Wednesday, November 22, 2017

NIH scientists and collaborators find infectious prion protein in skin of CJD patients

Wednesday, November 22, 2017

 NIH scientists and collaborators find infectious prion protein in skin of CJD patients

 National Institutes of Health scientists and collaborators at Case Western Reserve University School of Medicine, Cleveland, have detected abnormal prion protein in the skin of nearly two dozen people who died from Creutzfeldt-Jakob disease (CJD). The scientists also exposed a dozen healthy mice to skin extracts from two of the CJD patients, and all developed prion disease. The study results, published in Science Translational Medicine, raise questions about the possible transmissibility of prion diseases via medical procedures involving skin, and whether skin samples might be used to detect prion disease. Researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) were co-leaders of the study, which included multiple collaborating groups. They stress that the prion-seeding potential found in skin tissue is significantly less than what they have found in studies using brain tissue.

CJD is an incurable — and ultimately fatal — transmissible, neurodegenerative disorder in the family of prion diseases. Prion diseases originate when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the human body and brain. The reasons for this process are not fully understood. The accumulation of these clusters has been associated with tissue damage that leaves sponge-like holes in the brain. Human prion diseases include fatal insomnia; kuru; Gerstmann-Straussler-Scheinker syndrome; and variant, familial and sporadic CJD. Sporadic CJD is the most common human prion disease, affecting about one in one million people annually worldwide. Other prion diseases include scrapie in sheep; chronic wasting disease in deer, elk and moose; and bovine spongiform encephalopathy, or mad cow disease, in cattle.

Most people associate prion diseases with the brain, although scientists have found abnormal infectious prion protein in other organs, including the spleen, kidney, lungs and liver. Sporadic CJD is known to be transmissible by invasive medical procedures involving the central nervous system and cornea, but transmission via skin had not been a common concern.

Using a test for prion diseases known as Real-Time Quaking-Induced Conversion (RT-QuIC), scientists analyzed skin tissue from 38 patients — 23 who had died from CJD, and 15 who died of other causes. They also collected brain tissue from the 23 CJD patients and from seven individuals who died of other causes. RT-QuIC correctly detected abnormal prion protein in each CJD patient sample tested and in none of the non-CJD group. The scientists noted that in the CJD group, the “seeding potential” for normal prion protein to convert to abnormal was 1,000 to 100,000 times lower in skin than brain tissue.

The scientists then exposed humanized laboratory mice to either brain or skin extracts from two of the CJD patients. All 12 mice inoculated with brain tissue developed prion disease, as did all 12 inoculated with skin extracts, though disease in the skin group took about twice as long — roughly 400 days — to develop. The group also reported that brain degeneration in both groups of infected mice was similar.

The study authors say the results should generate discussion about potential surgical instrument contamination and risk associated with procedures involving CJD patients.

“Perspective is important when interpreting these outcomes,” said Byron Caughey, Ph.D., a senior investigator at NIAID’s Rocky Mountain Laboratories (RML) who helped oversee the study. “This study used humanized mice with tissue extracts directly inoculated into the brain, so the system was highly primed for infection. There is no evidence that transmission can occur in real-world situations via casual skin contact. However, the results raise transmission questions that warrant further study.”

The study also raises the possibility of using RT-QuIC with skin tissue samples as a diagnostic test for human and animal prion diseases. The test is widely used with samples of brain and spinal-fluid for the diagnosis of CJD, but such samples are not always available.

“Our objective has always been to facilitate RT-QuIC testing using the most broadly available and least-invasive sample possible, whether that is blood, skin, nasal brushings, or other samples,” Dr. Caughey said. His research group has developed RT-QuIC over the past decade at RML, where he also has trained many international colleagues to use and advance the test.

Dr. Caughey’s group is continuing its development of RT-QuIC applications, including further studies of when and where the pathological prion protein appears in skin, and how to effectively inactivate its infectious forms.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

Reference

C Orru et al. Prion seeding activity and infectivity in the skin of sporadic Creutzfeldt-Jakob disease patients. Science Translational Medicine, DOI: http://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aam7785 (link is external) (2017).



TUESDAY, JUNE 20, 2017 Prion 2017 Conference Transmissible prions in the skin of Creutzfeldt-Jakob disease patients

Prion 2017 Conference Transmissible prions in the skin of Creutzfeldt-Jakob disease patients 

Dr. Wenguan Zou1, Dr. Christina Orru2, Jue Yuan1, Brian Appleby1, Baiya Li1, Dane Winner1, Yian Zhan1,3, Mark Rodgers1, Jason Rarick1, Robert Wyza1, Tripti Joshi1, Gongxian Wang3, Mark Cohen1, Shulin Zhang1, Bradley Groveman2, Robert Petersen1, James Ironside4, Miguel Quinones-Mateu1, Jiri Safar1, Qingzhong Kong1, Byron Caughey2 

1Case Western Reserve University, Cleveland, United States, 2Rocky Mountain Laboratories, National Institutes of Health, Hamilton, United States, 3Nanchang University, Nanchang, China, 4Universitv of Edinburgh, Edinburgh, United Kingdom 

Aims: Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is transmissible by neuroinvasive iatrogenic routes due to abundant prion infectivity in the central nervous system (CNS). The disease-associated prion protein (PrPSc) and its infectivity have never been detected in skin from sCJD patients; however, some epidemiological studies have associated sCJD risk with skin-involved non-CNS surgeries. The aims of our study were to explore potential prion seeding activity and infectivity of skin and the feasibility of skin-based CJD diagnosis. 

Methods: Skin samples were collected at autopsy or biopsy from twenty-one sCJD, two variant CJD, and fifteen non-CJD patients and analysed by Western blotting and real-time quaking-induced conversion (RT- QulC) for PrPSc. Infectivity of skin from two sCJD patients was determined by bioassay using two lines of humanized transgenic (Tg) mice. 

Results: Western blotting demonstrated PrPSc in the skin of one of five deceased sCJD patients examined. However, the more sensitive RT-QuIC assay detected prion-seeding activity in skin from all 23 CJD decedents but not in non-CJD controls, indicating preliminary ClD diagnostic sensitivities and specificities of 100% (95% confidence intervals of 85-100%, and 78-100%, respectively). Although sCJD skins contained ~102-105-fold lower RT-QuIC seeding activity than sCJD brains, ten out of twelve mice from two Tg mouse lines inoculated with skin homogenates of two patients with two different subtypes of sCJD succumbed to prion disease within 450 days after inoculation. 

Conclusions: O sCJD patients' skin may contain both detectable prion seeding activity and transmissible prions. Our findings not only suggest a new basis for diagnostic sCJD testing, but also raise concerns about the potential for iatrogenic sCJD transmission via skin. (Funded by the CJD Foundation, the National Institute of Neurological Disorders and Stroke, the Centers for Disease Control and Prevention, as well as others) 

DISORDERS PRION 2017 DECIPHERING NEURODEGENERATIVE 


*sCJD patients' skin may contain both detectable prion seeding activity and transmissible prions. 

*Our findings not only suggest a new basis for diagnostic sCJD testing, but also raise concerns about the potential for iatrogenic sCJD transmission via skin. 

Oral Session14：45～15：00O-12 Wenquan Zou

*** PrPSc in the skin of CJD patients


Accessing transmissibility and diagnostic marker of skin prions.

Kong, Qingzhong Safar, Jiri G. Zou, Wen-Quan

Case Western Reserve University, Cleveland, OH, United States

Abstract The fatal, transmissible animal and human prion diseases are characterized by the deposition in the brain of a proteinase K (PK)-resistant infectious prion protein (PrPSc), an isoform derived from the cellular protein (PrPC) through misfolding. A definitive antemortem diagnosis is virtually impossible for most patients because of the difficulty in obtaining the brain tissues by biopsy. Recently, PrPSc has been reported to be detected in the skin of experimentally or naturally scrapie-infected animals (Thomzig et al., 2007). Consistent with this finding, we have observed PK-resistant PrP in the skin of a patient with variant Creutzfeldt-Jakob disease (vCJD), an acquired form of human prion disease caused by bovine prion (Notari et al., 2010). Unexpectedly, our latest preliminary study identified two types of PK-resistant PrP molecules [with gel mobility similar to the PrPSc types 1 and 2 from the brain of sporadic CJD (sCJD)] in the fibroblast cells extracted from the skin of clinical sCJD patients and asymptomatic subjects carrying PrP mutations linked to familial CJD (fCJD). We also detected PrPSc in the skin of humanized transgenic (Tg) mice inoculated intracerebrally with a human prion. Moreover, prion infectivity has been observed in the skin of infected greater kudu (Cunningham et al., 2004) and a murine prion inoculated to mice via skin scarification can not only propagate in the skin, but also spread to the brain to cause prion disease (Wathne et al., 2012). We hypothesize that the skin of patients with prion disease harbors prion infectivity and the presence of PK-resistant PrP in the skin is a novel diagnostic marker for preclinical CJD patients. To test the hypotheses, we propose to (1) determine prion infectivity of the skin- derived fibroblasts and skin of sCJD patients and asymptomatic PrP-mutation carriers using humanized Tg mouse bioassay, (2) to pinpoint the earliest stage at which PrPSc becomes detectable in the skin of prion- infected Tg mice, and (3) to detect PrPSc in the skin of various human prion diseases, using conventional as well as highly sensitive RT-QuIC assays for both (2) and (3). If successful, our proposal may not only help prevent potential transmission of human prion diseases but also enable definitive and less intrusive antemortem diagnosis of prion diseases. Finally, knowledge generated from this study may also enhance our understanding of other neurodegenerative diseases such as Alzheimer's disease.

Public Health Relevance Currently it is unclear whether or not the skin of patients with prion diseases is infectious and, moreover, there is no alternative preclinical definitive testing or the brain biopsy in the prion diseases. The aim of our proposal is to address the issues by detection of the infectivity of patients' skin samples using animal bioassay and a new highly sensitive RT-QuIC assay. We believe that our study will not only provide insights into the pathogenesis and transmissibility of prion disease but also will develop preclinical definitive testing for prion disease.

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Neurological Disorders and Stroke (NINDS)

Type Exploratory/Developmental Grants (R21)

Project # 1R21NS096626-01

Application # 9092119

Study Section Special Emphasis Panel (ZRG1)

Program Officer Wong, May Project Start 2016-02-01

Project End 2018-01-31

Budget Start 2016-02-01

Budget End 2017-01-31

Support Year 1

Fiscal Year 2016

Total Cost

Indirect Cost Institution Name Case Western Reserve University

Department Pathology

Type Schools of Medicine

DUNS # 077758407

City Cleveland

State OH

Country United States

Zip Code 44106



TUESDAY, MAY 10, 2016 

Accessing transmissibility and diagnostic marker of skin prions


Accumulation of Pathological Prion Protein PrPSc in the Skin of Animals with Experimental and Natural Scrapie

Achim Thomzig ,Walter Schulz-Schaeffer ,Arne Wrede,Wilhelm Wemheuer,Bertram Brenig,Christine Kratzel,Karin Lemmer,Michael Beekes Published: May 25, 2007 http://dx.doi.org/10.1371/journal.ppat.0030066

Abstract

Prion infectivity and its molecular marker, the pathological prion protein PrPSc, accumulate in the central nervous system and often also in lymphoid tissue of animals or humans affected by transmissible spongiform encephalopathies. Recently, PrPSc was found in tissues previously considered not to be invaded by prions (e.g., skeletal muscles). Here, we address the question of whether prions target the skin and show widespread PrPSc deposition in this organ in hamsters perorally or parenterally challenged with scrapie. In hamsters fed with scrapie, PrPScwas detected before the onset of symptoms, but the bulk of skin-associated PrPSc accumulated in the clinical phase. PrPSc was localized in nerve fibres within the skin but not in keratinocytes, and the deposition of PrPSc in skin showed no dependence from the route of infection and lymphotropic dissemination. The data indicated a neurally mediated centrifugal spread of prions to the skin. Furthermore, in a follow-up study, we examined sheep naturally infected with scrapie and detected PrPSc by Western blotting in skin samples from two out of five animals. Our findings point to the skin as a potential reservoir of prions, which should be further investigated in relation to disease transmission. Author Summary

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative diseases affecting the central nervous system. According to the prion hypothesis, TSEs are caused by proteinaceous infectious particles (“prions”) that consist essentially of PrPSc, an aberrant form of the prion protein with a pathologically altered folding and/or aggregation structure. Scrapie of sheep, chronic wasting disease (CWD) of deer, bovine spongiform encephalopathy (BSE) of cattle, and variant Creutzfeldt-Jakob disease (vCJD) of humans are prominent examples of acquired prion diseases. To further pinpoint the peripheral tissues that could serve as reservoirs of prions in the mammalian body and from which these pathogens could be potentially disseminated into the environment and transmitted to other individuals, we examined the skin of hamsters perorally challenged with scrapie and of naturally infected scrapie sheep for the presence of PrPSc. We show that PrPSc can accumulate in the skin at late stages of incubation, and that the protein is located primarily in small nerve fibres within this organ. The question of whether the skin may also provide a reservoir for prions in CWD, BSE, or vCJD, and the role of the skin in relation to the natural transmission of scrapie in the field needs further investigation. Discussion In this study we have shown that the skin provides a reservoir for PrPSc, the biochemical marker of prion infectivity, in five different hamster TSE models, independently of whether the animals were challenged with scrapie via the p.o., i.c., or f.p. route, cerebral implantation of scrapie-contaminated s.w., or i.c. inoculation of a hamster-adapted BSE agent. Furthermore, PrPSc could be demonstrated for the first time in skin specimens from sheep naturally infected with scrapie, though in a limited number of sites investigated and at low amounts. In a time-course study using hamsters fed with scrapie agent, we were able to detect PrPSc in the skin before the onset of clinical symptoms, but the bulk of skin-associated PrPSc accumulated in the clinical phase of the disease. From our Western blot findings, the final concentration of PrPSc in the skin of hamsters seems to be approximately 5,000–10,000 times lower than that found in the brain. This would correspond to an infectivity titre of ~ 1 × 105 to 2 × 105 50% i.c. infective doses (ID50i.c.) per gram of skin tissue. A similar infectivity titre was previously estimated from Western blot findings for skeletal muscle tissue of clinically ill hamsters perorally challenged with 263K scrapie [23]. 


PLoS One. 2010; 5(1): e8765. Published online 2010 Jan 19. doi: 10.1371/journal.pone.0008765 

Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States

In addition to the brain and other organs known to be prion positive in vCJD, such as the lymphoreticular system, pituitary and adrenal glands, and gastrointestinal tract, PrPres was also detected for the first time in the dura mater, liver, pancreas, kidney, ovary, uterus, and skin.

Conclusions/Significance

Our results indicate that the number of organs affected in vCJD is greater than previously realized and further underscore the risk of iatrogenic transmission in vCJD. 

 The major finding of the present study is the demonstration that PrPres is present in a number of non-CNS tissues and organs which previous studies had reported as free of PrPres (Table 1 and ​and2)2) [14]–[19, P. Brown, unpublished data]. These tissues include the dura mater, skin, liver, kidney, pancreas, descending colon, uterus and ovary (Table 2 and Fig. 3). 

 The present study also demonstrates for the first time the presence of PrPres in the skin in a human prion disease. Previously, PrPres has been detected in the skin from animals with experimental or naturally occurring scrapie [47] as well as in the antler velvet of elk affected by CWD [48]. 

All these considerations notwithstanding, the widespread presence of PrPres in visceral organs that we observed in the present case further reinforces the concerns over iatrogenic transmission of vCJD. These concerns are already compelling given the multiple reports of vCJD transmission by blood transfusion. 


Thursday, January 28, 2010

Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States


A Kiss of a Prion: New Implications for Oral Transmissibility 

The transmissibility of scrapie among sheep (intraspecies) is well recognized. It must be emphasized that horizontal transfer (from one individual to another) of scrapie is the main route of infection, because vertical transmission of disease from mother to offspring via milk or placental tissue occurs infrequently. Thus, in view of the report by Maddison et al, the oral transmissibility of prions among sheep may serve as a major route for horizontal scrapie transfer. This occurrence is plausible because sheep often lick each other. Maddison et al [10] indicate that, because of the similarities in prion tissue distribution, their implications for the oral transmission of ovine scrapie might be true for other prion diseases, such as cervid chronic wasting disease and human vCJD. If this is true for humans, a kiss of a prion may sometimes have lethal consequences.



PERSON TO PERSON TRANSMISSION OF THE TSE PRION DISEASE, never say never. as the disease mutates, it becomes more virulent in some cases, and cwd is efficiently transmitted from cervid to cervid. there are now multiple strains of CWD in cervids, as with the TSE prion disease in bovine, sheep and goats, and we now have the atypical TSE in these species, that have mutated, and some strains _have_ become more virulent. we now have younger humans dying from the TSE prion disease, with shorter incubation period, and that are much younger. human to human casual transmission of the TSE prion disease...again, never say never. ...TSS

see more here;


The occurrence of the disease in a patient who had contact with cases of familial C.J.D., but was not genetically related, has been described in Chile (Galvez et al., 1980) and in France (Brown et al., 1979b). In Chile the patient was related by marriage, but with no consanguinity, and had social contact with subsequently affected family members for 13 years before developing the disease. The contact case in France also married into a family in which C.J.D. was prevalent and had close contact with an affected member. In neither instance did the spouse of the non-familial case have the disease. The case described in this report was similarly related to affected family members and social contact had occurred for 20 years prior to developing C.J.D. If contact transmission had occurred, the minimum transmission period would be 11 years. Contact between sporadic cases has not been described and it is remarkable that possible contact transmissions have all been with familial cases. No method of transmission by casual social contact has been suggested.

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent.

snip...see full text here;



TUESDAY, SEPTEMBER 13, 2016

Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients


MONDAY, NOVEMBER 06, 2017 

Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque

''On secondary and tertiary transmissions, however, the proportion of PrPres positive animals gradually increased to almost 100%. Recent communications suggest that a similar situation might exist in other models of experimental exposure to prions involving swine32 and cattle33. '' 

''Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque''


Abstract

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snip...

This report strongly suggests that prions might remain hidden in the population and as the majority of healthy carriers may never develop a prion disease, an even greater proportion of contaminated individuals may never be diagnosed as healthy carriers, currently diagnosed according to the presence of PrPd in their lymphoid tissues. Moreover, should such atypical agents or their subsequent passages in humans lead to neurological impairment, there is a significant risk that they would not be diagnosed as related to prion infection in the absence of detectable PrPres and a quasi-exclusive spinal involvement. Our results enlarge the range of prion diseases that is already no longer restricted to PrPres positive diseases that target the brain47,48,49.

In conclusion, the range of incomplete syndromes that we observed between healthy carriers and typical vCJD indicates that multiple forms of prion variants can coexist and may emerge in different forms depending upon the conditions under which transmission occurred. This has obvious consequences for public health, and questions the uniqueness of the BSE/vCJD strain50 and our capacity to detect and prevent all infectious forms of prion disease. 



10,000,000 Pounds of Blood Laced Meat and Bone Meal in Commerce in the USA 2007


RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling’s 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI ___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot-Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI – 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J – PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A-BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

###



SATURDAY, NOVEMBER 4, 2017 

FDA 589.2000, Section 21 C.F.R. Animal Proteins Prohibited in Ruminant Feed WARNING Letters and FEED MILL VIOLATIONS OBSERVATIONS 2017 to 2006



FRIDAY, NOVEMBER 3, 2017

BSE MAD COW TSE PRION DISEASE PET FOOD FEED IN COMMERCE INDUSTRY VS TERRY S. SINGELTARY Sr. A REVIEW

''I have a neighbor who is a dairy farmer. He tells me that he knows of several farmers who feed their cattle expired dog food. These farmers are unaware of any dangers posed to their cattle from the pet food contents. For these farmers, the pet food is just another source of protein.''

IN CONFIDENCE


WEDNESDAY, OCTOBER 4, 2017 

EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) a review 2017


THURSDAY, AUGUST 17, 2017 

JAVMA NEWS Atypical BSE found in Alabama cow September 01, 2017


2017

TUESDAY, JULY 18, 2017 

USDA announces Alabama case of Bovine Spongiform Encephalopathy Alabama



THURSDAY, JULY 20, 2017 

USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200


SUNDAY, JULY 23, 2017

atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION


SUNDAY, JULY 23, 2017

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy



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

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

doi:10.1038/srep11573

Download Citation

EpidemiologyNeurological manifestationsPrion diseases

Received: 16 February 2015

Accepted: 28 May 2015

Published online: 30 June 2015

Abstract

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

snip...

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

SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY

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


O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 


Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 



Saturday, April 23, 2016 

Scrapie ZOONOSIS PRION CONFERENCE TOKYO 2016 

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

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


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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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

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

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

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

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

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

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.



MONDAY, OCTOBER 02, 2017 

Creutzfeldt Jakob Disease United States of America USA and United Kingdom UK Increasing and Zoonotic Pontential From Different Species


THURSDAY, AUGUST 17, 2017 

*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017

Singeltary et al


TUESDAY, AUGUST 03, 2010 

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein 

Here we go folks. AS predicted. THIS JUST OUT !



Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009 


Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009 


FRIDAY, AUGUST 11, 2017 

Infectivity in bone marrow from sporadic CJD patients

Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease. 


*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery *** 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them. 


THURSDAY, AUGUST 10, 2017 

*** Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017


2017

Subject: ***CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 

Chronic Wasting Disease (CWD) 

Prevention 

If CWD could spread to people, it would most likely be through eating of infected deer and elk. In a 2006-2007 CDC survey of U.S. residents, nearly 20 percent of those surveyed said they had hunted deer or elk and more than two-thirds said they had eaten venison or elk meat. However, to date, no CWD infections have been reported in people. 

Hunters must consider many factors when determining whether to eat meat from deer and elk harvested from areas with CWD, including the level of risk they are willing to accept. Hunters harvesting wild deer and elk from areas with reported CWD should check state wildlife and public health guidance to see whether testing of animals is recommended or required in a given state or region. In areas where CWD is known to be present, CDC recommends that hunters strongly consider having those animals tested before eating the meat. 

Tests for CWD are monitoring tools that some state wildlife officials use to look at the rates of CWD in certain animal populations. Testing may not be available in every state, and states may use these tests in different ways. A negative test result does not guarantee that an individual animal is not infected with CWD, but it does make it considerably less likely and may reduce your risk of exposure to CWD. 

To be as safe as possible and decrease their potential risk of exposure to CWD, hunters should take the following steps when hunting in areas with CWD: 

Do not shoot, handle or eat meat from deer and elk that look sick or are acting strangely or are found dead (road-kill). When field-dressing a deer: Wear latex or rubber gloves when dressing the animal or handling the meat. Minimize how much you handle the organs of the animal, particularly the brain or spinal cord tissues. Do not use household knives or other kitchen utensils for field dressing. Check state wildlife and public health guidance to see whether testing of animals is recommended or required. Recommendations vary by state, but information about testing is available from many state wildlife agencies. Strongly consider having the deer or elk tested for CWD before you eat the meat. If you have your deer or elk commercially processed, consider asking that your animal be processed individually to avoid mixing meat from multiple animals. If your animal tests positive for CWD, do not eat meat from that animal. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service regulates commercially farmed deer and elk. The agency operates a national CWD herd certification program. As part of the voluntary program, states and individual herd owners agree to meet requirements meant to decrease the risk of CWD in their herds. Privately owned herds that do not participate in the herd certification program may be at increased risk for CWD. 

Page last reviewed: August 17, 2017 Page last updated: August 17, 2017 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of High-Consequence Pathogens and Pathology (DHCPP) 


 > However, to date, no CWD infections have been reported in people. 

key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry 

LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** 



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. 


TUESDAY, SEPTEMBER 12, 2017 

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 


Prion 2017 Conference Abstracts CWD

 2017 PRION CONFERENCE 

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

Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS 

Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO 

PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS 

*** PRION 2017 CONFERENCE VIDEO 



 TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT 

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


TUESDAY, JULY 04, 2017

*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD


Wednesday, May 24, 2017 

PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1 


SATURDAY, JULY 29, 2017 

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 


National Prion Center could lose all funding just as concern about CWD jumping to humans rises

SATURDAY, JULY 15, 2017 

*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises


2015 PRION CONFERENCE

*** RE-P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. ***

P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA

Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’ infections in UK residents emphasize the continued need for information about disease risk in humans. A large study of blood component infectivity in a non-human primate model has now been completed and analyzed. Among 1 GSS, 4 sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6 year surveillance period. A transmission study in recipients of multiple whole blood transfusions during the incubation and clinical stages of sCJD and vCJD in ic-infected donor animals was uniformly negative. These results, together with other laboratory studies in rodents and nonhuman primates and epidemiological observations in humans, suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. The issue of decades-long incubation periods in ‘silent’ vCJD carriers remains open.


ran across an old paper from 1984 ;

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent. ***


snip...see full text ;



Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS. snip...

In conclusion, we propose that VPSPr is transmissible and, therefore, is an authentic prion disease. However, transmissibility cannot be sustained through serial passages presumably because human PrPC (or the mouse brain environment) cannot efficiently convert and propagate the VPSPr PrPSc species. If this is the case, uncovering the properties of human PrP that are required to replicate more efficiently the prion strains associated with VPSPr may help clarify the PrPSc mode of formation in this intriguing disease. 





Friday, January 10, 2014

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???


WEDNESDAY, NOVEMBER 09, 2011

Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS 

HOW TO TURN A POTENTIAL MAD COW VICTIM IN THE USA, INTO A HAPPENSTANCE OF BAD LUCK, A SPONTANEOUS MUTATION FROM NOTHING. 

OR WAS IT $$$ 





FRIDAY, NOVEMBER 3, 2017 

GSS Gerstmann-Sträussler-Scheinker disease with atypical presentation


WEDNESDAY, NOVEMBER 1, 2017 

Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies


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. 


Tracking spongiform encephalopathies in North America

Xavier Bosch

Published: August 2003


Summary;

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.”

49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD) the relative of mad cow disease seen among deer and elk in the USA. Although his feverish search did not lead him to the smoking gun linking CWD to a similar disease in North American people, it did uncover a largely disappointing situation.

Singeltary was greatly demoralised at the few attempts to monitor the occurrence of CJD and CWD in the USA. Only a few states have made CJD reportable. Human and animal TSEs should be reportable nationwide and internationally, he complained in a letter to the Journal of the American Medical Association (JAMA 2003; 285: 733). "I hope that the CDC does not continue to expect us to still believe that the 85% plus of all CJD cases which are sporadic are all spontaneous, without route or source."

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.


Until recently, CWD was thought to be confined to the wild in a small region in Colorado. But since early 2002, it has been reported in other areas, including Wisconsin, South Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD in states that were not endemic previously increased concern about a widespread outbreak and possible transmission to people and cattle.

To date, experimental studies have proven that the CWD agent can be transmitted to cattle by intracerebral inoculation and that it can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue before invasion of the central nervous system. Yet the plausibility of CWD spreading to people has remained elusive.

Part of the problem seems to stem from the US surveillance system. CJD is only reported in those areas known to be endemic foci of CWD. Moreover, US authorities have been criticised for not having performed enough prionic tests in farm deer and elk.

Although in November last year the US Food and Drug Administration issued a directive to state public-health and agriculture officials prohibiting material from CWD-positive animals from being used as an ingredient in feed for any animal species, epidemiological control and research in the USA has been quite different from the situation in the UK and Europe regarding BSE.

"Getting data on TSEs in the USA from the government is like pulling teeth", Singeltary argues. "You get it when they want you to have it, and only what they want you to have."

Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that "current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings"; adding that, "the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure". The USA should develop a system modelled on that established in the UK, he points out.

Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunters "two of whom were friends" who died from pathologically confirmed CJD, says that "at present there are insufficient data to claim transmission of CWD into humans"; adding that "[only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further". Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison.

CDC spokesman Ermias Belay says that the CDC "will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat". He notes that although "the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100%" and that "[we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited". 



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? 


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 hvCJD in the USA * BSE in U.S. 


 *** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001 


2001 FDA CJD TSE Prion Singeltary Submission 



Alzheimer's disease

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

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




Terry S. Singeltary Sr.

posted by Terry S. Singeltary Sr. at 1:48 PM