CWD TSE PRION ZOONOSIS TRANSMISSION TO HUMANS BY BLOOD TRANSFUSION, iatrogenic CJD, WHAT IF?
Successful transmission of the chronic wasting disease (CWD) agent to white-tailed deer by intravenous blood transfusion
Author links open overlay panel Najiba Mammadova ab Eric Cassmann ab Justin J.Greenlee
https://doi.org/10.1016/j.rvsc.2020.10.009Get rights and content
Under a Creative Commons licenseopen access
Highlights
•The chronic wasting disease (CWD) agent efficiently transmits between white-tailed deer.
•Blood from CWD infected deer contains infectious prions.
•A single intravenous blood transfusion resulted in CWD transmission with an incubation of 25.6 months for the GG96 recipient.
•The GS96 recipient had a longer incubation of 43.6 months.
Abstract
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSEs) that affects free-ranging and captive cervid species. The infectious agent of CWD may be transmitted from ingestion of prions shed in bodily fluids (e.g. feces, urine, saliva, placenta tissue) of infected animals, contaminated pastures, and/or decomposing carcasses from dead animals. Studies have also demonstrated prion infectivity in whole blood or blood fractions of CWD infected animals. To determine if CWD-infected blood contained sufficient levels of prion infectivity to cause disease, recipient deer were inoculated intravenously (IV) with blood derived from a CWD-infected white-tailed deer. We found that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion. The incubation period was associated with recipient prion protein genotype at codon 96 with the GG96 recipient incubating for 25.6 months and the GS96 recipient incubating for 43.6 months. This study complements and supports an earlier finding that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD.
snip...
This study complements and reinforces earlier findings that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD (Mathiason et al., 2010; Mathiason et al., 2006). In a previous study, a group of eight, 6-month-old fawns were IV inoculated with ~250 mL of whole blood derived from experimentally IC inoculated CWD positive white-tailed deer (Mathiason et al., 2010). In this study, all eight deer were determined to be CWD positive by IHC of all relevant tissues, and began to show clinical signs of TSE between 15 and 26 months post inoculation (Mathiason et al., 2010). While similar results were obtained in our study, we determined that only 100 mL of CWD-infected blood contained sufficient levels of prion infectivity to cause disease compared to the 250 mL of whole blood used by Mathiason et al. (Mathiason et al., 2010). In an earlier study, a cohort of three 6-month-old white-tailed deer fawns were exposed to the agent of CWD via either a single intraperitoneal (IP) inoculation (n = 2) or an IV transfusion (n = 1) of blood derived from a naturally infected CWD positive mule deer (Mathiason et al., 2006). Similar to our findings, the fawn that received blood via IV transfusion had detectable PrPSc in the CNS (medulla at the level of the obex), tonsil, and retropharyngeal lymph nodes (Mathiason et al., 2006); however, it did not present with clinical signs and was euthanized 18 months post inoculation (Mathiason et al., 2006).
We demonstrate here that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion from CWD-infected white-tailed deer. The incubation period appeared to be associated with recipient genotype with the GG96 deer (940) incubating for 25.6 months, while the GS96 deer (941) incubated for 43.6 months; however, we take into consideration the limitation of the small sample size in this study. While a previous and larger study showed similar results, we determined that only 100 mL of CWD-infected blood (~2.5 times less than previously shown in (Mathiason et al., 2010)) contained sufficient levels of prion infectivity to cause disease. The identification of blood-borne transmission of the CWD agent is important in reinforcing the risk of exposure to CWD via blood as well as the possibility of hematogenous transmission of the CWD agent through insect vector. Finally, these results further highlight the importance of developing a sensitive and reproducible blood-based test to detect pre-clinical CWD, and warrant the continued advancement and evaluation of sensitive antemortem diagnostic tests for the detection of PrPSc in blood of asymptomatic cervids early in the incubation period.
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Successful transmission of the chronic wasting disease (CWD) agent to white-tailed deer by intravenous blood transfusion
Author item MAMMADOVA, NAJIBA - Orise Fellow item CASSMAN, ERIC - Orise Fellow item Greenlee, Justin Submitted to: Research in Veterinary Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/14/2020 Publication Date: 12/20/2020 Citation: Mammadova, N., Cassman, E., Greenlee, J.J. 2020. Successful transmission of the chronic wasting disease (CWD) agent to white-tailed deer by intravenous blood transfusion. Research in Veterinary Science. 133:304-306. https://doi.org/10.1016/j.rvsc.2020.10.009. DOI: https://doi.org/10.1016/j.rvsc.2020.10.009 Interpretive Summary: Chronic wasting disease (CWD) is a fatal disease of cervids that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. Chronic wasting disease may be transmitted from ingestion of prions shed in bodily fluids (e.g. feces, urine, saliva, placenta tissue) of infected animals. Few studies have also reported detection of infectious prions in blood. To determine if CWD-infected blood can transmit prion disease, recipient deer were inoculated intravenously (IV) with blood derived from a CWD-infected white-tailed deer. We found that two out of three animals developed disease. This study complements and supports an earlier finding that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD. This information is useful to wildlife and agricultural officials that are involved in efforts to control the spread of chronic wasting disease.
Technical Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSEs) that affects free-ranging and captive cervid species. The infectious agent of CWD may be transmitted from ingestion of prions shed in bodily fluids (e.g. feces, urine, saliva, placenta tissue) of infected animals, contaminated pastures, and/or decomposing carcasses from dead animals. Studies have also demonstrated prion infectivity in whole blood or blood fractions of CWD infected animals. To determine if CWD-infected blood contained sufficient levels of prion infectivity to cause disease, recipient deer were inoculated intravenously (IV) with blood derived from a CWD-infected white-tailed deer. We found that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion with a mean incubation period of approximately 35 months and an attack rate of 100%. This study complements and supports an earlier finding that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD.
A number of animal studies have investigated blood as a route of transmission of prion disease [3]. Seminal studies in sheep models of prion disease demonstrated that BSE could be transmitted via blood transfusion [14]. Further studies demonstrated that all blood components were capable of transmitting disease during the subclinical period [15]. The blood-transfusion–related human cases demonstrate that individuals of the 129MM genotype can transmit infectivity prior to developing clinical signs of disease.
It can be concluded that the animal host, especially cattle, exerts considerable influence over the pathogenesis of a prion disease in terms of what tissues are involved and what can be seen in one animal species does not always extrapolate to another. In particular, no evidence exists to suggest that infectivity can be found in the blood of cattle with BSE as tested by bioassay of spleen and/or blood in bovinized transgenic mice,17,34 whereas lines of evidence exist that suggest that infectivity can be found in the blood of cervids with CWD, scrapie in sheep, and vCJD in human beings. Whole blood transfusion studies in sheep using donor sheep with experimental BSE or with natural scrapie have shown that infectivity resides in the blood of sheep.51–54 Similarly, transmissibility by blood transfusion has been reported for deer with experimental CWD.73
Subject: Transmission of BSE by blood transfusion in sheep...
Date: Thu, 14 Sep 2000 18:19:06 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
More Dredful news, but predictable...
kind regards,
Terry S. Singeltary Sr., Bacliff, Texas USA
===========================================
It is possible to transmit BSE to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection'
It is well known that variant Creutzfeldt-Jakob disease (vCJD) is caused by the same strain of agent that causes bovine spongiform encephalopathy (BSE) in cattle. F Houston and colleagues report the preliminary findings of transfusing blood from 19 UK Cheviot sheep fed with 5 g BSE-affected cattle brain into Cheviot sheep from scrapie-free flock of New Zealand-derived animals. The investigators found BSE clinical signs and pathology in one recipient of blood taken from a BSE infected animal. Immunocytochemistry on tissues taken from the transfused sheep showed widespread PrPSC deposition throughout the brain and the periphery. This finding suggests that blood donated by symptom-free vCJD-infected human beings could transmit infection to recipients of blood transfusions. In a Commentary, Paul Brown states that these observations are consistent with previous reports in experimentally infected rodents.
==================
Research letters
Volume 356, Number 9234 16 September 2000
Transmission of BSE by blood transfusion in sheep
Lancet 2000; 356: 999 - 1000
Download PDF (1 Mb)
F Houston, J D Foster, Angela Chong, N Hunter, C J Bostock
See Commentary
We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) in human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission--this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK.
The demonstration that the new variant of Creutzfeldt-Jakob disease (vCJD) is caused by the same agent that causes bovine spongiform encephalopathy (BSE) in cattle1 has raised concerns that blood from human beings in the symptom-free stages of vCJD could transmit infection to recipients of blood transfusions. There is no evidence that iatrogenic CJD has ever occurred as a result of the use of blood or blood products, but vCJD has a different pathogenesis and could present different risks. CJD is one of the transmissible spongiform encephalopathies (TSEs) characterised by the deposition of an abnormal form of a host protein, PrPSc; the normal isoform (PrPC) is expressed in many body tissues. Available evidence, based on detection of infectivity in blood in rodent models, and absence of infectivity in naturally occurring TSEs, adds to the uncertainty in risk assessments of the safety of human blood. PrPSc has been reported in blood taken from preclinical TSE-infected sheep,2 but it does not follow that blood is infectious. Bioassays of human blood can only be carried out in non-human species, limiting the sensitivity of the test. One way of avoiding such a species barrier is to transfer blood by transfusion in an appropriate animal TSE model. BSE-infected sheep harbour infection in peripheral tissues3 and are thus similar to humans infected with vCJD.4 BSE infectivity in cattle does not have widespread tissue distribution.
We report preliminary data from a study involving blood taken from UK Cheviot sheep challenged orally with 5 g BSE-affected cattle brain and transfused into Cheviot sheep from a scrapie-free flock of New Zealand-derived animals (MAFF/SF flock). MAFF/SF sheep do not develop spontaneous TSE and the transfused animals are housed separately from other sheep. All sheep in the study have the PrP genotype AA136QQ171 which has the shortest incubation period of experimental BSE in sheep.5 19 transfusions from BSE-challenged sheep have been done, mostly with whole blood. Sheep have complex blood groups and only simple cross-matching can be done by mixing recipient serum and donor erythrocytes and vice versa. Therefore single transfusions only were made between sedated cross-matched animals to minimise the risk of severe reactions. Negative controls were MAFF/SF sheep transfused with blood from uninfected UK Cheviot sheep. As a positive control, MAFF/SF sheep were intravenously injected with homogenised BSE-affected cattle brain.
We have seen BSE clinical signs and pathological changes in one recipient of blood from a BSE-infected animal, and we regard this finding as sufficiently important to report now rather than after the study is completed, several years hence. The blood donation resulting in transmission of BSE to the recipient was 400 mL of whole blood taken from a healthy sheep 318 days after oral challenge with BSE. BSE subsequently developed in this donor animal 629 days after challenge, indicating that blood was taken roughly half way through the incubation period. 610 days after transfusion, the transfused sheep (D505) itself developed typical TSE signs: weight loss, moderate pruritus, trembling and licking of the lips, hind-limb ataxia, and proprioceptive abnormalities. This is the first experimental transmission of BSE from sheep to sheep and so we have nothing with which to compare this incubation period directly. In cross-species transmissions, bovine BSE injected intracerebrally gives incubation periods of about 450 days in these sheep,5 and the donor animal had an oral BSE incubation period of 629 days (see above). There are no similar data available on other infection routes. Immunocytochemistry with the antibody BG4 on tissues taken from sheep D505 showed widespread PrPSc deposition throughout the brain and periphery. Western blot analysis of brain tissue with the antibody 6H4 showed that the PrPSc protein had a glycoform pattern similar to that of experimental BSE in sheep and unlike that of UK natural scrapie (figure), indicating that the TSE signs resulted from transmission of the BSE agent. All other recipients of transfusions and positive and negative controls are alive and healthy. The positive controls, which involve a species barrier, are expected to have lengthy incubation periods. With one exception, all transfused animals are at earlier stages post-transfusion than was D505. The exception is a sheep which is healthy 635 days after transfusion with BSE-blood donated at less than 30% of the BSE incubation period of the donor sheep.
PrPSc (proteinase K treated) analysed by SDS-PAGE, immunoblotted with 6H4, and visualised with a chemiluminescent substrate
All lanes are from the same gel with different exposure times. Size markers are to the left of lane 1. Lane1: natural scrapie sheep brain, 3 min exposure. Lane 2: as lane 1, 10 min exposure. Lane 3: sheep D505, blood-transfusion recipient, 10 min exposure. Lane 4: experimental BSE-affected sheep brain, 30 s exposure. Lane 5: as lane 4, 10 min exposure. Each lane loaded with amount of protein extracted from 0·1 g wet weight of brain, except lane 3 which was extracted from 0·2 g brain.
Although this result was in only one animal, it indicates that BSE can be transmitted between individuals of the same species by whole-blood transfusion. We have no data on blood fractions or on levels of infectivity in blood of preclinical vCJD cases, but whole blood is not now used in UK transfusions. The presence of BSE infectivity in sheep blood at an early stage in the incubation period suggests that it should be possible to identify which cells are infected, to test the effectiveness of leucodepletion, and to develop a diagnostic test based on a blood sample.
We thank Karen Brown, Moira Bruce, Calum McKenzie, David Parnham, Diane Ritchie, and the Scottish Blood Transfusion Service. The project is funded by the Department of Health.
1 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 488-501 [PubMed].
2 Schmerr MJ, Jenny A, Cutlip RC. Use of capillary sodium dodecyl sulfate gel electrophoresis to detect the prion protein extracted from scrapie-infected sheep. J Chromatogr B Biomed Appl 1997; 697: 223-29 [PubMed].
3 Foster JD, Bruce M, McConnell I, Chree A, Fraser H. Detection of BSE infectivity in brain and spleen of experimentally infected sheep. Vet Rec 1996; 138: 546-48 [PubMed].
4 Hill AF, Zeidler M, Ironside J, Collinge J. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 1997; 349: 99-100.
5 Goldmann W, Hunter N, Smith G, Foster J, Hope J. PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 1994; 75: 989-95 [PubMed].
Institute for Animal Health, Compton, Newbury, UK (F Houston PhD, CJ Bostock PhD); and Institute for Animal Health, Neuropathogenesis Unit, Edinburgh, EH9 3JF, UK (N Hunter PhD, JD Foster BSc, Angela Chong BSc)
Correspondence to: Dr N Hunter
=======================
Commentary
Volume 356, Number 9234 16 September 2000
BSE and transmission through blood
Lancet 2000; 356: 955 - 956
Download PDF (55 Kb)
Wether the outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the UK will ultimately affect hundreds, or tens of thousands of people, cannot yet be predicted.1 If large numbers of apparently healthy people are now silently incubating infections with bovine spongiform encephalopathy (BSE), the implications for public health include the possiblity that blood from such individuals may be infectious. Established facts about infectivity in the blood of human beings and animals with transmissible spongiform encephalopathies (TSEs) are as follows:2-4
Blood, especially the buffy-coat component, from animals experimentally infected with scrapie or CJD and from either a clinical or preclinical incubation phase, is consistently infectious when bioassayed by intracerebral or intraperitoneal inoculation into the same species;
In naturally infected animals (sheep and goats with scrapie, mink with transmissible mink encephalopathy, and cows with BSE), all attempts to transmit disease through the inoculation of blood have failed;
Blood from four of 37 human beings with clinically evident sporadic CJD has been reported to transmit the disease after intracerebral inoculation into guineapigs, mice, or hamsters. But each success has been questioned on technical grounds and has not been reproducible; and
Epidemiological data have not revealed a single case of CJD that could be attributed to the administration of blood or blood products among patients with CJD, or among patients with haemophilia and other congenital clotting or immune deficiencies who receive repeated doses of plasma concentrates.
No comparable information about vCJD is available. However, since lymphoreticular organs, such as tonsils have been shown to contain the prion protein (which is an excellent index of infectivity), whereas it is not detectable in patients with sporadic CJD, there is some reason to worry that blood from individuals incubating vCJD might be infectious.5 Data from studies into the ability of blood from experimentally infected rodents and primates with vCJD to transmit the disease will not be available for months or years.
In this issue of The Lancet, F Houston and co-workers report convincing evidence that blood from a seemingly healthy sheep incubating BSE (infected by the oral route with brain from a diseased cow) was able to cause the disease when transfused into another sheep. This observation is entirely consistent with past experience in experimentally infected rodents. It extends current knowledge about blood infectivity in experimental models to a host/TSE strain pair that is closer to the human vCJD situation than the earlier rodent studies. It is also the first successful transfusion of BSE from blood taken during the all-important incubation period of infection. This result is part of a larger study (n=19) that includes both positive and negative control animals, all still healthy and in various early stages of the incubation period.
Is it appropriate to publish an experimental result from a single animal in a study that is not far enough along even to have validated its positive controls? Especially a result that does not in any fundamental way change our current thinking about BSE and vCJD and which would not seem to have any practical consequences for public health? The UK National Blood Transfusion Service has already implemented leucodepletion of donated blood, and imports all plasma and plasma derivatives from BSE-free countries. No further measures would seem possible--short of a draconian decision to shut down the whole UK blood-donor system. What, therefore, is the rationale for this publishing urgency? The answer, evidently, is a perceived need to "defuse", by an immediate and accurate scientific report, public reaction to possibly inaccurate media accounts. The full study, when it appears, will be an important addition to our knowledge of TSEs, but science should not be driven to what in certain medical quarters might be termed a premature emission through fear of media misrepresentation.
Paul Brown
Laboratory of Central Nervous System Studies, National Institutes of Health, Bethesda, MD 20892, USA
1 Ghani AC, Ferguson NM, Donnelly CA, Anderson RM. Predicted vCJD mortality in Great Britain. Nature 2000; 406: 583-84 [PubMed].
2 Brown P. Can Creutzfeldt-Jakob disease be transmitted by transfusion? Curr Opin Hematol 1995; 2: 472-77 [PubMed].
3 Brown P, Cervenáková L, McShane LM, Barber P, Rubenstein R, Drohan WN. Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt-Jakob disease in humans. Transfusion 1999; 39: 1169-78 [PubMed].
4 Rohwer RG. Titer, distribution, and transmissibility of blood-borne TSE infectivity. Presented at Cambridge Healthtech Institute 6th Annual Meeting "Blood Product Safety: TSE, Perception versus Reality", MacLean, VA, USA, Feb 13-15, 2000.
5 Hill AF, Butterworth RJ, Joiner S, et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999; 353: 183-89.
http://www.thelancet.com/
===================
TSS
From: Terry S. Singeltary Sr. (216-119-130-97.ipset10.wt.net)
Subject: Other Transmission Studies of CJD from Blood and Urine Into Mice...
Date: September 18, 2000 at 2:01 pm PST
In Reply to: Transmission of BSE by blood transfusion in sheep... posted by Terry S. Singeltary Sr. on September 15, 2000 at 9:29 am:
Transmission of Creutzfeldt-Jakob Disease from Blood and Urine Into Mice
The Lancet, November 9, 1985
Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from whole blood samples of a patient (and of mice) infected with CJD.1 Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.
A 70-year-old man was noted to have a slowing of speech and writing and some disorientation, all of which progressed rapidly. Decorticate rigidity, forced grasping, positive snout reflex, and myoclonus appeared within 2 months. Electroencephalogram revealed typical periodic synchronous discharge, and he died of pneumonia and upper gastrointestinal haemorrhage, about 3 months after onset of the symptoms. The Brain weighed 1290g and showed severe histological changes diagnostic of CJD, including spongiform change, loss of nerve cells, and diffuse proliferation of astrocytes. There were no inflammatory cells, microglia, neurofibrillary tangles, and amyloid plaques, although virus-like particles were detected by electron microscopy.
Results of innoculation in Mice
Inocula NO* Incubation period (days)+ Brain 7/10 (4) 789 (+ or - 112) Cornea 1/6 (0) 1037 Blood 2/13 (0) 1080 (+ or - 69) Urine 5/10 (1) 880 (+ or - 55) CSF 0/10
* Number of mice with CJD change/number examined histologically. Number with amyloid plaques shown in parentheses.
+ means + or - SD
Samples were taken aseptically at necropsy. 10% crude homogenates of brain and cornea in saline, whole blood (after crushing a clot), and untreated CSF and urine were innoculated intracerebrally into CF1 strain mice (20 ul per animal). Some mice showed emaciation, bradykinesia, rigidity of the body and tail, and sometimes tremor after long incubation periods. Tissues obtained after the animal died (or was killed) were studied histologically (table). Animals infected by various inocula showed common pathological changes, consisting of severe spongiform changes, glial proliferation, and a moderate loss of nerve cells. A few mice inoculated with brain tissue or urine had the same amyloid plaques found in patients and animals with CJD.3
In our long-term experiments, inoculating materials taken from twenty patients with CJD or Gerstmann-Straussler-Scheinker's disease (GSS) into rodents, positive results were obtained in seventeen cases, including this patient. Brain tissue transmitted the disease most frequently within the shortes incubation period, except for one case where the lymph node was the most infectious. Transmission through the cornea has been noted in man4 and in guineapigs.5 Whole blood samples taken from three patients were inoculated and a positive transmission occured only in the case recorded here. Mouse-to-mouse transmission through blood inoculation was successful after a mean incubation period of 365 days.1 Transmission through urine was positive in this patient only, and negative in one other patient and in many infected animals. Transmission through the CSF from eight patients was negative, yet transmission via the CSF of infected rats was positive.1
As viraemia has been proved in guineapigs,6 mice,1,7 and lately in patients with CJD, blood for transfusion or blood products for medical use must be tested for unconventional pathogens. For this purpose, we inoculated blood products inot rodents.8 The CJD pathogen was not found in the products examined. However, this approach takes too long to be of practical value. More efficient methods must be developed to detect pathogens and to eliminate them from blood. One proposal9 is to apply membrane filtration to the pruification protocol of human growth hormone suspected of being contaminated with CJD. Similar methods are needed for blood contamination.
Department of Neuropathology, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka812, Japan
JUN TATEISHI
1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmission of human subacute spongiform encephalopathy to small rodents 1: Clinical and histological observations. Acta Neuropathol (Berl) 1980; 51: 127.
2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob disease with demonstration of virus-like particles. Acta pathol Jpn 1982;32: 695.
3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the brains of mice with Creutzfeldt-Jakob disease. Ann Neurol 1984; 15: 278.
4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974; 290: 692.
5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L. Experimental Creutzfeldt-Jakob disease transmitted via the eye with infected cornea. N Engl J Med 1977; 296: 1334.
6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental Creutzfeldt-Jakob disease. Science 1978: 200: 1069.
7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC. Creutzfeldt-Jakob disease in mice. Persistent viremiam and preferential replication of virus in low-density lymphocytes. Infect Immun 1983; 41: 154.
8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform encephalopathis absent in blood products. J Med Virol 1985; 15: 11.
9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease pathogen in growth hormone preparations is eliminatable. Lancet (in press).
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also, this from the Her Majesty's Government...TSS
Subject: Transmission of TSEs through blood
Date: Tue, 28 Mar 2000 14:48:35 +0100
From: Ralph Lucas
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
The Lord Lucas asked Her Majesty's Government:
Whether there is any evidence that any Transmissible Spongiform Encephalopathy in any species can be transmitted through blood; and whether they will place in the Library of the House copies of the principal relevant scientific papers. (HL1545)
The Parliamentary Under-Secretary of State, Department of Health (Lord Hunt of Kings Heath):
Some animal studies have shown that certain transmissible spongiform encephalopathies can be experimentally transmitted from animal to animal through blood components. However, the Spongiform Encephalopathy Advisory Committee at its February meeting reviewed recent research undertaken in this area and did not consider any measures were necessary, in addition to those already in place, to reduce any potential risk to public health from human blood and blood products.
Copies of the following relevant scientific papers are being placed in the Library.
Brown P, 1995, "Can Creutzfeldt-Jakob Disease be transmitted by Transfusion?" Haematology 2: 472 - 477.
Brown et al 1999, Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt - Jakob disease in humans.
Transfusion Vol. 39, November/December 1169 - 1178.
Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection
M. Khalid F. Salamat ,A. Richard Alejo Blanco ,Sandra McCutcheon ,Kyle B. C. Tan,Paula Stewart,Helen Brown,Allister Smith,Christopher de Wolf,Martin H. Groschup,Dietmar Becher,Olivier Andréoletti,Marc Turner,Jean C. Manson,E. Fiona Houston
Published: February 18, 2021https://doi.org/10.1371/journal.ppat.1009276
Abstract
Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. All components were capable of transmitting prion disease when donors were in the preclinical phase of infection, with the highest rates of infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<106 WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post infection. However, in donor sheep (orally infected), the onset of detection of PrPSc in blood was much more variable, and generally later, compared to recipients (intravenous infection). This shows that the route and method of infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that blood transfusion can be a highly efficient route of transmission for prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.
Author summary
Variant Creutzfeldt-Jakob disease (vCJD) resulted from zoonotic transmission of bovine spongiform encephalopathy (BSE), and has also been transmitted by blood transfusion. One of the most important risk reduction measures introduced by human transfusion services to safeguard the blood supply is leucodepletion (removal of white blood cells) of blood components. This study represents the largest experimental analysis to date of the risks of prion infection associated with transfusion of labile blood components, and the effectiveness of leucodepletion in preventing transmission. Using a BSE-infected sheep model, we found that red blood cells, platelets and plasma from preclinical donors were all infectious, even after leucodepletion, although leucodepletion significantly reduced transmission rates. In addition, the time course of detection of prions in blood varied significantly depending on the route and method of infection. This has important implications for the risk of onward transmission, and suggests that further improvements in sensitivity of diagnostic tests will be required for reliable preclinical diagnosis of vCJD and other prion diseases. The results of this study support the continuation of current measures to reduce the risk of vCJD transmission by blood products, and suggest areas for further improvement.
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
***> Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
Prion Conference 2018 Abstracts
BSE aka MAD COW DISEASE, was first discovered in 1984, and it took until 1995 to finally admit that BSE was causing nvCJD, the rest there is history, but that science is still evolving i.e. science now shows that indeed atypical L-type BSE, atypical Nor-98 Scrapie, and typical Scrapie are all zoonosis, zoonotic for humans, there from.
HOW long are we going to wait for Chronic Wasting Disease, CWD TSE Prion of Cervid, and zoonosis, zoonotic tranmission to humans there from?
Studies have shown since 1994 that humans are susceptible to CWD TSE Prion, so, what's the hold up with making CWD a zoonotic zoonosis disease, the iatrogenic transmissions there from is not waiting for someone to make a decision.
***> 2021
GUIDANCE DOCUMENT
Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components
Guidance for Industry
AUGUST 2020
WEDNESDAY, SEPTEMBER 02, 2020
Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components Guidance for Industry
I believe it is very foolish to start relaxing safety measures for blood products via Sporadic Creutzfeldt Jakob Disease sCJD TSE Prion, since sCJD is not a single strain of TSE Prion, but many different strains of CJD, now even including VPSPr. also, what about sporadic FFI and sporadic GSS?
THURSDAY, JULY 02, 2020
Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure
Friday, February 19, 2021
Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection
***> 2021
Wide distribution of prion infectivity in the peripheral tissues of vCJD and sCJD patients
Jean‑Yves Douet1 · Alvina Huor1 · Hervé Cassard1 · Séverine Lugan1 · Naima Aron1 · Mark Arnold2 · Didier Vilette1 · Juan‑Maria Torres3 · James W. Ironside4 · Olivier Andreoletti1
Received: 17 December 2020 / Revised: 18 January 2021 / Accepted: 19 January 2021 © The Author(s) 2021
Abstract
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease, occurring most likely as the consequence of spontaneous formation of abnormal prion protein in the central nervous system (CNS). Variant Creutzfeldt–Jakob disease (vCJD) is an acquired prion disease that was first identified in 1996. In marked contrast to vCJD, previous investigations in sCJD revealed either inconsistent levels or an absence of PrPSc in peripheral tissues. These findings contributed to the consensus that risks of transmitting sCJD as a consequence of non-CNS invasive clinical procedures were low. In this study, we systematically measured prion infectivity levels in CNS and peripheral tissues collected from vCJD and sCJD patients. Unexpectedly, prion infectivity was detected in a wide variety of peripheral tissues in sCJD cases. Although the sCJD infectivity levels varied unpredictably in the tissues sampled and between patients, these findings could impact on our perception of the possible transmission risks associated with sCJD.
snip...
Recently, bioassays in transgenic mice that express the human PrP gene and display a high sensitivity to sCJD demonstrated the presence of prion infectivity in the plasma and bone marrow of several sCJD patients [17, 32]. These results raised questions about the overall distribution of prion infectivity and transmission risks associated with other peripheral tissues from sCJD patients.
In this study, we measured the prion infectivity levels in a panel of tissues collected from vCJD and sCJD MM1 cases. These bioassays demonstrated that, as expected, consistent titres of infectivity were present in lymphoid tissues from vCJD patients. However, for the non-lymphoid peripheral tissues studied, variable and lower titres of infectivity were detected in both sCJD and vCJD patients. These findings could impact on our perception of the possible transmission risks associated with sCJD involving non-CNS invasive procedures.
snip...
In the sCJD cases 2, 4 and 5, the lymphoid tissues dis-played maximal level of infectivity that were 3–3.5 log10 lower than those observed in the frontal cortex (Table 2, Fig. 3). Strikingly, the infectivity levels associated with some peripheral tissues such as salivary gland (sCJD2), heart (sCJD2), kidney (sCJD 2) or bone marrow (sCJD 5) could be equivalent or even higher than those measured in the lymphoid organs of the same patient (Table 2, Fig. 3).
Our detection of low levels of sCJD infectivity in nonCNS tissues such as lung, heart, muscle or even salivary gland was unexpected. We next reviewed the medical histories for the sCJD patients that we studied (Table 1), which revealed surgical procedures (s-CJD-2 and 4) and/or invasive medical examinations (polypectomy under colonoscopy sCJD-5) only few years before the clinical disease in these patients. Some years ago, the presence of infectivity in the plasma and the detection of abnormal prion protein in the urine of sCJD patients raised concerns about the risks of sCJD transmission by blood transfusion and plasma/urinederived medical products [17, 38]. The detection, in our study, of infectivity in the bone marrow and the kidney of sCJD patients further reinforces these concerns.
Many uncertainties remain on the early stages of the prion accumulation and infectivity in the peripheral tis-sues in patients infected with sCJD. However, the results of this study suggest that the iatrogenic transmission risks associated with sCJD peripheral tissues should not be disregarded.
FRIDAY, JANUARY 31, 2020
CJD TSE Prion Blood Products, iatrogenic transmission, Confucius is confused again, WHAT IF? Docket Number: FDA-2012-D-0307
Volume 26, Number 8—August 2020
Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993–2018 high proportion of physicians with sCJD were surgeons
SUNDAY, JULY 19, 2020
Joseph J. Zubak Orthopaedic surgeon passed away Monday, July 6, 2020, Creutzfeldt-Jakob Disease (CJD)
all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, provern, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd, PLUS, SPORADIC CJD HAS NOW BEEN LINKED TO ATYPICAL AND TYPICAL BSE, SCRAPIE, AND NOW CWD. ...terry
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???
Greetings Friends, Neighbors, and Colleagues,
TUESDAY, JUNE 1, 2021
Alzheimer’s disease neuropathological change three decades after iatrogenic amyloid-β transmission
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
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ? Posted by flounder on 05 Nov 2014 at 21:27 GMT Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.
Conclusions
There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.
end...tss
Ann N Y Acad Sci. 1982;396:131-43.
Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob disease).
Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC.
Abstract
Ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for AD and the spongiform virus encephalopathies. However, the crux of the comparison rests squarely on results of attempts to transmit AD to experimental animals, and these results have not as yet validated a common etiology. Investigations of the biologic similarities between AD and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoculated animals will be continued in the hope that incubation periods for AD may be even longer than those of CJD.
http://onlinelibrary.wile...
CJD1/9 0185 Ref: 1M51A
IN STRICT CONFIDENCE
Dr McGovern From: Dr A Wight Date: 5 January 1993 Copies: Dr Metters Dr Skinner Dr Pickles Dr Morris Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC. 2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegenerative disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion. 93/01.05/4.1
http://collections.europa...
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
http://web.archive.org/web/20090506012455/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992 CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognized the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed'. As the report emphasizes the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible. What are the implications for public health?
3. The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1-1 BSE101/1 0137
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 121/YdeS 92/11.4/1.2
http://collections.europa...
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://collections.europa...
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight Date: 5 January 1993
Copies:
Dr Metters Dr Skinner Dr Pickles Dr Morris Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://collections.europa...
No competing interests declared.
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.]
Singeltary Comment at very bottom of this Nature publishing;
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease To the Editor:
In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally..
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
Monday, September 14, 2020
Assessing the aggregated probability of entry of a novel prion disease agent into the United Kingdom
TUESDAY, DECEMBER 01, 2020
Sporadic Creutzfeldt Jakob Disease sCJD and Human TSE Prion Annual Report December 14, 2020
SATURDAY, FEBRUARY 20, 2021
Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt–Jakob disease
SUNDAY, AUGUST 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
TUESDAY, AUGUST 18, 2009
BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
Subject: Re: Hello Dr. Gibbs...........
Date: Wed, 29 Nov 2000 14:14:18 -0500
From: "Clarence J. Gibbs, Jr., Ph.D."
To: "Terry S. Singeltary Sr." References: <3a254430.9fb97284@wt.net>
Hi Terry:
xxxx xxxx xxxx Washington, D. C. 20002.
Better shrimp and oysters than cards!!!!
Have a happy holiday and thanks for all the information you bring to the screen.
Joe Gibbs ==========
TUESDAY, MAY 11, 2021
A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet
Monday, April 12, 2021
Improving the Predictive Value of Prion Inactivation Validation Methods to Minimize the Risks of Iatrogenic Transmission With Medical Instruments
***> 2021 ZOONOSIS ZOONOTIC TRANSMISSION OF CWD TSE PRION TO HUMANS <***
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 # 1R01NS088604-01A1 Application # 9037884 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 2015-09-30 Budget End 2016-07-31 Support Year 1 Fiscal Year 2015 Total Cost $337,507 Indirect Cost $118,756
snip...
Professor Kongs reply to me just this month about above grant study that has NOT been published in peer reveiw yet...
=================================
SNIP...can't post publically yet...terry
On Sat, Apr 3, 2021 at 12:19 PM Terry Singeltary <flounder9@verizon.net> wrote:
snip...
end...tss
==============
CWD ZOONOSIS ZOONOTIC THE FULL MONTY TO DATE
International Conference on Emerging Diseases, Outbreaks & Case Studies & 16th Annual Meeting on Influenza March 28-29, 2018 | Orlando, USA
Qingzhong Kong
Case Western Reserve University School of Medicine, USA
Zoonotic potential of chronic wasting disease prions from cervids
Chronic wasting disease (CWD) is the prion disease in cervids (mule deer, white-tailed deer, American elk, moose, and reindeer). It has become an epidemic in North America, and it has been detected in the Europe (Norway) since 2016. The widespread CWD and popular hunting and consumption of cervid meat and other products raise serious public health concerns, but questions remain on human susceptibility to CWD prions, especially on the potential difference in zoonotic potential among the various CWD prion strains. We have been working to address this critical question for well over a decade. We used CWD samples from various cervid species to inoculate transgenic mice expressing human or elk prion protein (PrP). We found infectious prions in the spleen or brain in a small fraction of CWD-inoculated transgenic mice expressing human PrP, indicating that humans are not completely resistant to CWD prions; this finding has significant ramifications on the public health impact of CWD prions. The influence of cervid PrP polymorphisms, the prion strain dependence of CWD-to-human transmission barrier, and the characterization of experimental human CWD prions will be discussed.
Speaker Biography Qingzhong Kong has completed his PhD from the University of Massachusetts at Amherst and Post-doctoral studies at Yale University. He is currently an Associate Professor of Pathology, Neurology and Regenerative Medicine. He has published over 50 original research papers in reputable journals (including Science Translational Medicine, JCI, PNAS and Cell Reports) and has been serving as an Editorial Board Member on seven scientific journals. He has multiple research interests, including public health risks of animal prions (CWD of cervids and atypical BSE of cattle), animal modeling of human prion diseases, mechanisms of prion replication and pathogenesis, etiology of sporadic Creutzfeldt-Jacob disease (CJD) in humans, normal cellular PrP in the biology and pathology of multiple brain and peripheral diseases, proteins responsible for the α-cleavage of cellular PrP, as well as gene therapy and DNA vaccination.
Prion Conference 2018 Abstracts
BSE aka MAD COW DISEASE, was first discovered in 1984, and it took until 1995 to finally admit that BSE was causing nvCJD, the rest there is history, but that science is still evolving i.e. science now shows that indeed atypical L-type BSE, atypical Nor-98 Scrapie, and typical Scrapie are all zoonosis, zoonotic for humans, there from.
HOW long are we going to wait for Chronic Wasting Disease, CWD TSE Prion of Cervid, and zoonosis, zoonotic tranmission to humans there from?
Studies have shown since 1994 that humans are susceptible to CWD TSE Prion, so, what's the hold up with making CWD a zoonotic zoonosis disease, the iatrogenic transmissions there from is not waiting for someone to make a decision.
Prion Conference 2018 Abstracts
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.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in freeranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
=====
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.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission
Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)
(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.
Background
Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.
Methods
We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.
Results
We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.
Conclusions
PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.
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P180 Clinico-pathological analysis of human prion diseases in a brain bank series
Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)
(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Background and objective:
The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.
Methods:
We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.
Results:
176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.
Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.
Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.
Discussion:
A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:
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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures
Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)
(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Aims:
Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.
Methods:
Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.
Results:
The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.
Conclusions:
Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.
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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
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 found in spinal cord and brain of 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 preclinical 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.
See also poster P103
***> 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.
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WA16 Monitoring Potential CWD Transmission to Humans
Belay ED
Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.
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P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan
Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)
(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.
Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.
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Source Prion Conference 2018 Abstracts
Volume 24, Number 8—August 2018 Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
snip...
Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).
A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.
The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.
In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).
The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.
Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.
Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.
This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.
Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.
Prion 2017 Conference Abstracts
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 ABSTRACTS REFERENCE
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.
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
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. "
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....
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.
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.
*** 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
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
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 ;
> However, to date, no CWD infections have been reported in people.
sporadic, spontaneous CJD, 85%+ of all human TSE, did not just happen. never in scientific literature has this been proven.
if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;
sporadic = 54,983 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic
spontaneous = 325,650 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** 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).***
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ References: <3daf5023 .4080804="" wt.net="">
Dear Terry,
An excellent piece of review as this literature is desparately difficult to get back from Government sites.
What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler ===============
''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).''
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).
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 ;
http://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
http://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
BSE Inquiry Steve Dealler
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
snip...see full text;
MONDAY, FEBRUARY 25, 2019
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
Jeff Schwan was 26 years old when he died from CJD.
***> I urge everyone to watch this video closely...terry
*** You can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
*** You can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
***> ''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).''
***> 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) <***
***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.***
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
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 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
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
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
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
reference...
RB3.20
TRANSMISSION TO CHIMPANZEES
1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.
2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, ilp and i/v) :
3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.
4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.
5. A positive result from a chimpanzee challenged severely 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.
6. A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday' s meeting.
R. Bradley
23 September 1990
CVO (+Mr Wells' comments)
Dr T W A Little
Dr B J Shreeve
90/9.23/1.1.
http://web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
IN CONFIDENCE CHIMPANZEES
CODE 18-77 Reference RB3.46
Some further information that may assist in decision making has been gained by discussion with Dr Rosalind Ridley.
She says that careful study of Gajdusek's work shows no increased susceptibility of chimpanzees over New World Monkeys such as Squirrel Monkeys. She does not think it would tell you anything about the susceptibility to man. Also Gajdusek did not, she believes, challenge chimpanzees with scrapie as severely as we did pigs and we know little of that source of scrapie. Comparisons would be difficult. She also would not expect the Home Office to sanction such experiments here unless there was a very clear and important objective that would be important for human health protection. She doubted such a case could be made. If this is the case she thought it would be unethical to do an experiment abroad because we could not do it in our own country.
Retrospectively she feels they should have put up more marmosets than they did. They all remain healthy. They would normally regard the transmission as negative if no disease resulted in five years.
We are not being asked for a decision but I think that before we made one we should gain as much knowledge as we can. If we decided to proceed we would have to bear any criticisms for many years if there was an adverse view by scientists ormedia. This should not be undertaken lightly. There is already some adverse comment here, I gather, on the pig experiment though that will subside.
The Gibbs' (as' distinct from Schellekers') study is somewhat different. We are merely supplying material for comparative studies in a laboratory with the greatest experience of human SEs in the world and it has been sanctioned by USDA (though we do not know for certain yet if chimpanzees specifically will be used). This would keep it at a lower profile than if we conducted such an experiment in the UK or Europe.
I consider we must have very powerful and defendable objectives to go beyond Gibbs' proposed experiments and should not initiate others just because an offer has been made.
Scientists have a responsibility to seek other methods of investigative research other than animal experimentation. At present no objective has convinced me we need to do research using Chimpanzees - a species in need of protection. Resisting such proposals would enable us to communicate that information to the scientist and the public should the need arise. A line would have been drawn.
CVO cc Dr T Dr B W A Little Dr B J Shreeve
R Bradley
26 September 1990
90/9.26/3.2
http://web.archive.org/web/20090506041605/http://www.bseinquiry.gov.uk/files/yb/1990/09/26003001.pdf
this is tse prion political theater here, i.e. what i call TSE PRION POKER...tss
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs.
snip...
PAGE 26
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.
The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province! ...page 26.
snip...see;
IN CONFIDENCE
PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASE OF ANIMALS IN THE USA
GAH WELLS
REPORT OF A VISIT TO THE USA
APRIL-MAY 1989
MONDAY, DECEMBER 16, 2019
Chronic Wasting Disease CWD TSE Prion aka mad cow type disease in cervid Zoonosis Update
***> ''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) <***
What if?
SATURDAY, MAY 29, 2021
Second passage of chronic wasting disease of mule deer to sheep by intracranial inoculation compared to classical scrapie
''Given the results of this study, current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally.''
TUESDAY, JUNE 01, 2021
The ultrastructure of infectious L-type bovine spongiform encephalopathy prions constrains molecular models
THURSDAY, JUNE 3, 2021
Porcine Spongiform Encephalopathy PSE TSE Prion disease Spongiform Encephalopathy In Pigs
CWD MAP UPDATED
Clayton: It was recently announced that deer in two parks and wildlife breeding facilities were discovered to have CWD. How concerning is this to you?
Lockwood: Well, it's very concerning. We actually have detected CWD in five breeding facilities since March 2013. Two of the facilities are at the same location. So you can think of it as four different permitted deer breeders of that have been directly affected by this.
But actually, there are a whole lot more people than that that have been affected by this, because these facilities, they buy and sell deer, they transfer deer in and out of the facilities. Two hundred and sixty seven different sites in Texas have received deer from at least one of these facilities in the past five years. But a lot of them are release sites where these deer released in the free range and deer population.
Sat, Apr 17, 2021 1:35 pm
Terry Singeltary
greetings BSE-L et al,
i finally got a recent copy of the CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties. seems to date, there are 181 CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties, and some our out of state/country in Mexico. i was told that in the coming weeks, some of the facilities will start testing for cwd, and those results will be forthcoming later on. i hope they don't flounder on depopulation efforts if any positives are found. sad for Mexico, they haven't a clue on cwd tse prion and surveillance there from...imo.
220 Cimarron, San Pedro Garza Garcia, NA, 66278
Maclovio Herrera N 4515 Col. Motomoros, Nuevo Laredo, NA, 88210
Conquistadores 2424, Monterrey, NA, 64610
104 Serafin Pena, Linares, NA, 67735
713 Guidoni, Gral Escobedo, NA, 00000
Maiz 204 Col Centro, Anahuac, NA, 85030
Calle Dos 219, Col. Jardin, Matamoros, TA, 87330
C Real Del Marquez #403, San Pedro Garza Garcia, NL, 66278
TUESDAY, APRIL 13, 2021
Implications of farmed-cervid movements on the transmission of chronic wasting disease
Conclusion
In conclusion, given that CWD transmission can occur through contact with infected body parts or through indirect contacts via contamination of feed and other fomites, understanding animal movements is critical for mitigating disease spread. Long distance commercial movements of cervids pose one risk for spread of CWD. This study approach can be used to understand disease transmission risks across the region and in North America in general.
terry
-----Original Message-----
From: Terry Singeltary <flounder9@verizon.net>
Sent: Wed, Mar 31, 2021 11:48 am
Subject: Texas TPWD TAHC Chronic Wasting Disease Discovered at Deer Breeding Facilities in Hunt and Uvalde Counties
WEDNESDAY, MARCH 31, 2021
Texas TPWD TAHC Chronic Wasting Disease Discovered at Deer Breeding Facilities in Hunt and Uvalde Counties
Sent: Wed, May 19, 2021 11:35 am
Subject: Texas CWD TSE Prion Discovered at Deer Breeding Facilities in Matagorda and Mason Counties With 228 Positive To Date Total
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.
Greetings, i thought you all might need an update on the chronic wasting disease epidemic and the new data out on zoonosis cwd to humans there from, that i cannot talk about, made a promise not to print until peer review complete, don't want to muck that up. but you should be keen to Kong et al from CWRU on cwd zoonosis. he thinks it's already happened and is being mask as sporadic CJD, and his studies are showing this, very concerning i.e. MM1 sporadic cjd. be sure to see grant down below, towards bottom, that grant is complete, and we spoke recently about said findings...not good! these tse prion disease are mutating and spreading. we now have a new mad cow type disease in a new livestock species i.e. THE CAMEL, and it's a rather large outbreak in Africa. science now showing that CWD of cervid and Scrapie of sheep, will transmit to PIGS by oral routes. our mad cow feed ban is/was a joke, still is, and surveillance for BSE has failed terribly, now only testing roughly less than 20k a year, a joke. so, here's the full monty...kindest regards, terry
Subject: Texas CWD TSE Prion Discovered at Deer Breeding Facilities in Matagorda and Mason Counties With 228 Positive To Date Total
Subject: Texas CWD TSE Prion Discovered at Deer Breeding Facilities in Matagorda and Mason Counties With 228 Positive To Date Total
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.
For Immediate Release
May 14, 2021
Chronic Wasting Disease Discovered at Deer Breeding Facilities in Matagorda and Mason Counties
AUSTIN, TX – Chronic Wasting Disease (CWD) has been discovered in deer breeding facilities in both Matagorda and Mason counties. This marks the first positive detection of the disease in each county.
An epidemiological investigation found that both deer breeding facilities had received deer from the Uvalde County premises confirmed positive with CWD on March 29, 2021. Postmortem tissue samples were submitted by the permitted deer breeders to assist Texas Parks and Wildlife Department (TPWD) and Texas Animal Health Commission (TAHC) with the epidemiological investigation. The National Veterinary Services Laboratory (NVSL) in Ames, Iowa, has since confirmed CWD in those tissue samples.
TPWD and TAHC officials have taken immediate action to secure all cervids at the Matagorda County and Mason County deer breeding facilities and plan to conduct additional investigations for CWD. In addition, other breeding facilities and release sites that have received deer from these facilities or shipped deer to these facilities during the last five years have been contacted by TPWD and cannot move or release deer at this time.
On March 31, 2021, TPWD and TAHC reported two CWD confirmations at breeding facilities in both Hunt and Uvalde counties. The Hunt facility underwent further DNA testing to confirm animal identification and origin, and on May 12 the DNA test results confirmed the deer’s connection to the premises.
TPWD and TAHC continue to work together to determine the extent of the disease within all the affected facilities and evaluate risks to Texas’ free ranging deer populations. Quick detection of CWD can help mitigate the disease’s spread.
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD. “Along with our partners at the Texas Animal Health Commission, we will continue to exercise great diligence and urgency with this ongoing investigation. Accelerating the testing at other exposed facilities will be critical in ensuring we are doing all we can to arrest the further spread of this disease, which poses great risks to our native deer populations, both captive and free-ranging alike.”
CWD was first recognized in the U.S. in 1967 and has since been documented in captive and/or free-ranging deer in 26 states and 3 Canadian provinces.
In Texas, the disease was first discovered in 2012 in free-ranging mule deer along a remote area of the Hueco Mountains near the Texas-New Mexico border and has since been detected in 228 captive or free-ranging cervids, including white-tailed deer, mule deer, red deer and elk in 13 Texas counties. For more information on previous detections visit the CWD page on the TPWD website. CWD is a fatal neurological disease found in certain cervids, including deer, elk, moose and other members of the deer family. CWD is a slow and progressive disease. Due to a long incubation, cervids infected with CWD may not produce any visible signs for a number of years after becoming infected. As the disease progresses, animals with CWD show changes in behavior and appearance. Clinical signs may include, progressive weight loss, stumbling or tremors with a lack of coordination, excessive thirst, salivation or urination, loss of appetite, teeth grinding, abnormal head posture, and/or drooping ears. To date there is no evidence that CWD poses a risk to humans or non-cervids. However, as a precaution, the U.S. Centers for Disease Control and the World Health Organization recommend not to consume meat from infected animals. For more information about CWD, visit the TPWD web site or the TAHC web site.
###
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.
Texas Chronic Wasting Disease CWD TSE Prion Positives Mounting 224 To Date
see the latest positives;
2021-04-27 Breeder Deer Mason Facility #10 White-tailed Deer M 2.482191781
2021-04-27 Breeder Deer Uvalde Facility #7 White-tailed Deer M 1.5
2021-04-27 Breeder Deer Uvalde Facility #7 White-tailed Deer M 1.5
2021-04-20 Breeder Deer Matagorda Facility #9 White-tailed Deer F 1.5
2021-03-29 Breeder Deer Uvalde Facility #7 White-tailed Deer F 3.536986301
2021-03-29 Breeder Deer Uvalde Facility #7 White-tailed Deer M 2.178082192
2021-03-29 Breeder Deer Uvalde Facility #7 White-tailed Deer M 3.5
2021-03-29 Breeder Deer Uvalde Facility #7 White-tailed Deer M 1.545205479
2021-03-29 Breeder Deer Uvalde Facility #7 White-tailed Deer M 2.482191781
2021-03-29 Breeder Deer Hunt Facility #8 White-tailed Deer F 2.482191781
THURSDAY, MAY 06, 2021
Texas Chronic Wasting Disease CWD TSE Prion Positives Mounting 224 To Date
Politicians and ANIMAL FREAK SHOWS IN TEXAS AND CWD
ALSO, IT'S ALWAYS A FREAK SHOW IN TEXAS, IF POLITICIANS ARE NOW JERKING DEER OFF FOR CAMPAIGN MONEY, THEY ARE NOW CLONING DEER, WHAT NEXT;
WEDNESDAY, APRIL 21, 2021
***> A Texas Rancher Cloned Deer For Years. Some Lawmakers Want To Legalize It (what about cwd tse prion)? <***
WHAT COULD GO WRONG, ASK BAMBI;
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.
TUESDAY, DECEMBER 31, 2019
In Vitro detection of Chronic Wasting Disease (CWD) prions in semen and reproductive tissues of white tailed deer bucks (Odocoileus virginianus
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?
SUNDAY, FEBRUARY 16, 2020
***> Jerking for Dollars, Are Texas Politicians and Legislators Masturbating Deer For Money, and likely spreading CWD TSE Prion?
***> 181 CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties, and some are out of state/country in Mexico
i finally got a recent copy of the CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties.
seems to date, there are 181 CWD-trace facilities associated with the CWD-positive deer breeding facilities in Hunt and Uvalde Counties, and some are out of state/country in Mexico. i was told that in the coming weeks, some of the facilities will start testing for cwd, and those results will be forthcoming later on. i hope they don't flounder on depopulation efforts if any positives are found. sad for Mexico (8 facilities).
Chronic Wasting Disease Discovered at Deer Breeding Facilities in Hunt and Uvalde Counties
MARCH 31, 2021
Texas Confirms CWD TSE Prion in 213 white-tailed deer, mule deer, red deer and elk to date, 148 connected to deer breeding facilities and release sites.
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.
TUESDAY, APRIL 13, 2021
Implications of farmed-cervid movements on the transmission of chronic wasting disease
Conclusion
In conclusion, given that CWD transmission can occur through contact with infected body parts or through indirect contacts via contamination of feed and other fomites, understanding animal movements is critical for mitigating disease spread. Long distance commercial movements of cervids pose one risk for spread of CWD. This study approach can be used to understand disease transmission risks across the region and in North America in general.
TUESDAY, APRIL 13, 2021
Implications of farmed-cervid movements on the transmission of chronic wasting disease
WEDNESDAY, MARCH 31, 2021
Texas TPWD TAHC Chronic Wasting Disease Discovered at Deer Breeding Facilities in Hunt and Uvalde Counties
THURSDAY, MARCH 25, 2021
Texas CWD suspect positive results for a couple of deer breeding facilities
TUESDAY, MARCH 02, 2021
Texas Confirms CWD TSE Prion in 213 white-tailed deer, mule deer, red deer and elk to date, 148 connected to deer breeding facilities and release sites
TEXAS BREEDER DEER ESCAPEE WITH CWD IN THE WILD, or so the genetics would show?
OH NO, please tell me i heard this wrong, a potential Texas captive escapee with cwd in the wild, in an area with positive captive cwd herd?
apparently, no ID though. tell me it ain't so please...
23:00 minute mark
''Free Ranging Deer, Dr. Deyoung looked at Genetics of this free ranging deer and what he found was, that the genetics on this deer were more similar to captive deer, than the free ranging population, but he did not see a significant connection to any one captive facility that he analyzed, so we believe, Ahhhhhh, this animal had some captive ahhh, whatnot.''
TEXAS CWD STRAIN
77. Assessing chronic wasting disease strain differences in free-ranging cervids across the United States
Kaitlyn M. Wagnera, Caitlin Ott-Connb, Kelly Strakab, Bob Dittmarc, Jasmine Battend, Robyn Piercea, Mercedes Hennessya, Elizabeth Gordona, Brett Israela, Jenn Ballarde and Mark D Zabela
aPrion Research Center at Colorado State University; bMichigan Department of Natural Resources; cTexas Parks and Wildlife Department; dMissouri Department of Conservation, 5. Arkansas Game and Fish Commission CONTACT Kaitlyn M. Wagner miedkait@rams.colostate.edu
ABSTRACT
Background/Introduction: Chronic wasting disease (CWD) is an invariably fatal prion disease affecting captive and free-ranging cervids, including white-tailed deer, mule deer, moose, elk, and reindeer. Since the initial description of the disease in the 1960’s, CWD has spread to 23 states, 3 Canadian Provinces, South Korea, Norway and, most recently, Finland. While some outbreaks of CWD were caused by transport of infected animals from endemic regions, the origin of CWD in other epizootics is unclear and has not been characterized. Previous studies have shown that there are two distinct strains of CWD. However, the continuous spread and the unclear origin of several outbreaks warrant continued surveillance and further characterization of strain diversity.
Materials and Methods: To address these knowledge gaps, we used biochemical tests to assess strain differences between CWD outbreaks in Michigan, Texas, Missouri, and Colorado, USA. Brain or lymph node samples were homogenized and digested in 50 µg/mL proteinase K (PK). These samples were then run on a Western blot to assess glycoform ratio and electrophoretic mobility. Texas samples were digested in 100 µg/mL PK. To assess conformational stability, brain or lymph node homogenates were incubated in increasing concentrations of guanidine hydrochloride from 0 M to 4 M in 0.5 M increments. Samples were then precipitated in methanol overnight, washed and PK digested in 50 µg/mL PK before slot blotting.
Results: Our results have found significant differences in glycoform ratio between CWD from Michigan and Colorado, but no differences were observed in conformational stability assays. Interestingly, when testing our CWD isolates from Texas to analyse electrophoretic mobility and glycoform ratio, we found that these samples did not exhibit the characteristic band shift when treated with PK, but PK resistant material remained. Additionally, results from our conformational stability assay demonstrate a unique profile of these Texas isolates. Testing of samples from Missouri is currently underway.
Conclusions: Thus far, our data indicate that there are strain differences between CWD circulating in Michigan and CWD in Colorado and provide important insight into CWD strain differences between two non-contiguous outbreaks. We have also identified a unique strain of CWD in Texas with biochemical strain properties not seen in any of our other CWD isolates. These results highlight the importance of continued surveillance to better understand this devastating disease. These results have important implications for CWD emergence, evolution and our understanding of prion strain heterogeneity on the landscape.
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.
The disease devastating deer herds may also threaten human health
Scientists are exploring the origins of chronic wasting disease before it becomes truly catastrophic.
Rae Ellen Bichell
Image credit: David Parsons/Istock
April 8, 2019
This story was published in collaboration with the Mountain West News Bureau, a collaboration between Wyoming Public Media, Boise State Public Radio in Idaho, KUER in Salt Lake City and KRCC and KUNC in Colorado.
Heather Swanson and Ryan Prioreschi stand in knee-high golden grass on a slope outside Boulder, Colorado, where the Rocky Mountains start slumping into the plains, at the epicenter of a now-international animal epidemic. The two ecologists, who monitor wildlife for the city, have their binoculars out, and they’re staring right at the problem.
A fawn runs circles around the rest of the herd, with the boing of a muscular slinky toy.
“He’s wired,” says Swanson, laughing. “He’s doing laps.”
A few other mule deer rear up on their hind legs and kick each other. Still others just hang out in the shade. It’s a beautiful spring morning and the animals look sleek and healthy. But all is not what it seems. This herd is harboring an infection — chronic wasting disease, or CWD.
Scientists have called this neurodegenerative disease, which attacks deer, elk and moose, a “nightmare” and a “state of emergency.” Lately, the media’s been calling it “zombie deer disease.” Lawmakers are calling it a “crisis” and currently considering at least three bills at the national level to combat it. Researchers, resource managers and others worry it could hurt hunting, alter the landscape, or even jump across species to infect people.
“That is buck number 46,” says Prioreschi, pointing to a deer. “He is positive.” Doe number 22, now lying in the grass, is also positive for chronic wasting disease. “Doesn’t show any symptoms,” he says. “She looks perfectly fine.”
But the mountain lions know that something is wrong. A number of years ago, Swanson and her colleagues studied which deer mountain lions prefer to attack. “The mountain lions were definitely preferentially selecting deer that had chronic wasting disease over those that were negative,” she says. “And for most of the ones that they had killed, we had not detected any chronic wasting disease symptoms yet. So certainly the lions were able to key in on far more subtle cues than we were.”
“To our eyes, they look fairly healthy, and within a number of weeks they reach that point — and then they're gone.”
Unlike us, the lions sense that while a deer might look vigorous and alert, it may actually be a ticking time bomb. That’s one of the many weird things about this disease. It isn’t like viral or bacterial illnesses. The infection can sit in a herd for years, crawling from animal to animal, before people notice anything is wrong.
Then, things can go downhill fast. “Through time (it) degrades, essentially, their brain tissue,” says Swanson. In just a few weeks, buck 46 or doe 22 could start to droop and drool, as an infection gnaws holes into the animal’s brain. “That seems to happen pretty rapidly,” she says. “To our eyes, they look fairly healthy, and within a number of weeks they reach that point — and then they’re gone.
IN EARLY FEBRUARY, Wyoming Senator John Barrasso got in front of a congressional hearing to introduce one of the bills aimed at addressing chronic wasting disease. “It's highly contagious and always fatal,” said Barrasso. “Unchecked, this disease could truly be catastrophic for wildlife and for local economies.”
Barrasso’s bipartisan bill, the Chronic Wasting Disease Transmission in Cervidae Study Act, was cosponsored by senators from across the country, including Idaho, Wyoming and Colorado. It would give federal dollars to the National Academies of Sciences to identify major gaps in scientific understanding of CWD and to better identify how to keep the disease from spreading further among animals, including between Canada and the U.S.
On the same day that Barrasso addressed his colleagues in Congress, epidemiologist Michael Osterholm spoke to state lawmakers in Minnesota. “This is kind of a worst-case nightmare,” said Osterholm. It’s a nightmare that’s hard to explain. Chronic wasting disease is not your garden-variety infectious disease. It’s not bacterial, viral or even fungal. It’s caused by something we all have inside our bodies — proteins called prions. As Osterholm put it to Minnesota lawmakers, “If Stephen King could write an infectious disease novel, he’d write it about prions.”
“They’re just very different from traditional pathogens,” says Kaitlyn Wagner, who researches prions at Colorado State University. The prions that cause chronic wasting disease start out as normal proteins, she says, noting that all mammals have normal prions, sitting on the surfaces of our healthy cells. The difference between a good prion and a bad one is the shape. The problem is that good ones can transform into bad ones, a process that has inspired comparisons to the transformation of Dr. Jekyll into Mr. Hyde.
Mark Zabel, who is associate director of the Prion Research Center at Colorado State University, says one way to think about it is origami. Imagine that healthy proteins are shaped like origami cranes. If an abnormal origami crane, with a bent wing, say, comes along, the normal origami cranes will start to copy it. One by one, their wings will bend as well. Eventually, when a badly folded prion has, as Zabel puts it, “coerced” enough healthy proteins to get bent out of shape, they can gather in clumps, killing off cells and riddling the brain with holes, like a sponge.
In the case of other prion diseases — like bovine spongiform encephalopathy, or “mad cow disease” — the badly folded proteins tend to stay contained in the brain and nervous system. But animals infected with chronic wasting disease scatter infectious proteins all over the place. The misshapen proteins have been found in urine, feces, blood and saliva. And they can stick around for a long time.
Zabel says that a virus might be able to survive for a few hours outside its host. A bacterium might be able to make it for a week or two. A prion, on the other hand, can linger for years — decades, even.
To further complicate things, studies have shown that plants can suck up prions through their roots and harbor them in their leaves, potentially infecting the next animal that comes around for a snack.
There’s a lot that’s still unknown. What is known is that chronic wasting disease was first identified in Colorado way back in the 1960s, and has now crawled its way across the country, infecting deer, elk and moose in at least 26 U.S. states and three Canadian provinces. It’s also turned up in South Korea, Finland, Sweden and Norway.
And it all started here, in the Mountain West. Or did it?
RESEARCHERS FIRST IDENTIFIED THE DISEASE in the 1960s. Soon after, Michael Miller, a senior wildlife veterinarian with Colorado Parks and Wildlife, got sucked into working on it. “Yeah, sucked into it is really right,” he says. Back then, local wildlife scientists were studying captive mule deer at a facility in Fort Collins, Colorado, trying to figure out how to help them survive harsh winters in the wild. But the animals kept getting sick and dying.
It didn’t seem to make any sense. Finally, the researchers looked at pieces of the animals’ brains and saw something disturbing: The brains were full of holes, in a pattern similar to what happens with mad cow disease — it was chronic wasting disease. And it was hard to beat.
“The folks who were running these research operations decided to try to get rid of the disease, so in the mid-’80s they gathered up and killed all the captive deer and elk they had and did what, at the time, seemed like a very thorough job of cleaning up the facility grounds,” Miller says. They cleaned the pens where the animals had been kept, turned the soil, brought in a helicopter to drop chlorine onto the site, and left it alone for a full year. Then, they brought in healthy wild elk calves.
“And we failed,” says Miller. Within a couple years, the disease was back. Miller and his colleagues worked hard to figure out how to contain it in northern Colorado over the next few years. “The idea at the time was that we would do what we needed to here, locally, to keep it from spreading to the Western Slope. What we didn’t realize is that it was actually more widespread. It was a really nice idea that was probably 10, 15, maybe 20 years too late,” he says.
Over the next few decades, cases kept showing up in new places, first in captive animals, then in the wild. The number of infected animals mushroomed across the U.S. and Canada. The disease even jumped continents, flying from Canada to South Korea in a shipment of infected elk. “The Panama Canal may well be a barrier to the spread of the disease,” one researcher noted in 2017. “But we can’t take that for given.”
Still, Miller says it’s unlikely that the illness will drive an entire species to extinction. “What is more likely is that we will have a deer herd that is unable to grow,” he said. A bad winter, for example, could do real damage to herds if enough animals are infected.
Meanwhile, people in Canada, the U.S. and Nordic countries are scrambling to keep the disease under control. Idaho is trying to tighten rules about moving animals across its borders. In Wyoming, environmental groups are suing the U.S. Fish and Wildlife Service for feeding elk in the winter, a practice they believe could contribute to the spread of CWD. Colorado, where 57% of deer herds and 37% of elk herds are infected, just came out with its latest management plan for chronic wasting disease. It includes testing animals, in some cases thinning out overly infected herds, warning hunters and taxidermists about how to handle tainted entrails and potentially investing in more incinerators to dispose of infected carcasses.
“We’re not talking about going in and annihilating deer over large tracts of land,” says Miller about the plan in Colorado. They already tried that, he says, and it didn’t work. Once again, the infection was more entrenched than biologists realized: “It isn’t something that lends itself to a quick fix, and we don't need to do draconian things, but we need to do something.”
Historically, a lot of agency plans have rested on one big assumption: That the disease started here in the Mountain West and then slunk its way across the world. But Mark Zabel, the prion researcher at Colorado State University, says that could be wrong in a big way.
“Most of the outbreaks in the U.S. can be traced back to movement of animals on the game farms from the Front Range to places like Saskatchewan in Canada to the Midwest and Wisconsin to South Dakota, repopulation in Arkansas,” he says. “But then there are some that have no known connection.”
Scientists were mystified in spring 2016, for example, when the disease unexpectedly showed up in Norway. Researchers were checking on wild reindeer when they noticed one animal had been left behind by a fleeing herd. “It was lying on the side, flat out — not very common for reindeer. And it had all these bubbles and stuff coming out of his mouth,” says Roy Anderson, a research technician with the Norwegian Institute for Nature Research. Just three or four minutes later, he says, the reindeer was dead. Samples from the sick animal eventually made their way over to the laboratory of Sylvie Benestad of the Norwegian Veterinary Institute. “And it was really strongly positive,” she says. “That started the problem.”
The Norwegians sent sharpshooters out in helicopters and snowmobiles to kill all the reindeer where the infection had been found, about 2,400 of them. But just two months later, the disease showed up in a couple of elderly moose. And this month, neighboring Sweden detected its first case of chronic wasting disease. “We still don't know how it came to Norway,” says Benestad.
And yet another mystery has arisen: Benestad and other researchers have concluded that the chronic wasting disease in Norwegian moose is not the same as the one circulating in North America. Upon closer inspection, the disease in reindeer is different, too. Scientists are trying to figure out what all this means. Are there multiple kinds of chronic wasting disease? And where are they coming from, anyway? “I think this question of what's going on is kind of opened up again,” says Kaitlyn Wagner.
Wagner and Zabel have suggested a possible answer: Perhaps, they say, there is not just one chronic wasting disease, but rather a bunch of different strains of it. And those different strains could be emerging at different times across the globe.
One day in late February, in their laboratory in Fort Collins, Colorado, Wagner and Zabel compared the prions from the brains of CWD-infected deer in Texas with those of elk in Colorado. They want to know if the proteins were all mangled in the same way, or not. “If they are different, this would suggest that we have different strain properties, which is evidence as we're building our case that we might have multiple strains of CWD circulating in the U.S.,” says Wagner.
Step one is to see if they’re equally easy to destroy using a chemical called guanidine. The shape of a prion dictates everything, including the way it interacts with an animal’s cells and the ease with which chemicals can unfold it.
“Moment of truth,” said Wagner, as she and Zabel huddled around a computer, waiting for results to come through. When they did, Zabel was surprised.
“Wow,” he said. “Unlike anything we've seen before.”
The prions from the Texas deer were a lot harder to destroy than the ones from the Colorado elk. In fact, the guanidine barely damaged them at all. “We’ve never seen that before in any prion strain, which means that it has a completely different structure than we've ever seen before,” says Zabel. And that suggests that it might be a very different kind of chronic wasting disease. The researchers ran the same test on another Texas deer, with the same results.
Now, these are only the preliminary results from a few animals. Wagner and Zabel have a lot more experiments to do. But if future tests come to the same conclusion, it would support their hypothesis that there are multiple strains of chronic wasting disease out there, all with different origins. That, in turn, could mean that this disease will become even trickier to manage than it already is.
And, Zabel adds, there’s something else. “If it's still evolving, it may still evolve into a form that could potentially, eventually affect humans,” he says.
Zabel is not the only one worried about that possibility.
OSTERHOLM, THE EPIDEMIOLOGIST from Minnesota, is also concerned. He directs the Center for Infectious Disease Research and Policy at the University of Minnesota, and is serving a one-year stint as a “Science Envoy for Health Security” with the U.S. State Department. In February, he told Minnesota lawmakers that when it comes to chronic wasting disease, we are playing with fire. “You are going to hear from people that this is not going to be a problem other than a game farm issue. You're going to hear from people that it's not going to transmit to people, and I hope they're right, but I wouldn't bet on it,” he said. “And if we lose this one and haven’t done all we can do, we will pay a price.”
If that wasn’t warning enough, he added: “Just remember what happened in England.”
He was talking about mad cow disease. Decades ago, Osterholm got involved in studying the potential for the newly emerging condition — bovine spongiform encephalopathy, or BSE for short — to be transmitted to humans.
At that point, researchers had yet to document a prion disease in animals that could infect people. They did, however, have a few pieces of the puzzle. For one, work in Papua New Guinea had shown that people could transmit prion diseases to each other if they practiced cannibalism, especially of the brain-eating variety. They also knew that BSE was spreading quickly between cattle. Osterholm says he and others worried that the more widespread it became, the more chances it might have to change into something that could sicken people.
“A lot of people thought that it was an overreaction,” says Osterholm. “Then, of course, in 1996, 10 years later, we recognized that in fact transmission had occurred.” Variant Creutzfeldt-Jakob disease, as the illness is called when it appears in human beings, has infected about 230 people worldwide. Osterholm says he feels like he’s having déjà vu, except that instead of mad cow, now it’s chronic wasting disease that’s spreading in animals, with the potential to cross the species barrier to infect humans.
But some view Osterholm’s statements as pure fear-mongering.“To say that without any concrete proof — I think that's irrational,” says Daniel Schmidt, the editor-in-chief of Deer & Deer Hunting. He says Osterholm needs to lower the fear flag. “If CWD is a threat, it is more to the lifestyle of the hunting public in America,” says Schmidt. “If you scare people enough in America, they're going to stop doing something.”
Schmidt and his family, who live in Wisconsin, eat wild venison almost every day, and he says they don’t give chronic wasting disease a second thought. If you need something to worry about, he says, how about climate change, or pesticides in your strawberries? “This is not a zombie apocalypse, and the hamster wheel of fear-mongering is nothing short of sensationalism, in my opinion,” Schmidt says.
So, who’s right? Could chronic wasting disease present a public health crisis? Or are we, as Schmidt put it, merely hamsters spinning the wheel of fear?
The answer to that question may largely depend on Stefanie Czub, a professor of veterinary medicine with the University of Calgary. Czub runs the Canadian Food Inspection Agency lab that tests for mad cow disease, and everyone is waiting for results from her decade-long study of chronic wasting disease in macaque monkeys, which is scheduled to end in March 2020.
“At this point, what we would like to stress — my collaborators and I — is that we have some evidence that it might infect non-human primates.”
While Czub cautions that the project isn’t yet complete, she does have some preliminary results: “At this point, what we would like to stress — my collaborators and I — is that we have some evidence that it might infect non-human primates.”
Czub and her collaborators exposed 18 macaque monkeys to chronic wasting disease prions. Some had the prions inserted straight into their brains. Some ate infected venison, while others were exposed via blood transfusion. And some were given little cuts that were wrapped in infected deer brain, which was meant to model how a hunter might be exposed to infectious viscera after getting nicked during field dressing. There were also three control animals, which were exposed to healthy deer and elk tissue.
So far, four out of the 18 monkeys developed what Czub calls “subtle and transient” symptoms that “could be indicative” of chronic wasting disease. Two of those animals had received CWD straight into their brains. Two had eaten infected meat.
Those four lost weight and became anxious. “Anxiety is a very common clinical expression in animal prion diseases,” says Czub. “It is one of the main symptoms in bovine spongiform encephalopathy, and that is the reason why some people decided to call it ‘mad cow disease.’ The animals are not mad, they are scared to death.” In monkeys, that involves crouching in the farthest corner of the cage. Czub says they shivered and had difficulties picking up pieces of food. One monkey lost a third of its body weight in just six months.
After the four symptomatic animals were euthanized, Czub and her colleagues ran a bunch of tests, which Czub says “suggested the presence of CWD.” But there are a number of factors that make this complicated. First off, three of the four sick monkeys also happened to have diabetes. “And it's really important to mention that, because diabetes — uncontrolled diabetes — really does induce wasting, so we need we need to be super careful in the interpretation of wasting,” says Czub.
Czub has presented her preliminary results at conferences, but they have not yet gone through the true scientific ringer: peer-reviewed publication. That’s a crucial step, because where one researcher might see an unusual level of anxiety, another might just see an animal in captivity and under stress. Even the results from more technical evaluations, like analyzing slices of the brain for neuron death, could be interpreted in different ways. “We'd like to see them published so we can get a better idea of how strong the data really is to support transmission,” says Brent Race, a staff scientist at Rocky Mountain Laboratories in Montana, which is part of the National Institutes of Health’s National Institute of Allergy and Infectious Diseases.
Race and his colleagues ran an experiment similar to Czub’s, in which they gave macaques deer and elk brain tainted with chronic wasting disease, in some cases injected into the monkeys’ brains and in others delivered to the stomach through a tube. In behavior and biochemical tests, the animals appeared no different from those in the control group.“We watched our macaque monkeys for over 13 years in some cases, and we were unable to find any evidence of transmission of chronic wasting disease,” says Race. A later study on “humanized” mice spliced with a human gene also showed no strong proof of transmission, despite the fact that Race and his colleagues tried to make it as easy as possible for the infection to take hold.
In a different study, however, Race’s research concluded that a different type of primate — squirrel monkeys — were highly susceptible to chronic wasting disease. Thirteen squirrel monkeys were exposed to the disease directly in their brains. Every one of them developed symptoms, including severe weight loss, tremors, drooling and weakness, after an average of about 4 years. The researchers fed another group of 12 squirrel monkeys infected meat and found that 11 of them developed chronic wasting disease an average of about half a dozen years after exposure. A systematic review of 23 studies cited the squirrel monkey findings as a reason that human infection “cannot be entirely ruled out.”
Still, human transmission remains uncertain. As the researchers noted in the journal Emerging Infectious Diseases, macaque monkeys are biologically much closer to humans than squirrel monkeys. “Aside from a few benchtop assays and the unpublished macaque study from Canada, news has been very encouraging,” says Race.
Christina Sigurdson, a professor of pathology at UC San Diego and UC Davis, did a study that hunting enthusiasts have pointed to as a reason not to worry about chronic wasting disease. It showed that a certain part of human prions makes it hard for chronic wasting disease prions to guide them into misfolding, kind of like how a zipper just won’t zip if there’s a pebble stuck somewhere in its teeth. “It suggested that this region was a barrier — at least, a partial barrier — for blocking infection,” says Sigurdson.
But only a partial barrier — and even then, it’s only against the particular versions of chronic wasting disease that Sigurdson tested from Colorado deer and elk. “We need more research to find out how many strains there are, how different are these different strains and would there potentially be some strains in the U.S. that could be infectious for people,” she says.
The Centers for Disease Control and Prevention has not yet found any evidence of chronic wasting disease in people, despite researchers actively looking for it. Epidemiologists in states like Colorado and Wyoming have also been watching for an elevated rate of prion disease in hunters — hunters like researcher Brent Race.
“I’m an avid hunter myself, and my entire family eats it,” Race says. “Actually, we raise cattle and we sell all of our cattle and eat deer and elk instead.” But Race wouldn’t go so far as to eat meat that hasn’t been tested for chronic wasting disease. That feeling is shared by pretty much every person in this story: If you’re hunting in an area with chronic wasting disease, get the animal tested before it ever hits your plate, and don’t eat meat that tests positive.
“Otherwise,” says Osterholm, “I wish you well and hope you enjoy your venison.”
Rae Ellen Bichell is a regional radio reporter with the Mountain West News Bureau. She’s based at KUNC in northern Colorado. She frequently covers science and health. Email High Country News at editor@hcn.org or submit a letter to the editor.
“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.
ORIGIN OF CHRONIC WASTING DISEASE TSE PRION?
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
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 contemplate 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
”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province!” page 26.
Colorado Chronic Wasting Disease Response Plan December 2018
I. Executive Summary Mule deer, white-tailed deer, elk and moose are highly valued species in North America. Some of Colorado’s herds of these species are increasingly becoming infected with chronic wasting disease (CWD). As of July 2018, at least 31 of Colorado's 54 deer herds (57%), 16 of 43 elk herds (37%), and 2 of 9 moose herds (22%) are known to be infected with CWD. Four of Colorado's 5 largest deer herds and 2 of the state’s 5 largest elk herds are infected. Deer herds tend to be more heavily infected than elk and moose herds living in the same geographic area. Not only are the number of infected herds increasing, the past 15 years of disease trends generally show an increase in the proportion of infected animals within herds as well. Of most concern, greater than a 10-fold increase in CWD prevalence has been estimated in some mule deer herds since the early 2000s; CWD is now adversely affecting the performance of these herds.
snip...
(the map on page 71, cwd marked in red, is shocking...tss)
Subject: Texas 85th Legislative Session 2017, bathroom politics, while Rome burns, CWD detected in 5th captive breeding facility
Subject: Texas 85th Legislative Session 2017, bathroom politics, while Rome burns, CWD detected in 5th captive breeding facility
thought i might comment on the bathroom politics in Austin, while Rome Burns...
Subject: Texas 85th Legislative Session 2017, bathroom politics, while Rome burns, CWD detected in 5th captive breeding facility
Subject: TEXAS CWD POLITICIANS, AND CORPORATE GREED
MONDAY, MAY 15, 2017
TEXAS New CWD TSE PRION Case Discovered at Fifth Captive Deer Breeding Facility
SUNDAY, MAY 14, 2017
85th Legislative Session 2017 AND THE TEXAS TWO STEP Chronic Wasting Disease CWD TSE Prion, and paying to play $$$
FRIDAY, OCTOBER 09, 2015
Texas TWA Chronic Wasting Disease TSE Prion Webinars and Meeting October 2015
http://chronic-wasting-disease.blogspot.com/2015/10/texas-twa-chronic-wasting-disease-tse.html
Thursday, August 20, 2015
*** TEXAS TAHC DEER BREEDER CWD PERMIT RULES EMERGENCY ADOPTION PREAMBLE ***
http://chronic-wasting-disease.blogspot.com/2015/08/texas-tahc-deer-breeder-cwd-permit.html
Under Texas law, though, breeder deer belong to the state, not the permittee. See, e.g., TEX. PARKS & WILD. CODE §§ 1.011 (“All wild animals . . . inside the borders of this state are the property of the people of this state.”); 43.364 (“All breeder deer . . . are under the full force of the laws of [Texas] pertaining to deer . . . .”). While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351. Nowhere do the statutes or regulations state that breeder deer become the property of a permit holder.4 Regardless, even if they did give ownership of breeder deer to permit holders, the Andertons were not permit holders when the deer were killed.
http://www.ca5.uscourts.gov/opinions%5Cunpub%5C14/14-10297.0.pdf
While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351
http://www.statutes.legis.state.tx.us/Docs/PW/htm/PW.43.htm
S.B. No. 820
http://www.legis.state.tx.us/tlodocs/83R/billtext/html/SB00820F.HTM
http://openstates.org/tx/bills/83/SB820/
Texas Senate Bill
Relating to the management, breeding, and destruction of deer and to procedures regarding certain deer permits.
View latest bill text Session:83rd Legislature (2013)
http://openstates.org/tx/bills/83/SB820/
Thursday, August 20, 2015
TEXAS CAPTIVE Deer Industry, Pens, Breeding, Big Business, Invites Crooks and CWD
http://chronic-wasting-disease.blogspot.com/2015/08/texas-captive-deer-industry-pens.html
Texas TWA Chronic Wasting Disease TSE Prion Webinars and Meeting October 2015
http://chronic-wasting-disease.blogspot.com/2015/10/texas-twa-chronic-wasting-disease-tse.html
Thursday, August 20, 2015
*** TEXAS TAHC DEER BREEDER CWD PERMIT RULES EMERGENCY ADOPTION PREAMBLE ***
http://chronic-wasting-disease.blogspot.com/2015/08/texas-tahc-deer-breeder-cwd-permit.html
Under Texas law, though, breeder deer belong to the state, not the permittee. See, e.g., TEX. PARKS & WILD. CODE §§ 1.011 (“All wild animals . . . inside the borders of this state are the property of the people of this state.”); 43.364 (“All breeder deer . . . are under the full force of the laws of [Texas] pertaining to deer . . . .”). While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351. Nowhere do the statutes or regulations state that breeder deer become the property of a permit holder.4 Regardless, even if they did give ownership of breeder deer to permit holders, the Andertons were not permit holders when the deer were killed.
http://www.ca5.uscourts.gov/opinions%5Cunpub%5C14/14-10297.0.pdf
While a permittee may have possession of the breeder deer, the deer are only “held under a permit[.]” Id. § 43.351
http://www.statutes.legis.state.tx.us/Docs/PW/htm/PW.43.htm
S.B. No. 820
http://www.legis.state.tx.us/tlodocs/83R/billtext/html/SB00820F.HTM
http://openstates.org/tx/bills/83/SB820/
Texas Senate Bill
Relating to the management, breeding, and destruction of deer and to procedures regarding certain deer permits.
View latest bill text Session:83rd Legislature (2013)
http://openstates.org/tx/bills/83/SB820/
Thursday, August 20, 2015
TEXAS CAPTIVE Deer Industry, Pens, Breeding, Big Business, Invites Crooks and CWD
http://chronic-wasting-disease.blogspot.com/2015/08/texas-captive-deer-industry-pens.html
Thursday, August 20, 2015
*** TEXAS TAHC DEER BREEDER CWD PERMIT RULES EMERGENCY ADOPTION PREAMBLE ***
Wednesday, October 28, 2015
Texas' wild deer herd must be protected
Terry S. Singeltary Sr. Your opinions and comments have been submitted successfully. Thank you for participating in the TPWD regulatory process.
Wednesday, October 28, 2015
Interim Chronic Wasting Disease Response Rules Comment online through 07:00 a.m. November 5, 2015
SATURDAY, OCTOBER 03, 2015
TEXAS CHRONIC WASTING DISEASE CWD TSE PRION GOD MUST NOT BE A TEXAN 2002 TO 2015
TEXAS HISTORY OF CWD
Singeltary telling TAHC, that CWD was waltzing into Texas from WSMR around Trans Pecos region, starting around 2001, 2002, and every year, there after, until New Mexico finally shamed TAHC et al to test where i had been telling them to test for a decade. 2012 cwd was detected first right there where i had been trying to tell TAHC for 10 years.
***> Singeltary on Texas Chronic Wasting Disease CWD TSE Prion History <***
wasted days and wasted nights...Freddy Fender
Terry S. Singeltary Sr.
