Wednesday, March 15, 2017

Clinical and laboratory features of 14 young Chinese probable sCJD patients

Clinical and laboratory features of 14 young Chinese probable sCJD patients

Qi Shi, Kang Xiao, Cao Chen, Wei Zhou, Chen Gao, Jing Wang, 

Page 00 | Received 02 Nov 2016, Accepted 20 Jan 2017, Accepted author version posted online: 09 Mar 2017

Full Article Figures & data References Citations Metrics Reprints & Permissions Get access Accepted author version


Sporadic Creutzfeldt-Jakob disease (sCJD) occurs frequently in the relatively older population, mainly in the groups of 60–69 and 70–79 year-old. Since 2006 when China carried out national CJD surveillance, 14 young probable sCJD patients below 40 year-old were identified, counting for 1.93% of all probable sCJD cases. The clinical features of young probable sCJD cases, including the onset feature, the presence of sCJD-associated signs and the clinical duration, are indistinguishable from those of older patients. Special sCJD-associated abnormalities on EEG and MRI were noticed in 7 and 10 cases. CSF 14-3-3 was positive in 7 cases. CSF RT-QuIC showed positive reactive curves in 9 cases, with short lag phases. PRNP sequencing did not find any mutation. Due to low rate of brain autopsy in China, performances of other CJD-associated examinations as much as possible are extremely important for the distinguish diagnosis of young probable sCJD patients.

Key words: Creutzfeldt-Jakob disease, sporadic, prion disease, young patient, surveillance Disclaimer

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Quality evaluation for the surveillance system of human prion diseases in China based on the data from 2010 to 2016 

Qi Shi, Wei Zhou, Cao Chen, Chen Gao, Kang Xiao, Jing Wang, show all Pages 484-491 | Received 07 Jul 2016, Accepted 22 Aug 2016, Accepted author version posted online: 03 Oct 2016, Published online: 03 Oct 2016 Download citation 

Select Language​▼ Translator disclaimer 


The surveillance of CJD or human prion diseases (PrDs) has been conducted for 10 y in China. To evaluate the quality of China CJD surveillance system, the collections of the clinical and epidemiological information, the sampling, the clinical examinations and laboratory tests and follow-up survey were separately analyzed based on the data from 2010 to 2015. The obtaining rates of clinical-information table, epidemiological-information table, sample inspection sheet and medical record of the referring patients from reporting units to the center of CJD surveillance maintained or reached at very high levels, being close to 100% in the past 3 y. 93.82%, 85.23%, 96.21% and 94.70% of the reported cases had the data of MRI, EEG, CSF 14-3-3 and PRNP sequencing, respectively. Follow-up surveys were conducted in about 50% cases in 2010 and 2011, 93.39% cases in 2012 and 100% cases in the last 3 y. High obtaining rates of the clinical and epidemiological data, high conducting rates of the relevant clinical examinations and laboratory tests, high performing rates of follow-up survey for every referring case reflect a good implemental capacity in China CJD surveillance system, which supplies solid basis for recognition and diagnosis of human prion diseases and guarantees good quality of China CJD surveillance system.

KEYWORDS: Creutzfeldt-Jakob disease, evaluation, human prion diseases, surveillance, quality


Surveillance for Creutzfeldt-Jakob disease in China from 2006 to 2007 Research article

Surveillance for Creutzfeldt-Jakob disease in China from 2006 to 2007

Qi Shi , Chen Gao , Wei Zhou , Baoyun Zhang , Jianming Chen , Chan Tian , Huiying Jiang , Jun Han , Nijuan Xiang , Xiaofang Wang , Yongjun Gao and Xiaoping Dong

BMC Public Health 2008, 8:360doi:10.1186/1471-2458-8-360

Published: 18 October 2008

Abstract (provisional) Background Human transmissible spongiform encephalopathies (HTSE), or Creutzfeldt-Jakob disease (CJD), is a group of rare and fatal diseases in central nervous system. Since outbreak of bovine spongiform encephalopathy (BSE) and variant CJD, a worldwide CJD surveillance network has been established under the proposition of WHO. In China, a national CJD surveillance system has started since 2002. The data of CJD surveillance from 2006 to 2007 was analyzed.

Methods Total 12 provinces are included in CJD surveillance system. The surveillance unit in each province consists of one or two sentinel hospitals and the provincial CDC. All suspected CJD cases reported from CJD surveillance were diagnosed and subtyped based on the diagnostic criteria for CJD issued by WHO.

Results Total 192 suspected CJD cases were reported and 5 genetic CJD, 51 probable and 30 possible sporadic CJD (sCJD) cases were diagnosed. The collected sCJD cases distribute sporadically without geographical clustering and seasonal relativity and the highest incidences in both probable and possible sCJD cases appeared in the group of 60-69 year. The most common three foremost symptoms were progressive dementia, cerebellum and mental-related symptoms. The probable sCJD patients owning both typical EEG alteration and CSF protein 14-3-3 positive have more characteristic clinical syndromes than the ones having only one positive. The polymorphisms of codon 129 of all tested reported cases shows typical patterns of Han Chinese as previous reports, that M129M are predominant whereas M129V are seldom.

Conclusion Chinese CJD patients possessed similar epidemiological and clinical characteristics as worldwide. 

snip...see full text ;

Voluntary Report - public distribution

Date: 3/27/2007

GAIN Report Number: CH7025


China, Peoples Republic of

Livestock and Products

China Proposes to Ease Certification Requirements for Cosmetics Imports


Approved by:

Maurice House U.S. Embassy Prepared by:

Casey Bean and Zhang Jianping

Report Highlights:

On February 21, 2007, China notified the World Trade Organization (WTO) of a draft policy change (G/SPS/N/CHN/100) on the BSE certification for cosmetic imports from BSE-infected countries. The closing date for submitting comments is April 20, 2007, and the new SPS measure will become effective on August 1, 2007. This announcement is positive news for the U.S. cosmetics industry since they will no longer be required to submit a CTFA certificate when shipping cosmetics to China. China's demand for cosmetic imports remains strong, and the country's imports increased in January 2007 by 40 and 84 percent respectively in volume and value when compared to January 2006. Included in this report is an unofficial translation of China's WTO notification.

Includes PSD Changes: No

Includes Trade Matrix: No

Unscheduled Report

Beijing [CH1]


GAIN Report - CH7025 Page 2 of 4

UNCLASSIFIED USDA Foreign Agricultural Service

Executive Summary

On February 21, 2007, China notified the World Trade Organization (WTO) of a draft policy change (G/SPS/N/CHN/100) on the BSE certification for cosmetic imports from countries infected by bovine spongiform encephalopathy (BSE). The closing date for submitting comments is April 20, 2007, and the new SPS measure will become effective on August 1, 2007.

According to the new policy, Chinese importers will no longer be requested to provide the Cosmetic Certificate for BSE issued by the health administrative department or officially authorized agencies in BSE-infected countries, including the United States, when they apply for health permits with the Ministry of Health (MOH) or declare for import inspection and quarantine with the Chinese entry-exit inspection and quarantine bureaus under the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ). MOH and AQSIQ have jointly listed forbidden high-risk materials in cosmetics from BSE-infected countries as a reference for those manufacturing countries. (Please refer to the unofficial translation of China’s notification to the WTO below.)

This announcement is positive news for U.S. suppliers since they will be no longer required to submit the BSE certificate issued by the Cosmetic, Toiletry and Fragrance Association (CTFA).

During 2004, in order to maintain market access for U.S. cosmetics in the wake of the December 2003 detection of BSE in the United States, FAS Beijing helped broker this interim certification requirement through CTFA.

China’s demand for cosmetic imports remains strong—imports in January 2007 increased by 40 and 84 percent, respectively, in volume and value compared to that in the previous year As China’s living standard and disposable incomes continue rising, so does consumer demand for cosmetic imports. China’s total cosmetic imports in 2006 increased by 62 percent to 12,988 MT from 8,019 MT in 2004, and China’s total import volume in the first month of 2007 increased by 40 percent compared to January 2006. China’s total import value for cosmetics in 2006 reached $276.5 million, a 94 percent increase from $142.8 million in 2004. China’s total import value in the first month in 2007 increased by 84 percent compared to January 2006. The United States is the second largest supplier to China after France, accounting for 26 and 21 percent respectively in China’s total import volume and value in 2006.

FAS Beijing believes this new policy will facilitate imports of cosmetic imports.

Table 1: China cosmetic imports in volume

China Cosmetics Imports, 2004-2007 (MT)

Jan-Dec Jan-Dec Jan-Dec Jan - Jan Jan - Jan Quantity Quantity Quantity Quantity Comparison % Change

Origin 2004 2005 2006 2006 2007 2007/06

World 8,019 10,515 12,988 779 1,092 40.18

France 2,163 2,752 3,506 159 319 100.63

United States 2,045 2,974 3,332 98 294 200.00

Japan 980 1,369 1,543 90 132 46.67

South Korea 276 675 1,038 131 102 -22.14

United Kingdom 250 315 470 23 52 126.09 

GAIN Report - CH7025 Page 3 of 4

UNCLASSIFIED USDA Foreign Agricultural Service

Taiwan 1,025 861 902 71 49 -30.99

Australia 50 53 63 3 36 1100.00

Monaco 120 230 303 12 18 50.00

Other 1,110 1,286 1,831 192 90 -53.13

HS Code: 3303.0000, 3304.1000, 3304.2000, 3304.3000, 3304.9010 and 3304.9900

Source: WTA China Statistics

Table 2: China cosmetic imports in value

China Cosmetics Imports, 2004-2007 ($1,000)

Jan-Dec Jan-Dec Jan-Dec Jan - Jan Jan - Jan

Value Value Value Value


% Change

Origin 2004 2005 2006 2006 2007 2007/06

World 142,754 210,032 276,452 15,118 27,787 83.80

France 50,774 66,992 97,562 4,765 10,696 124.47

United States 27,204 50,251 58,288 2,083 5,493 163.71

Japan 29,756 43,689 50,884 3,371 5,023 49.01

South Korea 3,562 11,388 15,600 1,832 1,799 -1.80

United Kingdom 591 545 10,458 676 1,155 70.86

Taiwan 4,132 4,384 5,733 528 388 -26.52

Australia 332 316 545 30 97 223.33

Monaco 3,707 6,856 6,917 247 606 145.34

Other 22,696 25,611 30,465 1,586 2,530 59.52

HS Code: 3303.0000, 3304.1000, 3304.2000, 3304.3000, 3304.9010 and 3304.9900

Source: WTA China Statistics

Begin Translation

Notification on Modifying the Management Measure For Cosmetic Imports From BSE-Infected Areas


(February 21, 2007)

To further strengthen the management on cosmetic imports, the measure on cosmetic imports from BSE-infected areas will be adjusted as follows.

I. It is forbidden to import cosmetics with high-risk materials from BSE-infected areas as listed in the appendix of this notification. The Ministry of Health (MOH) and the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) will revise and announce the list of high-risk materials based on risk assessments result.

II. Importers will no longer be requested to provide the Cosmetics Certificate for BSE issued by the health administrative department or officially authorized agencies in BSE countries when applying for a health permit (or recorded certificate) with the health administrative department or declaring for inspection and quarantine with the entry-exit inspection and quarantine authorities, which are under the State Council. 

GAIN Report - CH7025 Page 4 of 4

UNCLASSIFIED USDA Foreign Agricultural Service

III. Cosmetic imports with high-risk materials listed in the Appendix from BSE-infected areas will be dealt with based on Chinese laws and regulations.

This notification will become effective on August 31, 2007


Forbidden High-Risk Materials in Cosmetic imports from BSE-infected Areas

1. Bovine and ovine brain, spinal cord, skull, vertebral column, eyes, tonsils, intestines, cerebrospinal fluid, pituitary, duramater spinalis, pineal, spleen, thymus and other lymph tissues, blood, umbilical cord, ovaries, placenta, tongue, livers, adrenal glands, pancreas, etc., as well as their products.

2. Gelatin or collagen derived from bovine or ovine bones without high pressure washing (fat skimming)—softening through acid washing—acid or alkaline treatment— filtration—sterilization with temperature at or above 138 degrees of centigrade no less than 4 seconds.

(End translation)

Thursday, April 17, 2008

Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47 

[Federal Register: April 17, 2008 (Volume 73, Number 75)] [Rules and Regulations] [Page 20785-20794] From the Federal Register Online via GPO Access [] [DOCID:fr17ap08-7] 

Monday, February 01, 2010

Import Alert 17-04 BSE CJD HIGH RISK TISSUES, Nutritional Supplements and Cosmetics


-------- Original Message -------- 

Subject: Docket No. 2004N-0081 and or RIN number RIN-0910-AF47 Use of Materials Derived From Cattle in Human Food and Cosmetics [comment submission]

Date: Tue, 13 Jul 2004 16:08:38 -0500

From: "Terry S. Singeltary Sr." T



COMMENT SUBMISSION [Docket No. 2004N-O081] RIN-0910--AF47 Use of Materials Derived From Cattle in Human Food and Cosmetics

THURSDAY, JULY 22, 2010 




In vitro amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification

"When considering the atypical L-BSE and H-BSE diseases of cattle, they have been assessed in both non-human primate and transgenic mouse bioassays (with mice transgenic for human PRNP) and both model systems indicate that H-BSE and L-BSE may have increased zoonotic potential compare with C-BSE. The detection of all types of BSE is therefore of significant importance."


***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.*** 

Primate Biol., 3, 47–50, 2016 doi:10.5194/pb-3-47-2016 © Author(s) 2016. CC

Attribution 3.0 License. 


Walter Bodemer German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany Correspondence to: Walter Bodemer (

Received: 15 June 2016 – Revised: 24 August 2016 – Accepted: 30 August 2016 – Published: 7 September 2016 


Prions gained widespread public and scientific interest in the year 2000. At that time, the human neurological Creutzfeldt–Jakob disease (CJD) was known. However, new CJD cases were diagnosed but they could not be ascribed to one of the classical CJD categories i.e. sporadic (sCJD), hereditary or acquired. Hence, they were classified as variant CJD (vCJD). Later on, experimental evidence suggested that vCJD was caused by prions postulated as unique novel infectious agents and, for example, responsible for bovine spongiform encephalopathy (BSE) also known as mad cow disease. The infection of humans by transmission of BSE prions also defined vCJD as a zoonotic disease. Prions, especially those associated with scrapie in sheep had been known for quite some time and misleadingly discussed as a slow virus. Therefore, this enigmatic pathogen and the transmission of this unusual infectious agent was a matter of a controversial scientific debate. An agent without nucleic acid did not follow the current dogma postulating DNA or RNA as inheritable information encoding molecules. Although numerous experimental results clearly demonstrated the infectious capacity of prions in several animal species, a model close to human was not readily available. Therefore, the use of rhesus monkeys (Macaca mulatta) served as a non-human primate model to elucidate prion infection under controlled experimental conditions. Not the least, transmission of BSE, human vCJD, and sCJD prions could be confirmed in our study. Any prion infection concomitant with progression of disease in humans, especially vCJD, could be analyzed only retrospectively and at late stages of disease. In contrast, the prion-infected rhesus monkeys were accessible before and after infection; the progression from early stage to late clinical stages – and eventually death of the animal–could be traced. Because of the phylogenetic proximity to humans, the rhesus monkey was superior to any rodent or other animal model. For these reasons an experimental approach had been conceived by J. Collinge in London and A. Aguzzi in Zurich and performed in a cooperative study with both research groups in the pathology unit of the German Primate Center (DPZ). The study in the DPZ lasted from 2001 until 2012. Our research in the pathology unit provided a temporal monitoring of how an initial prion infection develops eventually into disease; an approach that would have never been possible in humans since the time point of infection with prions from, for example, BSE is always unknown. Telemetry revealed a shift in sleep– wake cycles early on, long before behavioral changes or clinical symptoms appeared. Pathology confirmed nonneuronal tissue as hidden places where prions exist. The rhesus model also allowed first comparative studies of epigenetic modifications on RNA in peripheral blood and brain tissue collected from uninfected and prion infected animals. To conclude, our studies clearly demonstrated that this model is valid since progression to disease is almost identical to human CJD. 

Published by Copernicus Publications on behalf of the Deutsches Primatenzentrum GmbH (DPZ).


2 Methods and results 

2.1 Animals The reason to perform prion research in rhesus monkeys was to monitor infection and the temporal progression of prion infection in the rhesus monkey. In contrast to studies of human CJD cases, we could decide on the infectious dose. We also could control behavior immediately after prion inoculation and during the rather long time until animals died from the prion infection. Hidden places where prions might exist were found. Even epigenetic modifications on RNA could be detected. Taken together, these experimental approaches depended on animals. Using rhesus monkeys as a model system required thorough ethic reasoning and consultation with authorities before we actually turned to conduct the experiments. The Number of animals was limited just to fulfill statistical conditions. The individual health status was obtained and health care was provided throughout the study. The animals underwent daily inspection to monitor any changes in health and behavior. The experiments were conceived with the aim of reducing pain, suffering, and harm. Groups of animals were preferred in order to keep them in a social environment. The animals were originally kept in Vienna at Baxter and transferred to the German Primate Center (DPZ) in 2001. J. Collinge, A. Aguzzi, and C. Weissmann were the scientists who recommended this well-controlled prion infection study, and financial support was provided by an EU grant.To ensure statistical significance four groups consisting of four rhesus macaques each were formed: one uninfected control group, one group infected with BSE prions, one with vCJD prions, and one with sCJD prions. Health of animals, infection, and progression to disease was looked at in our pathology department and in cooperation with W. Schulz-Schaeffer at the UMG (University Medicine, Göttingen). Besides, neurologists from the UMG also observed the animals whenever clinical symptoms seemed to appear. This close observation and comparison with human CJD cases demonstrated how close clinical progression of human disease resembles the experimental infection in the non-human primate. 

2.2 Infection Infectious prions from brain tissue of one sCJD and one vCJD case (provided by J. Collinge) as well as BSE prions (from a “German” madcow case and provided by W. Schulz Schaeffer) were intraperitoneally administered into the rhesus monkeys. 

2.3 Monitoring of behavior and telemetry Early behavioral monitoring was carried out by the ethologists I. Machatschke and J. Dittami from Vienna University. Transmitters were used to record changes in the circadian rhythms. Body temperature, sleep–wake cycles, and activity profiles could be obtained over a time span of 2 years. Up to half a year after infection animals did not show any signs of prion infection. However, after 6 months and persisting for another few months some animals had some disturbances in circadian rhythms which disappeared and then never appeared again(I. Machatschke, personal communication,2006).For a rather long time of about 4–5 years animals seemed to be healthy. But then, almost all animals rapidly progressed to symptoms. Symptoms were highly similar or even identical to those seen in human CJD. 

2.4 Pathology Blood and necropsy specimens from the animals served as a valuable source to detect pathologically associated prion protein even in non-neuronal skeletal and cardiac tissue. These “hidden places” of prion pathology and replication were clearly demonstrated and extended our view where prions might spread within an organism. Not only leukocytes and neuronal tissue harbor abnormal prion protein isoforms but also other tissues can propagate prion protein isoforms leading to toxicity, cell degeneration, and eventually transmissible prions (Krasemann et al., 2010, 2013).


3 Conclusion 

Most importantly, early signs of an altered circadian rhythm, sleep–wake cycle, and activity and body temperature were recorded in prion-infected animals. This experimental approach would have never been feasible in studies with human CJD cases. After 4–6 years animals developed clinical symptoms highly similar to those typical for CJD. Clinicians confirmed how close the animal model and the human disease matched. Non-neuronal tissue like cardiac muscle and peripheral blood with abnormal, disease-related prion protein were detected in rhesus monkey tissues. 

Molecular changes in RNA from repetitive Alu and BC200 DNA elements were identified and found to be targets of epigenetic editing mechanisms active in prion disease. To conclude, our results with the rhesus monkey model for prion disease proved to be a valid model and increased our knowledge of pathogenic processes that are distinctive to prion disease.


*** WDA 2016 NEW YORK *** 

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. 

Student Presentations Session 2 

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

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

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. 

Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders


Zoonotic Potential of CWD Prions: An Update

Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6 1Department of Pathology, 3National Prion Disease Pathology Surveillance Center, 5Department of Neurology, 6National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. 4Department of Biological Sciences and Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada, 2Encore Health Resources, 1331 Lamar St, Houston, TX 77010

Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions.

PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016 PRION 2016 Tokyo Prion 2016

Monday, May 02, 2016

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

Saturday, April 23, 2016


Saturday, April 23, 2016 

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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

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

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

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

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

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

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

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. 



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

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

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

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

P.110: Prion protein gene sequences analysis in twelve sheep breeds of Pakistan

Mohammad Farooque Hassan*

China Agricutural University; Beijing, China

Prions are considered the only agents of Transmissible Spongiform Encephalopathies (TSEs) and are harmful pathogens of mammals. These infectious agents of host are made up through aggregation of conformational isomers (PrPSc) and encode glycoprotein (PrPC) of 33–35 kDa. TSEs are fatal group of diseases which are neurodegenerative and include chronic wasting disease in deer and elk, Creutzfeldt-Jakob disease (CJD) and transmissible mink encephalopathy (TME) in humans and scrapie in goats and sheep. The accumulation of abnormal form of the normal protein (PrP) is common in all diseases related TSE. This abnormal form of PrP called PrPSc is resistant to proteolysis as well as infectious. Present study was conducted in order to do sequence analysis of prion protein gene in 12 breeds (n = 129) of the sheep from all provinces of Pakistan including Azad Jammu and Kashmir. We amplified 771 bp of PrP gene in selected 12 sheep breeds followed by sequencing. We identified single nucleotide polymorphisms (SNPs) and some heterozygous sites were detected in aligned sequences using CodonCode Aligner. We compared the results with other sheep breeds of the word and reported mammalian species sequences in GenBank NCBI through UPGMA phylogenetic analysis using MEGA 6.1. This study provided useful PrP gene based information in sheep population across the country.

Ireland earlier this year signed export deals with China and the United States, making it the only European country to be allowed to export beef to both countries.

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. 


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

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

MONDAY, MARCH 13, 2017


Thursday, December 08, 2016

USDA APHIS National Scrapie Eradication Program October 2016 Monthly Report Fiscal Year 2017 atypical NOR-98 Scrapie

Wednesday, December 21, 2016


Monday, January 2, 2017

Bovine Spongiform Encephalopathy Induces Misfolding of Alleged Prion-Resistant Species Cellular Prion Protein without Altering Its Pathobiological Features Articles, Neurobiology of Disease

Monday, January 09, 2017

Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle CDC Volume 23, Number 2—February 2017


APHIS Bovine Spongiform Encephalopathy (BSE): Ongoing Surveillance Program Last Modified: Jan 5, 2017




EU-approved rapid tests might underestimate bovine spongiform encephalopathy infection in goats 

15 November 1999 

British Medical Journal 

vCJD in the USA * BSE in U.S. 

2 January 2000 

British Medical Journal 

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

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? 

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. 

see full text ; 

*** Needless conflict ***

 Nature 485, 279–280 (17 May 2012) doi:10.1038/485279b

 Published online 16 May 2012

 Terry S. Singeltary Sr. said:

 I kindly wish to submit the following please ; 

Thursday, July 24, 2014 

*** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations 

*** Singeltary reply ; 

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

Monday, June 20, 2016 

Specified Risk Materials SRMs BSE TSE Prion Program 

Wednesday, July 15, 2015 

Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed? 

***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE. ***

Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only. IBNC Tauopathy or TSE Prion disease, it appears, no one is sure. 

Posted by flounder on 03 Jul 2015 at 16:53 GMT 


***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.*** 

Saturday, June 25, 2011 

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque 

"BSE-L in North America may have existed for decades" 

Tuesday, July 26, 2016 

*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016 ***


He says that when he worked at MAFF, ''the way it was structurally set up was not that science would drive the politics, but that the politics will drive the science. And that's wrong.''

11/3/96 DGRC alerts DTI Ministers and CSA to discovery of nvCJD on basis of letter from MRC Chief Executive dated 11/3/96

BIRTH OF THE UKBSEnvCJD ONLY THEORY, the birth of the 'BIG LIE' begins. ...tss


5. This case may raise fears of a link between BSE and CJD. Current advice is that there is no scientific evidence of a link between BSE in cattle and CJD in humans. Furthermore advice from the Spongiform Encephalopathy Advisory Committee is that they are satisified that all necessary safeguards are in place to minimise further spread of spongiform encephalopathies in animals and to prevent any risk of transmission to humans. ...

To ask the Secretary of State for Health, how many people under the age of 20 years in each of the last five years have suffered from Creutzfeldt-Jakob disease; and of these how many had not had any growth treatment previously.


We are not aware of any people under the age of 20 in the UK suffering from Creutzfeldt-Jakob Disease in the last five years.





A TEENAGE GIRL may have caught the human form of MAD COW DISEASE by eating a contaminated burger it was claimed last night.

VICKY RIMMER, 16, has the killer Creutzfeldt-Jakob disease (CJD).




I have interviewed Mrs Rimmer at my constituency surgery

IF there is nothing to hide, why is there so much SECRECY? WHY is the Government and other Bodies trying to stop any CHANCE OF PEOPLE CONNECTING THE TWO DISEASES. The B.S.E. problem is obvious, but if the correct measures are taken, surely the problem could be contained, however, as it stands the lack of investigation and interest of the possibility of B.S.E. and C.J.D. being linked is open for speculation and surely someone has to account for peoples lives! WHY is so much trouble being taken to convice people that B.S.E. and C.J.D. are not linked? Guilty Conscience perhaps ? - or cover up?



22 FEBRUARY 1994

Alleged Case of Creutzfeld Jakob Disease: Victoria Rimmer.

(now story changes that biopsy shows she does not have CJD...tss)


''This year's findings shows a number of associations but the strongest is for veal.''


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


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). 


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). 


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. ... 


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) 


see full report ; 


October 1994 

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

Dear Mr Elmhirst, 


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. 

From: TSS ( 

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

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

From: "Belay, Ermias" 


Cc: "Race, Richard (NIH)" ; 

"Belay, Ermias" 

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


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----- 



Sunday, September 29, 2002 10:15 AM 


Sunday, November 10, 2002 6:26 PM ......



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. 


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

snip... full text ; 

CJD is so rare in people under age 30, one case in a billion (leaving out medical mishaps), that four cases under 30 is "very high," says Colorado neurologist Bosque. "Then, if you add these other two from Wisconsin [cases in the newspaper], six cases of CJD in people associated with venison is very, very high." Only now, with Mary Riley, there are at least seven, and possibly eight, with Steve, her dining companion. "It's not critical mass that matters," however, Belay says. "One case would do it for me." The chance that two people who know each other would both contact CJD, like the two Wisconsin sportsmen, is so unlikely, experts say, it would happen only once in 140 years. Given the incubation period for TSEs in humans, it may require another generation to write the final chapter on CWD in Wisconsin. "Does chronic wasting disease pass into humans? We'll be able to answer that in 2022," says Race. Meanwhile, the state has become part of an immense experiment. 

I urge everyone to watch this video closely...terry 

*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans *** 

new url 


Monday, May 19, 2008



Thursday, April 14, 2016 

Arizona 22 year old diagnosed with Creutzfeldt Jakob Disease CJD 

Tuesday, July 12, 2016 

Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE, TSE, Prion Zoonosis Science History see history of NIH may destroy human brain collection 


Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129


Many more people could still die from mad cow disease in the UK 

Sunday, January 17, 2016 

Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease 

Creutzfeldt Jakob Disease CJD 


In vitro amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification

"When considering the atypical L-BSE and H-BSE diseases of cattle, they have been assessed in both non-human primate and transgenic mouse bioassays (with mice transgenic for human PRNP) and both model systems indicate that H-BSE and L-BSE may have increased zoonotic potential compare with C-BSE. The detection of all types of BSE is therefore of significant importance."

Sent: Monday, January 08,2001 3:03 PM 


CJD BSE TSE Prion Scientific Advisors and Consultants Staff January 2001 Meeting 

Singeltary Submission 


FDA CJD TSE Prion Singeltary Submission 

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. 


Many more people could still die from mad cow disease in the UK 


Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129

Terry S. Singeltary Sr. 


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