free-ranging or co-housed on farms presents a potential risk of CWD transmission. The aims of this study were to 1) investigate the transmission of CWD from white-tailed deer (Odocoileus virginianus; CWD-wtd), mule deer (Odocoileus hemionus; CWD-md), or elk (Cervus elaphus nelsoni; CWD-elk) to reindeer via the intracranial route, and 2) to assess for direct and indirect horizontal transmission to non-inoculated sentinels. Three groups of 5 reindeer fawns were challenged intracranially with CWD-wtd, CWD-md, or CWD-elk. Two years after challenge of inoculated reindeer, non-inoculated control reindeer were introduced into the same pen as the CWD-wtd inoculated reindeer (n=4) or into a pen adjacent to the CWD-md inoculated reindeer (n=2). Reindeer were allowed to develop clinical disease. At death/euthanasia a complete necropsy examination was performed, including immunohistochemical testing of tissues for disease-associated CWD prion protein (PrP-CWD). Intracranially challenged reindeer developed clinical disease from 21 months post-inoculation (MPI). PrP-CWD was detected in 5/6 sentinel reindeer although only 2/6 developed clinical disease during the study period (<57 div="" mpi="">
 
***We have shown that reindeer are susceptible to CWD from various cervid sources and can transmit CWD to naive reindeer both directly and indirectly.
 
Last Modified: 12/3/2015
 
 
***PrP-CWD was detected in 5/6 sentinel reindeer although only 2/6 developed clinical disease during the study period (<57 div="" mpi="">
 
***We have shown that reindeer are susceptible to CWD from various cervid sources and can transmit CWD to naive reindeer both directly and indirectly.
 
Tuesday, September 29, 2015
 
*** Transmission of chronic wasting disease to sentinel reindeer (Rangifer tarandus tarandus) can transmit CWD to naive reindeer both directly and indirectly
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
 
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
 
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
 
 
*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
 
 
HIGHEST INFECTION RATE ON SEVERAL CWD CONFIRMED CAPTIVES
 
CHRONIC WASTING DISEASE CWD WISCONSIN Almond Deer (Buckhorn Flats) Farm Update DECEMBER 2011
 
The CWD infection rate was nearly 80%, the highest ever in a North American captive herd.
 
RECOMMENDATION: That the Board approve the purchase of 80 acres of land for $465,000 for the Statewide Wildlife Habitat Program in Portage County and approve the restrictions on public use of the site.
 
SUMMARY:
 
 
For Immediate Release Thursday, October 2, 2014
 
Dustin Vande Hoef 515/281-3375 or 515/326-1616 (cell) or Dustin.VandeHoef@IowaAgriculture.gov
 
*** TEST RESULTS FROM CAPTIVE DEER HERD WITH CHRONIC WASTING DISEASE RELEASED 79.8 percent of the deer tested positive for the disease
 
DES MOINES – The Iowa Department of Agriculture and Land Stewardship today announced that the test results from the depopulation of a quarantined captive deer herd in north-central Iowa showed that 284 of the 356 deer, or 79.8% of the herd, tested positive for Chronic Wasting Disease (CWD).
 
 
*** see history of this CWD blunder here ;
 
 
On June 5, 2013, DNR conducted a fence inspection, after gaining approval from surrounding landowners, and confirmed that the fenced had been cut or removed in at least four separate locations; that the fence had degraded and was failing to maintain the enclosure around the Quarantined Premises in at least one area; that at least three gates had been opened;and that deer tracks were visible in and around one of the open areas in the sand on both sides of the fence, evidencing movement of deer into the Quarantined Premises.
 
 
The overall incidence of clinical CWD in white-tailed deer was 82%
 
Species (cohort) CWD (cases/total) Incidence (%) Age at CWD death (mo)
 
 
”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” page 26.
 
 
Sunday, January 06, 2013
 
USDA TO PGC ONCE CAPTIVES ESCAPE
 
*** "it‘s no longer its business.”
 
 
CWD, spreading it around...
 
for the game farm industry, and their constituents, to continue to believe that they are _NOT_, and or insinuate that they have _NEVER_ been part of the problem, will only continue to help spread cwd. the game farming industry, from the shooting pens, to the urine mills, the antler mills, the sperm mills, velvet mills, shooting pens, to large ranches, are not the only problem, but it is painfully obvious that they have been part of the problem for decades and decades, just spreading it around, as with transportation and or exportation and or importation of cervids from game farming industry, and have been proven to spread cwd. no one need to look any further than South Korea blunder ;
 
===========================================
 
spreading cwd around...
 
Between 1996 and 2002, chronic wasting disease was diagnosed in 39 herds of farmed elk in Saskatchewan in a single epidemic. All of these herds were depopulated as part of the Canadian Food Inspection Agency’s (CFIA) disease eradication program. Animals, primarily over 12 mo of age, were tested for the presence CWD prions following euthanasia. Twenty-one of the herds were linked through movements of live animals with latent CWD from a single infected source herd in Saskatchewan, 17 through movements of animals from 7 of the secondarily infected herds.
 
***The source herd is believed to have become infected via importation of animals from a game farm in South Dakota where CWD was subsequently diagnosed (7,4). A wide range in herd prevalence of CWD at the time of herd depopulation of these herds was observed. Within-herd transmission was observed on some farms, while the disease remained confined to the introduced animals on other farms.
 
 
spreading cwd around...
 
Friday, May 13, 2011
 
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the Republic of Korea
 
Hyun-Joo Sohn, Yoon-Hee Lee, Min-jeong Kim, Eun-Im Yun, Hyo-Jin Kim, Won-Yong Lee, Dong-Seob Tark, In- Soo Cho, Foreign Animal Disease Research Division, National Veterinary Research and Quarantine Service, Republic of Korea
 
Chronic wasting disease (CWD) has been recognized as an important prion disease in native North America deer and Rocky mountain elks. The disease is a unique member of the transmissible spongiform encephalopathies (TSEs), which naturally affects only a few species. CWD had been limited to USA and Canada until 2000.
 
On 28 December 2000, information from the Canadian government showed that a total of 95 elk had been exported from farms with CWD to Korea. These consisted of 23 elk in 1994 originating from the so-called “source farm” in Canada, and 72 elk in 1997, which had been held in pre export quarantine at the “source farm”.Based on export information of CWD suspected elk from Canada to Korea, CWD surveillance program was initiated by the Ministry of Agriculture and Forestry (MAF) in 2001.
 
All elks imported in 1997 were traced back, however elks imported in 1994 were impossible to identify. CWD control measures included stamping out of all animals in the affected farm, and thorough cleaning and disinfection of the premises. In addition, nationwide clinical surveillance of Korean native cervids, and improved measures to ensure reporting of CWD suspect cases were implemented.
 
Total of 9 elks were found to be affected. CWD was designated as a notifiable disease under the Act for Prevention of Livestock Epidemics in 2002.
 
Additional CWD cases - 12 elks and 2 elks - were diagnosed in 2004 and 2005.
 
Since February of 2005, when slaughtered elks were found to be positive, all slaughtered cervid for human consumption at abattoirs were designated as target of the CWD surveillance program. Currently, CWD laboratory testing is only conducted by National Reference Laboratory on CWD, which is the Foreign Animal Disease Division (FADD) of National Veterinary Research and Quarantine Service (NVRQS).
 
In July 2010, one out of 3 elks from Farm 1 which were slaughtered for the human consumption was confirmed as positive. Consequently, all cervid – 54 elks, 41 Sika deer and 5 Albino deer – were culled and one elk was found to be positive. Epidemiological investigations were conducted by Veterinary Epidemiology Division (VED) of NVRQS in collaboration with provincial veterinary services.
 
Epidemiologically related farms were found as 3 farms and all cervid at these farms were culled and subjected to CWD diagnosis. Three elks and 5 crossbreeds (Red deer and Sika deer) were confirmed as positive at farm 2.
 
All cervids at Farm 3 and Farm 4 – 15 elks and 47 elks – were culled and confirmed as negative.
 
Further epidemiological investigations showed that these CWD outbreaks were linked to the importation of elks from Canada in 1994 based on circumstantial evidences.
 
In December 2010, one elk was confirmed as positive at Farm 5. Consequently, all cervid – 3 elks, 11 Manchurian Sika deer and 20 Sika deer – were culled and one Manchurian Sika deer and seven Sika deer were found to be positive. This is the first report of CWD in these sub-species of deer. Epidemiological investigations found that the owner of the Farm 2 in CWD outbreaks in July 2010 had co-owned the Farm 5.
 
In addition, it was newly revealed that one positive elk was introduced from Farm 6 of Jinju-si Gyeongsang Namdo. All cervid – 19 elks, 15 crossbreed (species unknown) and 64 Sika deer – of Farm 6 were culled, but all confirmed as negative.
 
 
 
 
 
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
 
The infectious agents responsible for transmissible spongiform encephalopathy (TSE) are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat. It has long been recognized, for example, that boiling is ineffective and that higher temperatures are most efficient when combined with steam under pressure (i.e., autoclaving). As a means of decontamination, dry heat is used only at the extremely high temperatures achieved during incineration, usually in excess of 600°C. It has been assumed, without proof, that incineration totally inactivates the agents of TSE, whether of human or animal origin.
 
 
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
 
Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.
 
 
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
 
The data presented here demonstrate that sPMCA can detect low levels of PrPCWD in the environment, corroborate previous biological and experimental data suggesting long term persistence of prions in the environment2,3 and imply that PrPCWD accumulation over time may contribute to transmission of CWD in areas where it has been endemic for decades. This work demonstrates the utility of sPMCA to evaluate other environmental water sources for PrPCWD, including smaller bodies of water such as vernal pools and wallows, where large numbers of cervids congregate and into which prions from infected animals may be shed and concentrated to infectious levels.
 
 
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
 
Keywords:Abattoir;bovine spongiform encephalopathy;QRA;scrapie;TSE
 
In this article the development and parameterization of a quantitative assessment is described that estimates the amount of TSE infectivity that is present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for cattle and classical/atypical scrapie for sheep and lambs) and the amounts that subsequently fall to the floor during processing at facilities that handle specified risk material (SRM). BSE in cattle was found to contain the most oral doses, with a mean of 9864 BO ID50s (310, 38840) in a whole carcass compared to a mean of 1851 OO ID50s (600, 4070) and 614 OO ID50s (155, 1509) for a sheep infected with classical and atypical scrapie, respectively. Lambs contained the least infectivity with a mean of 251 OO ID50s (83, 548) for classical scrapie and 1 OO ID50s (0.2, 2) for atypical scrapie. The highest amounts of infectivity falling to the floor and entering the drains from slaughtering a whole carcass at SRM facilities were found to be from cattle infected with BSE at rendering and large incineration facilities with 7.4 BO ID50s (0.1, 29), intermediate plants and small incinerators with a mean of 4.5 BO ID50s (0.1, 18), and collection centers, 3.6 BO ID50s (0.1, 14). The lowest amounts entering drains are from lambs infected with classical and atypical scrapie at intermediate plants and atypical scrapie at collection centers with a mean of 3 × 10−7 OO ID50s (2 × 10−8, 1 × 10−6) per carcass. The results of this model provide key inputs for the model in the companion paper published here.
 
 
PL1
 
Using in vitro prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.
 
Claudio Soto
 
Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.
 
Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.
 
=========================
 
***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
 
========================
 
Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
 
 
see ;
 
 
 
 
 
 
Wednesday, December 16, 2015
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
 
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
 
Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.
 
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Discussion
 
Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).
 
Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.
 
This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.
 
PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.
 
In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.
 
Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification
 
 
Wednesday, December 16, 2015
 
*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission ***
 
 
Circulation of prions within dust on a scrapie affected farm
 
Kevin C Gough1, Claire A Baker2, Hugh A Simmons3, Steve A Hawkins3 and Ben C Maddison2*
 
Abstract
 
Prion diseases are fatal neurological disorders that affect humans and animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs have a direct link to the transmission of disease. Using protein misfolding cyclic amplification we demonstrate that scrapie PrPSc can be detected within circulating dusts that are present on a farm that is naturally contaminated with sheep scrapie. The presence of infectious scrapie within airborne dusts may represent a possible route of infection and illustrates the difficulties that may be associated with the effective decontamination of such scrapie affected premises.
 
snip...
 
Discussion
 
We present biochemical data illustrating the airborne movement of scrapie containing material within a contaminated farm environment. We were able to detect scrapie PrPSc within extracts from dusts collected over a 70 day period, in the absence of any sheep activity. We were also able to detect scrapie PrPSc within dusts collected within pasture at 30 m but not at 60 m distance away from the scrapie contaminated buildings, suggesting that the chance of contamination of pasture by scrapie contaminated dusts decreases with distance from contaminated farm buildings. PrPSc amplification by sPMCA has been shown to correlate with infectivity and amplified products have been shown to be infectious [14,15]. These experiments illustrate the potential for low dose scrapie infectivity to be present within such samples. We estimate low ng levels of scrapie positive brain equivalent were deposited per m2 over 70 days, in a barn previously occupied by sheep affected with scrapie. This movement of dusts and the accumulation of low levels of scrapie infectivity within this environment may in part explain previous observations where despite stringent pen decontamination regimens healthy lambs still became scrapie infected after apparent exposure from their environment alone [16]. The presence of sPMCA seeding activity and by inference, infectious prions within dusts, and their potential for airborne dissemination is highly novel and may have implications for the spread of scrapie within infected premises. The low level circulation and accumulation of scrapie prion containing dust material within the farm environment will likely impede the efficient decontamination of such scrapie contaminated buildings unless all possible reservoirs of dust are removed. Scrapie containing dusts could possibly infect animals during feeding and drinking, and respiratory and conjunctival routes may also be involved. It has been demonstrated that scrapie can be efficiently transmitted via the nasal route in sheep [17], as is also the case for CWD in both murine models and in white tailed deer [18-20].
 
The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.
 
 
Friday, December 14, 2012
 
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
 
snip...
 
In the USA, under the Food and Drug Administration’s BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.
 
Animals considered at high risk for CWD include:
 
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
 
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
 
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
 
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
 
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
 
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
 
snip...
 
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.
 
snip...
 
The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
 
snip...
 
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
 
snip...
 
In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
 
snip...
 
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
 
snip...
 
 
P.97: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum
 
Justin Greenlee1, S Jo Moore1, Jodi Smith1, M Heather West Greenlee2, and Robert Kunkle1 1National Animal Disease Center; Ames, IA USA; 2Iowa State University; Ames, IA USA
 
The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n D 5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the 2 inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, 2 distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
 
 
Saturday, January 31, 2015
 
European red deer (Cervus elaphus elaphus) are susceptible to Bovine Spongiform Encephalopathy BSE by Oral Alimentary route
 
 
I strenuously once again urge the FDA and its industry constituents, to make it MANDATORY that all ruminant feed be banned to all ruminants, and this should include all cervids as soon as possible for the following reasons...
 
======
 
In the USA, under the Food and Drug Administrations BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system.
 
***However, this recommendation is guidance and not a requirement by law.
 
======
 
31 Jan 2015 at 20:14 GMT
 
*** Ruminant feed ban for cervids in the United States? ***
 
31 Jan 2015 at 20:14 GMT
 
 
98 | Veterinary Record | January 24, 2015
 
EDITORIAL
 
Scrapie: a particularly persistent pathogen
 
Cristina Acín
 
Resistant prions in the environment have been the sword of Damocles for scrapie control and eradication. Attempts to establish which physical and chemical agents could be applied to inactivate or moderate scrapie infectivity were initiated in the 1960s and 1970s,with the first study of this type focusing on the effect of heat treatment in reducing prion infectivity (Hunter and Millson 1964). Nowadays, most of the chemical procedures that aim to inactivate the prion protein are based on the method developed by Kimberlin and collaborators (1983). This procedure consists of treatment with 20,000 parts per million free chlorine solution, for a minimum of one hour, of all surfaces that need to be sterilised (in laboratories, lambing pens, slaughterhouses, and so on). Despite this, veterinarians and farmers may still ask a range of questions, such as ‘Is there an official procedure published somewhere?’ and ‘Is there an international organisation which recommends and defines the exact method of scrapie decontamination that must be applied?’
 
From a European perspective, it is difficult to find a treatment that could be applied, especially in relation to the disinfection of surfaces in lambing pens of affected flocks. A 999/2001 EU regulation on controlling spongiform encephalopathies (European Parliament and Council 2001) did not specify a particular decontamination measure to be used when an outbreak of scrapie is diagnosed. There is only a brief recommendation in Annex VII concerning the control and eradication of transmissible spongiform encephalopathies (TSE s).
 
Chapter B of the regulation explains the measures that must be applied if new caprine animals are to be introduced to a holding where a scrapie outbreak has previously been diagnosed. In that case, the statement indicates that caprine animals can be introduced ‘provided that a cleaning and disinfection of all animal housing on the premises has been carried out following destocking’.
 
Issues around cleaning and disinfection are common in prion prevention recommendations, but relevant authorities, veterinarians and farmers may have difficulties in finding the specific protocol which applies. The European Food and Safety Authority (EFSA ) published a detailed report about the efficacy of certain biocides, such as sodium hydroxide, sodium hypochlorite, guanidine and even a formulation of copper or iron metal ions in combination with hydrogen peroxide, against prions (EFSA 2009). The report was based on scientific evidence (Fichet and others 2004, Lemmer and others 2004, Gao and others 2006, Solassol and others 2006) but unfortunately the decontamination measures were not assessed under outbreak conditions.
 
The EFSA Panel on Biological Hazards recently published its conclusions on the scrapie situation in the EU after 10 years of monitoring and control of the disease in sheep and goats (EFSA 2014), and one of the most interesting findings was the Icelandic experience regarding the effect of disinfection in scrapie control. The Icelandic plan consisted of: culling scrapie-affected sheep or the whole flock in newly diagnosed outbreaks; deep cleaning and disinfection of stables, sheds, barns and equipment with high pressure washing followed by cleaning with 500 parts per million of hypochlorite; drying and treatment with 300 ppm of iodophor; and restocking was not permitted for at least two years. Even when all of these measures were implemented, scrapie recurred on several farms, indicating that the infectious agent survived for years in the environment, even as many as 16 years after restocking (Georgsson and others 2006).
 
In the rest of the countries considered in the EFSA (2014) report, recommendations for disinfection measures were not specifically defined at the government level. In the report, the only recommendation that is made for sheep is repopulation with sheep with scrapie-resistant genotypes. This reduces the risk of scrapie recurrence but it is difficult to know its effect on the infection.
 
Until the EFSA was established (in May 2003), scientific opinions about TSE s were provided by the Scientific Steering Committee (SSC) of the EC, whose advice regarding inactivation procedures focused on treating animal waste at high temperatures (150°C for three hours) and high pressure alkaline hydrolysis (SSC 2003). At the same time, the TSE Risk Management Subgroup of the Advisory Committee on Dangerous Pathogens (ACDP) in the UK published guidance on safe working and the prevention of TSE infection. Annex C of the ACDP report established that sodium hypochlorite was considered to be effective, but only if 20,000 ppm of available chlorine was present for at least one hour, which has practical limitations such as the release of chlorine gas, corrosion, incompatibility with formaldehyde, alcohols and acids, rapid inactivation of its active chemicals and the stability of dilutions (ACDP 2009).
 
In an international context, the World Organisation for Animal Health (OIE) does not recommend a specific disinfection protocol for prion agents in its Terrestrial Code or Manual. Chapter 4.13 of the Terrestrial Code, General recommendations on disinfection and disinsection (OIE 2014), focuses on foot-and-mouth disease virus, mycobacteria and Bacillus anthracis, but not on prion disinfection. Nevertheless, the last update published by the OIE on bovine spongiform encephalopathy (OIE 2012) indicates that few effective decontamination techniques are available to inactivate the agent on surfaces, and recommends the removal of all organic material and the use of sodium hydroxide, or a sodium hypochlorite solution containing 2 per cent available chlorine, for more than one hour at 20ºC.
 
The World Health Organization outlines guidelines for the control of TSE s, and also emphasises the importance of mechanically cleaning surfaces before disinfection with sodium hydroxide or sodium hypochlorite for one hour (WHO 1999).
 
Finally, the relevant agencies in both Canada and the USA suggest that the best treatments for surfaces potentially contaminated with prions are sodium hydroxide or sodium hypochlorite at 20,000 ppm. This is a 2 per cent solution, while most commercial household bleaches contain 5.25 per cent sodium hypochlorite. It is therefore recommended to dilute one part 5.25 per cent bleach with 1.5 parts water (CDC 2009, Canadian Food Inspection Agency 2013).
 
So what should we do about disinfection against prions? First, it is suggested that a single protocol be created by international authorities to homogenise inactivation procedures and enable their application in all scrapie-affected countries. Sodium hypochlorite with 20,000 ppm of available chlorine seems to be the procedure used in most countries, as noted in a paper summarised on p 99 of this issue of Veterinary Record (Hawkins and others 2015). But are we totally sure of its effectiveness as a preventive measure in a scrapie outbreak? Would an in-depth study of the recurrence of scrapie disease be needed?
 
What we can conclude is that, if we want to fight prion diseases, and specifically classical scrapie, we must focus on the accuracy of diagnosis, monitoring and surveillance; appropriate animal identification and control of movements; and, in the end, have homogeneous and suitable protocols to decontaminate and disinfect lambing barns, sheds and equipment available to veterinarians and farmers. Finally, further investigations into the resistance of prion proteins in the diversity of environmental surfaces are required.
 
References
 
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98 | Veterinary Record | January 24, 2015
 
 
Persistence of ovine scrapie infectivity in a farm environment following cleaning and decontamination
 
Steve A. C. Hawkins, MIBiol, Pathology Department1, Hugh A. Simmons, BVSc MRCVS, MBA, MA Animal Services Unit1, Kevin C. Gough, BSc, PhD2 and Ben C. Maddison, BSc, PhD3 + Author Affiliations
 
1Animal and Plant Health Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK 2School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington, Loughborough, Leicestershire LE12 5RD, UK 3ADAS UK, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington, Loughborough, Leicestershire LE12 5RD, UK E-mail for correspondence: ben.maddison@adas.co.uk Abstract Scrapie of sheep/goats and chronic wasting disease of deer/elk are contagious prion diseases where environmental reservoirs are directly implicated in the transmission of disease. In this study, the effectiveness of recommended scrapie farm decontamination regimens was evaluated by a sheep bioassay using buildings naturally contaminated with scrapie. Pens within a farm building were treated with either 20,000 parts per million free chorine solution for one hour or were treated with the same but were followed by painting and full re-galvanisation or replacement of metalwork within the pen. Scrapie susceptible lambs of the PRNP genotype VRQ/VRQ were reared within these pens and their scrapie status was monitored by recto-anal mucosa-associated lymphoid tissue. All animals became infected over an 18-month period, even in the pen that had been subject to the most stringent decontamination process. These data suggest that recommended current guidelines for the decontamination of farm buildings following outbreaks of scrapie do little to reduce the titre of infectious scrapie material and that environmental recontamination could also be an issue associated with these premises.
 
SNIP...
 
Discussion
 
Thorough pressure washing of a pen had no effect on the amount of bioavailable scrapie infectivity (pen B). The routine removal of prions from surfaces within a laboratory setting is treatment for a minimum of one hour with 20,000 ppm free chlorine, a method originally based on the use of brain macerates from infected rodents to evaluate the effectiveness of decontamination (Kimberlin and others 1983). Further studies have also investigated the effectiveness of hypochlorite disinfection of metal surfaces to simulate the decontamination of surgical devices within a hospital setting. Such treatments with hypochlorite solution were able to reduce infectivity by 5.5 logs to lower than the sensitivity of the bioassay used (Lemmer and others 2004). Analogous treatment of the pen surfaces did not effectively remove the levels of scrapie infectivity over that of the control pens, indicating that this method of decontamination is not effective within a farm setting. This may be due to the high level of biological matrix that is present upon surfaces within the farm environment, which may reduce the amount of free chlorine available to inactivate any infectious prion. Remarkably 1/5 sheep introduced into pen D had also became scrapie positive within nine months, with all animals in this pen being RAMALT positive by 18 months of age. Pen D was no further away from the control pen (pen A) than any of the other pens within this barn. Localised hot spots of infectivity may be present within scrapie-contaminated environments, but it is unlikely that pen D area had an amount of scrapie contamination that was significantly different than the other areas within this building. Similarly, there were no differences in how the biosecurity of pen D was maintained, or how this pen was ventilated compared with the other pens. This observation, perhaps, indicates the slower kinetics of disease uptake within this pen and is consistent with a more thorough prion removal and recontamination. These observations may also account for the presence of inadvertent scrapie cases within other studies, where despite stringent biosecurity, control animals have become scrapie positive during challenge studies using barns that also housed scrapie-affected animals (Ryder and others 2009). The bioassay data indicate that the exposure of the sheep to a farm environment after decontamination efforts thought to be effective in removing scrapie is sufficient for the animals to become infected with scrapie. The main exposure routes within this scenario are likely to be via the oral route, during feeding and drinking, and respiratory and conjunctival routes. It has been demonstrated that scrapie infectivity can be efficiently transmitted via the nasal route in sheep (Hamir and others 2008), as is the case for CWD in both murine models and in white-tailed deer (Denkers and others 2010, 2013). Recently, it has also been demonstrated that CWD prions presented as dust when bound to the soil mineral montmorillonite can be infectious via the nasal route (Nichols and others 2013). When considering pens C and D, the actual source of the infectious agent in the pens is not known, it is possible that biologically relevant levels of prion survive on surfaces during the decontamination regimen (pen C). With the use of galvanising and painting (pen D) covering and sealing the surface of the pen, it is possible that scrapie material recontaminated the pens by the movement of infectious prions contained within dusts originating from other parts of the barn that were not decontaminated or from other areas of the farm.
 
Given that scrapie prions are widespread on the surfaces of affected farms (Maddison and others 2010a), irrespective of the source of the infectious prions in the pens, this study clearly highlights the difficulties that are faced with the effective removal of environmentally associated scrapie infectivity. This is likely to be paralleled in CWD which shows strong similarities to scrapie in terms of both the dissemination of prions into the environment and the facile mode of disease transmission. These data further contribute to the understanding that prion diseases can be highly transmissible between susceptible individuals not just by direct contact but through highly stable environmental reservoirs that are refractory to decontamination.
 
The presence of these environmentally associated prions in farm buildings make the control of these diseases a considerable challenge, especially in animal species such as goats where there is lack of genetic resistance to scrapie and, therefore, no scope to re-stock farms with animals that are resistant to scrapie.
 
Scrapie Sheep Goats Transmissible spongiform encephalopathies (TSE) Accepted October 12, 2014. Published Online First 31 October 2014
 
 
Monday, November 3, 2014
 
Persistence of ovine scrapie infectivity in a farm environment following cleaning and decontamination
 
 
PPo3-22:
 
Detection of Environmentally Associated PrPSc on a Farm with Endemic Scrapie
 
Ben C. Maddison,1 Claire A. Baker,1 Helen C. Rees,1 Linda A. Terry,2 Leigh Thorne,2 Susan J. Belworthy2 and Kevin C. Gough3 1ADAS-UK LTD; Department of Biology; University of Leicester; Leicester, UK; 2Veterinary Laboratories Agency; Surry, KT UK; 3Department of Veterinary Medicine and Science; University of Nottingham; Sutton Bonington, Loughborough UK
 
Key words: scrapie, evironmental persistence, sPMCA
 
Ovine scrapie shows considerable horizontal transmission, yet the routes of transmission and specifically the role of fomites in transmission remain poorly defined. Here we present biochemical data demonstrating that on a scrapie-affected sheep farm, scrapie prion contamination is widespread. It was anticipated at the outset that if prions contaminate the environment that they would be there at extremely low levels, as such the most sensitive method available for the detection of PrPSc, serial Protein Misfolding Cyclic Amplification (sPMCA), was used in this study. We investigated the distribution of environmental scrapie prions by applying ovine sPMCA to samples taken from a range of surfaces that were accessible to animals and could be collected by use of a wetted foam swab. Prion was amplified by sPMCA from a number of these environmental swab samples including those taken from metal, plastic and wooden surfaces, both in the indoor and outdoor environment. At the time of sampling there had been no sheep contact with these areas for at least 20 days prior to sampling indicating that prions persist for at least this duration in the environment. These data implicate inanimate objects as environmental reservoirs of prion infectivity which are likely to contribute to disease transmission.
 
 
Willingham, Erin McNulty, Kelly Anderson, Jeanette Hayes-Klug, Amy Nalls, and Candace Mathiason Colorado State University; Fort Collins, CO USA
 
Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy (TSE), of free-ranging and captive cervids (deer, elk and moose).
 
The presence of infectious prions in the tissues, bodily fluids and environments of clinical and preclinical CWD-infected animals is thought to account for its high transmission efficiency. Recently it has been recognized that mother to offspring transmission may contribute to the facile transmission of some TSEs. Although the mechanism behind maternal transmission is not yet known, the extended asymptomatic TSE carrier phase (lasting years to decades) suggests that it may have implications in the spread of prions.
 
Placental trafficking and/or secretion in milk are 2 means by which maternal prion transmission may occur. In these studies we explore these avenues during early and late infection using a transgenic mouse model expressing cervid prion protein. Na€ıve and CWD-infected dams were bred at both timepoints, and were allowed to bear and raise their offspring. Milk was collected from the dams for prion analysis, and the offspring were observed for TSE disease progression. Terminal tissues harvested from both dams and offspring were analyzed for prions.
 
We have demonstrated that
 
(1) CWDinfected TgCerPRP females successfully breed and bear offspring, and
 
(2) the presence of PrPCWD in reproductive and mammary tissue from CWD-infected dams.
 
We are currently analyzing terminal tissue harvested from offspring born to CWD-infected dams for the detection of PrPCWD and amplification competent prions. These studies will provide insight into the potential mechanisms and biological significance associated with mother to offspring transmission of TSEs.
 
==============
 
P.157: Uptake of prions into plants
 
Christopher Johnson1, Christina Carlson1, Matthew Keating1,2, Nicole Gibbs1, Haeyoon Chang1, Jamie Wiepz1, and Joel Pedersen1 1USGS National Wildlife Health Center; Madison, WI USA; 2University of Wisconsin - Madison; Madison, WI USA
 
Soil may preserve chronic wasting disease (CWD) and scrapie infectivity in the environment, making consumption or inhalation of soil particles a plausible mechanism whereby na€ıve animals can be exposed to prions. Plants are known to absorb a variety of substances from soil, including whole proteins, yet the potential for plants to take up abnormal prion protein (PrPTSE) and preserve prion infectivity is not known. In this study, we assessed PrPTSE uptake into roots using laser scanning confocal microscopy with fluorescently tagged PrPTSE and we used serial protein misfolding cyclic amplification (sPMCA) and detect and quantify PrPTSE levels in plant aerial tissues. Fluorescence was identified in the root hairs of the model plant Arabidopsis thaliana, as well as the crop plants alfalfa (Medicago sativa), barley (Hordeum vulgare) and tomato (Solanum lycopersicum) upon exposure to tagged PrPTSE but not a tagged control preparation. Using sPMCA, we found evidence of PrPTSE in aerial tissues of A. thaliana, alfalfa and maize (Zea mays) grown in hydroponic cultures in which only roots were exposed to PrPTSE. Levels of PrPTSE in plant aerial tissues ranged from approximately 4 £ 10 ¡10 to 1 £ 10 ¡9 g PrPTSE g ¡1 plant dry weight or 2 £ 105 to 7 £ 106 intracerebral ID50 units g ¡1 plant dry weight. Both stems and leaves of A. thaliana grown in culture media containing prions are infectious when intracerebrally-injected into mice. ***Our results suggest that prions can be taken up by plants and that contaminated plants may represent a previously unrecognized risk of human, domestic species and wildlife exposure to prions.
 
===========
 
***Our results suggest that prions can be taken up by plants and that contaminated plants may represent a previously unrecognized risk of human, domestic species and wildlife exposure to prions.***
 
SEE ;
 
Friday, May 15, 2015
 
Grass Plants Bind, Retain, Uptake, and Transport Infectious Prions
 
Report
 
 
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;
 
 
Monday, October 26, 2015
 
*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015
 
 
Sunday, October 25, 2015
 
USAHA Detailed Events Schedule – 119th USAHA Annual Meeting CAPTIVE LIVESTOCK CWD SCRAPIE TSE PRION
 
 
*** Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation ***
 
 
Saturday, September 12, 2015
 
In utero transmission and tissue distribution of chronic wasting disease-associated prions in free-ranging Rocky Mountain elk
 
>>>Interestingly, five of fifteen sPMCA positive dams showed no evidence of PrPCWD in either CNS or LRS, sites typically assessed in diagnosing CWD. Analysis of fetal tissues harvested from the fifteen sPMCA positive dams revealed PrPCWD in 80% of fetuses (12/15), regardless of gestational stage. These findings demonstrate that PrPCWD is more abundant in peripheral tissues of CWD exposed elk than current diagnostic methods suggest, and that transmission of prions from mother to offspring may contribute to the efficient transmission of the CWD in naturally exposed cervid populations.<<<
 
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Title: Transmission of scrapie prions to primate after an extended silent incubation period
 
Authors
 
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -
 
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.
 
Interpretive Summary:
 
The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.
 
Technical Abstract:
 
Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
 
***This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
 
 
Saturday, December 12, 2015
 
CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015
 
 
Tuesday, December 29, 2015
 
TEXAS MONTHLY CHRONIC WASTING DISEASE CWD JANUARY 2016 DEER BREEDERS STILL DON'T GET IT $
 
Chronic Wasting Unease
 
The emergence of a deadly disease has wildlife officials and deer breeders eyeing each other suspiciously.
 
 
Wednesday, March 18, 2015
 
*** Chronic Wasting Disease CWD Confirmed Texas Trans Pecos March 18, 2015 ***
 
 
Wednesday, March 25, 2015
 
*** Chronic Wasting Disease CWD Cases Confirmed In New Mexico 2013 and 2014 UPDATE 2015 ***
 
 
 
*** Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population Monitoring and Capture-Recapture Data
 
‘’Mountain lions prey selectively on CWD infected deer [33] and CWD could result in an abundance of vulnerable prey, thereby enhancing mountain lion survival and reproduction [20].’’
 
please see  ;
 
‘’preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.’’
 
Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay
 
Christopher J. Johnson1, Christina M. Carlson2, Aaron R. Morawski3, Alyson Manthei4, Neil R. Cashman5
 
1USGS National Wildlife Health Center, 2Department of Soil Science, University of Wisconsin–Madison, 3Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4Merial Veterinary Scholars Program, School of Veterinary Medicine, University of Wisconsin–Madison, 5Department of Neurology, University of British Columbia
 
Summary
 
Measuring the barrier to the interspecies transmission of prion diseases is challenging and typically involves animal challenges or biochemical assays. Here, we present an in vitro prion protein conversion assay with the ability to predict species barriers.
 
Date Published: 3/10/2015, Issue 97; doi: 10.3791/52522
 
Keywords: Medicine, Issue 97, Prion, species barrier, conversion, immunoblotting, transmissible spongiform encephalopathy, interspecies transmission Cite this Article
 
Johnson, C. J., Carlson, C. M., Morawski, A. R., Manthei, A., Cashman, N. R. Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay. J. Vis. Exp. (97), e52522, doi:10.3791/52522 (2015). Abstract
 
Studies to understanding interspecies transmission of transmissible spongiform encephalopathies (TSEs, prion diseases) are challenging in that they typically rely upon lengthy and costly in vivo animal challenge studies. A number of in vitro assays have been developed to aid in measuring prion species barriers, thereby reducing animal use and providing quicker results than animal bioassays. Here, we present the protocol for a rapid in vitro prion conversion assay called the conversion efficiency ratio (CER) assay. In this assay cellular prion protein (PrPC) from an uninfected host brain is denatured at both pH 7.4 and 3.5 to produce two substrates. When the pH 7.4 substrate is incubated with TSE agent, the amount of PrPC that converts to a proteinase K (PK)-resistant state is modulated by the original host’s species barrier to the TSE agent. In contrast, PrPC in the pH 3.5 substrate is misfolded by any TSE agent. By comparing the amount of PK-resistant prion protein in the two substrates, an assessment of the host’s species barrier can be made. We show that the CER assay correctly predicts known prion species barriers of laboratory mice and, as an example, show some preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.
 
 
>>> show some preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.
 
AD.63: Susceptibility of domestic cats to chronic wasting disease
 
Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1
 
1Colorado State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN USA
 
Domestic and nondomestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated cats developed signs consistent with prion disease, including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from these two cats were pooled and inoculated into cohorts of cats by IC, PO, and intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the symptomatic cats by western blotting and immunohistochemistry and abnormalities were seen in magnetic resonance imaging, including multifocal T2 fluid attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4 IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns consistent with the early stage of feline CWD. These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to- feline transmission in nature.
 
 
www.landesbioscience.com
 
PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)
 
 
 
 
 
PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)
 
 
 
Thursday, May 31, 2012
 
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission, Scrapie, cats, species barrier, burial, and more
 
 
Monday, August 8, 2011
 
Susceptibility of Domestic Cats to CWD Infection
 
 
Sunday, August 25, 2013
 
Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission
 
 
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. J.et 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.
 
 
3 further cheetah cases have occured, plus 1 lion, plus all the primates, and 20 additional house cats. Nothing has been published on any of these UK cases either. One supposes the problem here with publishing is that many unpublished cases were _born_ long after the feed "ban". Caught between a rock and a hard place: leaky ban or horizontal transmission (or both).
 
 
 
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...
 
 
 
on occassions, materials obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture...
 
 
*** Meldrum's notes on pet foods and materials used
 
 
*** BSE & Pedigree Petfoods ***
 
 
In 2003, Denver Post reporter Theo Stein interviewed scientists about CWD spreading though deer and elk in Colorado. Dr. Valerius Geist, who paradoxically has become a darling of anti-wolfers, made this assertion about the significance of wolves in containing CWD spread via proteins called prions.
 
“Wolves will certainly bring the disease to a halt,” he said. “They will remove infected individuals and clean up carcasses that could transmit the disease.”
 
Stein added that “Geist and Princeton University biologist Andrew Dobson theorize that killing off the wolf allowed CWD to take hold in the first place.”
 
Wolves aren’t alone. In a 2009 study titled “Mountain lions prey selectively on prion-infected mule deer,” researchers in Colorado discovered that “adult mule deer killed by mountain lions were more likely to be prion-infected than were deer killed more randomly … suggesting that mountain lions were selecting for infected individuals when they targeted adult deer.”
 
 
NO, NO, NOT NO, BUT HELL KNOW !!!
 
PLEASE be careful what you ask for.
 
recently, canine spongiform encephalopathy has been confirmed.
 
I proved this in 2005, with a letter from MAFF/DEFRA et al confirming my suspicions of the ‘hound study’ way back. this was covered up. see documents below.
 
also, recently, cwd to the domestic cat is a great concern.
 
even though to date, as far as I am aware of, the cwd study on the mountain lion has not produced any confirmation yet, we already know that the feline species is highly succeptible to the TSE prion. domestic cats and the exotic zoo big cats.
 
so in my honest opinion, any program that would use wild animals to prey on other wild animals, as a tool to help curb CWD TSE prion disease, would only help enhance the spread of disease, and it would only help spread the disease to other species. ...TSS
 
Monday, February 14, 2011
 
THE ROLE OF PREDATION IN DISEASE CONTROL: A COMPARISON OF SELECTIVE AND NONSELECTIVE REMOVAL ON PRION DISEASE DYNAMICS IN DEER
 
NO, NO, NOT NO, BUT HELL NO !
 
Journal of Wildlife Diseases, 47(1), 2011, pp. 78-93 © Wildlife Disease Association 2011
 
 
snip...
 
Friday, April 17, 2015
 
Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay
 
>>> show some preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.
 
 
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
 
Emmanuel Comoy, Jacqueline Mikol, Val erie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
 
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. *** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
 
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold longe incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
 
***is the third potentially zoonotic PD (with BSE and L-type BSE),
 
***thus questioning the origin of human sporadic cases.
 
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
 
===============
 
***thus questioning the origin of human sporadic cases...TSS
 
===============
 
 
==========================================
 
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
 
==========================================
 
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
 
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
 
O18
 
Zoonotic Potential of CWD Prions
 
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA
 
*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.
 
==================
 
***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***
 
==================
 
P.105: RT-QuIC models trans-species prion transmission
 
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA
 
Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.
 
================
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***
 
================
 
 
From: Terry S. Singeltary Sr.
 
Sent: Saturday, November 15, 2014 9:29 PM
 
To: Terry S. Singeltary Sr.
 
Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984
 
THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE
 
R. G. WILL
 
1984
 
*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;
 
snip...
 
 
85%+ of all human tse prion disease is sporadic CJD.
 
see what the NIH prion Gods say themselves ;
 
‘’In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD. That assumption would be wrong.’’
 
‘’Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.’’
 
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
 
 
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
 
 
now, let’s see what the authors said about this casual link, personal communications years ago. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”
 
From: TSS (216-119-163-189.ipset45.wt.net)
 
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
 
Date: September 30, 2002 at 7:06 am PST
 
From: "Belay, Ermias"
 
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
 
Sent: Monday, September 30, 2002 9:22 AM
 
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
 
Dear Sir/Madam,
 
In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
 
Ermias Belay, M.D. Centers for Disease Control and Prevention
 
-----Original Message-----
 
From: Sent: Sunday, September 29, 2002 10:15 AM
 
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
 
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
 
Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS
 
Thursday, April 03, 2008
 
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
 
snip...
 
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
 
snip... full text ;
 
 
CJD is so rare in people under age 30, one case in a billion (leaving out medical mishaps), that four cases under 30 is "very high," says Colorado neurologist Bosque. "Then, if you add these other two from Wisconsin [cases in the newspaper], six cases of CJD in people associated with venison is very, very high." Only now, with Mary Riley, there are at least seven, and possibly eight, with Steve, her dining companion. "It's not critical mass that matters," however, Belay says. "One case would do it for me." The chance that two people who know each other would both contact CJD, like the two Wisconsin sportsmen, is so unlikely, experts say, it would happen only once in 140 years.
 
Given the incubation period for TSEs in humans, it may require another generation to write the final chapter on CWD in Wisconsin. "Does chronic wasting disease pass into humans? We'll be able to answer that in 2022," says Race. Meanwhile, the state has become part of an immense experiment.
 
 
I urge everyone to watch this video closely...terry
 
*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
 
 
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
 
 
Monday, November 16, 2015
 
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***
 
 
 
Saturday, December 12, 2015
 
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015
 
 
Thursday, December 24, 2015
 
Infectious disease spread is fueled by international trade
 
 
Thursday, December 17, 2015
 
Annual report of the Scientific Network on BSE-TSE 2015 EFSA-Q-2015-00738 10 December 2015
 
 
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***
 
 
 
Thursday, December 17, 2015
 
Annual report of the Scientific Network on BSE-TSE 2015 EFSA-Q-2015-00738 10 December 2015
 
 
Saturday, December 12, 2015
 
CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015
 
 
Thursday, December 24, 2015
 
Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings
 
Article type: Research Article
 
 
 
Terry S. Singeltary Sr.

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