Sunday, July 06, 2014

Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study

Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study

 

Zoreh Davanipour1,6,*, Eugene Sobel2,3,6, Argyrios Ziogas3,7, Carey Smoak1,8, Thomas Bohr1,9, Keith Doram4,10, and Boleslaw Liwnicz5,# 1Department of Neurology, Loma Linda University School of Medicine, Loma Linda, CA, USA 2Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA 3Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA 4Department of Internal Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA 5Department of Pathology, Loma Linda University School of Medicine, Loma Linda, CA, USA

 

Abstract

 

Aims—This study’s primary purpose was to determine whether earlier findings suggesting an association between sporadic Creutzfeldt-Jakob disease (sCJD), a transmissible spongiform encephalopathy of humans and specific dietary components could be replicated. The a priori hypotheses were that consumption of (i) foods likely to contain organ tissue and (ii) raw/rare meat are associated with increased sCJD risk.

 

Keywords

 

Sporadic Creutzfeldt-Jakob disease; dietary risk factors; confirmatory case-control study; prion diseases; neuroepidemiology

 

Study Design—Population-based case-control study.

 

© 2014 Davanipour et al.

 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

 

*Corresponding author: zdavani@earthlink.net.

 

6Current affiliation: Friends Research Institute, Los Angeles, CA, USA. 7Current affiliation: University of California-Irvine, Irvine, CA, USA. 8Current affiliation: Roche Molecular System, Pleasanton, CA, USA. 9Current affiliation: Jerry L Pettis VA Medical Center, Loma Linda, CA, USA. 10Current affiliation: Adventist Health, Roseville, CA, USA. #Dr. Liwnicz significantly contributed to this research. Dr. Liwnicz passed away in 2003.

 

Authors’ contributions

 

Author ZD conceived and designed the study. Author ZD was the PI of the study (R01 NS26732, funded by the National Institute of Neurological Disorders and Stroke, National Institutes of Health) and oversaw the conduct of the study, including the data collection and analysis. Author ES was the study statistician. Author CS coordinated the study and data collection. Author AZ did the statistical programming for the data analyses. Author TB was the study neurologist and BL was the study neuropathologist. Together they determined the final diagnoses. Author KD was the study geriatrician-internist and together with Authors TB and BL provided diagnostic and medical expertise for the study.

 

ETHICAL APPROVAL AND CONSENT

 

This study was approved by the Institutional Review Board (IRB) of the Loma Linda University School of Medicine. The study participant subjects have signed the IRB approved informed consent form.

 

COMPETING INTERESTS

 

The authors declare that they have no competing interests.

 

NIH Public Access

 

Author Manuscript

 

Br J Med Med Res. Author manuscript; available in PMC 2014 June 25.

 

Published in final edited form as:

 

Br J Med Med Res. 2014 April 21; 4(12): 2388–2417. doi:10.9734/BJMMR/2014/7209. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

 

Place and Duration of Study—Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 4 years.

 

Methodology—An 11-state case-control study of pathologically confirmed, definite sCJD cases, matched controls, and a sample of control-surrogates was conducted. Ninety-six percent (106/110) of the case data was obtained in 1991-1993, prior to variant CJD publicity.

 

Results—Using control self-responses, consumption of hot dogs, sausage, pepperoni, kielbasa, “other” canned meat, poultry liver, any stomach/intestine, beef stomach/intestine, any organ tissue, and beef organ tissue was individually associated with increased sCJD risk; odds ratios (OR) ranged from 2.4 to 7.2 (0.003

 

*** Conclusions—The a priori hypotheses were supported. Consumption of various meat products may be one method of transmission of the infectious agent for sCJD.

 

1. INTRODUCTION

 

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal transmissible spongiform encephalopathy (TSE, prion disease) of humans. In 1979, Hadlow et al. [1] reported that the infectious agent (prion proteins or PrPSc; Sc stands for scrapie, a prion disease in sheep and goats) was found in non-neural tissue, e.g., stomach, intestine, and the lymphatic system, even prior to clinical symptoms. More recently, Bosque et al. [2] found PrPSc in the skeletal muscle of mice inoculated with murine PrPSc. Furthermore, they showed that substantial titers can be propagated within the skeletal muscle. Bosque et al. called for a concerted effort to determine the distribution and concentration of prions in animals (e.g., cows, sheep, deer) in the human food chain. Andréoletti et al. [3] investigated the prion distribution and titers in sheep which were either naturally or experimentally infected with scrapie. They found accumulation of PrPSc in muscles, with the titer being up to 5,000 times lower than in brain. However, as noted by Andréoletti et al. [3], van Keulen et al. [4] found much higher titers of PrPSc in lymph nodes located within muscles of scrapie-infected sheep. We note that the quantity of animal muscle consumed by humans is probably well over 5,000 times higher than the quantity of brain consumed.

 

In 1985, we reported on dietary risk factors associated with sCJD in a case-control study of 26 sCJD patients and 40 hospital and family controls from 5 states in the USA [5]. Combining the dietary findings with the findings of our report [6] of weak links in the human food chain (e.g., sheep raisers’ lack of awareness of scrapie in epidemic areas, the preclinical presence of the infectious agent(s) in non-neural organs of infected animals and the use of organs in certain meat products), we suggested that sCJD might be acquired through ingestion of contaminated food products, particularly processed foods which are likely to contain organ tissue. Four other epidemiologic studies of sCJD with dietary information were published prior to 1990 [7-10]. Two other studies were published in 1998 [11] and 2009 [12]. The findings of these studies are considered in the Discussion section.

 

snip...

 

1.1 Possibly Porous Species Barrier

 

The hypothesized species barrier may be more porous than previously thought. The question of dietary transmission of sCJD to humans is contentious [e.g., 11,26]. However, laboratory evidence provides credence to the possibility of such transmission, albeit somewhat inefficiently, e.g., (1) an in vitro study has identified a specific biological process by which human PrPSc may be chaperoned in vivo across the human intestinal epithelial cell barrier [39]; (2) it is now well-established that animals which do not manifest clinical signs of disease or only temporarily manifest such signs can harbor sufficiently high titers of infectious prions for disease to be transmitted at least through inoculation [40,41]; (3) prions can gain infectivity ability through passage from one animal to another [42] and (4) a second strain of prions in cattle has been identified which has molecular similarities with a specific subtype of sCJD [43]. It is also important to note that different prion strains, while derived from the same species-specific prion proteins, have different conformations which play an important role in the degree of infectivity, varying clinical signs and symptoms, and progression. Current evidence indicates that there are several different human PrPSc conformations [44]. These recent findings are discussed immediately below.

 

Crossing the Intestinal Epithelial Cell Barrier—Using an in vitro model of the human intestinal epithelial cell barrier, Mishra et al. [39] found that PrPSc is chaperoned by ferritin across the barrier. They concluded that, due to ferritin’s considerable homology across species, their study indicates that “PrPSc-associated proteins, in particular ferritin, may facilitate PrPSc uptake in the intestine from distant species, leading to a carrier state in humans” or animals in the human food chain.

 

Subclinical Disease with Infectivity—Thackray et al. [40] studied two mouse-adapted scrapie strains (ME7 and RML) which were intracerebrally injected in a specific transgenic mouse model (Tga20) and two species of wild-type mice. Low doses of the inoculum caused the oscillation of appearance and then disappearance of clinical signs, sometimes for many months but did not induce terminal disease. The authors refer to this status as subclinical disease. PrPSc was identified in the brains of these mice at similar concentrations as found in mice with terminal disease. All titers were higher than contained in the original inoculate. Brain homogenates from these mice contained as much or nearly as much infectivity as brain homogenates from mice with terminal disease. This was determined by passage in Tga20 mice. When inoculated with brain homogenates from non-infected wild-type mice, none of the Tga20 mice developed disease. Thus, the brains of mice with subclinical disease contained sufficient quantities of PrPSc to induce terminal disease.

 

Hill et al. [41] studied a different strain of hamster prions considered nonpathologic to mice. When inoculated, the mice developed high titers of PrPSc in their brains, but were without clinical symptoms and had a normal lifespan. Upon transmission to a second generation of mice or to hamsters, all animals eventually developed clinical prion disease. Hill et al. suggested that there might be evolution of the PrPSc strain and that their data “seriously question our current understanding of species barriers”. We note that other researchers have also identified subclinical disease along with infectivity [45-47].

 

Gain in Infectivity with Transmission—Work by Race et al. [42] also suggests that apparently dormant PrPSc can evolve into a virulent form. They studied mice inoculated with a specific strain of hamster PrPSc. They found that, despite not developing clinical disease, the brains and spleens of these mice remained infectious for the lifetimes of the mice. Furthermore, there was no evidence that the hamster PrPSc replicated within the brains for a period of at least one year. After this period of persistence, replication occurred and new strains were identified which caused disease in mice. Thus, new strains of PrPSc might develop in transmission between sheep (scrapie), deer or elk (chronic wasting disease) and cows (BSE). Some of these strains might be more easily transmitted and virulent to susceptible humans through diet.

 

Second TSE Strain in Cattle and sCJD—Casalone et al. [43] have recently identified a second TSE of cattle, with a molecular signature similar to a particular strain of sCJD (M/V2 CJD): type-2 PrPSc with a methionine/valine (M/V) polymorphism at codon 129 of the human prion protein gene. To date, this strain has been identified in two cattle. Casalone et al. have named the disease associated with this new prion strain bovine amyloidotic spongiform encephalopathy (BASE). The authors point out that there are differences in the distribution of PrPSc in BASE and M/V2 CJD. In M/V2 CJD, the largest amount of PrPSc is found in the cerebellum, brainstem and striatum, while in BASE the predominant areas are the thalamus and olfactory regions. Casalone et al. suggest that lack of substantial involvement of the motor dorsal nucleus of the vagus (MDNV) and the brainstem in BASE indicates that the route of transmission of BASE is perhaps not the alimentary tract. On the other hand, the brainstem is involved in sCJD. Unfortunately, no information concerning MDNV involvement in human sCJD appears to be available. We note that, given Casalone et al.’s suggestion [43], involvement of the brainstem would indicate that transmission could be through the alimentary tract.

 

Colitis and Increased Susceptibility of Mice to Oral Prion Infection—A recent study by Sigurdson et al. [48] has convincingly shown that C57BL/6 mice, after developing moderate colitis due to exposure of an attenuated strain of Salmonella, had more than double the usual susceptibility to oral prion infection and experienced a somewhat accelerated disease development. The authors conclude that “moderate intestinal inflammation at the time of prion may constitute one of the elusive risk factors underlying the development of TSE”.

 

In a review article, Collins et al. [49] concluded convincing evidence that high titers of infectious PrPSc can be present in asymptomatic animals. Their conclusion was that these findings “challenge previous ideas of species barrier”.

 

snip...

 

5. CONCLUSIONS

 

In general, there is a contrast between the occurrence of CJD cases and the large number of individuals consuming these food items. It should be noted that TSE is a rare disease in animals. In addition to a low TSE exposure rate, TSE infectivity and viability are likely low. Moreover, human susceptibility to TSE may be related to rare genetic make-up. Consequently, it should not be surprising that sCJD is, fortunately, rare. Ecological and other issues are discussed in reference [69].

 

Over all, we found evidence that consumption of certain beef products may be associated with increased risk of sCJD and that consumption of certain items of pork and poultry were associated with an increased risk. In addition, many of the food items likely to contain brain, e.g., various sausages, may contain meat and organs from animals besides cows. This study should be interpreted as providing evidence that sCJD is, at times, a zoonotic disease, with possible transmission via dietary items. TSE occurs naturally in wide range of animal hosts, e.g., sheep, goats, bovine, mink, white-tailed deer.

 

It has been established that cows in Great Britain and perhaps elsewhere probably developed BSE by eating contaminated food products, e.g., sheep products. It has also been established that cows which consumed contaminated cow offal have developed BSE. Earlier, mink which ate contaminated feed, perhaps bovine, in the US developed a spongiform encephalopathy (TME). The literature has other examples of transmission of spongiform encephalopathy between species through contaminated feed. One reason for increased transmission of this disease by ingestion within and between species may be an unfortunate change in the processing procedures of offal during rendering, making it more likely that the infectiousness of the agent survives [26,70,71].

 

*** In summary, the findings in this study support the hypothesis that one way for humans to develop sCJD is consumption of animal products containing the infectious agent for TSE. Processed food items which may contain organ tissue products may represent a risk. Some of these food items are not sufficiently cooked.

 

Davanipour et al. Br J Med Med Res. Author manuscript; available in PMC 2014 June 25. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

 


 

Neuroepidemiology. 1985;4(4):240-9.

 

 Sheep consumption: a possible source of spongiform encephalopathy in humans.

 

 Davanipour Z, Alter M, Sobel E, Callahan M.

 

 Abstract

 

 A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania. PMID: 3915057 [PubMed - indexed for MEDLINE]

 


 

 

 EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

 

 This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........

 


 

 RISK OF BSE TO SHEEP VIA FEED

 


 

 Marion Simmons communicated surprising evidence for oral transmissibility of Nor98/atypical scrapie in neonatal sheep and although bioassay is ongoing, infectivity of the distal ileum of 12 and 24 month infected sheep is positive in Tg338 mice.

 


 

 SUMMARY REPORTS OF MAFF BSE TRANSMISSION STUDIES AT THE CVL ;

 


 

 THE RISK TO HUMANS FROM SHEEP;

 


 

 EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP

 


 

 SHEEP AND BSE

 

 PERSONAL AND CONFIDENTIAL

 

 SHEEP AND BSE

 

 A. The experimental transmission of BSE to sheep.

 

 Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).

 


 

 RB264

 

 BSE - TRANSMISSION STUDIES

 


 

 

BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

 

*** Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2.

 

These data suggest that more than one BSEderived prion strain might infect humans;

 

***it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

 

snip...

 

These studies further strengthen the evidence that vCJD is caused by a BSE-like prion strain.

 

Also, remarkably, the key neuropathological hallmark of vCJD, the presence of abundant florid PrP plaques, can be recapitulated on BSE or vCJD transmission to these mice.

 

***However, the most surprising aspect of the studies was the finding that an alternate pattern of disease can be induced in 129MM Tg35 mice from primary transmission of BSE, with a molecular phenotype indistinguishable from that of a subtype of sporadic CJD. This finding has important potential implications as it raises the possibility that some humans infected with BSE prions may develop a clinical disease indistinguishable from classical CJD associated with type 2 PrPSc. This is, in our experience, the commonest molecular sub-type of sporadic CJD. In this regard, it is of interest that the reported incidence of sporadic CJD has risen in the UK since the 1970s (Cousens et al., 1997)...

 


 

-------- Original Message --------

 

Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD

 

Date: Thu, 28 Nov 2002 10:23:43 -0000

 

From: "Asante, Emmanuel A" e.asante@ic.ac.uk

 

To: "'flounder@wt.net'" flounder@wt.net

 

Dear Terry,

 

I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.

 

Thank you for your interest in the paper.

 

In respect of your first question, the simple answer is, ***yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.

 

I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

 

Emmanuel Asante

 

<>

 

____________________________________

 

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)

 

____________________________________

 

Thursday, August 12, 2010

 

Seven main threats for the future linked to prions

 

First threat

 

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

 

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

 

Second threat

 

snip...

 


 

Monday, October 10, 2011

 

EFSA Journal 2011 The European Response to BSE: A Success Story

 

snip...

 

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far

 

*** but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

 

snip...

 


 


 

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE.

 

***In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

 


 

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

 

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

 

snip...

 

R. BRADLEY

 


 

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

 


 

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 acrapie 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

 


 

Sunday, December 12, 2010

 

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

 


 

Sunday, April 18, 2010

 

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

 


 

Saturday, May 2, 2009

 

APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH

 


 

Monday, November 30, 2009

 

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

 


 

RESEARCH

 

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011

 

Experimental Oral Transmission of Atypical Scrapie to Sheep

 

Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos

 

To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals’ peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.

 

SNIP...

 

Although we do not have epidemiologic evidence that supports the effi cient spread of disease in the fi eld, these data imply that disease is potentially transmissible under fi eld situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed. Additionally, almost no data are available on the potential for atypical scrapie to transmit to other food animal species, certainly by the oral route. However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing fi nding that the biochemical properties of the resulting PrPSc have changed on transmission (40). The implications of this observation for subsequent transmission and host target range are currently unknown.

 

How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantified, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confirmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected.

 

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011

 


 

*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

 

Increased Atypical Scrapie Detections

 

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.

 


 

Thursday, March 29, 2012

 

*** atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012

 

NIAA Annual Conference April 11-14, 2011San Antonio, Texas

 


 

Monday, April 25, 2011

 

Experimental Oral Transmission of Atypical Scrapie to Sheep

 

Volume 17, Number 5-May 2011 However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing finding that the biochemical properties of the resulting PrPSc have changed on transmission (40).

 


 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 

(hmmm, this is getting interesting now...TSS)

 

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

 

see also ;

 

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

 


 

see full text ;

 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 


 

***P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion

 

Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food Inspection Agency; Lethbridge, AB Canada

 

Keywords: Atypical BSE, oral transmission, RT-QuIC

 

The detection of bovine spongiform encephalopathy (BSE) has had a significant negative impact on the cattle industry worldwide. In response, governments took actions to prevent transmission and additional threats to animal health and food safety. While these measures seem to be effective for controlling classical BSE, the more recently discovered atypical BSE has presented a new challenge. To generate data for risk assessment and control measures, we have challenged cattle orally with atypical BSE to determine transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon presentation of clinical symptoms, animals were euthanized and tested for characteristic histopathological changes as well as PrPSc deposition.

 

The H-type challenged animal displayed vacuolation exclusively in rostral brain areas but the L-type challenged animal showed no evidence thereof. To our surprise, neither of the animals euthanized, which were displaying clinical signs indicative of BSE, showed conclusive mis-folded prion accumulation in the brain or gut using standard molecular or immunohistochemical assays. To confirm presence or absence of prion infectivity, we employed an optimized real-time quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain Laboratory, Hamilton, USA.

 

Detection of PrPSc was unsuccessful for brain samples tests from the orally inoculated L type animal using the RT-QuIC. It is possible that these negative results were related to the tissue sampling locations or that type specific optimization is needed to detect PrPSc in this animal. We were however able to consistently detect the presence of mis-folded prions in the brain of the H-type inoculated animal. Considering the negative and inconclusive results with other PrPSc detection methods, positive results using the optimized RT-QuIC suggests the method is extremely sensitive for H-type BSE detection. This may be evidence of the first successful oral transmission of H type atypical BSE in cattle and additional investigation of samples from these animals are ongoing.

 

Monday, June 23, 2014

 

PRION 2014 TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES

 


 

Friday, March 09, 2012

 

Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

 

Research article

 


 

Thursday, June 23, 2011

 

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

 


 

P03.141

 

Aspects of the Cerebellar Neuropathology in Nor98

 

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

 

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

 

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

 


 

PR-26

 

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

 

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

 

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

 

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

 

119

 


 

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

 

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations

 

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

 

***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

 

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice.

 

*** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

 


 

Monday, December 1, 2008

 

When Atypical Scrapie cross species barriers

 

Authors

 

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

 

Content

 

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

 

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

 

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

 

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

 

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

 

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

 

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

 


 

Friday, February 11, 2011

 

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

 


 

Sunday, May 18, 2008

 

*** BSE, CJD, and Baby foods (the great debate 1999 to 2005)

 


 

Wednesday, October 09, 2013

 

*** WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281 in compensation ***

 

*** SPORADIC CJD IN FARMERS AND FARMERS WIVES WITH BSE DOCUMENTED HERDS ***

 


 

Monday, May 19, 2008

 

*** SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS ***

 


 

***********CJD REPORT 1994 increased risk for consumption of veal and venison and lamb***********

 

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 ;

 


 

Thursday, October 10, 2013

 

*************CJD REPORT 1994 increased risk for consumption of veal and venison and lamb**************

 


 

CJD9/10022

 

October 1994

 

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

 

Dear Mr Elmhirst,

 

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

 

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

 

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

 

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

 

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

 

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

 


 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 


 

Tuesday, July 01, 2014

 

*** CHRONIC WASTING DISEASE CWD TSE PRION DISEASE, GAME FARMS, AND POTENTIAL RISK FACTORS THERE FROM ***

 


 

*** REPORT OF THE MEETING OF THE OIE TERRESTRIAL ANIMAL HEALTH STANDARDS COMMISSION Paris, 19–28 February 2013

 

In response to a Member Country’s detailed justification for listing of chronic wasting disease of cervids (CWD) against the criteria of Article 1.2.2., the Code Commission recommended this disease be reconsidered for listing.

 


 

Monday, May 05, 2014

 

*** Member Country details for listing OIE CWD 2013 against the criteria of Article 1.2.2., the Code Commission recommends consideration for listing ***

 


 

*** 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).

 


 

as I said, what if ?

 

*** our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals, e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions. ***

 


 

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

 

Thursday, January 2, 2014

 

*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? ***

 

WHAT IF ?

 


 

Saturday, April 19, 2014

 

Exploring the zoonotic potential of animal prion diseases: In vivo and in vitro approaches

 


 

*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent

 

*** Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP,

 

*** indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains.

 

PPo2-27:

 

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

 

*** Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

 

PPo2-7:

 

Biochemical and Biophysical Characterization of Different CWD Isolates

 

*** The data presented here substantiate and expand previous reports on the existence of different CWD strains.

 


 

Envt.07:

 

Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease

 

***The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

 


 

>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO CONVERSION OF THE HUMAN PRION PROTEIN<<<

 

*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***

 

Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

 

Wednesday, January 01, 2014

 

Molecular Barriers to Zoonotic Transmission of Prions

 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 

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

 


 


 

PRION2013 CONGRESSIONAL ABSTRACTS CWD

 

Sunday, August 25, 2013

 

HD.13: CWD infection in the spleen of humanized transgenic mice

 

***These results indicate that the CWD prion may have the potential to infect human peripheral lymphoid tissues.

 

Oral.15: Molecular barriers to zoonotic prion transmission: Comparison of the ability of sheep, cattle and deer prion disease isolates to convert normal human prion protein to its pathological isoform in a cell-free system ***However, they also show that there is no absolute barrier ro conversion of human prion protein in the case of chronic wasting disease.

 

PRION2013 CONGRESSIONAL ABSTRACTS CWD

 

Sunday, August 25, 2013

 

***Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission

 


 

Friday, November 09, 2012

 

*** Chronic Wasting Disease CWD in cervidae and transmission to other species

 


 

there is in fact evidence that the potential for cwd transmission to humans can NOT be ruled out.

 

I thought your readers and hunters and those that consume the venison, should have all the scientific facts, personally, I don’t care what you eat, but if it effects me and my family down the road, it should then concern everyone, and the potential of iatrogenic transmission of the TSE prion is real i.e. ‘friendly fire’, medical, surgical, dental, blood, tissue, and or products there from...like deer antler velvet and TSE prions and nutritional supplements there from, all a potential risk factor that should not be ignored or silenced. ...

 

the prion gods at the cdc state that there is ;

 

''no strong evidence''

 

but let's see exactly what the authors of this cwd to human at the cdc state ;

 

now, let’s see what the authors said about this casual link, personal communications years ago. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ????

 

“Our conclusion stating that we found no strong evidence of CWD transmission to humans”

 

From: TSS (216-119-163-189.ipset45.wt.net)

 

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

 

Date: September 30, 2002 at 7:06 am PST

 

From: "Belay, Ermias"

 

To:

 

Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

 

Sent: Monday, September 30, 2002 9:22 AM

 

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

 

Dear Sir/Madam,

 

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.

 

That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

 

Ermias Belay, M.D. Centers for Disease Control and Prevention

 

-----Original Message-----

 

From:

 

Sent: Sunday, September 29, 2002 10:15 AM

 

To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV

 

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

 

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

 

Thursday, April 03, 2008

 

A prion disease of cervids: Chronic wasting disease

 

2008 1: Vet Res. 2008 Apr 3;39(4):41

 

A prion disease of cervids: Chronic wasting disease

 

Sigurdson CJ.

 

snip...

 

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

 

snip...

 

full text ;

 


 


 


 

Wednesday, October 17, 2012

 

Prion Remains Infectious after Passage through Digestive System of American Crows (Corvus brachyrhynchos)

 


 

A CONTRIBUTION TO THE NEUROPATHOLOGY OF THE RED-NECKED OSTRICH (STRUTHIO CAMELUS) - SPONGIFORM ENCEPHALOPATHY

 


 

4.21 Three cases of SE’s with an unknown infectious agent have been reported in ostriches (Struthio Camellus) in two zoos in north west Germany (Schoon @ Brunckhorst, 1999, Verh ber Erkeg Zootiere 33:309-314). These birds showed protracted central nervous symptoms with ataxia, disturbances of balance and uncoordinated feeding behaviour. The diet of these birds had included poultry meat meal, some of which came from cattle emergency slaughter cases.

 


 

SE1806

 

TRANSMISSION STUDIES OF BSE TO DOMESTIC FOWL BY ORAL EXPOSURE TO BRAIN HOMOGENATE

 

1 challenged cock bird was necropsied (41 months p.i.) following a period of ataxia, tremor, limb abduction and other neurological signs. Histopathological examination failed to reveal any significant lesions of the central or peripheral nervous systems...

 

1 other challenged cock bird is also showing ataxia (43 months p.i.).

 

snip...

 

94/01.19/7.1

 


 

A notification of Spongiform Encephalopathy was introduced in October 1996 in respect of ungulates, poultry and any other animal.

 

4.23 MAFF have carried out their own transmission experiments with hens. In these experiments, some of the chickens exposed to the BSE agent showed neurological symptoms. However MAFF have not so far published details of the symptoms seen in chickens. Examination of brains from these chickens did not show the typical pathology seen in other SE’s. 4.24 A farmer in Kent in November 1996 noticed that one of his 20 free range hens, the oldest, aged about 30 months was having difficulty entering its den and appeared frightened and tended to lose its balance when excited. Having previously experienced BSE cattle on his farm, he took particular notice of the bird and continued to observe it over the following weeks. It lost weight, its balance deteriorated and characteristic tremors developed which were closely associated with the muscles required for standing. In its attempts to maintain its balance it would claw the ground more than usual and the ataxia progressively developed in the wings and legs, later taking a typical form of paralysis with a clumsy involuntary jerky motion. Violent tremors of the entire body, particularly the legs, became common, sparked off by the slightest provocation. This is similar to that seen in many BSE cases where any excitement may result in posterior ataxia, often with dropping of the pelvis, kicking and a general nervousness. Three other farmers and a bird breeder from the UK are known to have reported having hens with similar symptoms. The bird breeder who has been exhibiting his birds for show purposes for 20 years noticed birds having difficulty getting on to their perch and holding there for any length of time without falling. Even though the bird was eating normally, he noticed a weight loss of more than a pound in a bird the original weight of which was 5 pounds. 4.25 Histological examination of the brain revealed degenerative pathological changes in hens with a minimal vacuolation. The presence of PrP immunostaining of the brain sections revealed PrP-sc positive plaques and this must be regarded as very strong evidence to demonstrate that the hens had been incubating Spongiform Encephalopathy.

 


 

OPINION on : NECROPHAGOUS BIRDS AS POSSIBLE TRANSMITTERS OF TSE/BSE ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 7-8 NOVEMBER 2002

 

OPINION

 

1. Necrophagous birds as possible transmitters of BSE. The SSC considers that the evaluation of necrophagous birds as possible transmitters of BSE, should theoretically be approached from a broader perspective of mammals and birds which prey on, or are carrion eaters (scavengers) of mammalian species. Thus, carnivorous and omnivorous mammals, birds of prey (vultures, falcons, eagles, hawks etc.), carrion eating birds (crows, magpies etc.) in general could be considered possible vectors of transmission and/or spread of TSE infectivity in the environment. In view also of the occurrence of Chronic Wasting Disease (CWD) in various deer species it should not be accepted that domestic cattle and sheep are necessarily the only source of TSE agent exposure for carnivorous species. While some information is available on the susceptibility of wild/exotic/zoo animals to natural or experimental infection with certain TSE agents, nothing is known of the possibility of occurrence of TSE in wild animal populations, other than among the species of deer affected by CWD in the USA.

 

1 The carrion birds are animals whose diet regularly or occasionally includes the consumption of carcasses, including possibly TSE infected ruminant carcasses.

 

C:\WINNT\Profiles\bredagi.000\Desktop\Necrophagous_OPINION_0209_FINAL.doc

 


 

snip...

 

skroll down to the bottom ;

 


 

Date: Mon, 11 Jun 2001 16:24:51 –0700

 

Reply-To: Bovine Spongiform Encephalopathy

 

Sender: Bovine Spongiform Encephalopathy

 

From: "Terry S. Singeltary Sr." Subject: The Red-Neck Ostrich & TSEs 'THE AUTOPSY'

 


 

Friday, April 20, 2012

 

Ultrastructural findings in pigs experimentally infected with bovine spongiform encephalopathy agent

 


 

Wednesday, July 06, 2011 Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation snip... In the US, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine, mink and poultry still occurs. Although unlikely, the potential for swine to have access to TSE-contaminated feedstuffs exists. snip... http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf Wednesday, July 06, 2011 Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation (see tonnage of mad cow feed in commerce USA...tss) http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=10684682&dopt=Abstract PLEASE NOTE, these old BSE Inquiry links take a while to open with the wayback machine, so be patient. ...tss Title: Experimental Intracerebral and Oral Inoculation of Scrapie to Swine: Preliminary Report In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility. snip... IN CONFIDENCE EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY 1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs. ...see full text ; http://web.archive.org/web/20040302031004/www.bseinquiry.gov.uk/files/yb/1990/08/23001001.pdf IN CONFIDENCE So it is plausible pigs could be preclinically affected with BSE but since so few are allowed to reach adulthood this has not been recognised through clinical disease. ... http://web.archive.org/web/20040904150118/www.bseinquiry.gov.uk/files/yb/1990/08/23002001.pdf snip... CONFIDENTIAL EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY snip... see full text ; Thursday, November 10, 2011 National Meat Association v. Harris Docket No., 10-224 DEADSTOCK DOWNER PIGS AND PORCINE SPONGIFORM ENCEPHALOPATHY PSE Court Likely to Overturn Calif. Law on Livestock http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/national-meat-association-v-harris.html

 

PORCINE SPONGIFORM ENCEPHALOPATHY PSE

 


 

Transmissible Spongiform Encephalopathy TSE Prion Disease North America 2014

 

Transmissible Spongiform Encephalopathy TSE Prion Disease have now been discovered in a wide verity of species across North America. typical C-BSE, atypical L-type BASE BSE, atypical H-type BSE, atypical H-G BSE, of the bovine, typical and atypical Scrapie strains, in sheep and goats, with atypical Nor-98 Scrapie spreading coast to coast in about 5 years. Chronic Wasting Disease CWD in cervid is slowly spreading without any stopping it in Canada and the USA and now has mutated into many different strains. Transmissible Mink Encephalopathy TME outbreaks. These Transmissible Spongiform Encephalopathy TSE Prion Disease have been silently mutating and spreading in different species in North America for decades.

 

The USDA, FDA, et al have assured us of a robust Triple BSE TSE prion Firewall, of which we now know without a doubt, that it was nothing but ink on paper. Since the 1997 mad cow feed ban in the USA, literally tons and tons of banned mad cow feed has been put out into commerce, never to return, as late as December of 2013, serious, serious breaches in the FDA mad cow feed ban have been documented. The 2004 enhanced BSE surveillance program was so flawed, that one of the top TSE prion Scientist for the CDC, Dr. Paul Brown stated ; Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive. see ; http://www.upi.com/Health_News/2006/03/15/Analysis-What-that-mad-cow-means/UPI-12841142465253/

 

The BSE surveillance and testing have also been proven to be flawed, and the GAO and OIG have both raised serious question as to just how flawed it has been (see GAO and OIG reports). North America has more documented TSE prion disease, in different documented species (excluding the Zoo BSE animals in the EU), then any other place on the Globe. This does not include the very likelihood that TSE prion disease in the domestic feline and canine have been exposed to high doses of the TSE prion disease vid pet food. To date, it’s still legal to include deer from cwd zone into pet food or deer food. Specified Risk Material i.e. SRM bans still being breach, as recently as just last month.

 

nvCJD or what they now call vCJD, another case documented in Texas last month, with very little information being released to the public on about this case? with still the same line of thought from federal officials, ‘it can’t happen here’, so another vCJD blamed on travel of a foreign animal disease from another country, while ignoring all the BSE TSE Prion risk factors we have here in the USA and Canada, and the time that this victim and others, do spend in the USA, and exposed to these risk factors, apparently do not count in any way with regard to risk factor. a flawed process of risk assessment.

 

sporadic CJD, along with new TSE prion disease in humans, of which the young are dying, of which long duration of illness from onset of symptoms to death have been documented, only to have a new name added to the pot of prion disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a familial type disease could be sporadic with no genetic link to any family member? when the USA is the only documented Country in the world to have documented two different cases of atypical H-type BSE, with one case being called atypical H-G BSE with the G meaning Genetic, with new science now showing that indeed atypical H-type BSE is very possible transmitted to cattle via oral transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada, USA, and the UK, with the same old excuse, better surveillance. You can only use that excuse for so many years, for so many decades, until one must conclude that CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a blip or a reason of better surveillance, it is a mathematical rise in numbers. More and more we are seeing more humans exposed in various circumstance in the Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same time in North America, more and more humans are becoming exposed to the TSE prion disease via consumption of the TSE prion via deer and elk, cattle, sheep and goats, and for those that are exposed via or consumption, go on to further expose many others via the iatrogenic modes of transmission of the TSE prion disease i.e. friendly fire. I pondered this mode of transmission via the victims of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone sub-clinical with sFFI or sGSS ? what if?

 

Two decades have passed since Dr. Ironside first confirmed his first ten nvCJD victims in 1995. Ten years later, 2005, we had Dr. Gambetti and his first ten i.e. VPSPR in younger victims. now we know that indeed VPSPR is transmissible. yet all these TSE prion disease and victims in the USA and Canada are being pawned off as a spontaneous event, yet science has shown, the spontaneous theory has never been proven in any natural case of TSE prion disease, and scientist have warned, that they have now linked some sporadic CJD cases to atypical BSE, to atypical Scrapie, and to CWD, yet we don’t here about this in the public domain. We must make all human and animal TSE prion disease reportable in every age group, in ever state and internationally, we must have a serious re-evaluation and testing of the USA cattle herds, and we must ban interstate movement of all cervids. Any voluntary effort to do any of this will fail. Folks, we have let the industry run science far too long with regards to the TSE prion disease. While the industry and their lobbyist continues to funnel junk science to our decision policy makers, Rome burns. ...end

 

REFERENCES

 

[all scientific peer review studies and other scientific information I have put into blogs, to shorten reference data. I DO NOT advertise or make money from this, this information is for education use...lost my mom to the hvCJD, and just made a promise, never forget, and never let them forget. ...TSS]

 

Sunday, June 29, 2014

 

Transmissible Spongiform Encephalopathy TSE Prion Disease North America 2014

 


 

Monday, June 23, 2014

 

PRION 2014 CHRONIC WASTING DISEASE CWD

 


 

Monday, June 23, 2014

 

PRION 2014 TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES

 


 

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $

 

OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles

 

Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA

 

Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.

 

Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.

 

Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.

 

In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.

 

Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.

 

The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

 


 

Wednesday, March 28, 2012

 

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion poker goes up again $

 


 

CANADA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss

 

PLEASE NOTE, type determination pending Creutzfeldt Jakob Disease (tdpCJD) in Canada is also on a steady increase.

 

please see ;

 

> 3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.

 

CJD Deaths Reported by CJDSS1, 1994-20122

 

As of May 31, 2012

 

Deaths of Definite and Probable CJD

 

Year Sporadic Iatrogenic Familial GSS FFI vCJD Total

 

1994 2 0 0 1 0 0 3

 

1995 3 0 0 0 0 0 3

 

1996 13 0 0 0 0 0 13

 

1997 16 0 1 1 0 0 18

 

1998 22 1 0 1 0 0 24

 

1999 26 2 2 1 0 0 31

 

2000 32 0 0 3 0 0 35

 

2001 27 0 2 1 0 0 30

 

2002 31 0 2 2 0 1 36

 

2003 27 1 1 0 0 0 29

 

2004 42 0 1 0 0 0 43

 

2005 42 0 0 2 0 0 44

 

2006 39 0 1 3 1 0 44

 

2007 35 0 0 4 0 0 39

 

2008 48 0 1 0 0 0 49

 

2009 48 0 3 2 0 0 53

 

2010 34 0 3 0 0 0 37

 

2011 37 0 2 1 0 1 41

 

2012 1 0 0 0 0 0 1

 

Total 525 4 19 22 1 2 573

 

1. CJDSS began in 1998

 

2. Data before 1998 are retrospective and partial, data from 1998 to 2008 are complete, and data for 2009 - 2012 are provisional

 

3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.

 

CJD Deaths Reported by CJDSS1, 1994-20122

 

As of May 31, 2012

 


 


 

SEE DECEMBER 2012 CANADA

 


 

USA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss

 

National Prion Disease Pathology Surveillance Center

 

Cases Examined1

 

(May 18, 2012)

 

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

 

1996 & earlier 50 32 28 4 0 0

 

1997 114 68 59 9 0 0

 

1998 88 52 44 7 1 0

 

1999 123 74 65 8 1 0

 

2000 145 103 89 14 0 0

 

2001 210 120 110 10 0 0

 

2002 248 149 125 22 2 0

 

2003 266 168 137 31 0 0

 

2004 326 187 164 22 0 13

 

2005 344 194 157 36 1 0

 

2006 382 196 166 28 0 24

 

2007 377 213 185 28 0 0

 

2008 396 232 206 26 0 0

 

2009 423 256 212 43 1 0

 

2010 413 257 216 41 0 0

 

2011 410 257 213 43 0 0

 

2012 153 82 51 15 0 0

 

TOTAL 44685 26406 2227 387 6 3

 

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

 

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

 

3 Disease acquired in the United Kingdom;

 

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

 

5 Includes 14 cases in which the diagnosis is pending, and 18 inconclusive cases;

 

6 Includes 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded. The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

 

Rev 5/18/2012

 


 

> 6 Includes

 

> 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded.

 

> The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

 

WELL, it seems the USA mad cow strains in humans classified as type determination pending tdpCJD, VPSPr, sFFI, and sCJD) have steadily increased over the years, and the same old song and dance continues with sporadic CJD cases $$$

 


 

*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

 

Increased Atypical Scrapie Detections

 

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.

 


 

Thursday, March 29, 2012

 

*** atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012

 

NIAA Annual Conference April 11-14, 2011San Antonio, Texas

 


 

Monday, June 02, 2014

 

Confirmed Variant CJD Case in Texas

 


 

Saturday, May 26, 2012

 

Are USDA assurances on mad cow case 'gross oversimplification'?

 


 


 

Singeltary submission to PLOS ;

 

RE: re-Human Prion Diseases in the United States part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT I would kindly like to add to my initial concerns, something I brought up years ago, and I believe that still hold true today, more so even than when I first stated these concerns in 2003 ;

 

routine passive mortality CJD surveillance USA ?

 

THIS has been proven not to be very useful in the U.K.;

 

THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)

 

snip...

 

One reason for this was the _inaccuracy_ in coding of cases correctly certified as CJD Coding is carried out by staff who are not medically qualified and it is not surprising that coding errors occur in the processing of large numbers of certificates. In 1982, 12,000 certificates per week were processed at the office of population censuses and surveys by 15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both inter- and intra-observer coding errors has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH certification and coding discovered in this study _support_ the introduction of a more accurate system of death certificates and a more detailed and specific coding system...

 

snip...

 


 

Draft Proposal For The Monitoring of Creutzfeldt-Kakob Disease 1989 Dr. R. Will

 

snip...

 

IDENTIFICATION OF CASES

 

Cases of CJD may be identified from death certificates, but this alone is unlikely to provide adequate monitoring. ERRORS are made in certification and diagnosis; in the Oxford study death certificates were obtained on a series of known confirmed cases and CJD was mentioned in only 66% of certificates. In another series of 175 certified cases, 42 patients were judged not to have suffered from CJD after examination of case notes (7)...

 

full text;

 


 

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

 

snip...

 


 

Confucius is confused again? how in 1996 and earlier can the 28 sporadic CJD victims and the one-in-a-million there from, how can it still be one in a million in 2008, with the sporadic CJD count rising to 205, still be one-in-a-million? and the years in-between, steady rise just about every year, and it still be only one-in-a-million, year after year after years? I suppose just more of that fuzzy math, which you can see here;

 


 

Please see my complete comment to this synopsis here ;

 

Saturday, January 2, 2010

 

Human Prion Diseases in the United States January 1, 2010

 


 

snip...see full text ;

 

Singeltary submission to PLOS ; RE: re-Human Prion Diseases in the United States part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT

 

No competing interests declared.

 

No competing interests declared.

 

see full text ;

 


 

26 March 2003

 

Terry S. Singeltary, retired (medically) CJD WATCH

 

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

 


 

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. FREE FULL TEXT

 


 

 

2 January 2000

 

British Medical Journal

 

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

 


 

15 November 1999

 

British Medical Journal

 

vCJD in the USA * BSE in U.S.

 


 

14th ICID International Scientific Exchange Brochure -

 

Final Abstract Number: ISE.114

 

Session: International Scientific Exchange

 

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

 

T. Singeltary

 

Bacliff, TX, USA

 

Background:

 

An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

 

Methods:

 

12 years independent research of available data

 

Results:

 

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

 

Conclusion:

 

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

 


 

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

 


 

Creutzfeldt-Jakob Disease Public Health Crisis

 


 


 


 


 

Friday, April 25, 2014

 

Accuracy of administrative diagnostic data for pathologically confirmed cases of Creutzfeldt-Jakob disease

 

Article in Press

 


 

Monday, May 19, 2014

 

Variant CJD: 18 years of research and surveillance

 


 

Saturday, June 14, 2014

 

Rep. Rosa DeLauro (D-CT) Calls for Briefing on Beef Recalled for Mad Cow Potential Rep. Rosa DeLauro (D-CT)

 


 

Monday, June 9, 2014

 

TEXAS MAD COW COVER UP (human BSE) AGAIN IN TEXAS, Mr. President Sir, we need your help please

 

Governor Rick Perry has done everything he can to cover up mad cow disease and human TSE prion disease there from in Texas over the last 15 years or so. We have another nvCJD case here in Texas i.e. human BSE, still no information there from, another lame excuse, typical though, and more junk science, we need help Mr. President...

 


 

TSS

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