Chronic Wasting Disease: Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019

Fatal Degenerative Neurologic Illnesses in Men Who Participated in Wild Game Feasts --- Wisconsin, 2002

Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue

(1). CJD has an annual incidence of approximately 1 case per million population in the United States (1) and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD)

(2). During 1993--1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.

Case Reports

Case 1. In December 1992, a Wisconsin man aged 66 years with a history of seizures since 1969 sought treatment for recurring seizures, increasing forgetfulness, and worsening hand tremors. Electroencephalographic (EEG) examination demonstrated focal epileptiform activity and nonspecific diffuse abnormalities, but no specific diagnosis was made. In February 1993, he was hospitalized for increasing confusion, ataxia, and movement tremors of his extremities. A magnetic resonance image (MRI) demonstrated mild, nonspecific enhancement along the inferior parasagittal occipital lobe. A repeat EEG showed bifrontal intermittent, short-interval, periodic sharp waves, suggesting a progressive encephalopathy; a diagnosis of CJD was suspected. The man died later that month; neuropathologic examination of brain tissue during autopsy indicated subacute spongiform encephalopathy, compatible with CJD.

The man was a lifelong hunter who ate venison frequently. He hunted primarily in northern Wisconsin but also at least once in Montana. He hosted wild game feasts at his cabin in northern Wisconsin from 1976 until shortly before his death. Fixed brain tissue obtained during the autopsy was sent for analysis to the National Prion Disease Pathology Surveillance Center (NPDPSC) and reexamined at the institution where the autopsy was conducted. Histopathologic examination did not substantiate the diagnosis of prion disease. In addition, 27 brain tissue sections were negative for prions by immunostaining despite positive antibody reactions against other proteins (controls), which indicated that other epitopes in the tissue samples were preserved.

Case 2. In May 1999, a Minnesota man aged 55 years with no previous history of a neurologic disease sought evaluation and treatment following a 3-month history of progressive difficulty in writing and unsteadiness of gait. A computerized tomography (CT) scan and MRI examination of his head did not indicate any abnormality. In June 1999, he was hospitalized following onset of dementia, speech abnormalities, and myoclonic jerking. An EEG indicated left-hemispheric periodic sharp waves and moderate generalized background slowing; CJD was diagnosed clinically. In July 1999, following worsening symptoms and development of right upper extremity dystonia, the patient died. Neuropathologic evaluation of brain tissue during autopsy demonstrated widespread subcortical spongiform lesions, consistent with CJD.

The man was not a hunter but had a history of eating venison. He made an estimated 12 visits to the cabin where the wild game feasts were held, but he participated in only one feast during the mid-1980s. Sections of fixed and frozen brain tissue obtained during autopsy were analyzed at NPDPSC, and prion disease was confirmed by immunohistochemical and Western blot testing. The Western blot characteristics and prion disease phenotype in this patient were consistent with the most common form of sporadic CJD, classified as M/M (M/V) 1 (3). Subsequent genetic typing confirmed the presence of methionine homozygosity (M/M) at codon 129 of the patient's prion protein gene.

Case 3. In June 1992, a Wisconsin man aged 65 years sought treatment for progressive slowing of speech, worsening memory, and personality changes. By January 1993, his speech was reduced to one-word utterances. Neurologic examination showed a flat affect, decreased reflexes, and apraxia. A CT head scan showed mild atrophy, and an EEG was normal. Pick's disease was diagnosed. By May, he was unable to perform any daily living activities; he died in August 1993. Neuropathologic evaluation of brain tissue during autopsy showed symmetrical frontal lobe cerebral cortical atrophy and mild temporal lobe atrophy. No Pick's bodies or spongiform lesions were observed.

The man had a history of eating venison and participated regularly in wild game feasts held at the cabin owned by patient 1. He was a lifelong hunter and hunted mostly in Wisconsin but also in Wyoming and British Columbia. No game was brought to the wild game feasts from his hunting trips outside of Wisconsin. Examination of fixed brain tissue sent to NPDPSC demonstrated no lesions indicative of CJD, and immunohistochemical testing with antibody to the prion protein did not demonstrate the granular deposits seen in prion diseases.

Epidemiologic Investigation

Wild game feasts consisting of elk, deer, antelope, and other game that occurred at a cabin in northern Wisconsin owned by patient 1 began in 1976 and continued through 2002. These feasts typically involved 10--15 participants and usually occurred on weekends before or during hunting seasons in the fall and occasionally in the spring. Wild game brought to these feasts usually were harvested in Wisconsin, but three men who attended these feasts reported hunting in the western United States and bringing game back to Wisconsin. These activities took place in Colorado (near the towns of Cortez, Trinidad, Collbran, Durango, and Meeker), Wyoming (near the towns of Gilette and Cody), and Montana (near the town of Malta). CWD was not known to be endemic in these areas at the time that these hunting activities took place.

Information was obtained for 45 (85%) of 53 persons who were identified as possibly participating in the wild game feasts; all were male. Information was obtained by direct interview or from family members of decedents. Of the 45 persons, for whom information was obtained, 34 were reported to have attended wild game feasts. Seven of the 34 feast attendees were deceased, including the three patients. None of the four other decedents had a cause of death attributed to or associated with a degenerative neurologic disorder. None of the living participants had any signs or symptoms consistent with a degenerative neurologic disorder.

Reported by: JP Davis, MD, J Kazmierczak, DVM, M Wegner, MD, R Wierzba, Div of Public Health, State of Wisconsin Dept of Health and Family Svcs. P Gambetti, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio. L Schonberger, MD, R Maddox, MPH, E Belay, MD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; V Hsu, MD, EIS Officer, CDC.

Editorial Note:

CWD was first described in the United States in the 1960s and classified as a TSE in 1978. Previously localized to a contiguous endemic area in northeastern Colorado and southeast Wyoming, since 2000, CWD has been found in free-ranging deer or elk in Illinois, Nebraska, New Mexico, South Dakota, Wisconsin, and outside the previously known endemic areas of Colorado and Wyoming. CWD has been identified also in captive deer or elk in Colorado, Kansas, Minnesota, Montana, Nebraska, Oklahoma, South Dakota, and Wisconsin (4). Because a variant form of CJD, with specific neuropathologic and molecular characteristics that distinguish it from sporadic CJD, has been associated with eating cattle products infected with a prion that causes bovine spongiform encephalopathy (5), concern has been raised about the possibility that the prion associated with CWD might be transmitted to humans in a similar way.

In this investigation, because only one of the three cases in Wisconsin had neuropathologic confirmation of a prion disease, no association could be made between case participation in the wild game feasts and the development of CJD. Although patient 2 had confirmed CJD, he was unlikely to have eaten CWD-infected venison at these feasts because venison and other game from outside Wisconsin that was served at these feasts did not originate from known CWD-endemic areas, and the man participated in the feasts only once. In addition, the prion disease in this case was consistent with the most common form of sporadic CJD, without apparent unusual neuropathologic or molecular characteristics that might occur if the prion related to CWD had been responsible for the disease.

The findings in this report are subject to at least two limitations. First, not all members participating in wild game feasts could be identified, and not all persons listed as participating could be contacted for interviews. Second, interviews that were conducted required recall of events that occurred up to 25 years ago, limiting the detail or accuracy of events. However, the similar responses obtained from different sources support the accuracy of the investigation findings.

A previous investigation of unusually young CJD patients in whom the transmission of CWD was suspected also did not provide convincing evidence for a causal relationship between CWD and CJD (2). However, limited epidemiologic investigations cannot rule out the possibility that CWD might play a role in causing human illness. Ongoing surveillance of CJD, particularly in states with CWD, is important to assess the risk, if any, for CWD transmission to humans. Because the confirmation of CJD and the detection of a new prion disease require neuropathologic study of brain tissue, physicians are encouraged to contact NPDPSC (http://www.cjdsurveillance.com; telephone, 216-368-0587) to confirm diagnoses of CJD and to distinguish its various subtypes. Because of the known severity of TSEs in humans and the possibility that the CWD prion can affect humans, animals with evidence of CWD should be excluded from the human food or animal feed chains. Hunters and wild venison consumers should follow precautionary guidelines available from the Wisconsin Department of Agriculture, Trade, and Consumer Protection (http://datcp.state.wi.us/core/consumerinfo) to prevent potential exposures to the CWD agent.

References

Belay E. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283--314.

Belay E, Gambetti P, Schonberger L, et al. Creutzfeldt-Jakob disease in unusually young patients who consumed venison. Arch Neurol 2001;58:1673--8.

Parchi P, Giese A, Capellari S, et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999;46:224--33.

U.S. Department of Agriculture. Positive CWD cases: cumulative through Dec 2002 (including farm herds already depopulated). Available at http://aphisweb.aphis.usda.gov/vs/nahps//cwd/USAMapOfInfectedHerds.jpg.

Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:921--5.

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5207a1.htm

CDC finds no CWD-CJD link in Wisconsin deaths

Filed Under: BSE

Feb 20, 2003

Feb 20, 2003 (CIDRAP News) An investigation of the deaths of three men who had shared wild game feasts at a Wisconsin cabin revealed no evidence that the men's degenerative brain diseases were related to chronic wasting disease (CWD) in deer, according to the Center for Disease Control and Prevention (CDC).

The CDC investigated the three deaths because of concern that CWD in deer might be able to jump to humans who eat infected venison. The concern is based on evidence that bovine spongiform encephalopathy (BSE), or mad cow disease, causes variant Creutzfeldt-Jakob disease (CJD) in people who eat beef from infected animals.

Only one of the three men who died had confirmed CJD, and he was unlikely to have eaten CWD-infected venison, the CDC reported in the Feb 21 issue of Morbidity and Mortality Weekly Report.

"Because only one of the three cases in Wisconsin had neuropathologic confirmation of a prion disease, no association could be made between case participation in the wild game feasts and the development of CJD," the article states. The man who died of CJD probably did not eat infected venison because the venison served at the meals did not come from CWD-endemic areas and because he shared only one of the meals.

In addition, the CDC found no evidence of degenerative neurologic disease in 31 other people who were reported to have shared in game feasts at the same Wisconsin cabin. Four of these had died of causes other than neurologic disease, and the rest were still living and had no signs or symptoms of brain disease, the article says.

One of the three men who died was a lifelong hunter and hosted wild game feasts at his Wisconsin cabin from 1976 until he died in 1993, the CDC reported. Evidence from autopsy initially suggested that he had died of CJD, but further tests did not support that finding. A second man was also a Wisconsinite and lifelong hunter who regularly took part in the game meals at the cabin. He died in 1993 of what was thought to be Pick's disease; postmortem examination did not point to CJD.

The man whose disease was found to be CJD was a Minnesotan who died in 1999, the report says. He had visited the Wisconsin cabin about a dozen times but had eaten wild game only once. Analysis of his brain tissue suggested that his disease was the most common form of sporadic CJD, "without apparent unusual neruopathologic or molecular characteristics that might occur if the prion related to CWD had been responsible for the disease," the CDC said.

The CDC reported it could not interview some of the people who were thought to have eaten game at the Wisconsin cabin. "Limited epidemiologic investigations cannot rule out the possibility that CWD might play a role in causing human illness," and continued surveillance of CJD is important, the article states.

CDC. Fatal degenerative neurologic illnesses in men who participated in wild game feastsWisconsin, 2002. MMWR 2003;52(7) [Full text]

http://www.cidrap.umn.edu/news-perspective/2003/02/cdc-finds-no-cwd-cjd-link-wisconsin-deaths

CWD tests negative

No evidence that deer meat infected Midwestern men with prion disease, US health officials say.

Nov 26, 2002

CHARLES CHOI(CQCHOI@NASW.ORG)

Three outdoorsmen suspected of having contracted lethal cases of chronic wasting disease (CWD) from contaminated venison instead were found to have died from other causes. These new lab findings, released by Wisconsin health officials November 21, are the latest evidence that the prion-linked illness spreading rapidly in North American deer and elk herds has not leapt to humans, as bovine spongiform encephalopathy (BSE) is believed to have crossed the species barrier to cause human Creutzfeldt-Jakob disease (CJD).

All three of the men died of degenerative brain conditions with elements of dementia in the 1990s. Investigators discovered the avid outdoorsmen ate venison at wild game feasts in Wisconsin from the 1970s onwards, prompting concern over a potential link to CWD. The transmissible spongiform encephalopathy, found in deer and elk in at least 10 US states and two Canadian provinces, riddles the brain with microscopic holes and is marked by the presence of aberrant prion proteins that infectiously convert their normal counterparts .

Specimens of brain tissue from each of the three men were collected during their autopsies and forwarded last August to the National Prion Disease Pathology Surveillance Center in Cleveland, Ohio. Pathologists there who analyzed the samples using monoclonal antibodies to detect the presence of prions found no evidence of the misfolded proteins in the tissues of two of the men.

One of the men, Wisconsin hunter Roger Marten, died in 1993. A necropsy later that year diagnosed a rare neurological disorder known as Pick's disease. While that finding was later amended to frontal temporal dementia, prions are not known to cause either illness. A second man in whose tissue no prions were detected, Wisconsin hunter Wayne Waterhouse, also died in 1993. The cause of his death was a degenerative neurological disease with no clear origin, which Wisconsin state epidemiologist Jeffrey Davis said is true in 10 percent of such illnesses.

The new test results reveal that the third man, Minnesota resident James Botts, who died in 1999, did have sporadic CJD, which appears with no known cause. Botts' CJD phenotype was type 1, the most common kind, and evidence that his illness was not associated with a CWD prion. Davis added that Botts only attended one-to-three wild game feasts. "We have not been able to determine whether all three of these men attended any one specific event, so it is difficult to say with certainty that they shared meat from the same source," he explained.

"This is consistent with the message from the CDC and WHO, that CWD prion has not been shown to cause human illness," Wisconsin state epidemiologist James Kazmierczak said. He noted, however, that absence of evidence is not evidence of absence. Davis said investigators are searching for some 75 other participants in the wild game feasts to ascertain their conditions, and have tracked down about 45 so far.

The US Food and Drug Administration, National Institutes of Health and Department of Agriculture have all recently launched new efforts against CWD to track its spread, determine if it poses as much risk to humans as BSE, or to find therapies for prevention or treatment.

https://www.the-scientist.com/news-analysis/cwd-tests-negative-52444

https://www.sciencedirect.com/science/article/pii/S0033350614001401?via%

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Confucius ponders, what if???

***> (2). During 1993--1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD

***> cdc report was dated; February 21, 2003 / 52(07);125-127

so, we are looking at a very very poorly developed case history study report, with outdated science, to evaluate whether or not these 3 men had cwd tse prion i.e. sporadic cjd, only a few years after consumption?

really?

hogwash imo!

i don't blame the cdc nih et al for hurrying out that report, no need for the incubation period to catch up and reality set in, and have to report the end product, and then report the facts.

let's evaluate the science today with cwd zoonosis, AND ALSO, what about today, this was February 21, 2003 report, only a few years after the feast, what about today, how are those victims today???

but really, the case history study of those that participated, was so poorly done, really it does not hold much water, but let's look at those 3 men and science today...terry

INCUBATION PERIODS FOR TSE PRION

KURU INCUBATION 50 TO 60 YEARS

The youngest patient with kuru was 5 years old, and the mean age at death in the 1950s was approximately 49 years. The age at death increased with time, and the final patients in the early years of the 21st century were >60 years old, with incubation periods of >40 years (Collinge et al. 2008). Kuru occurred in patients of all PRNP codon 129 genotypes; heterozygotes appear to have had significantly longer incubation periods than homozygotes (Collinge et al. 2006).

The occurrence of CJD in relatively small cohorts of individuals exposed to human tissues in the course of medical treatment provides strong circumstantial evidence of iatrogenic transmission of this condition. CJD has occurred in over 200 cases treated with human pituitary hormones and similar numbers of recipients of human dura mater grafts (Brown et al. 2012). There have also been a few cases of CJD causally linked to corneal grafts, depth electrodes, and contaminated neurosurgical instruments (Table 3). The latter iatrogenic cases are largely historical, but cases linked to human growth hormone (hGH) and human dura mater grafts continue to occur, reflecting extended incubation periods of up to 42 and 30 years, respectively, although the numbers of such cases are gradually declining overall.

The incubation period in vCJD is unknown in individual cases, but a mean of 15 years has been suggested by mathematical models (Valleron et al. 2001) and extrapolation from descriptive epidemiological data. This estimate indicates that it may be some years before the full extent of the vCJD outbreak can be determined with confidence, not least because of the possibility of further cases in codon 129 heterozygotes.

Clinical Features/Investigations

Variant CJD affects younger age groups than sCJD, with a mean age at death of 30 years (Heath and Will 2008). Thirty-four of the cases in the United Kingdom were under the age of 20 years at onset, and a case with an onset at 11 years has been reported from Portugal (Barbot et al. 2010). The reason for this age distribution is uncertain but may relate to patterns of dietary exposure varying with age (Cooper and Bird 2002) or age-related susceptibility (Boelle et al. 2003; St Rose et al. 2006).

http://perspectivesinmedicine.cshlp.org/content/7/1/a024364.full

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620512/

The size of the variant Creutzfeldt-Jakob Disease (vCJD) epidemic in the United Kingdom is a major public health concern and a subject of speculation. The cases are young (mean age = 28). Assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.7 years [95% confidence interval (CI): 12.4 to 23.2] and that the total number of cases will be 205 (upper limit of the 95% CI: 403).

The distribution of the vCJD incubation period that best fits the data within the framework of our model has a mean of 16.7 years, with a standard deviation of 2.6 years. The 95% upper percentile of this distribution is 21.4 years. The 95% confidence interval (CI) of the estimates of the mean and standard deviation is relatively narrow: The 95% CI for the estimate of the mean incubation period is 12.4 to 23.2 years, and the 95% CI of the standard deviation is 0.9 to 8 years (10). The decrease in susceptibility to infection in exposed subjects older than 15 years, as estimated from the parameter α, was found to be very sharp: 16% per year of age (CI: 12 to 23%). This means that, under the best fitting hypothesis, an individual aged 20 years in 1981 had 55% less risk of becoming infected than a child aged 15 years (99.9% for an individual aged 70).

http://science.sciencemag.org/content/294/5547/1726.full

Incubation period: The estimated mean incubation period (defined as the time from infection to death) for infection via primary transmission is estimated to be approximately the delay from the peak of exposure to BSE which occurred in 1989/1990 to the peak in the vCJD deaths which occurred in 2000 [12-14]..The incubation period in transfusion transmitted vCJD has been between 6.5 and 8 years.

In a recent study of French vCJD cases, the incubation period has been estimated to be around 13 years (95% CI: 9,7-17,9 years) [15]. The incubation period is not dependant on age [16], however age-dependent susceptibility/exposure is estimated to be highest in teenagers and young adults in line with previous estimates [13].

https://ecdc.europa.eu/en/vcjd/facts

Classic CJD OR sporadic CJD, now linked to both atypical and typical BSE, atypical and typical Scrapie, and to CWD, usually has a long incubation period before symptoms appear. In some cases, this may be as long as 40 years. The incubation period for vCJD is unknown but is likely measured in terms of many years or decades.

Incubation Period The incubation period for naturally occurring sCJD is not known. In iCJD, the incubation period and clinical presentation are determined by the titre of inoculum and site of inoculation.(2) With iCJD, the mean incubation period is 1.5 – 1.6 years following direct intracerebral contact of infectious material by neurosurgery of depth electrodes.(7) As the inoculation site moves further away from the brain to other tissues, the incubation period is extended. For example, incubation periods ranged from 1.5 – 18 years after exposure to contaminated dura mater, while transmission from exposure through a peripheral route (as with human growth hormone [hGH] injections) is associated with an incubation period ranging from 5 – 30 years.(15) The incubation period for vCJD is unknown, however, it is likely the incubation period will be measured in terms of many years or decades.(30) The concept of incubation period is not applicable to genetic forms of CJD.(31) Period of Communicability In prion diseases, generally the highest levels of infectivity are associated with the central nervous system (CNS) and related tissues (e.g., parts of the eye) during, and throughout clinical illness. In sCJD, non-CNS tissues may be infective, but at much lower levels, probably during the period of clinical illness. In vCJD, infection is present in lymphoid tissues and blood during the incubation period and during clinical illness. Late in the incubation period, the level of infectivity in the CNS rises, and high levels of infectivity occur in the CNS throughout symptomatic illness.(29)

https://open.alberta.ca/dataset/e115841b-696f-42e0-91a8-fdcfba7e537a/resource/da8ae624-434b-4c0c-937e-71fc4520df59/download/guidelines-creutzfeldt-jakob-disease-2018-05.pdf

A person could possibly be infected with bovine spongiform encephalopathy (BSE) prions for over 50 years before developing variant Creutzfeldt-Jakob disease (vCJD), according to a study on another human prion disease called kuru in this week's issue of The Lancet. The findings suggest that the eventual size of a vCJD epidemic could be much bigger than previously thought, state the authors.

https://www.eurekalert.org/pub_releases/2006-06/l-ipf062106.php

***> A REVIEW OF UPDATE SCIENCE ON EACH SUSPECTED CASES THAT WAS RULED OUT...

Case Reports

***> UPDATED SCEINCE

***> We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state.

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer Clare E. Hoover, Kristen A. Davenport, Davin M. Henderson, Nathaniel D. Denkers, Candace K. Mathiason, Claudio Soto, Mark D. Zabel, Edward A. Hoover Stanley Perlman, Editor DOI: 10.1128/JVI.00077-17

ArticleFigures & DataInfo & Metrics PDF ABSTRACT Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion.

IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion accumulation and pathways of prion spread during early CWD infection remain unknown. To investigate the chronological events of early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrPCWD over the first 4 months of infection. We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state.

https://jvi.asm.org/content/91/10/e00077-17

REVIEW

***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***

***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***

***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***

***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***

***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***

Thursday, March 8, 2018

Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein

https://familialcjdtseprion.blogspot.com/2018/03/familial-human-prion-diseases.html

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***> UPDATED SCEINCE

*** 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).***

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true

https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article

P172 Peripheral Neuropathy in Patients with Prion Disease

Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..

IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,

AND

included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),

AND

THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.

snip...

P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States

Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..

SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.

https://prion2018.org/wp-content/uploads/2018/05/program.pdf

https://prion2018.org/

***2018***

Cervid to human prion transmission

Kong, Qingzhong

Case Western Reserve University, Cleveland, OH, United States

Abstract

Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans.

We hypothesize that:

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

(3) Reliable essays can be established to detect CWD infection in humans; and

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of humanized Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental human CWD samples will also be generated for Aim 3.

Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1.

Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental human CWD samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.

Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.

Public Health Relevance

There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.

Funding Agency

Agency

National Institute of Health (NIH)

Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Type

Research Project (R01)

Project #

5R01NS088604-04

Application #

9517118

Study Section

Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2018-08-01 Budget End 2019-07-31 Support Year 4 Fiscal Year 2018 Total Cost Indirect Cost Institution Name Case Western Reserve University Department Pathology Type Schools of Medicine DUNS # 077758407 City Cleveland State OH Country United States Zip Code 44106

Related projects

NIH 2018 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University

NIH 2017 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University

NIH 2016 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University

NIH 2015 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University $337,507

http://grantome.com/grant/NIH/R01-NS088604-04

ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

here is the latest;

PRION 2018 CONFERENCE

Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice

Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge). To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.

After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.

Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.

The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.

Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.

The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..

***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***

https://prion2018.org/

Molecular Barriers to Zoonotic Transmission of Prions

Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author

snip...

The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine.

***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

snip...

However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring.

***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884726/

Prion 2017 Conference Abstracts

CWD 2017 PRION CONFERENCE

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen

This is a progress report of a project which started in 2009.

21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes.

Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product.

Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain).

Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments.

We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem.

Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes.

All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.

Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.

At present, a total of 10 animals are sacrificed and read-outs are ongoing.

Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years.

Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.

PRION 2017

DECIPHERING NEURODEGENERATIVE DISORDERS

Subject: PRION 2017 CONFERENCE

DECIPHERING NEURODEGENERATIVE DISORDERS

VIDEO PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS

*** PRION 2017 CONFERENCE VIDEO

https://www.youtube.com/embed/Vtt1kAVDhDQ http://prion2017.org/programme/

https://www.cste2.org/Webinars/files/CWD_Slides_FINAL.pdf

ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION

10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question...

''In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II)

EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors

First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132 ;

also, see;

8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.

snip...

The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure.

https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132

zoonosis zoonotic cervid tse prion cwd to humans, preparing for the storm

***An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE..116***

https://www.tandfonline.com/doi/pdf/10.4161/pri.29237

To date there is no direct evidence that CWD has been or can be transmitted from animals to humans.

However, initial findings from a laboratory research project funded by the Alberta Prion Research Institute (APRI) and Alberta Livestock Meat Agency (ALMA), and led by a Canadian Food Inspection Agency (CFIA) scientist indicate that CWD has been transmitted to cynomolgus macaques (the non-human primate species most closely related to humans that may be used in research), through both the intracranial and oral routes of exposure.

Both infected brain and muscle tissues were found to transmit disease.

Health Canada’s Health Products and Food Branch (HPFB) was asked to consider the impact of these findings on the Branch’s current position on CWD in health products and foods.

Summary and Recommendation:

snip...

Health Portfolio partners were recently made aware of initial findings from a research project led by a CFIA scientist that have demonstrated that cynomolgus macaques can be infected via intracranial exposure and oral gavage with CWD infected muscle.

These findings suggest that CWD, under specific experimental conditions, has the potential to cross the human species barrier, including by enteral feeding of CWD infected muscle.

https://www.thetyee.ca/Documents/2017/06/24/Risk-Advisory-Opinion-CWD-2017.pdf

*** WDA 2016 NEW YORK ***

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions.

In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.

Student Presentations Session 2

The species barriers and public health threat of CWD and BSE prions

Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein.

These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species.

The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time.

We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations.

We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders

http://programme.exordo.com/wda2016/delegates/presentation/157/

*** 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.

http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf

Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS

resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip....

https://web.archive.org/web/20090506002237/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.

http://jvi.asm.org/content/83/18/9608.full

Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

http://science.sciencemag.org/content/311/5764/1117..long

*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.

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 ;

http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html

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

Monday, May 23, 2011

CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

Public release date: 23-May-2011

Contact: Francesca Costanzo adajmedia@elsevier.com 215-239-3249 Elsevier Health Sciences

CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association

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

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

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

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

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

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

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

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

###

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

In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at http://adajournal.org/content/podcast. ;

http://www.eurekalert.org/pub_releases/2011-05/ehs-cap051811.php

Thursday, May 26, 2011

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

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

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

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

Accepted 15 November 2010. Abstract Full Text PDF References .

Abstract

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

http://www.adajournal.org/article/S0002-8223(11)00278-1/abstract

PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;

Thursday, May 26, 2011

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

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

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html

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

Wednesday, March 18, 2009

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

http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html

Transmissible Spongiform Encephalopathies

Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY

https://web.archive.org/web/20090506001201/http://www.bseinquiry.gov.uk/files/mb/m09a/tab03.pdf

BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

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

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

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

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

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

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

*** 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). ***

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02)..

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;

https://web.archive.org/web/2 0170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

==========END

***> UPDATE SCIENCE

Pick's disease

Other Names: Pick disease of the brain; Lobar atrophy of the brain; Dementia with lobar atrophy and neuronal cytoplasmic inclusions

Categories: Nervous System Diseases

This disease is grouped under: Frontotemporal dementia

Summary

Pick’s disease is a neurological condition characterized by a slowly progressive deterioration of behavior, personality, or language.[1] People with Pick's disease have abnormal substances (called Pick bodies) inside nerve cells in the damaged areas of the brain. Pick bodies contain an abnormal form of a protein called tau. This protein is found in all nerve cells, but people with Pick's disease have an abnormal amount or type of this protein.[2] Symptoms often present sometime in the 50s, though it can occur as early as age 20 or as late as age 80. The course of the disease varies from person to person.[1] The underlying cause of Pick's disease is unknown.[2] In some cases, the disease runs in families. While there is no treatment to slow the progression of the disease, medications can be used to treat individual symptoms.[1]

https://rarediseases.info.nih.gov/diseases/7392/picks-disease#ref_5830

Pick’s disease is caused by a buildup of tau proteins, called “Pick bodies,” in the brain. Pick bodies cause neurological damage in areas where they are present, which includes (but is not limited to) the frontal lobes. Tau proteins also build up in the brains of Alzheimer’s patients, though, only one form of these tau proteins is prevalent in the brains of those with Pick’s disease. This difference allows Pick’s disease to be differentiated from Alzheimer’s disease postmortem by researchers and pathologists. Pick’s Disease Treatment and Prognosis

Like Alzheimer’s disease, Pick’s disease is currently untreatable. “As far as I know, there are no successful interventions in the treatment of frontotemporal dementia,” dementia expert Howard Crystal, professor of neurology and pathology at New York Downstate Medical College, told Psychiatric Times. While Pick’s disease cannot be slowed or stopped, medical professionals have had mixed success addressing specific symptoms of the disease. The goal is to maximize the functioning and comfort of those with Pick’s disease as much as possible. Care for Seniors with Pick’s Disease

Pick’s disease can be an enormous challenge for caregivers. Patients with Pick’s disease may have personality changes so severe that their loved ones do not recognize them as the people they formerly were. As Pick’s disease progresses, patients become unable to complete activities of daily living, such as dressing, grooming and toileting. The combination of personality changes and inability to function can require caregivers to place loved ones with Pick’s disease into professional dementia care at residential communities.

https://www.alzheimers.net/what-is-picks-disease/

https://secure.ssa.gov/apps10/poms.nsf/lnx/0423022170

Published: 29 August 2018

Structures of filaments from Pick’s disease reveal a novel tau protein fold

Benjamin Falcon, Wenjuan Zhang, Alexey G. Murzin, Garib Murshudov, Holly J. Garringer, Ruben Vidal, R. Anthony Crowther, Bernardino Ghetti, Sjors H. W. Scheres & Michel Goedert

Nature volume 561, pages 137–140 (2018) | Download Citation

Abstract

The ordered assembly of tau protein into abnormal filamentous inclusions underlies many human neurodegenerative diseases1. Tau assemblies seem to spread through specific neural networks in each disease2, with short filaments having the greatest seeding activity3. The abundance of tau inclusions strongly correlates with disease symptoms4. Six tau isoforms are expressed in the normal adult human brain—three isoforms with four microtubule-binding repeats each (4R tau) and three isoforms that lack the second repeat (3R tau)1. In various diseases, tau filaments can be composed of either 3R or 4R tau, or of both. Tau filaments have distinct cellular and neuroanatomical distributions5, with morphological and biochemical differences suggesting that they may be able to adopt disease-specific molecular conformations6,7. Such conformers may give rise to different neuropathological phenotypes8,9, reminiscent of prion strains10. However, the underlying structures are not known. Using electron cryo-microscopy, we recently reported the structures of tau filaments from patients with Alzheimer’s disease, which contain both 3R and 4R tau11. Here we determine the structures of tau filaments from patients with Pick’s disease, a neurodegenerative disorder characterized by frontotemporal dementia. The filaments consist of residues Lys254–Phe378 of 3R tau, which are folded differently from the tau filaments in Alzheimer’s disease, establishing the existence of conformers of assembled tau. The observed tau fold in the filaments of patients with Pick’s disease explains the selective incorporation of 3R tau in Pick bodies, and the differences in phosphorylation relative to the tau filaments of Alzheimer’s disease. Our findings show how tau can adopt distinct folds in the human brain in different diseases, an essential step for understanding the formation and propagation of molecular conformers.

https://www.nature.com/articles/s41586-018-0454-y#ref-CR10

Discussion Emerging evidence indicates that pathogenic tau assemblies can propagate and spread between synaptically connected neurons in a prion-like manner.

https://www.tandfonline.com/doi/pdf/10.1080/19336896.2018.1545524?needAccess=true

Prion-like Spreading in Tauopathies

Jacob I. Ayers, Benoit I. Giasson, David R. Borchelt'Correspondence information about the author David R. BorcheltEmail the author David R. Borchelt

PlumX Metrics

DOI: https://doi.org/10.1016/j.biopsych.2017.04.003

Abstract

Tau is a microtubule-associated protein that functions in regulating cytoskeleton dynamics, especially in neurons. Misfolded and aggregated forms of tau produce pathological structures in a number of neurodegenerative diseases, including Alzheimer’s disease (AD) and tauopathy dementias. These disorders can present with a sporadic etiology, such as in AD, or a familial etiology, such as in some cases of frontotemporal dementia with parkinsonism. Notably, the pathological features of tau pathology in these diseases can be very distinct. For example, the tau pathology in corticobasal degeneration is distinct from that of an AD patient. A wealth of evidence has emerged within the last decade to suggest that the misfolded tau in tauopathies possesses prion-like features and that such features may explain the diverse characteristics of tauopathies. The prion-like concept for tauopathies arose initially from the observation that the progressive accumulation of tau pathology as the symptoms of AD progress seemed to follow anatomically linked pathways. Subsequent studies in cell and animal models revealed that misfolded tau can propagate from cell to cell and from region to region in the brain through direct neuroanatomical connections. Studies in these cell and mouse models have demonstrated that experimentally propagated forms of misfolded tau can exist as conformationally distinct “strains” with unique biochemical, morphological, and neuropathological characteristics. This review discusses the clinical, pathological, and genetic diversity of tauopathies and the discoveries underlying the emerging view that the unique features of clinically distinct tauopathies may be a reflection of the strain of misfolded tau that propagates in each disease.

Keywords:

Alzheimer’s disease, Animal models, Prion, Strains, Tau, Transmission

https://www.biologicalpsychiatryjournal.com/article/S0006-3223(17)31473-7/fulltext

Distinct differences in prion-like seeding and aggregation between Tau protein variants provide mechanistic insights into tauopathies

Kevin H. Strang‡,§, Cara L. Croft‡,§, Zachary A. Sorrentino‡,§,Paramita Chakrabarty‡,§,¶, Todd E. Golde‡,§,¶ and Benoit I. Giasson‡,§,¶1 +Author Affiliations

From the ‡Department of Neuroscience, the §Center for Translational Research in Neurodegenerative Disease, and the ¶McKnight Brain Institute, College of Medicine University of Florida, Gainesville, Florida 32610 ↵1 To whom correspondence should be addressed: BMS J483/CTRND, 1275 Center Dr., Gainesville, FL 32610. Tel.: 352-273-9363; E-mail: bgiasson@ufl.edu. Edited by Paul E. Fraser

Abstract

The accumulation of aberrantly aggregated MAPT (microtubule-associated protein Tau) defines a spectrum of tauopathies, including Alzheimer's disease. Mutations in the MAPT gene cause frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), characterized by neuronal pathological Tau inclusions in the form of neurofibrillary tangles and Pick bodies and in some cases glial Tau pathology. Increasing evidence points to the importance of prion-like seeding as a mechanism for the pathological spread in tauopathy and other neurodegenerative diseases. Herein, using a cell culture model, we examined a multitude of genetic FTDP-17 Tau variants for their ability to be seeded by exogenous Tau fibrils. Our findings revealed stark differences between FTDP-17 Tau variants in their ability to be seeded, with variants at Pro301 and Ser320 showing robust aggregation with seeding. Similarly, we elucidated the importance of certain Tau protein regions and unique residues, including the role of Pro301 in inhibiting Tau aggregation. We also revealed potential barriers in cross-seeding between three-repeat and four-repeat Tau isoforms. Overall, these differences alluded to potential mechanistic differences between wildtype and FTDP-17 Tau variants, as well as different Tau isoforms, in influencing Tau aggregation. Furthermore, by combining two FTDP-17 Tau variants (either P301L or P301S with S320F), we generated aggressive models of tauopathy that do not require exogenous seeding. These models will allow for rapid screening of potential therapeutics to alleviate Tau aggregation without the need for exogenous Tau fibrils. Together, these studies provide novel insights in the molecular determinants that modulate Tau aggregation.

http://www.jbc.org/content/293/7/2408.abstract

Prion-like transmission and spreading of tau pathology

Invited Review

Prion-like transmission and spreading of tau pathology Florence Clavaguera1, Jürgen Hench1, Michel Goedert2 and Markus Tolnay1,* DOI: 10.1111/nan.12197

Additional Information(Hide All) Author InformationPublication History Author Information 1 Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, CH-4031 Basel, Switzerland 2 MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK * Please send correspondence to Markus Tolnay at the above address. Email: markus.tolnay@usb.ch

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nan.12197

Publication History Accepted manuscript online: 17 NOV 2014 01:23AM EST Manuscript Accepted: 13 NOV 2014

Abstract

Filaments made of hyperphosphorylated tau protein are encountered in a number of neurodegenerative diseases referred to as “tauopathies”. In the most prevalent tauopathy, Alzheimer's disease, tau pathology progresses in a stereotypical manner with the first lesions appearing in the locus coeruleus and the entorhinal cortex from where they appear to spread to the hippocampus and neocortex. Propagation of tau pathology is also characteristic of argyrophilic grain disease, where the tau lesions appear to spread throughout distinct regions of the limbic system. These findings strongly implicate neuron-to-neuron propagation of tau aggregates. Isoform composition and morphology of tau filaments can differ between tauopathies suggesting the existence of conformationally diverse tau strains. ***Altogether, this points to prion-like mechanisms in the pathogenesis of tauopathies.

http://onlinelibrary.wiley.com/doi/10.1111/nan.12197/abstract?campaign=wolacceptedarticle

Characterization of tau prion seeding activity and strains from formaldehyde-fixed tissue

Sarah K. Kaufman, Talitha L. Thomas, Kelly Del Tredici, Heiko Braak and Marc I. DiamondEmail author Acta Neuropathologica CommunicationsNeuroscience of Disease20175:41

DOI: 10.1186/s40478-017-0442-8 © The Author(s). 2017

Received: 11 May 2017 Accepted: 11 May 2017 Published: 7 June 2017

Abstract

Tauopathies such as Alzheimer’s disease (AD) feature progressive intraneuronal deposition of aggregated tau protein. The cause is unknown, but in experimental systems trans-cellular propagation of tau pathology resembles prion pathogenesis.

https://tauopathies.blogspot.com/2017/06/characterization-of-tau-prion-seeding.html

As has been documented with distinct TSE prion strains, we provide evidence that the distinct structures of tau aggregates that accumulate in different diseases have self-propagating activities that were readily distinguished by their relative abilities to seed the polymerization of various tau substrates under suitable conditions.

https://link.springer.com/article/10.1007%2Fs00401-018-1947-3

https://www.cdc.gov/prions/cjd/occurrence-transmission.html

TUESDAY, JANUARY 1, 2019

CHILDHOOD EXPOSURE TO CADAVERIC DURA

https://betaamyloidcjd.blogspot.com/2019/01/childhood-exposure-to-cadaveric-dura.html

Singeltary comments;

Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

>>> The only tenable public line will be that "more research is required’’ <<<

>>> possibility on a transmissible prion remains open<<<

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)

snip...see full Singeltary Nature comment here;

Alzheimer's disease

let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...

Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

http://journals.plos.org/plosone/article/comment?id=info:doi/10.1371/annotation/933cc83a-a384-45c3-b3b2-336882c30f9d

http://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0111492

http://journals.plos.org/plosone/article/comment?id=10.1371/annotation/933cc83a-a384-45c3-b3b2-336882c30f9d

https://www.frontiersin.org/articles/10.3389/fnagi.2016.00005/full

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

*** Singeltary comment PLoS ***

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

Posted by flounder on 05 Nov 2014 at 21:27 GMT

http://www.plosone.org/annotation/listThread.action?root=82860

IN CONFIDENCE

5 NOVEMBER 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication.

There are also results to be made available shortly

(1) concerning a farmer with CJD who had BSE animals,

(2) on the possible transmissibility of Alzheimer’s and

(3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]

https://web.archive.org/web/20170126060344/http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf

https://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

https://web.archive.org/web/20040315075058/www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

https://www.nature.com/articles/nature15369

MY next comment below, can be found at the very bottom of the above link, wait for it to load...tss

I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.

First, I applaud Nature, the Scientist and Authors of the Nature paper, for bringing this important finding to the attention of the public domain, and the media for printing said findings.

Secondly, it seems once again, politics is getting in the way possibly of more important Transmissible Spongiform Encephalopathy TSE Prion scientific findings. findings that could have great implications for human health, and great implications for the medical surgical arena. but apparently, the government peer review process, of the peer review science, tries to intervene again to water down said disturbing findings.

where have we all heard this before? it's been well documented via the BSE Inquiry. have they not learned a lesson from the last time?

we have seen this time and time again in England (and other Country's) with the BSE mad cow TSE Prion debacle.

That 'anonymous' Lancet editorial was disgraceful. The editor, Dick Horton is not a scientist.

The pituitary cadavers were very likely elderly and among them some were on their way to CJD or Alzheimer's. Not a bit unusual. Then the recipients, who got pooled extracts injected from thousands of cadavers, were 100% certain to have been injected with both seeds. No surprise that they got both diseases going after thirty year incubations.

That the UK has a "system in place to assist science journalists" to squash embargoed science reports they find 'alarming' is pathetic.

Sounds like the journalists had it right in the first place: 'Alzheimer's may be a transmissible infection' in The Independent to 'You can catch Alzheimer's' in The Daily Mirror or 'Alzheimer?s bombshell' in The Daily Express

if not for the journalist, the layperson would not know about these important findings.

where would we be today with sound science, from where we were 30 years ago, if not for the cloak of secrecy and save the industry at all cost mentality?

when you have a peer review system for science, from which a government constantly circumvents, then you have a problem with science, and humans die.

to date, as far as documented body bag count, with all TSE prion named to date, that count is still relatively low (one was too many in my case, Mom hvCJD), however that changes drastically once the TSE Prion link is made with Alzheimer's, the price of poker goes up drastically.

so, who makes that final decision, and how many more decades do we have to wait?

the iatrogenic mode of transmission of TSE prion, the many routes there from, load factor, threshold from said load factor to sub-clinical disease, to clinical disease, to death, much time is there to spread a TSE Prion to anywhere, but whom, by whom, and when, do we make that final decision to do something about it globally? how many documented body bags does it take? how many more decades do we wait? how many names can we make up for one disease, TSE prion?

Professor Collinge et al, and others, have had troubles in the past with the Government meddling in scientific findings, that might in some way involve industry, never mind human and or animal health.

FOR any government to continue to circumvent science for monetary gain, fear factor, or any reason, shame, shame on you.

in my opinion, it's one of the reasons we are at where we are at to date, with regards to the TSE Prion disease science i.e. money, industry, politics, then comes science, in that order.

greed, corporate, lobbyist there from, and government, must be removed from the peer review process of sound science, it's bad enough having them in the pharmaceutical aspect of healthcare policy making, in my opinion.

my mother died from confirmed hvCJD, and her brother (my uncle) Alzheimer's of some type (no autopsy?). just made a promise, never forget, and never let them forget, before I do.

I kindly wish to remind the public of the past, and a possible future we all hopes never happens again. ...

[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on the possible transmissibility of Alzheimer's and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]

http://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk:80/files/yb/1992/12/16005001.pdf

https://web.archive.org/web/20170126060344/http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf

https://journals.plos.org/plosone/article/comment?id=info:doi/10.1371/annotation/933cc83a-a384-45c3-b3b2-336882c30f9d

please see more of this history and references there from (these blogs are for educational use, I do not advertise or make money from this. just made a promise to mom dod 12/14/97 hvCJD, never forget, and never let them forget.) human transmission of amyloid-β pathology and cerebral amyloid angiopathy, Singeltary Submission to Nature

https://betaamyloidcjd.blogspot.com/2015/10/alzheimergate-re-evidence-for-human.html

P132 Aged cattle brain displays Alzheimer’s-like pathology that can be propagated in a prionlike manner

Ines Moreno-Gonzalez (1), George Edwards III (1), Rodrigo Morales (1), Claudia Duran-Aniotz (1), Mercedes Marquez (2), Marti Pumarola (2), Claudio Soto (1)

snip...

These results may contribute to uncover a previously unsuspected etiology surrounding some cases of sporadic AD. However, the early and controversial stage of the field of prion-like transmission in non-prion diseases added to the artificial nature of the animal models utilized for these studies, indicate that extrapolation of the results to humans should not be done without further experiments.

P75 Determining transmissibility and proteome changes associated with abnormal bovine prionopathy

Dudas S (1,2), Seuberlich T (3), Czub S (1,2)

1. Canadian Food Inspection Agency, NCAD Lethbridge Laboratory, Canada 2. University of Calgary, Canada 3. University of Bern, Switzerland.

In prion diseases, it is believed that altered protein conformation encodes for different pathogenic strains. Currently 3 different strains of bovine spongiform encephalopathy (BSE) are confirmed. Diagnostic tests for BSE are able to identify animals infected with all 3 strains, however, several diagnostic laboratories have reported samples with inconclusive results which are challenging to classify. It was suggested that these may be novel strains of BSE; to determine transmissibility, brain material from index cases were inoculated into cattle.

In the first passage, cattle were intra-cranially challenged with brain homogenate from 2 Swiss animals with abnormal prionopathy. The challenged cattle incubated for 3 years and were euthanized with no clinical signs of neurologic disease. Animals were negative when tested on validated diagnostic tests but several research methods demonstrated changes in the prion conformation in these cattle, including density gradient centrifugation and immunohistochemistry. Currently, samples from the P1 animals are being tested for changes in protein levels using 2-D Fluorescence Difference Gel Electrophoresis (2D DIGE) and mass spectrometry. It is anticipated that, if a prionopathy is present, this approach should identify pathways and targets to decipher the source of altered protein conformation. In addition, a second set of cattle have been challenged with brain material from the first passage. Ideally, these cattle will be given a sufficient incubation period to provide a definitive answer to the question of transmissibility.

=====prion 2018===

https://prion2018.org/wp-content/uploads/2018/05/program.pdf

https://prion2018.org/

***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts

S67 PrPsc was not detected using rapid tests for BSE.

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT

http://www.plosone.org/annotation/listThread.action?root=86610

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.

*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

see page 176 of 201 pages...tss

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2009/prion2009_bookofabstracts.pdf

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;

http://www.plosone.org/annotation/listThread.action;jsessionid=635CE9094E0EA15D5362B7D7B809448C?root=7143

http://bovineprp.blogspot.com/2018/02/

THURSDAY, FEBRUARY 7, 2019

In Alzheimer's Mice, Decades-Old Human Cadaveric Pituitary Growth Hormone Samples Can Transmit and Seed Amyloid-Beta Pathology

https://betaamyloidcjd.blogspot.com/2019/02/in-alzheimers-mice-decades-old-human.html

=========end

ANOTHER CWD FEAST, WITH NO FOLLOW UP???

TUESDAY, NOVEMBER 04, 2014

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011

Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "

http://chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html

CHRONIC WASTING DISEASE CONGRESS Serial No. 107-117 May 16, 2002

CHRONIC WASTING DISEASE

JOINT OVERSIGHT HEARING BEFORE THE SUBCOMMITTEE ON FORESTS AND FOREST HEALTH JOINT WITH THE SUBCOMMITTEE ON FISHERIES CONSERVATION, WILDLIFE AND OCEANS OF THE COMMITTEE ON RESOURCES U.S. HOUSE OF REPRESENTATIVES ONE HUNDRED SEVENTH CONGRESS SECOND SESSION

May 16, 2002

Serial No. 107-117

snip...

Mr. MCINNIS. Today, this joint Subcommittee hearing will explore an issue of immeasurable importance to the growing number of communities in wide-ranging parts of this country, the growing incidence of Chronic Wasting Disease in North America’s wild and captive deer and elk populations. In a matter of just a few months, this once parochial concern has grown into something much larger and much more insidious than anyone could have imagined or predicted.

As each day passes, this problem grows in its size, scope, and consequence. One thing becomes clear. Chronic Wasting Disease is not a Colorado problem. It is a Wisconsin problem or a Nebraska or Wyoming problem. It is a national problem and anything short of a fully integrated, systematic national assault on this simply will not do, which is precisely why we brought our group together here today.

snip...

So this is a disease that is spreading throughout the continent and it is going to require a national response as well as the efforts that are currently taking place in States like Wisconsin, Colorado, Nebraska, Wyoming, the interest they now have down in Texas and some of the neighboring States that have large white-tailed deer population and also elk.

This is a huge issue for us, Mr. Chairman, in the State of Wisconsin. I want to commend Governor McCallum and your staff and the various agencies for the rapid response that you have shown, given the early detection of CWD after the last deer hunting season. The problem that we have, though, is just a lack of information, good science in regards to what is the best response, how dangerous is this disease. We cannot close the door, quite frankly, with the paucity of scientific research that is out there right now in regards to how the disease spreads, the exposure of other livestock herds—given the importance of our dairy industry in the State, that is a big issue—and also the human health effects.

https://www.govinfo.gov/content/pkg/CHRG-107hhrg79658/pdf/CHRG-107hhrg79658.pdf?fbclid=IwAR1-dMPpYLher4m8SyMICwoGXNyQcVjcinPvAw8CvIys1lEG7hxgzWplJlk

WEDNESDAY, FEBRUARY 20, 2019

CHRONIC WASTING DISEASE CONGRESS Serial No. 107-117 May 16, 2002 Updated 2019

https://chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-congress-serial.html

THURSDAY, FEBRUARY 21, 2019

CWD TSE PRION UPDATE, ARK, TENN, MS, PA, TX, AND CONGRESS 2002

https://transmissiblespongiformencephalopathy.blogspot.com/2019/02/cwd-tse-prion-update-ark-tenn-ms-pa-tx.html

then they fumbled the football, and big industry, legislators, and the very politicians that accepted their bribe, opened the flood gates of cwd via shooting pens, breeders, antler mills, velvet mills, and oh hell, don't forget the sperm mills and what just came out Prion 2018 conference...i.e. HAVE YOU BEEN THUNDERSTRUCK!

P74 High Prevalence of CWD prions in male reproductive samples

Carlos Kramm (1,2), Ruben Gomez-Gutierrez (1,3), Tracy Nichols (4), Claudio Soto (1) and Rodrigo Morales (1) (1) Mitchell Center for Alzheimer´s disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA (2) Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile (3) Universidad de Málaga, Málaga, Spain (4) National Wildlife Research Center, United States Department of Agriculture, Fort Collins, CO 80521, USA.

Chronic wasting disease (CWD) is a highly infectious and fatal illness affecting captive and free-ranging cervids. Mother-to-offspring prion transmission has been described in some animal prion diseases, including CWD. However, few studies have been performed to analyze the prevalence of CWD prions in reproductive male tissues and fluids. Here, we optimized the Protein Misfolding Cyclic Amplification (PMCA) assay for the efficient detection of CWD prions in these samples. This study was done in collaboration with United States Department of Agriculture (USDA) scientists who provided blindly field-collected testes, epididymis and seminal fluid samples from 21 white-tailed deer that were analyzed for prion infection by post-mortem histological studies in brain stem and lymphoid tissues. The results showed positive CWD prion detection in testes, epididymis and seminal fluid samples. A high prevalence of CWD-PrPSc was found in samples collected at the late-presymptomatic stage of the disease. Our results showed a correlation between the presence of CWD-PrPSc in male reproductive organs and blood. These findings demonstrate a high efficiency of CWD prion detection by PMCA in testes, epididymis and seminal fluid, and offer a possibility for a routine screening of semen samples to be commercially distributed for artificial insemination. Our results may uncover new opportunities to understand the mechanisms of CWD spreading and decrease putative inter-individual transmission associated to insemination using CWD contaminated specimens.

https://prion2018.org/wp-content/uploads/2018/05/program.pdf

https://prion2018.org/

SUNDAY, AUGUST 02, 2015

TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if?

http://chronic-wasting-disease.blogspot.com/2015/08/texas-cwd-have-you-been-thunderstruck.html

SATURDAY, JANUARY 19, 2019

Texas Chronic Wasting Disease CWD TSE Prion Symposium 2018 posted January 2019 VIDEO SET 18 CLIPS

https://chronic-wasting-disease.blogspot.com/2019/01/texas-chronic-wasting-disease-cwd-tse.html

MONDAY, JANUARY 14, 2019

Evaluation of iatrogenic risk of CJD transmission associated with Chronic Wasting Disease TSE Prion in Texas TAHC TPWD It is a dimension as vast as space and as timeless as infinity. It is the middle ground between light and shadow, between science and superstition, and it lies between the pit of man's fears and the summit of his knowledge. This is the dimension of imagination. It is NOT, an area which we call the Twilight Zone, but an area that believes junk science, and the very industries and lobbyist some Texas Hunters, the cervid industry, that insist on shoving the fake news down their throats, we call this ted nugent junk science, and in TEXAS, sometimes you just can't fix stupid, this is where the rubber meets the road, here's your sign!

chronic wasting disease cwd tse prion aka mad deer elk disease, if you consume a cwd tse prion positive cervid, then months, years, decades later, go on to have surgery, dental, ophthalmology, endoscopy, donate tissue, blood, organs, you then expose those medical theaters and tissue, blood, organs, that are incubating the infectious cwd tse prion disease, to everyone that comes in contact. these are not memes, these are actual statements from hunters/industry in Texas about CWD tse prion.

God help them, and us...terry

''Got a call today from TPWD, I’ve got a mule deer that tested early positive for CWD. I’m soon to turn into a zombie because I have already been eating it. They advised not to consume any of the meat...too late! They want to come confiscate what meat is left once they get more results back from another lab.''

snip...

https://chronic-wasting-disease.blogspot.com/2019/01/evaluation-of-iatrogenic-risk-of-cjd.html

snip...see;

THURSDAY, FEBRUARY 07, 2019

CWD TSE Prion, and Processing your own meat

https://chronic-wasting-disease.blogspot.com/2019/02/cwd-tse-prion-and-processing-your-own.html

BACK IN TIME!

Date: Tue, 06 Aug 2002 15:55:07 -0700 From: "Terry S. Singeltary Sr." To: BSE-L@uni-karlsruhe.de Subject: APOCALYPSE NOW--CHRONIC WASTING DISEASE, it's not wasting away...

Subject: CHRONIC WASTING DISEASE, it's not wasting away... September 2002 APOCALYPSE NOW WHY CHRONIC WASTING DISEASE MIGHT RUIN OUR HUNTING TRADITION

Chronic wasting disease in whitetails threatens to change deer hunting as we know it. What's most troubling is CWD was discovered more than 30 years ago, and researchers know little more now about its origin than they did then.

Editor's note: Without a doubt, this is the most comprehensive article on chronic wasting disease D&DH has ever published. Dr. Dave Samuel, a retired wildlife professor from West Virginia University, has more than 30 years of professional experience covering such issues. With volumes of false information being disseminated in newspaper and television reports, Samuel spent several weeks in early April and May 2002 researching the facts on CWD in North America. Here's what he found...

What a difference a few months makes. In January 2002, few whitetail hunters east of the Mississippi River had ever heard of chronic wasting disease. Today, it is a scary reality for nearly everyone who hunts whitetails in North America. CWD is an insidious infective disease in deer and elk, first found in 1967 in a captive mule deer research facility run by the Colorado Division of Wildlife. Affected deer drank incessantly, urinated often, and spent much of their time standing listlessly, heads down, ears drooping and saliva dripping from their mouths. Within weeks, they all died. When examining the deer's brains, Beth Williams, now with the Wyoming State Veterinary Laboratory, found tiny holes that resembled other "spongiform" diseases such as scrapie in sheep and bovine spongiform encephalitis -- "mad cow disease" -- in cattle. Over the next 20 years, CWD turned up in wild elk, whitetails and mule deer in Colorado and Wyoming. There was no massive die-off, just a few animals dying at random. However, the disease was there, moving in ways no one understood. Since then, CWD has been found in wild deer and/or elk in Colorado, Wyoming, Nebraska, South Dakota, Saskatchewan and Wisconsin, and in captive elk in Colorado, Kansas, Nebraska, Oklahoma, South Dakota, Montana, Alberta and Saskatchewan. CWD can remain latent in animals for up to five years before it manifests. Animals do not develop immunity. Once infected, they will die. Each time CWD surfaces, wildlife officials usually prescribe mass culling in attempts to keep it from spreading. For many game farms, this means killing the whole herd. Although mass culling is expensive and cannot guarantee CWD won't reappear, it's the only method that has proven somewhat effective in reducing further outbreaks. In Colorado, officials sterilized the facility where CWD was discovered, but when animals were reintroduced, they still contracted the disease. Through extensive and innovative study, researchers learned CWD is caused by infectious proteins called prions (pronounced "pree-ons"). In ways biologists cannot understand, naturally occurring prions occasionally go bad and corrupt healthy prions. Researchers don't know how CWD originated. Some biologists believe the corrupt prions that cause scrapie in sheep

ALTHOUGH RESEARCHERS are searching for alternative test methods, obtaining brain tissue samples is currently the only reliable method to detect CWD. Above, Wisconsin Department of Natural Resources employees collect the head of an adult doe.

somehow mutated, jumped the so-called "species barrier" and infected deer and elk. One problem with this theory is CWD has not been found in captive or wild deer from areas in North America or the United Kingdom where scrapie is most prevalent. Others believe proteins in healthy animals sometimes spontaneously become bad, causing brain and nervous-tissue damage. Some believe CWD is passed along in saliva and feces. In short, we know where it was discovered, but we might never know how it got there. Furthermore, as I will discuss later, whether CWD originated in the wild or in a pen is no longer issue. It's much more important to focus on damage control.

Important Health Issues Although researchers have not learned much about CWD the past 10 years, they do know it can spread within a herd without animal-to-animal contact. It also seems that CWD can spread more rapidly in areas high deer densities, hence the problems at game farms. CWD originally found in the wild in Colorado and Wyoming, a wasn't initially considered a major threat because deer and elk densities were relatively low. However, now that CWD has found in southwestern Wisconsin -- where wild deer densities exceed a mind-boggling 50 deer per square mile of habitat -- researchers fear the disease could spread to surrounding states. Only time will tell. Mad cow disease was first reported in 1985, and infected cows showed some of the same symptoms seen in CWD-infected deer. There are other similarities. Both diseases involve infected prions, and the brains of infected animals look the same. However, there are differences. Mad cow was spread by ingesting contaminated food, whereas CWD probably was not. mad cow spread to humans, whereas CWD has not. Some rumors state that CWD has killed three people who ate venison, but this is not true. Those rumors probably stem from the fact one woman and two men who regularly ate venison died of Creutzfeldt-Jakob disease, a rare spongiform disease among humans. One of the cases involved a 30-year-old hunter from Kaysville Utah, who died of CJD in 1999. According to a report in the Street Journal, this case caught the attention of activist groups that were lobbying for stricter surveillance of mad cow disease in the United States. The Centers for Disease Control and Prevention studied the Utah man's case and the two other cases, and ruled out mad cow disease. Epidemiologists quizzed family members about the victims' lifestyles and eating habits, and concluded there was "no strong evidence for a causal link" to CWD. Still, similarities between CWD and other brain spongiform diseases make many people nervous, including farmers who worry CWD might infect their cattle. Researchers immediately responded to those concerns and conducted myriad tests to determine if and how CWD can infect cattle. They concluded CWD cannot infect a cow unless corrupt prions are injected directly into the cow's brain. However, CWD is the only known brain spongiform disease that is not species specific. It has been shown to infect elk, mule deer and white-tailed deer, and researchers don't know why. That's what makes it so puzzling.

Recent Outbreaks in Colorado Major CWD outbreaks occurred in the 1990s on game farms in Saskatchewan and in wild herds in Saskatchewan and

CWD TIMELINE

1967 -- Mule deer at a Fort Collins, Colo., wildlife research facility become thin and listless, and then die. Biologists are uncertain of the cause.

1978 -- Beth Williams, now with the Wyoming State Veterinary Laboratory finds evidence that the disease affect the brain. She observes tiny holes in nerve cells that create a sponge-like appearance.

1980 -- Chronic wasting disease is identified.

1981 -- First wild elk with CWD detected, in Colorado.

1983 -- Surveillance for CWD in free-ranging deer begins in Colorado and Wyoming.

1985 --"Mad cow" disease, also a brain spongiform disease, is first reported

1986 --Wyoming elk diagnosed with CWD. It's the first free-ranging case the state.

1990- Hunter-harvest surveillance CWD begins in Colorado.

1997 -- First captive elk herds test positive in South Dakota. Extensive surveillance of CWD in farmed elk begins nationwide.

1999 -- Wisconsin begins precautionary testing for CWD in wild white-tailed deer.

1999 -- Montana and Colorado begin depopulating wild herds.

2000 -- In November, Nebraska records its first wild mule deer with CWD. In December, elk from a ranch test positive.

April 2001 -- CWD moves to Saskatchewan's wild deer. Two mule deer test positive.

September 2001 -- CWD is found on several Colorado game farms, which are quarantined.

February 2002 -- South Dakota reports its first wild case of CWD. Wisconsin reports CWD in its wild deer herd. It's the first time CWD has been four east of the Mississippi River.

March 2002 -- Illinois creates a task force to deal with CWD possibilities. Alberta reports its first case of CWD in a captive elk.

April 2002 -- CWD reported west of the Continental Divide. Wisconsin enforces an emergency ban on importing exporting deer and elk. Other states pass similar laws.

-- Jennifer A. Pillath

Nebraska. However, what's occurred since Fall 2001 is most concerning. In September, CWD was found on several Colorado game farms, which were all subsequently quarantined. The Elk Echo farm alone had 29 elk that contracted the disease and died. The entire herd was slaughtered, and officials then traced elk that were shipped elsewhere. They found 11 more cases at other game farms. With the exception of one elk in Kansas, Elk Echo elk transported to other states all tested negative. In April 2002, CWD was found west of the Continental Divide. Reports allege the owner of a game farm near Craig, Colo., erected a fence and trapped wild animals inside. Because laws do not permit farm-raised deer and elk to mix with wild animals, state officials responded and killed 280 wild deer and 30 elk inside the pen. As of this writing, two of 164 tests indicated CWD infections. It is not known how the farm's animals contracted CWD. Owner Wes Adams said he believes the deer were infected before the fence was erected. In a Denver Post article, Adams was quoted as saying he complied with all CWD regulations and that he is the victim, not the cause of the problem. Nevertheless, all 100 elk on his farm will be killed and tested. The farm is 130 miles west of where CWD was found in the wild. On April 3, Colorado officials began sampling 329 animals within five miles of the farm. On April 9, they reported two deer outside the game farm's fence tested positive. Another deer tested positive a week later, prompting officials to increase their sample quotas. In Summer 2002, Colorado officials hoped to test at least 300 more deer from areas farther from the CWD epicenter. If no cases are found in fringe areas, it's likely CWD originated in or immediately near the farm. In that case, the state would likely eradicate the farm's animals and nearby wild herds in attempts to slow the disease's spread. Colorado officials also found CWD near Lyons in Boulder County, where 16 of 77 mule deer from the Rabbit Mountain area tested positive. This 21 percent positive rate is one of the highest ever found in the wild. The discovery caused Boulder County commissioners to approve massive cull hunts aimed at slowing a southerly movement of CWD. The outbreak near Craig also triggered a reaction from Governor Bill Owens, who formed a CWD task force with a charge to review and oversee proactive CWD action in Colorado. It was also announced that 24 game farmers living near the CWD endemic area agreed to sell their herds to the Department of Agriculture. The USDA planned to slaughter all of the animals and dispose of the carcasses.

Bad News From Wisconsin

As troubling as the news from Colorado, the public has shown even more concern over recent happenings in Wisconsin. In February 2002, Wisconsin learned that three free-ranging deer shot during the state's November 2001 gun-hunt tested positive for CWD. Subsequent tests showed the disease now infects more than 2 percent of a densely populated whitetail herd in a 415-square-mile area. (See Ryan Gilligan's article, "Fatal Deer Disease Makes Giant Leap Eastward" in the August 2002 issue of D&DH) Because this is the first time CWD has been found east of the Mississippi River, thousands of hunters from surrounding states worry if their state is next. Wisconsin's problem is perhaps most severe, because the state harbors more than 1.6 million whitetails. The state is also home to 947 deer/elk game ranches, with a combined captive herd of nearly 35,000 animals. In a move that shocked some residents, the DNR announced a plan to eradicate every deer in a 287-square-mile "hot zone" and another that would drastically reduce the herd in the region. In all, 15,000 whitetails are to be killed in hopes of stopping the disease from spreading farther. Although officials admit it might take several years to complete the job, they believe quick action is necessary. To further prevent CWD transmission, Wisconsin banned the transport of farm-raised deer and elk, and pushed for bans on baiting and recreational feeding. On May 15 in Washington, a key House committee approved a $29.4 billion spending bill that allocated $10 million in emergency funds to states coping with chronic wasting disease. That same day, the Wisconsin

Legislature met in special session a approved legislation that provided $4 million in funding. Much of that money will be used to build a CWD testing facility. The legislation also granted wildlife officials authority to shoot deer from helicopters and roadways, and -- as a last resort -- to shoot deer on private land even if landowners do not want deer killed. "The scientists are telling us -- from other states who have dealt with this problem -- that we've got one shot, one shot to try to eradicate this disease", state Senator Mark Meyer of Wisconsin told the Milwaukee JournalSentinel. "If we fail in our actions today, what it's going to mean in 15 to 20 years (is) the white-tailed deer population in this state will be decimated." To say Wisconsinites are nervous is a gross understatement. In fact, the fear of the unknown has forced many hunters -- even though no human has ever contracted CWD -- to empty their freezers on the highly remote chance their venison is contaminated with CWD. Up to 250,000 others indicate they might skip this year's hunt.

On to Alberta

In Alberta, the game-farm industry suffered another setback with the discovery of CWD in a 2 1/2-year-old elk. The animal came from a farm north of Edmonton and was one of 160 elk slaughtered at a packing plant in southern Alberta on March 7, 2002. The 32 tons of resulting meat were destroyed, and veterinarians from Canadian Food Inspection Agency imposed a three-week freeze on movements of elk within or out of Alberta. Alberta's captive elk herd is estimated at 43,000 head, and the province has no regulations for CWD testing. However, several farms voluntarily test their herds. The infected elk was found via routine surveillance. Although biologists don't know how the infection entered Alberta, it's possible the disease came from a wild deer or was in the herd before the province's 1988 ban on importation. It is also possible an infected animal was brought into Alberta after the ban.

Nebraska and South Dakota

Nebraska is becoming a CWD hot zone. The state began testing wild deer from hunter-killed samples in Fall 1997, and the first wild case was a mule deer killed in November 2000. The Game and Parks Commission responded by culling 104 deer in that region, and one more mule deer tested positive. Then in December 2000, an elk from a game farm in northern Sioux County tested positive. By March 2001, officials killed and tested all of the farm's elk. From that sample, 11 had CWD. Nebraska's situation grew worse when a whitetail from the same game farm contracted CWD in December 2001. This discovery led to the slaughter of the farm's other 174 whitetails. Alarmingly, 83 of 159 tested so far -- 52 percent --had CWD. Biologists then shot 113 wild deer in the area surrounding the game farm and found nine of them had the disease. Interestingly, CWD was not found in any deer collected more than 10 miles from the farm. However, in late March 2002, a wild mule deer was seen acting abnormally near Scottsbluff, Neb. It was killed, and subsequently tested positive for CWD. Since then, 54 deer were killed near the Wyoming border. Those tests were not complete as of this writing. Of 804 deer sampled during Nebraska's 2001 hunting season, two tested positive -- once each in Kimball and Cheyenne counties. With the exception of the mule deer killed in March, all of Nebraska's CWD-positive animals were found within 10 miles of the Sioux County game farm. This fact suggests the game farm did not get CWD from the wild. It got CWD from contaminated animals it received. To slow CWD's spread, Nebraska is considering culling 50 percent of its northwestern deer herd over the next five years. It is also considering lengthening the season from the current 1O-day schedule to nearly five months in Sioux and western Dawes counties. South Dakota has tested for CWD since 1997. After three years of no positive tests, the state proclaimed its wild herd CWD-free. Sadly, that wasn't the case, because in February 2002, biologists discovered CWD in a wild whitetail. The deer was killed near a Fall River County game farm where CWD had been found previously.

How States React To CWD

Although many researchers believe CWD might have something to do with game-farmed animals, they can do nothing but formulate systematic plans for controlling the disease until more research is done. Assume a state's wildlife officials sample hunter kills for CWD, and agriculture officials test all game-farmed deer and elk that are slaughtered or die (since the Wisconsin incident, more states are considering making testing mandatory). When CWD appears, in the case of farmed animals, the first step is to kill all of them, conduct tests and quarantine the farm. This allows officials to trace the records for other animals that were imported/exportd to or from the farm. If animals were exported, the next step is to locate the other farms and continue the eradication process. When CWD is found in the wild, the first step is to shut down that area's borders to all imports and exports of deer and elk. Even states with no history of CWD -- including Texas, Louisiana, Illinois, Indiana, Minnesota and even New York, Massachusetts and North Carolina --have adopted similar regulations. Some states allow importing and exporting deer and elk from herds that have remained CWD-free for five or more years, but this is essentially a total ban because few farms have tested their herds that long. The next step is to use hunter-killed animals to sample large wild herds.

Study: Diseased Prions Can Infect Mule Deer Fawns

Although full-blown cases of chronic disease have been limited to adult elk and deer, recent research indicates corrupt brain proteins can appear in young fawns. Researchers have also discovered that baiting and feeding practices can lead to the transmission of these proteins.

According to a report in the Journal of General Virology, researchers 'made the discoveries while studying mule deer fawns that were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease. After being inoculated, fawns were killed at 10, 42, 53, 77, 78 and 80 days. Necropsies were then performed to determine if any of the fawns had acquired PrP-res, a protein marker for CWD infection. The protein was found in some fawns as early as 42 days after inoculation. Even lived 53 days or more indicates mule deer can be infected with CWD for at least 16 months before clinical signs appear. The study's results were published in an article authored by researchers from the University of Wyoming, Colorado State University and the Colorado Division of Wildlife. Exactly how CWD is transmitted among ruminants is unknown, but the fawns in the study contracted diseased proteins through exposure to contaminated feed. This discovery has caused some researchers to presume CWD can be spread at contaminated feeding and bedding areas, and in instances where deer congregate and engage in nose-to-nose contact. -- Daniel E. Schmidt

It's common for officials to sample a 5-mile radius around an area where CWD is found. In Wisconsin, however, officials tested an area encompassing more than 415 square miles. After gauging the disease's prevalence, states usually conduct massive cull htmts to severely reduce -- even eradicate --local herds. The idea for massive culling came from scientific research by John Gross of Colorado State University and Michael Miller of the Colorado Division of Wildlife. In their research paper, "Chronic Wasting Disease in Mule Deer: Disease Dynamics and Control" Gross and Miller present all the science known on CWD and offer a model to determine the best management strategies for wild herds. The model shows how culling infected areas can reduce CWD incidence by reducing deer dispersal. The paper was

SHORTLY AFTER LEARNING chronic wasting disease infected wild deer in Wisconsin, state officials announced a plan to eradicate every deer in a 287-square-mile "hot zone" in hopes of stopping the disease from spreading farther. Above, more than 1,300 residents showed up for an informational meeting on CWD in Mount Horeb, Wis., the town nearest the recent CWD outbreak.

printed in the Journal of Wildlife Management in 2001. Gross and Miller conclude that "selective culling may offer the greatest promise of reducing CWD incidence, particularly when infected populations are detected early in the course of an epidemic and tested aggressively for several decades." Therefore, the best approach to CWD is to hit the herd hard and, most importantly, early in outbreak areas.

In northeastern Colorado, where CWD incidence in mule deer approaches 5 percent, an estimated 2,200 mule deer live in 1,250 square miles. Through hunting, officials expect to drastically reduce the herd over the next several years.

Costly Changes

The CWD outbreaks in Colorado, Wisconsin and Nebraska have led many states to seek better control of importing, exporting and testing animals. In Colorado alone, hunting and wildlife viewing is worth billions. Thus, the state is making changes to protect those valuable resources. Wisconsin's Department of Natural Resources also fears a widespread outbreak might cripple the state's economy. In 2001, the state sold 952,942 deer hunting licenses, generating more than $20 million in revenue for the DNR. Furthermore, deer hunting in Wisconsin generates $1 billion in economic activity each year. In neighboring Minnesota, retail sales from deer hunting generate $270 million annually. Deer hunting has a similar economic impact in Iowa, lllinois and Michigan, making swift action in Wisconsin crucial.

How is CWD Spreading?

This is the main question everyone is asking. Is CWD originating on game farms, or is it occurring in the wild and being passed through the fences? Unfortunately, we might never know. CWD infects captive and wild animals, and it might take years of surveillance until we know the problem's true scope. Some biologists believe CWD originated in game farms because clinical signs-- head drooping, salivating, emaciated bodies -- were not reported in wild deer before the outbreaks. When such behavior was observed in Colorado in 1967, no one knew its cause because it did not match any known disease. Furthermore, similar behaviors of sick deer were next observed at a facility in Wyoming that had imported deer from the Colorado facility. Also, CWD has been confirmed at 40 farms in Saskatchewan.

As of October 2001, the Canadian Food Inspection Agency found 159 CWD-positive elk on game farms, of which 52 were imported from a South Dakota facility. It was later learned the South Dakota facility had imported elk from a Colorado farm that had CWD-infected elk. Of course, there's another side to this story -- the game farmers who are suffering huge financial losses from CWD. The North American Elk Breeders Association believes CWD, "in all likelihood

Studies Link Bacteria, Copper to Brain Disease (spiroplasmas and copper deficiencies) [thank God my scanner did not pick this junk up...TSS]

has existed in wild animals for hundreds of years," and blames the Colorado Division of Wildlife for "starting" the disease at its deer research facility. The association cites the Nebraska case as proof CWD came from wild animals. Again, CWD was discovered on a game farm in Nebraska, but it was later learned the disease was prevalent in wild deer living within 10 miles of the farm. "The ranch is only a few miles from the endemic area in Wyoming, so it's only logical some animals came across the border and brought CWD into Nebraska," said Eric Mohlman, president of the Nebraska Elk Breeders Association. Others note that although Saskatchewan farms have had CWD, only two wild deer have been found from several thousand tests and, therefore, farmed animals are not spreading it to the wild. That's a stretch, however, because it is not known how easily CWD can be passed from elk to deer. Of course, it's possible the disease goes both ways -- sometimes starting on farms and other times in the wild. Regardless of where CWD originates, mandatory testing is on the horizon. Although some farmers have been compensated for their losses, many have quit the business.

Most Commonly Asked Questions About CWD

Can I contract chronic wasting disease?

Probably not. However, because CWD, "mad cow" disease and Creutzfeldt-Jakob disease are all brain spongiform diseases, and because the latter two can infect humans, it is only logical that people fear CWD. Because two spongiform diseases have been transmitted to humans, no one can say with certainty that CWD will never infect humans. However, asking if you can get CWD from eating venison is like asking your doctor if you can get cancer from eating nitrate-laden hot dogs. Another point to remember is the odds of contracting a spongiform disease like mad cow or CJD are nearly astronomical. It's true that about 100 people contracted mad cow disease in Great Britain, but it's estimated that 80 million people might have been exposed to it.

Should I worry about eating venison?

That can be answered with a qualified "no." The World Health Organization has said there is no scientific evidence the disease can infect humans. However, the agency says no part of a deer or elk with evidence of the disease should be eaten by people or other animals Bad prions congregate in nervous tissue, and lymph nodes. Therefore, boning out meat -- without cutting into the brain or spine -- a discardingblood vessels and internal organs should protect you even if the animal is infected.

How does a deer get CWD?

According to the Agricultural Research Service, "the natural route of transmission these diseases (i.e., spongiforms, including CWD) in ruminant animals is unknown, but oral exposure to contaminated feeds, bedding or tissues is presumed to be a major source infection."

Can prions infect the ground?

Although this has not been proven, some studies indicate CWD-causing prions remain active in soil for years.

Will CWD invade my state?

CWD could pop up anywhere deer or elk live. However, it seems prevalent in high-density herds.

Root Causes

When analyzing how CWD affects North American deer herds, I can't help but think of what my friend Steve Fausel said in 2000.

"When we allow deer and elk numbers to reach high densities, we are asking for trouble," Fausel said. Although he was referring to habit damage, his words ring true. Ironically my brother Bill, a wildlife disease professor at the University of Alberta, expressed similar concerns in 1987 -- when game farming started in Alberta. In fact, he presented a paper on the subject at the annual conference of the Game Growers of Alberta. The paper, "Moving the Zoo, or the Potential for Introducing a Dangerous Parasite into Alberta with its Tranlsocated Host," piqued the interest of several biologists, but it didn't trigger enough action. Within a short time, several game farms experienced a serious outbreak of bovine tuberculosis, and now they have CWD.

Conclusion

Based on what's been learned over the past six months, we cannot stand pat on CWD and hope it goes away. Time is of the essence, especially when dealing with wild deer. The longer it takes to implement a plan, the farther CWD will spread, making it even more difficult to control. There are no quick fixes. All strategies take time and money. We haven't heard the last of new outbreaks and, unfortunately, CWD will more than likely appear in other Midwestern states -- and possibly Southern and Eastern states, too.

What's most important is that all parties refrain from pointing fingers and work together to solve this mysterious and troublesome disease...

DEER & DEER HUNTING WWW.DEERANDDEERHUNTING.COM

speaking of volumes of false information being disseminated in newspaper and television reports AND D & D HUNTING !

RE-

> Mad cow was spread by ingesting contaminated food,

> whereas CWD probably was not.

> And mad cow spread to humans, whereas CWD has not

why do educated folks refuse to look at the transmission studies and the most likely route (FEED). we been feeding the same SRMs to deer and elk as we have been to cattle for decades. in the only part i was not able to scan, they speak of OPs and copper deficient and spiro plasma, but not a word about the SRMs (specified risk materials) from dead deer, sheep, and cows along with other road-kill, that have been fed to these deer.

why do most refuse to look at this route? sure, it may not be the only route, but a most likely one.

and the statement that CWD has not transmitted to humans, is a most rediculous statement, one not backed up with any substantial proof. if i make a statement that indeed, CWD has passed to humans, i would have the same proof, that these folks saying it does not. but what about 'the feast', will be an interesting case study (kinda), considering some 100 of people ate there, but when/what was tainted, and who ate it or gutted it?

comments of CDC on CWD in the past;

Unlike patients with new variant CJD, the 3 patients did not have a unique neuropathologic manifestation, clinicopathologic homogeneity, uniformity in the codon 129 of the prion protein gene, or prion characteristics different from those of classic variants. CONCLUSIONS: Although the occurrence of 3 unusually young patients with CJD who consumed venison suggested a possible relationship with CWD, our follow-up investigation found no strong evidence for a causal link. Ongoing CJD surveillance remains important for continuing to assess the risk, if any, of CWD transmission to humans.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11594928&dopt=Abstract

we see 3 more CJD victims under 30 in 2001, and now 3 or 4 more at 'THE FEAST';

3 deaths probed for link to deer disease Jill Burcum and Kavita Kumar Star Tribune

Published Aug 1, 2002 WAST01

Federal health officials are investigating whether the deaths of a Blaine man and two friends, fellow sportsmen from Wisconsin, suggest a link between eating wild animals infected with chronic wasting disease and fatal brain illnesses in people.

The men often gathered at a cabin in Wisconsin, near Superior, in the late '80s and early '90s to eat elk and deer meat and swap hunting and fishing stories. They died of brain diseases in the 1990s. James Botts Courtesy Botts family

The Blaine man, James Botts, a chemical engineer, turned 55 just before he died in the summer of 1999 from Creutzfeldt-Jakob disease (CJD), a rare, mysterious and always-fatal disease that causes holes in the brain.

The owner of the cabin, Wayne Waterhouse of Chetek, Wis., also died of CJD. The third man, Roger Marten of Mondovi, Wis., died of a more common brain illness called Pick's disease.

CJD is similar to chronic wasting disease in wild animals and mad cow disease in cattle. All are caused by mutant proteins, prions, that make spongelike holes in the brain.

There has never been a documented case of someone developing a brain-destroying disease from eating animals infected with chronic wasting disease. Scientists have not ruled it out, however.

"We are not saying it absolutely can't happen. We know that it's a mistake to say that," said Dr. Larry Schonberger, a specialist at the U.S. Centers for Disease Control and Prevention. The agency and Wisconsin's health department are leading the investigation.

Wisconsin health officials said the death of Botts and his friends are worth investigating because of the rarity of their illnesses and because the men knew one another and attended game feasts at the cabin.

"It's certainly unusual," said Jeff Davis, Wisconsin's state epidemiologist. "But whether it is coincidental or otherwise remains to be seen."

He said he learned of a possible link among three cases about two weeks ago from someone who called the Wisconsin Division of Health. He declined to identify the caller.

Davis said as many as 100 people are thought to have attended the feasts at the cabin over the years.

State helping Wisconsin

The investigation is the first of its kind in Wisconsin, but he said that there have been similar inquiries of cases involving people who had CJD and that consumption of venison appeared to be a factor in them. But after the investigations, it was decided that they were simply sporadic cases of CJD, he said.

http://www.startribune.com/stories/1556/3131888.html

but, if i was betting, when the CDC/NIH gets done with this one, it will also be nothing more than sporadic CJD...

TSS

POTENTIAL SOURCE FOR CWD, FEED AND DOPE PEE DOE HUNTERS;

Subject: MAD DEER/ELK DISEASE AND POTENTIAL SOURCES Date: Sat, 25 May 2002 18:41:46 -0700 From: "Terry S. Singeltary Sr." Reply-To: BSE-L

BSE-L

MAD DEER/ELK DISEASE AND POTENTIAL SOURCES

8420-20.5% Antler Developer For Deer and Game in the wild Guaranteed Analysis Ingredients / Products Feeding Directions Crude Protein (min) 20.50% Crude Fat (min) 2.50% Crude Fiber (max) 15.00% Calcium (min) 1.50% Calcium (max) 1.90% Phosphorus (min) 1.25% Potassium (min) 1.00% Magnesium (min) 0.45% Zinc (min) 450ppm Manganese (min) 250ppm Copper (min) 40ppm Copper (max) 60ppm Selenium (min) 0.30ppm Vitamin A (min) 25,000IU/LB Vitamin E (min) 20IU/LB Plant Protein, Soybean Hulls (16%), Grain, Processed Grain By-Products, Dehydrated Alfalfa Meal, Molasses, Defluorinated Phosphate, Monocalcium Phosphate, Dicalcium Phosphate, Calcium Carbonate, Sodium Bicarbonate, __Animal Protein__, Vitamin A Supplement, Vitamin D3 Supplement, Vitamin E Supplement, Magnesium Oxide, Soybean Oil, DL-Mdethionine, Zinc Sulfate, Manganese Sulfate, Copper Sulfate, Ferrous Sulfate, Ethylenediamine Dihydriodide, Cobalt Carbonate, Sodium Selenite and Artificial Flavoring Feed to wildlife as a supplement to pasture and browse, or hay. Feed at a rate to maintain desired growth rate and body condition, antler development and fawn survival. For optimal results feed during times of nutrient stress, such as drought or when nutrient requirements are elevated such as lactation antler growth, or rapid fawn growth. Provide animals access to fresh clean water at all times.

CAUTION: This product contains high levels of copper. Do not feed to sheep.

http://www.surefed.com/deer.htm ================================

animal sterol????????????????TSS

Ingredients

Grain Products, Plant Protein Products, Forage Products, Roughage Products 30%, Calcium Carbonate, Processed Grain By-Products, Deflourinated Phosphate, Salt, Molasses Products, Vitamin A Acetate with D-activated Animal Sterol (source of Vitamin D3, di-alpha-Tocopheryl Acetate, Artificial flavors added.

http://www.bodefeed.com/prod3.htm =================================

[MORE ANIMAL PROTEIN PRODUCTS.....tss]

BODE'S GAME FEED SUPPLEMENT #400 A RATION FOR DEER NET WEIGHT 50 POUNDS 22.6 KG.

GUARANTEED ANALYSIS Crude Protein (Min) 15.5% Crude Fat (Min) 2.0% Crude Fiber (Max) 8.0% Calcium (Min) 0.30% Calcium (Max) 0.70% Phosphorus (Min) 0.30% Salt (Min) 0.05% Salt (Max) 0.25%

Ingredients

Grain Products, Plant Protein Products, Processed Grain By-Products, Forage Products, Roughage Products 15%, Molasses Products, __Animal Protein Products__, Monocalcium Phosphate, Dicalcium Pyosphate, Salt, Calcium Carbonate, Vitamin A Acetate with D-activated Animal Sterol ( source of Vitamin D3), Vitamin E Supplement, Vitamin B12 Supplement, Riboflavin Supplement, Niacin Supplement, Calcium Panothenate, Choline Chloride, Folic Acid, Menadione Soduim Bisulfite Complex, Pyridoxine Hydorchloride, Thiamine Mononitrate, d-Biotin, Manganous Oxide, Zinc Oxide, Ferrous Carbonate, Calcium Iodate, Cobalt Carbonate, Dried Sacchoromyces Berevisiae Fermentation Solubles, Cellulose gum, Artificial Flavors added.

Ration CORN 666.67 LBS PEAS 666.67 LBS F# 3153 666.67 LBS

FEEDING DIRECTIONS Feed Free Choice

http://www.bodefeed.com/prod7.htm ===================================

[MORE ANIMAL PROTEIN...TSS]

Ingredients

http://www.bodefeed.com/prod6.htm ===================================

MORE ANIMAL PROTEIN PRODUCTS FOR DEER

Bode's #1 Game Pellets A RATION FOR DEER F3153

GUARANTEED ANALYSIS Crude Protein (Min) 16% Crude Fat (Min) 2.0% Crude Fiber (Max) 19% Calcium (Ca) (Min) 1.25% Calcium (Ca) (Max) 1.75% Phosphorus (P) (Min) 1.0% Salt (Min) .30% Salt (Max) .70%

Ingredients

Grain Products, Plant Protein Products, Processed Grain By-Products, Forage Products, Roughage Products, 15% Molasses Products, __Animal Protein Products__, Monocalcium Phosphate, Dicalcium Phosphate, Salt, Calcium Carbonate, Vitamin A Acetate with D-activated Animal Sterol ( source of Vitamin D3) Vitamin E Supplement, Vitamin B12 Supplement, Roboflavin Supplement, Niacin Supplement, Calcium Pantothenate, Choline Chloride, Folic Acid, Menadione Sodium Bisulfite Complex, Pyridoxine Hydrochloride, Thiamine Mononitrate, e - Biotin, Manganous Oxide, Zinc Oxide, Ferrous Carbonate, Calcium Iodate, Cobalt Carbonate, Dried Saccharyomyces Cerevisiae Fermentation Solubles, Cellulose gum, Artificial Flavors added.

FEEDING DIRECTIONS Feed as Creep Feed with Normal Diet

http://www.bodefeed.com/prod8.htm [PROBABLY MORE HERE, JUST FOLLOW THE ''NEXT BUTTON PRODUCTS''...TSS] ================= [MORE ANIMAL PROTEIN DEER FEED...TSS]

Selling Tips

* Designed to improve the nutritional health of your herd * Provides consistent protein source * High levels of Vitamin E and Selenium * Yeast culture * Available in pellet form

Profile^(TM) Deer Builder Pellets Product Features: Product Benefits:

* High quality protein

* Balanced for demanding nutritional stages of post and pre rut deer

* Extremely palatable

* Keeps deer coming to the feeding area

* Quality ingredients

* Assures that the deer is receiving a consistent source of quality nutrients

* Yeast culture

* For increased feed efficiency and increased fiber digestion

* Fortified with the proper balance of vitamins and minerals

* Especially Vitamin E and Selenium for reproduction efficiency, prevent white muscle disease and boost the immune system under stress

General Description: For deer with higher nutrient needs.

PROFILE Deer Builder Pellets

GUARANTEED ANALYSIS

Crude Protein, Not less than......................................................................................................20.0

% Crude Fat, Not less than................................................................................................................2.0

% Crude Fiber, Not more than........................................................................................................18.0

% Calcium (Ca), Not less than.........................................................................................................1.0

% Calcium (Ca), Not more than........................................................................................................1.5

% Phosphorus (P), Not less than..................................................................................................0.95

% Salt (NaCl), Not less than..............................................................................................................0.1

% Salt (NaCl), Not more than............................................................................................................0.6

% Potassium (K), Not less than.......................................................................................................1.0

% Selenium (Se), ppm, Not less than..................................................................................................0.6 Copper (Cu), ppm, Not less than......................................................................................................20 Zinc (Zn), ppm, Not less than...........................................................................................................250 Vitamin A, I.U./lb, Not less than..................................................................................................10,000 Vitamin D3, I.U./lb, Not less than.....................................................................................................600 Vitamin E, I.U./lb, Not less than..........................................................................................................70

INGREDIENTS

Grain Products, Roughage Products (not more than 35%), Processed Grain By-Products, Plant Protein Products, Forage Products, __Animal Protein Products__, L-Lysine, Calcium Carbonate, Salt, Monocalcium/Dicalcium Phosphate, Yeast Culture, Magnesium Oxide, Cobalt Carbonate, Basic Copper Chloride, Manganese Sulfate, Manganous Oxide, Sodium Selenite, Zinc Sulfate, Zinc Oxide, Sodium Selenite, Potassium Iodide, Ethylenediamine Dihydriodide, Vitamin E Supplement, Vitamin A Supplement, Vitamin D3 Supplement, Mineral Oil, Mold Inhibitor, Calcium Lignin Sulfonate, Vitamin B12 Supplement, Menadione Sodium Bisulfite Complex, Calcium Pantothenate, Riboflavin, Niacin, Biotin, Folic Acid, Pyridoxine Hydrochloride, Mineral Oil, Chromium Tripicolinate

DIRECTIONS FOR USE

Deer Builder Pellets is designed to be fed to deer under range conditions or deer that require higher levels of protein. Feed to deer during gestation, fawning, lactation, antler growth and pre-rut, all phases which require a higher level of nutrition. Provide adequate amounts of good quality roughage and fresh water at all times.

http://www.profilenutrition.com/Products/Specialty/deer_builder_pellets.html

[OR HOW ABOUT SOME ANIMAL FAT FOR YOUR ELK...TSS]

Selling Tips

* Elk Lactation Cow Gest is for elk cows from 45 days prior to calving through weaning * Provides needed protein, energy, vitamins and minerals created by calving and milk production.

Profile^(TM) Elk Lactation Cow Gest Product Features: Product Benefits:

* High quality plant protein

* Supply protein requirements during this high demand period

* Complex carbohydrates and fats

* Provide needed energy to help maintain body condition

* Highly digestible fiber

* Lowers risk of acidosis, while providing a high level of energy

* Highly fortified; complete vitamins and trace minerals with Zinpro organic trace minerals

* Meets trace nutrient requirements during this period of high-nutrient demand even in the presence of interfering trace elements

* Diamond V's XP Yeast

* Increases palatability and forage digestibility

* Pelleted

* Convenient and easy for the producer to handle

* Mold Inhibitor

* Feed stays fresh longer

* Apple Flavored

General Description: For elk cows from 45 days prior to calving through weaning.

PROFILE Elk Lactation Cow Gest

GUARANTEED ANALYSIS

Crude Protein, Not less than.......................................................................................................16.0% Crude Fat, Not less than.................................................................................................................3.0% Crude Fiber, Not more than.........................................................................................................20.0% Calcium (Ca), Not less than..........................................................................................................1.0% Phosphorus (P), Not less than......................................................................................................0.4% Salt (NaCl), Not less than...............................................................................................................0.1% Salt (NaCl), Not more than.............................................................................................................0.6% Potassium (K), Not less than........................................................................................................1.1% Magnesium (Mg), Not less than....................................................................................................0.3% Zinc (Zn), ppm, Not less than...........................................................................................................190 Copper (Cu), ppm, Not less than......................................................................................................50 Selenium (Se), ppm, Not less than..................................................................................................0.5 Vitamin A, I.U./lb, Not less than..................................................................................................15,000 Vitamin D3, I.U./lb, Not less than.................................................................................................4,000 Vitamin E, I.U./lb, Not less than..........................................................................................................75

INGREDIENTS

Grain Products, Roughage Products (Not more than 50%), Processed Grain By-Products, Forage Products, Plant Protein Products, Molasses Products, Animal Fat (Preserved with BHA and Citric Acid), Monocalcium/Dicalcium Phosphate, Calcium Carbonate, Salt, Potassium Chloride, Sodium Selenite, Copper Sulfate, Potassium Iodide, Cobalt Carbonate, Basic Copper Chloride, Manganese Sulfate, Manganous Oxide, Zinc Sulfate, Zinc Oxide, Ethylenediamine Dihydriodide, Manganese Amino Acid Complex, Zinc Methionine Complex, Copper Amino Acid, Complex, Cobalt Glucoheptonate, Mineral Oil, Propionic Acid, Vitamin A Supplement, Vitamin D3 Supplement, Vitamin E Supplement, Sodium Propionate, Natural & Artificial flavors

DIRECTIONS FOR USE

Feed at 1 to 1.5 lb per 100 lb body weight (ideally 3 to 8 lb) per head daily to lactating elk cows. Always provide adequate forage and fresh, clean water. If body condition is not being maintained at these recommended feeding rates, evaluate forage quality and health status before increasing the amount of Elk Lactation Gest fed beyond 8 lb per head per day. The maximum feeding rate for this product is 13 lb per head daily. Always follow good feeding and health management procedures.

Previous Product Next Product

http://www.profilenutrition.com/Products/Specialty/elk_lactationcowgest.html ===================================================

considering 1/2 to 1 gram of TSE material is lethal;

DEPARTMENT OF HEALTH & HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION

April 9, 2001 WARNING LETTER

01-PHI-12 CERTIFIED MAIL RETURN RECEIPT REQUESTED

Brian J. Raymond, Owner Sandy Lake Mills 26 Mill Street P.O. Box 117 Sandy Lake, PA 16145 PHILADELPHIA DISTRICT

Tel: 215-597-4390

Dear Mr. Raymond:

Food and Drug Administration Investigator Gregory E. Beichner conducted an inspection of your animal feed manufacturing operation, located in Sandy Lake, Pennsylvania, on March 23, 2001, and determined that your firm manufactures animal feeds including feeds containing prohibited materials. The inspection found significant deviations from the requirements set forth in Title 21, code of Federal Regulations, part 589.2000 - Animal Proteins Prohibited in Ruminant Feed. The regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE) . Such deviations cause products being manufactured at this facility to be misbranded within the meaning of Section 403(f), of the Federal Food, Drug, and Cosmetic Act (the Act).

Our investigation found failure to label your swine feed with the required cautionary statement "Do Not Feed to cattle or other Ruminants" The FDA suggests that the statement be distinguished by different type-size or color or other means of highlighting the statement so that it is easily noticed by a purchaser.

In addition, we note that you are using approximately 140 pounds of cracked corn to flush your mixer used in the manufacture of animal feeds containing prohibited material. This flushed material is fed to wild game including deer, a ruminant animal. Feed material which may potentially contain prohibited material should not be fed to ruminant animals which may become part of the food chain.

The above is not intended to be an all-inclusive list of deviations from the regulations. As a manufacturer of materials intended for animal feed use, you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance with the law. We have enclosed a copy of FDA's Small Entity Compliance Guide to assist you with complying with the regulation... blah, blah, blah...

http://www.fda.gov/foi/warning_letters/g1115d.pdf =================================================== now, what about those 'deer scents' of 100% urine', and the prion that is found in urine, why not just pass the prion with the urine to other deer...

Mrs. Doe Pee Doe in Estrus Model FDE1 Mrs. Doe Pee's Doe in Estrus is made from Estrus urine collected at the peak of the rut, blended with Fresh Doe Urine for an extremely effective buck enticer. Use pre-rut before the does come into heat. Use during full rut when bucks are most active. Use during post-rut when bucks are still actively looking for does. 1 oz.

http://www.gamecalls.net/huntingproducts/deerlures.html

ELK SCENT/SPRAY BOTTLE

Works anytime of the year *

100 % Cow Elk-in-Heat urine (2oz.) *

Economical - mix with water in spray mist bottle *

Use wind to your advantage

Product Code WP-ESB $9.95

http://www.elkinc.com/Scent.asp

prions in urine?

[PDF] A URINE TEST FOR THE IN-VIVO DIAGNOSIS OF PRION DISEASES

http://www.sigov.si/vurs/PDF/diagnoastika-bse-urin.pdf

something of interest;

snip...

The recent experimental demonstration in cattle of a neuropathology indistinguishable from that of BSE when inoculated with a specific isolate of TME and the association of the disease origin of that isolate with feeding to mink of cattle tissues, but not sheep tissues, raises also the possibility of a cattle origin of TME. There is concern too that in both TME and CWD the absence of evidence of the origins of infection could be explained by the occurrence of unconventional viral agent subclinical or carrier disease states in domestic and/or wild species.

Pathogenesis of unconventional viral agent diseases presenting naturally in ruminant species cannot be assumed to mimic mechanisms determined in experimental models.

snip...

Because of the successful transmission of the Brecke (Stetsonville) isolate of TME to cattle and the subsequent passage history in mink it was generally considered important that comparisons be made with BSE isolates in mink. Is BSE like scrapie in mink? Is BSE like the Brecke isolate of TME?

Very little was said about CWD but some present considered that its occurrence may indicate a sylvatic origin of agent. It was also agreed that the role of possible subclinical infection in the epidemiology of transmissible spongiform encephalopathies could well be important but was unknown. Marsh remarked on the possibility that BSE was due to an extremely thermostable strain of agent. His experience in the past with one particular Wisconsin isolate of TME (Hayward strain) suggested that i/c biopsy needles could not be effectively "scrapie sterilised", even employing an experimental autoclave system capable of 60 psi and 300"C+ for 5 hours. This experience led him to the policy that in scrapie or TME transmission studies re-use of instruments or glassware that had contained agent was an unacceptable protocol.

snip...

1963 'Hayward' outbreak in Wisconsin. This was discovered in May in females nursing kits. In the following December (pelting season) 10 males were sold off and these subsequently became affected. Hartsough recognised that in this outbreak the clinical signs were similar to those cf sheep scrapie and at this time Hadlow was consulted. He concurred that clinically it was "just like Scrapie in mink" and confirmed the nature of the encephalopathy.

PAGE 14

1963 Outbreak in Blackfoot, Idaho.

1985 The Stetsonville outbreak (farmer's name: Brecke). In addition to the downer cows and horses Brecke's mink received a cereal supplement. Hartsough's view was that this would contain bone meal and would be from a commercial source. If this were so and it was contaminated with a TME agent why were there no other ranches affected?

Many mink ranches now feed a commercial pelleted diet. Brecke was equipped to process large carcasses using a crusher/mixer which could accommodate a whole cow!

Idaho is the only US state other than Wisconsin in which primary outbreaks of TME have been recorded.

The largest mink farms in the USA are in Wisconsin, Utah and Minnesota but several other states, including Georgia have smaller units.

[[hmmm, could mink TSE be a source for the deer/elk TSE? and you have the commingling of deer and elk with cows? course they would never know if a cow had a TSE? and John, check out the ''big crusher'' whole cows (TSS)]]

Utah mink ranches feed out of a large cooperative mixer-of poultry and fish sources (but no beef sources) mainly originating in California.

Dead mink go for rendering but are used only in poultry feed.

snip...

PAGE 16

A commercial mink ranch was visited. This was Johny Werth's, Capitol Fur Farm comprising 1400 breeding females. The feed is bought in from a commercial supplier in the form of frozen packs of "poultry", "fish", "dried egg" or "tripe". A commercial mink cereal supplement is used and contains "animal meat meal" which was said to contain material mainly from poultry or fish origin but occasionally from beef sources, the partially thawed packs were tipped into an augur mixer which has a fully loaded capacity of 60001b and this would feed approximately 15000 mink per day.

In the fall at pelting time the skinned carcasses of the mink are placed in large barrels which are left in the open to freeze. When full, a renderer collects "for use in poultry feeds".

[[could this feed have been cross-contaminated or just plain contaminated? i remember fish feed mad cow warning letters, AND even if the chicken can not become clinical, does not mean the TSE agent is not in the gut...TSS]]

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

http://www.vegsource.com/talk/lyman/messages/7535.html

part 2

snip...

PAGE 25

Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculam (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in all of these species with the shortest incubation period in the ferret.

[hmmm, CWD transmission to squirrel monkey. are humans primates?TSS]

snip...

The occurrence of CWD must be viewed against the context of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province!

[figures...TSS]

snip...

VISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE

1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine and caprine scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is:-

COLORADO THE ORIGIN OF CHRONIC WASTING DISEASE CWD TSE PRION?

*** 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.

IN CONFIDENCE, REPORT OF AN UNCONVENTIONAL SLOW VIRUS DISEASE IN ANIMALS IN THE USA 1989

http://webarchive.nationalarchives.gov.uk/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

ALSO, one of the most, if not the most top TSE Prion God in Science today is Professor Adriano Aguzzi, and he recently commented on just this, on a cwd post on my facebook page August 20 at 1:44pm, quote;

''it pains me to no end to even comtemplate the possibility, but it seems entirely plausible that CWD originated from scientist-made spread of scrapie from sheep to deer in the colorado research facility. If true, a terrible burden for those involved.'' August 20 at 1:44pm ...end

MONDAY, SEPTEMBER 25, 2017

Colorado Chronic Wasting Disease CWD TSE Prion Mandatory Submission of test samples in some areas and zoonosis

http://chronic-wasting-disease.blogspot.com/2017/09/colorado-chronic-wasting-disease-cwd.html

CHRONIC WASTING DISEASE CONGRESS Serial No. 107-117 May 16, 2002

CHRONIC WASTING DISEASE

May 16, 2002

Serial No. 107-117

snip...

https://www.govinfo.gov/content/pkg/CHRG-107hhrg79658/pdf/CHRG-107hhrg79658.pdf?fbclid=IwAR1-dMPpYLher4m8SyMICwoGXNyQcVjcinPvAw8CvIys1lEG7hxgzWplJlk

THURSDAY, FEBRUARY 21, 2019

Professor Richard Lacey, microbiologist rubbished but later vindicated for warning that BSE could be transmitted to humans – obituary

https://bseinquiry.blogspot.com/2019/02/professor-richard-lacey-microbiologist.html

CDC

New Outbreak of TSE Prion in NEW LIVESTOCK SPECIES

Mad Camel Disease

Volume 24, Number 6—June 2018 Research

Prion Disease in Dromedary Camels, Algeria

Abstract

Prions cause fatal and transmissible neurodegenerative diseases, including Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE). After the BSE epidemic, and the associated human infections, began in 1996 in the United Kingdom, general concerns have been raised about animal prions. We detected a prion disease in dromedary camels (Camelus dromedarius) in Algeria. Symptoms suggesting prion disease occurred in 3.1% of dromedaries brought for slaughter to the Ouargla abattoir in 2015–2016. We confirmed diagnosis by detecting pathognomonic neurodegeneration and disease-specific prion protein (PrPSc) in brain tissues from 3 symptomatic animals. Prion detection in lymphoid tissues is suggestive of the infectious nature of the disease. PrPSc biochemical characterization showed differences with BSE and scrapie. Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.

SNIP...

The possibility that dromedaries acquired the disease from eating prion-contaminated waste needs to be considered.

Tracing the origin of prion diseases is challenging. In the case of CPD, the traditional extensive and nomadic herding practices of dromedaries represent a formidable factor for accelerating the spread of the disease at long distances, making the path of its diffusion difficult to determine. Finally, the major import flows of live animals to Algeria from Niger, Mali, and Mauritania (27) should be investigated to trace the possible origin of CPD from other countries.

Camels are a vital animal species for millions of persons globally. The world camel population has a yearly growth rate of 2.1% (28). In 2014, the population was estimated at ≈28 million animals, but this number is probably underestimated.. Approximately 88% of camels are found in Africa, especially eastern Africa, and 12% are found in Asia. Official data reported 350,000 dromedaries in Algeria in 2014 (28).

On the basis of phenotypic traits and sociogeographic criteria, several dromedary populations have been suggested to exist in Algeria (29). However, recent genetic studies in Algeria and Egypt point to a weak differentiation of the dromedary population as a consequence of historical use as a cross-continental beast of burden along trans-Saharan caravan routes, coupled with traditional extensive/nomadic herding practices (30).

Such genetic homogeneity also might be reflected in PRNP. Studies on PRNP variability in camels are therefore warranted to explore the existence of genotypes resistant to CPD, which could represent an important tool for CPD management as it was for breeding programs for scrapie eradication in sheep.

In the past 10 years, the camel farming system has changed rapidly, with increasing setup of periurban dairy farms and dairy plants and diversification of camel products and market penetration (13). This evolution requires improved health standards for infectious diseases and, in light of CPD, for prion diseases.

The emergence of another prion disease in an animal species of crucial importance for millions of persons worldwide makes it necessary to assess the risk for humans and develop evidence-based policies to control and limit the spread of the disease in animals and minimize human exposure. The implementation of a surveillance system for prion diseases would be a first step to enable disease control and minimize human and animal exposure. Finally, the diagnostic capacity of prion diseases needs to be improved in all countries in Africa where dromedaries are part of the domestic livestock.

https://wwwnc.cdc.gov/eid/article/24/6/17-2007_article

***> IMPORTS AND EXPORTS <***

***SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BAN ***

http://camelusprp.blogspot.com/2018/04/dromedary-camels-algeria-prion-mad.html

USA MAD COW CASE 2018 FLORIDA

WEDNESDAY, SEPTEMBER 26, 2018

JAVMA In Short Update USDA announces detection of atypical BSE

http://bovineprp.blogspot.com/2018/09/javma-in-short-update-usda-announces.html

ZOONOSIS OF SCRAPIE TSE PRION

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, Valerie 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 long 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***

===============

***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.

==============

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efﬁciency comparable to that of cattle BSE. While the efﬁciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

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

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man.

***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough.

***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY

https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** 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.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

***> Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility. <***

Transmission of scrapie prions to primate after an extended silent incubation period

Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation

Abstract

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

SNIP...

Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.

The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.

We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.

Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.

The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.

Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.

Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.

Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.

Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

https://www.nature.com/articles/srep11573

Saturday, December 15, 2018

***> ADRD Summit RFI Singeltary COMMENT SUBMISSION BSE, SCRAPIE, CWD, AND HUMAN TSE PRION DISEASE December 14, 2018

https://prionprp.blogspot.com/2018/12/adrd-summit-rfi-singeltary-comment.html

SATURDAY, JANUARY 5, 2019

Low levels of classical BSE infectivity in rendered fat tissue

https://bovineprp.blogspot.com/2019/01/low-levels-of-classical-bse-infectivity.html

***> FRIDAY, DECEMBER 14, 2018 MAD COW USA FLASHBACK Texas Style

FRIDAY DECEMBER 14, 2018

https://madcowusda.blogspot.com/2018/12/mad-cow-usa-flashback-friday-december.html

THURSDAY, JANUARY 3, 2019

MAD COW USDA DISEASE BSE TSE Prion

https://madcowusda.blogspot.com/2019/01/mad-cow-usda-disease-bse-tse-prion.html

THURSDAY, OCTOBER 22, 2015

Former Ag Secretary Ann Veneman talks women in agriculture and we talk mad cow disease USDA and what really happened

HOW TO COVER UP MAD COW DISEASE IN TEXAS

http://madcowusda.blogspot.com/2015/10/former-ag-secretary-ann-veneman-talks.html

http://madcowusda.blogspot.com/2012/06/johanns-introduces-legislation-banning.html

http://madcowusda.blogspot.com/2012_06_01_archive.html

WEDNESDAY, AUGUST 29, 2018

OIE Bovine spongiform encephalopathy, United States of America Information received on 29/08/2018 from Dr John Clifford, Official Delegate, Chief Trade Advisor, APHIS USDA

''The event is resolved. No more reports will be submitted.''

well, so much for those herd mates exposed to this atypical BSE cow, and all those trace in and trace outs.

The OIE, USDA, and the BSE MRR policy is a joke, a sad, very sad joke...

http://bovineprp.blogspot.com/2018/08/oie-bovine-spongiform-encephalopathy.html

Saturday, July 23, 2016

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

http://bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html

Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

http://bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html

Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program

http://specifiedriskmaterial.blogspot.com/2016/06/specified-risk-materials-srms-bse-tse.html

Wednesday, January 23, 2019

CFIA SFCR Guidance on Specified risk material (SRM) came into force on January 15, 2019

https://specifiedriskmaterial.blogspot.com/2019/01/cfia-sfcr-guidance-on-specified-risk.html

MONDAY, JANUARY 21, 2019

Bovine Spongiform Encephalopathy BSE TSE Prion Surveillance FDA USDA APHIS FSIS UPDATE 2019

https://bovineprp.blogspot.com/2019/01/bovine-spongiform-encephalopathy-bse.html

FRIDAY, FEBRUARY 01, 2019

Poland Exported 5,500 Pounds of Meat From Sick Cows to EU, what about mad cow disease?

Poland is Proof atypical BSE is NOT an old cow spontaneous disease...tss

https://bse-atypical.blogspot.com/2019/02/poland-exported-5500-pounds-of-meat.html

creutzfeldt jakob disease cjd tse prion

sporadic cjd cases in 1999 were 65 steady slow increase with a few blips to 233 in 2017, and 2018 has not been completed yet, takes a while. body count to date seems low, but the exposure, the sub-clinical carriers, friendly fire iatrogenic pass it foward there from via, blood, tissue, medical, dental, surgical.

tse prion in livestock spreading to pigs and camels and who knows what else, tse prion strains mutating with some of the atypicals becoming more virulent. we have been extremely lucky imo to date. but with cwd now, it's a whole new ballgame, price of poker goes up, and the strains of cwd are growing. it's just a crap shoot until one comes up and spreads to humans like cwd and scrapie spread to cervid, vertical, lateral, and God help us if a strain shows up that is transmissible by contact or via air borne, which has been proven with other tse prion disease...

***> U.S.A. CJD

Tables of Cases Examined

National Prion Disease Pathology Surveillance Center Cases Examined¹

(September 18, 2018)

Year Total Referrals² Prion Disease Sporadic Familial Iatrogenic vCJD

1998 & earlier 259 157 135 20 2 0

1999 121 73 65 7 1 0

2000 145 102 90 12 0 0

2001 209 118 110 8 0 0

2002 241 144 124 18 2 0

2003 259 160 137 21 2 0

2004 315 180 163 16 0 1³

2005 328 179 157 21 1 0

2006 365 179 159 17 1 2⁴

2007 374 210 191 19 0 0

2008 384 221 205 16 0 0

2009 397 231 210 20 1 0

2010 402 246 218 28 0 0

2011 392 238 214 24 0 0

2012 413 244 221 23 0 0

2013 416 258 223 34 1 0

2014 354 208 185 21 1 1⁵

2015 402 264 244 20 0 0

2016 397 278 247 29 0 0

2017 370 263 233 19 0 0

2018 188 129 114 7 0 0

TOTAL 6734 4085⁷ 3656⁸ 400⁹ 12 4

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

2Cases with suspected prion disease for which brain tissue was submitted;

3Disease acquired in the United Kingdom;

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

5Disease possibly acquired in a Middle Eastern or Eastern European country;

6Includes 12 cases in which the diagnosis is pending, and 20 inconclusive cases;

7Includes 13 (8 from 2018) cases with type determination pending in which the diagnosis of vCJD has been excluded.

8The sporadic cases include 3560 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 63 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 33 cases of sporadic Fatal Insomnia (sFI).

9Total does not include 247 Familial cases diagnosed by blood test only.

https://case.edu/medicine/pathology/divisions/prion-center/resources-for-professionals/tables-of-cases-examined

https://case.edu/medicine/pathology/divisions/prion-center

https://case.edu/medicine/pathology/divisions/prion-center/resources-for-professionals

UK 1990 28 sporadic cjd cases

UK 2018 131 sporadic cjd case

http://www.cjd.ed.ac.uk/sites/default/files/figs.pdf

https://creutzfeldt-jakob-disease.blogspot.com/2018/12/creutzfeldt-jakob-disease-cjd-bse.html

Terry S. Singeltary Sr., Bacliff, Texas USA, flounder9@verizon.net Galveston Bay...on the bottom!