Thursday, January 3, 2019

MAD COW USDA DISEASE BSE TSE Prion

skin and tse prion

Even though B-834 produced short incubation periods when inoculated intracerebrally, exposure by the oral route was ineffective during an observation period of two years. Thus, we once again seem to have a conflict between field and experimental data. 

***> However, Gajdusek has suggested that the main route of entry for these transmissible agents is not the oral route per se, but rather via breaks or abrasions of skin and mucosal surfaces (11).

full text;


Accessing transmissibility and diagnostic marker of skin prions. 

          
Case Western Reserve University, Cleveland, OH, United States


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.










APRIL-MAY 1989


In Confidence

Perceptions of unconventional slow virus diseases of animals in the USA 

- APRIL-MAY 1989 - 

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

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...


snip...see full text ;


Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle... 




The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province! ...page 26. 


2019

''due to lapse in federal funding, this USDA website will not be actively updated''

i refrain with great disgust and great fortitude from posting a political comment about this, God help me please...tss

Docket Management Docket: 02N-0273 - Substances Prohibited From Use inAnimal Food or Feed; Animal Proteins Prohibited in Ruminant FeedComment Number: EC -10Accepted - Volume 2


PART 2

http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be09.html

2003D-0186Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

EMC 7

01N-0423 Substances Prohibited from use in animal food/Feed Ruminant

APE 5 National Renderers Association, Inc. Vol#: 2APE 6 Animal Protein Producers Industry Vol#: 2APE 7 Darling International Inc. Vol#: 2EMC 1 Terry S. Singeltary Sr. Vol#: 3

http://www.fda.gov/ohrms/dockets/dailys/01/Oct01/101501/101501.htm

suppressed peer review of Harvard study October 31, 2002

http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006 

Greetings FSIS,


[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of BovineSpongiform Encephalopathy (BSE)

FSIS ET AL RESPONSE TO SINGELTARY


THE SEVEN SCIENTIST REPORT ***

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine
Spongiform Encephalopathy (BSE)

http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf

THE SEVEN SCIENTIST REPORT ***



9 December 2005 Division of Dockets Management (RFA-305)

SEROLOGICALS CORPORATION James J. Kramer, Ph.D. Vice President, Corporate Operations

http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000383-01-vol35.pdf

Embassy of Japan

http://www.fda.gov/ohrms/dockets/dockets/02n0273/02N-0273-EC240.htm

[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
03-025IFA 03-025IFA-2 Terry S. Singeltary Page 1 of 17 9/13/2005

http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf

THE 8/4/97 FAILED, partial, and voluntary, ruminant-to-ruminant feed ban was just that, and blaming it on the terrorist will not make it any better, and or handing out a million bucks in some bogus awarding program. IF they have not got it right by now, giving away a million bucks, or 100 million bucks will not solve the continued, blatant, disregard of the original partial and voluntary 8/4/97 mad cow feed ban. AS long as it is voluntary, the USA will still be feeding cows to cows, thus, the mad cow agent will continue to spread. i really don't understand this? it seems to be another fema-like pay out $$$ one million dollars, divided 4 ways, to award whom, for what ??? for something that was nothing more than ink on paper in the first place, something that was never enforced, and under the circumstances then and now, still cannot be enforced. ...

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

The goal of enhancing their feed/BSE safety programs is to increase State, territory, and tribal inspections under section 702 of the Federal Food, Drug, and Cosmetic Act (act) (21 U.S.C. 372) of renderers, protein blenders, and feed mills that manufacture animal feeds and feed ingredients, and inspections of salvagers of food and feed, and transporters of animal feed and feed ingredients utilizing materials prohibited under the ruminant feed ban. Finally, the Feed Ban Support Project funds are intended to supplement, not replace, State funding for program improvement. The following are seven key project areas identified for this effort: ...snip...end

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

WE are still floundering on mad cow feed regulations that were put in place in August of 1997. this is nothing more than a band aid approach to something that needs tourniquets. ...TSS

ON THE OTHER HAND, i tried to warn them about biological AND OR PRIONIC 'suitcase bombs' in 2002 ;

# Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of 2002; 

[TSS SUBMISSION ON POTENTIAL FOR BSE/TSE & FMD 'SUITCASE BOMBS'] -TSS 1/27/03 (0) 

Docket Management Docket: 02N-0276 - Bioterrorism Preparedness; Registration of FoodFacilities, Section 305 Comment Number: EC-254 [TSS SUBMISSION]

Subject: Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of 2002;Date: Mon, 27 Jan 2003 15:54:57 -0600From: "Terry S. Singeltary Sr." To: regulations@aphis.usda.gov
Docket No: 02-088-1

Title: Agricultural Bioterrorism Protection Act of 2002;Possession, Use, and Transfer of Biological Agents and Toxins

http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2002_register&docid=fr13de02-15.pdf

Greetings,

i would like to kindly submit to this docket and warn ofthe potential for biological 'suitcase bombs' from civilian air-traffic populations from known BSE/FMD and other exotic animal disease pathogens coming into the USA.

please be warned;

Date: Thu, 21 Mar 2002 08:42:56 -0800
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: USA SEALED BORDERS AND THE ''USCS'' (unspecified speciescoding system) MORE POTENTIAL B.S.eee

snip...see full text;


2015 APHIS SINGELTARY COMMENT BSE TSE PRION


THIS WAS MY FIRST SUBMISSION TO FEDERAL DOCKETS BACK IN 2001 ABOUT MAD COW DISEASE TO THE FDA, THIS STAYED ON THE WWW UNTIL THE YEAR 2018, IN WHICH IT WAS REMOVED $$$
Sent: Monday, January 08,2001 3:03 PM
TO: freas@CBS5055530.CBER.FDA.GOV
FDA CJD BSE TSE Prion Scientific Advisors and Consultants Staff January 2001 Meeting Singeltary Submission
2001 FDA CJD TSE Prion Singeltary Submission 
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
SEE FULL TEXT THAT FDA ET AL REMOVED FROM 2001;

TUESDAY, JUNE 5, 2018


Prion Scientific Advisors and Consultants Staff Meeting Singeltary Submission Freas Monday, January 08,2001 3:03 PM


PLEASE be aware, my submission here has now been removed from the www, or changed to a different url that no one knows now, and does not come up in search engines anymore, after 17 years...wonder why that could be, i guess the truth just hurt to much$$$


Freas, William

From: Terry S. Singeltary Sr. [flounder@wt.net]

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

TO: freas@CBS5055530.CBER.FDA.GOV

Subject: CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)

CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)

Greetings again Dr. Freas and Committee Members,

I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version).

I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:

remember AIDS/HIV, 'no problem to heterosexuals in the U.S.? no need to go into that, you know of this blunder:

DO NOT make these same stupid mistakes again with human/animal TSE's aka MADCOW DISEASE. I lost my Mom to hvCJD, and my neighbor lost his Mother to sCJD as well (both cases confirmed). I have seen many deaths, from many diseases. I have never seen anything as CJD, I still see my Mom laying helpless, jerking tremendously, and screaming "God, what's wrong with me, why can't I stop this". I still see this, and will never forget. Approximately 10 weeks from 1st of symptoms to death. This is what drives me. I have learned more in 3 years about not only human/animal TSE's but the cattle/rendering/feeding industry/government than i ever wished to.

I think you are all aware of CJD vs vCJD, but i don't think you all know the facts of human/animal TSE's as a whole, they are all very very similar, and are all tied to the same thing, GREED and MAN.

I am beginning to think that the endless attempt to track down and ban, potential victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually? AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, .eyelid test, anything at whatever cost, we need a test FAST.

DO NOT let the incubation time period of these TSEs fool you.

To think of Scrapie as the prime agent to compare CJD, but yet overlook the Louping-ill vaccine event in 1930's of which 1000's of sheep where infected by scrapie from a vaccine made of scrapie infected sheep brains, would be foolish. I acquired this full text version of the event which was recorded in the Annual Congress of 1946 National Vet. Med. Ass. of Great Britain and Ireland. from the BVA and the URL is posted in my (long version).

U.S.A. should make all human/animal TSE's notifiable at all ages, with requirements for a thorough surveillance and post-mortem examinations free of charge, if you are serious about eradicating this horrible disease in man and animal.

There is histopathology reports describing o florid plaques" in CJD victims in the USA and some of these victims are getting younger. I have copies of such autopsies, there has to be more. PLUS, sub-clinical human TSE's will most definitely be a problem.

THEN think of vaccineCJD in children and the bovine tissues used in the manufacturing process, think of the FACT that this agent surviving 6OO*C. PNAS -- Brown et al. 97 (7): 3418 scrapie agent live at 600*C

Then think of the CONFIDENTIAL documents of what was known of human/animal TSE and vaccines in the mid to late 80s, it was all about depletion of stock, to hell with the kids, BUT yet they knew. To think of the recall and worry of TSE's from the polio vaccine, (one taken orally i think?), but yet neglect to act on the other potential TSE vaccines (inoculations, the most effective mode to transmit TSEs) of which thousands of doses were kept and used, to deplete stockpile, again would be foolish.

--Oral polio; up to 1988, foetal calf serum was used from UK and New Zealand (pooled); since 1988 foetal calf serum only from New Zealand. Large stocks are held.

--Rubella; bulk was made before 1979 from foetal calf serum from UK and New Zealand. None has been made as there are some 15 years stock.

--Diphtheria; UK bovine beef muscle and ox heart is used but since the end of 1988 this has been sourced from Eire. There are 1,250 litres of stock.

--Tetanus; this involves bovine material from the UK mainly Scottish. There are 21,000 litres of stock.

--Pertussis; uses bovine material from the UK. There are 63,000 litres of stock. --They consider that to switch to a non-UK source will take a minimum of 6-18 months and to switch to a non-bovine source will take a minimum of five years.

3. XXXXXXXXXXX have measles, mumps, MMR, rubella vaccines. These are sourced from the USA and the company believes that US material only is used.

89/2.14/2.1

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

BSE3/1 0251

4. XXXXXXXXXXX have a measles vaccine using bovine serum from the UK. there are 440,000 units of stock. They have also got MMR using bovine serum from the UK.

5. XXXXXXXXXXX have influenza, rubella, measles,' MMR vaccines likely to be used in children. Of those they think that only MMR contains bovine material which is probably a French origin.

6. XXXXXXXXXXX have diphtheria/tetanus and potasses on clinical trial. hese use veal material, some of which has come from the UK and has been ade by XXXXXXXXXXX (see above).

I have documents of imports from known BSE Countries, of ferments, whole blood, antiallergenic preparations,

2 

human blood plasma, normal human blood sera, human immune blood sera, fetal bovine serum, and other blood fractions not elsewhere specified or included, imported glands, catgut, vaccines for both human/animal, as late as 1998. Let us not forget about PITUITARY EXTRACT. This was used to help COWS super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.

ANNEX 6

MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TO BIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIAL

How much of this was used in the U.S.?

Please do not keep making the same mistakes; 'Absence of evidence is not evidence of absence'.

What are the U.S. rules for importing and manufacturing vaccines, medicines and medical devices?

Does the U.S.A. allow sourcing of raw material of ruminants from the U.S.A.?

U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds? . The U.S. rendering system would easily amplify T.S.E.'s:

Have we increased the stability of the system (improved heat treatments) since the EU SSC report on the U.S.A. was published in july 2000?

What is done to avoid cross-contaminations in the U.S.A.?

How can the U.S. control absence of cross-contaminations of animal TSE's when pig and horse MBM and even deer and elk are allowed in ruminant feed, as well as bovine blood? I sadly think of the rendering and feeding policy before the Aug. 4, 1997 'partial' feed ban, where anything went, from the city police horse, to the circus elephant, i will not mention all the scrapie infected sheep. I am surprised that we have not included man 'aka soyent green'. It is a disgusting industry and nothing more than greed fuels it.

When will the U.S.. start real surveillance of the U.S. bovine population (not passive, this will not work)?

When will U.S. start removing SRMs?

Have they stopped the use of pneumatic stunners in the U.S.?

If so, will we stop it in all U.S. abattoirs or only in those abattoirs exporting to Europe?

If not, WHY NOT?

same questions for removal of SRM in the U.S.A., or just for export?

If not, WHY NOT?

How do we now sterilize surgical/dental instruments in the U.S.A.?

Where have we been sourcing surgical catgut?

(i have copies of imports to U.S., and it would floor you) hen will re-usable surgical instruments be banned?

'Unregulated "foods" such as 'nutritional supplements' containing various extracts from ruminants, whether imported or derived from

3 

US cattle/sheep/cervids ("antler velvet" extracts!) should be forbidden or at least very seriously regulated. (neighbors Mom, whom also died from CJD, had been taking bovine based supplement, which contained brain, eye, and many other bovine/ovine tissues for years, 'IPLEX').

What is the use of banning blood or tissue donors from Germany, France, etc... when the U.S.A. continues exposing cattle, sheep and people to SRM, refuses to have a serious feed ban, refuses to do systematic BSE-surveillance?

The FDA should feel responsible for the safety of what people eat, prohibit the most dangerous foods, not only prohibit a few more donors - the FDA should be responsible for the safe sourcing of medical devices, not only rely on banning donors "from Europe", The 'real' risks are here in the U.S. as well, and nave been for some time.

We must not forget the studies that have proven infectivity in blood from TSE's.

The Lancet, November 9, 1985

Sir, --Professor Manuelidis and his colleagues (Oct 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from, whole blood samples of a patient (and of mice) infected with CJD.l Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.

snip...

Samples,were taken aseptically at necropsy. 10% crude homogenates of brain and cornea in saline, whole blood (after crushing a clot), and untreated CSF and urine were innoculated intracerebrally into CFl strain mice (20 ul per animal). Some mice showed emaciation, bradykinesia, rigidity of the body and tail, and sometimes tremor after long incubation periods. Tissues obtained after the animal died (or was killed) were studied histologically (table). Animals infected by various inocula showed common pathological changes, consisting of severe spongiform changes, glial proliferation, and a moderate loss of nerve cells. A few mice inoculated with brain tissue or urine had the same amyloid plaques found in patients and animals with CJD.3

snip...

Department of Neuropathology,. Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka812, Japan JUN TATEISHI

(full text-long version)

and

CWD and transmission to man will be no different than other TSE's.

"Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has

4

caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs,"

G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O'Rourke3, L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M. Smits2 and B. Caughey1,7

or more recently transmission of BSE to sheep via whole blood Research letters Volume 356, Number 9234 16 September 2000

Transmission of BSE by blood transfusion in sheep

Lancet 2000; 356: 999 – 1000

F Houston, J D Foster, Angela Chong, N Hunter, C J Bostock

See Commentary

"We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) in human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission-- this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK."

"The demonstration that the new variant of Creutzfeldt-Jakob disease (vCJD) is caused by the same agent that causes bovine spongiform encephalopathy (BSE) in cattle1 has raised concerns that blood from human beings in the symptom-free stages of vCJD could transmit infection to recipients of blood transfusions (full text long version)"

and...

"The large number of cases (1040), temporal clustering of the outbreaks (15 in the first 6 months of 1997), the high in-flock incidence, and the exceptional involvement of goats (390 cases), suggested an accidental infection. The source of the epidemic might have been TSE-contaminated meat and bonemeal, but eight flocks had never been fed any commercial feedstuff. Infection might have risen from the use of a formol-inactivated vaccine against contagious agalactia prepared by a single laboratory with brain and mammary gland homogenates of sheep infected with Mycoplasma agalactiae. Although clinical signs of TSE in the donor sheep have not been found, it is possible that one or more of them were harbouring the

5

infectious agent. Between 1995 and 1996, this vaccine was given subcutaneously to 15 of the affected flocks (to one flock in 1994) ; in these animals the disease appeared between 23 and 35 months after vaccination. No information is available for herd 13 because it was made up of stolen animals. Sheep from the remaining three flocks (1-3, figure) did not receive the vaccine, thus suggesting a naturally occurring disease.’’ (again, full text long version).

IN SHORT, please do under estimate this data and or human/animal TSE's including CWD in the U.S.A.

A few last words, please.

The cattle industry would love to have us turn our focus to CWD and forget about our own home grown TSE in Bovines. This would be easy to do. Marsh's work was from downer cattle feed, NOT downer deer/elk feed. This has been proven.

DO NOT MAKE THAT MISTAKE.

There should be NO LESS THAN 1,000,000 tests for BSE/TSE ' in 2001 for U.S.A. French are testing 20,000 a week. The tests are available. Why wait until we stumble across a case from passive surveillance, by then it is to late. IF we want the truth, this is a must???

United States Total ,Bovine Brain Submissions by State,

May 10 ,1990 thru October 31, 2000

Total 11,700

FROM 1.5 BILLION HEAD OF CATTLE since 1990 ???

with same feeding and rendering practices as that of U.K. for years and years, same scrapie infected sheep used in feed, for years and years, 950 scrapie infect FLOCKS in the U.S. and over 20 different strains of scrapie known to date. (hmmm, i am thinking why there is not a variant scrapie, that is totally different than all the rest)? just being sarcastic.

with only PARTIAL FEED BAN implemented on Aug. 4, 1997??? (you really need to reconsider that blood meal etc. 'TOTAL BAN')

http://www.aphis.usda.gov/oa/bse/bsesurv,ey.html#charts

AND PLEASE FOR GODS SAKE, STOP saying vCJD victims are the only ones tied to this environmental death sentence. "PROVE IT". It's just not true. The 'CHOSEN ONES' are not the only ones dying because of this man-made death sentence. When making regulations for human health from human/animal TSEs, you had better include ALL human TSE's, not just vCJD. Do NOT underestimate sporadic CJD with the 'prehistoric' testing available to date. This could be a deadly mistake. Remember, sCJD kills much faster from 1st onset of symptoms to death, and hvCJD is the fastest. Could it just be a higher titre of infectivity, or route or source, or all three?

Last, but not least. The illegal/legal harvesting of body parts and tissues will come back to haunt you. Maybe not morally, but due to NO background checks and human TSEs, again it will continue to spread.

Stupidity, Ignorance and Greed is what fuels this disease. You must stop all of this, and ACT AT ONCE...

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

TO: freas@CBS5055530.CBER.FDA.GOV

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

2001 FDA CJD TSE Prion Singeltary Submission


i wonder if the Government FDA et al, or whom ever removed my submission to fda from 2001 from the www after 17 years, where most every thing i said has come true, i wonder if the government wonders by removing my submission they will change the science and the truth? 


reasons for Government FDA removal of Singeltary Submission materials to federal dockets;








Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de



*** remember what deep throat told me long ago ;

DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ....tss)

The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why????than the UK....then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......

I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie 

Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes......well it takes a whole lot longer if you whine for a year and then start the research!!! 

Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year........it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....

Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!

And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...

Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"

again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.

You need to watch your back.........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.) 

END...TSS 

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006 


2018

FRIDAY, DECEMBER 14, 2018 

MAD COW USA FLASHBACK FRIDAY DECEMBER 14, 2018


***>2018 TSE PRION WARNING<***

***> RUMINANT MAMMALIAN FEED BAN BSE TSE PRION

***> WARNING, WARNING, WARNING

***> UPDATE 2018 CWD AND SCRAPIE TRANSMITS TO PIGS ORALLY

***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <*** 

 >*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <*** 

***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" oral="">6 months group.. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). 

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. 

***> This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. 

***> Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains. 

>>>> The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans.





MONDAY, NOVEMBER 26, 2018 

***>The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...


we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.


Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....


5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products for injection or surgical implantation which are prepared from bovine tissues, or which utilise bovine serum albumin or similar agents in their manufacture, might also be capable of transmitting infectious agents. All medicinal products are licensed under the Medicines Act by the Licensing Authority following guidance, for example from the Committee on Safety of Medicines (CSM), the Committee on Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing Authority have been alerted to potential concern about BSE in medicinal products and will ensure that scrutiny of source materials and manufacturing processes now takes account of BSE agent. 


see new url...tss


snip...see much more here ;

WEDNESDAY, APRIL 05, 2017

Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease




TUESDAY, OCTOBER 17, 2017 

EFSA asked to review risk from processed animal proteins in feed PIG PAP and CWD TSE Prion Oral Transmission


***> PRION CONFERENCE 2018 <***

O3 Experimental studies on prion transmission barrier and TSE pathogenesis in large animals 

Rosa Bolea(1), Acín C(1)Marín B(1), Hedman C(1), Raksa H(1), Barrio T(1), Otero A(1), LópezPérez O(1), Monleón E(1),Martín-Burriel(1), Monzón M(1), Garza MC(1), Filali H(1),Pitarch JL(1), Garcés M(1), Betancor M(1), GuijarroIM(1), GarcíaM(1), Moreno B(1),Vargas A(1), Vidal E(2), Pumarola M(2), Castilla J(3), Andréoletti O(4), Espinosa JC(5), Torres JM(5), Badiola JJ(1). 

1Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, VeterinaryFaculty, Universidad de Zaragoza; Zaragoza,Spain.2 RTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) 3 4 INRA, ÉcoleVétérinaire, Toulouse, France.5CIC bioGUNE, Prion researchlab, Derio, Spain CISA- INIA, Valdeolmos, Madrid 28130, Spain. 

Experimental transmission of Transmissible Spongiform Encephalopathies (TSE) has been understood and related with several factors that could modify the natural development of these diseases. In fact, the behaviour of the natural disease does not match exactly in each animal, being modified by parameters such as the age at infection, the genotype, the breed or the causative strain. Moreover, different TSE strains can target different animal species or tissues, what complicate the prediction of its transmissibility when is tested in a different species of the origin source. The aim of the experimental studies in large animals is to homogenize all those factors, trying to minimize as much as possible variations between individuals. These effects can be flattened by experimental transmission in mice, in which a specific strain can be selected after several passages. With this objective, several experimental studies in large animals have been developed by the presenter research team. 

Classical scrapie agent has been inoculated in cow, with the aim of demonstrate the resistance or susceptibility of this species to the first well known TSE; Atypical scrapie has been inoculated in sheep (using several routes of infection), cow and pig, with the objective of evaluating the potential pathogenicity of this strain; Classical Bovine Spongiform Encephalopathy (BSE) has been inoculated in goats aiming to demonstrate if the genetic background of this species could protect against this strain; goat BSE and sheep BSE have been inoculated in goats and pigs respectively to evaluate the effect of species barrier; and finally atypical BSE has been inoculated in cattle to assess the transmissibility properties of this newly introduced strain. 

Once the experiments have been carried out on large animal species, a collection of samples from animals studied were inoculated in different types of tg mice overexpressing PrPcin order to study the infectivity of the tissues, and also were studied using PMCA. 

In summary, the parameters that have been controlled are the species, the strain, the route of inoculation, the time at infection, the genotype, the age, and the environmental conditions. 

To date, 

***> eleven of the atypical scrapie intracerebrally inoculated sheep have succumbed to atypical scrapie disease; 

***> six pigs to sheep BSE; 

***> one cow to classical scrapie; 

***> nine goats to goat BSE and 

***> five goats to classical BSE. 

***> PrPSC has been demonstrated in all cases by immunohistochemistry and western blot. 

=====> PRION CONFERENCE 2018 


Prion Conference 2018

O5 Prion Disease in Dromedary Camels 

Babelhadj B (1), Di Bari MA (2), Pirisinu L (2), Chiappini B (2), Gaouar SB (3), Riccardi G (2), Marcon S (2), Agrimi U (2), Nonno R (2), Vaccari G (2) (1) École Normale Supérieure Ouargla. Laboratoire de protection des écosystèmes en zones arides et semi arides University Kasdi Merbah Ouargla, Ouargla, Algeria; (2) Istituto Superiore di Sanità, Department of Food Safety, Nutrition and Veterinary Public Health, Rome, Italy (3) University Abou Bekr Bélkaid, Tlemcen, Algeria. 

Prions are responsible for fatal and transmissible neurodegenerative diseases including CreutzfeldtJakob disease in humans, scrapie in small ruminants and bovine spongiform encephalopathy (BSE). Following the BSE epidemic and the demonstration of its zoonotic potential, general concerns have been raised on animal prions. 

Here we report the identification of a prion disease in dromedary camels (Camelus dromedarius) in Algeria and designate it as Camel Prion Disease (CPD). In the last years, neurological symptoms have been observed in adult male and female dromedaries presented for slaughter at the Ouargla abattoir. The symptoms include weight loss, behavioral abnormalities and neurological symptoms such as tremors, aggressiveness, hyper-reactivity, typical down and upwards movements of the head, hesitant and uncertain gait, ataxia of the hind limbs, occasional falls and difficult getting up. During 2015 and 2016, symptoms suggestive of prion disease were observed in 3.1% of 2259 dromedaries presented at ante-mortem examination. Laboratory diagnosis was obtained in three symptomatic dromedaries, sampled in 2016 and 2017, by the detection of typical neurodegeneration and disease-specific prion protein (PrPSc) in brain tissues. 

Histopathological examination revealed spongiform change, gliosis and neuronal loss preferentially in grey matter of subcortical brain areas. Abundant PrPSc deposition was detected in the same brain areas by immunohistochemistry and PET-blot. Western blot analysis confirmed the presence of PK-resistant PrPSc, whose N-terminal cleaved PK-resistant core was characterized by a mono-glycosylated dominant form and by a distinctive N-terminal cleavage, different from that observed in BSE and scrapie. 

PrPSc was also detected, by immunohistochemistry, in all sampled lymph nodes (cervical, prescapular and lumbar aortic) of the only animal from which they were collected. 

The PRNP sequence of the two animals for which frozen material was available, showed 100% nucleotide identity with the PRNP sequence already reported for dromedary camel. 

Overall, these data demonstrate the presence of a prion disease in dromedary camelswhose nature, origin and spread need further investigations. However, our preliminary observations on the rather high prevalence of symptomatic dromedaries and the involvement of lymphoid tissues, are consistent with CPD being an infectious disease. In conclusion, the emergence of a new prion disease in a livestock species of crucial importance for millions of people around the world, makes urgent to assess the risk for humans and to develop policies able to control the spread of the disease in animals and to minimize human exposure. 


CDC

New Outbreak of TSE Prion in NEW LIVESTOCK SPECIES

Mad Camel Disease

Volume 24, Number 6—June 2018 Research 

Prion Disease in Dromedary Camels, Algeria

Abstract

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

SNIP...

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

Tracing the origin of prion diseases is challenging. In the case of CPD, the traditional extensive and nomadic herding practices of dromedaries represent a formidable factor for accelerating the spread of the disease at long distances, making the path of its diffusion difficult to determine. Finally, the major import flows of live animals to Algeria from Niger, Mali, and Mauritania (27) should be investigated to trace the possible origin of CPD from other countries.
Camels are a vital animal species for millions of persons globally. The world camel population has a yearly growth rate of 2.1% (28). In 2014, the population was estimated at ≈28 million animals, but this number is probably underestimated.. Approximately 88% of camels are found in Africa, especially eastern Africa, and 12% are found in Asia. Official data reported 350,000 dromedaries in Algeria in 2014 (28).
On the basis of phenotypic traits and sociogeographic criteria, several dromedary populations have been suggested to exist in Algeria (29). However, recent genetic studies in Algeria and Egypt point to a weak differentiation of the dromedary population as a consequence of historical use as a cross-continental beast of burden along trans-Saharan caravan routes, coupled with traditional extensive/nomadic herding practices (30).
Such genetic homogeneity also might be reflected in PRNP. Studies on PRNP variability in camels are therefore warranted to explore the existence of genotypes resistant to CPD, which could represent an important tool for CPD management as it was for breeding programs for scrapie eradication in sheep.
In the past 10 years, the camel farming system has changed rapidly, with increasing setup of periurban dairy farms and dairy plants and diversification of camel products and market penetration (13). This evolution requires improved health standards for infectious diseases and, in light of CPD, for prion diseases.
The emergence of another prion disease in an animal species of crucial importance for millions of persons worldwide makes it necessary to assess the risk for humans and develop evidence-based policies to control and limit the spread of the disease in animals and minimize human exposure. The implementation of a surveillance system for prion diseases would be a first step to enable disease control and minimize human and animal exposure. Finally, the diagnostic capacity of prion diseases needs to be improved in all countries in Africa where dromedaries are part of the domestic livestock.

***> IMPORTS AND EXPORTS <***

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


TUESDAY, APRIL 18, 2017 

*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***


USA MAD COW CASE 2018 FLORIDA

WEDNESDAY, SEPTEMBER 26, 2018 

JAVMA In Short Update USDA announces detection of atypical BSE


 WEDNESDAY, SEPTEMBER 26, 2018

JAVMA In Short Update USDA announces detection of atypical BSE

-----Original Message----- 
From: Terry Singeltary 
To: bse-l 
Cc: vlc ; medialibrary ; DBanasiak ; rvalentine ; llien ; jhorvath ; kbrandt ; agonda ; DBanasiak ; AVMAinfo 
Sent: Wed, Sep 26, 2018 11:10 am 
Subject: JAVMA In Short Update USDA announces detection of atypical BSE

USDA announces detection of atypical BSE

On Aug. 29, the Department of Agriculture announced an atypical case of bovine spongiform encephalopathy in a 6-year-old mixed-breed beef cow in Florida. The animal was never brought to slaughter. The National Veterinary Services Laboratories of the USDA Animal and Plant Health Inspection Service confirmed that the cow tested positive for atypical H-type BSE. The animal was initially tested at the Colorado State University Veterinary Diagnostic Laboratory as part of routine surveillance of cattle that are deemed unsuitable for slaughter. Of the five previous U.S. cases of BSE, the first was a case of classical BSE in a cow imported from Canada. The primary source of infection for classical BSE is feed contaminated with the infectious prion agent. The rest of the cases were atypical BSE, which seems to arise rarely and spontaneously in all cattle populations.


''Atypical BSE is different, and it generally occurs in older cattle, usually 8 years of age or greater. It seems to arise rarely and spontaneously in all cattle populations.''

FALSE!

''The primary source of infection for classical BSE is feed contaminated with the infectious prion agent, such as meat-and-bone meal containing protein derived from rendered infected cattle. Regulations from the Food and Drug Administration (FDA) have prohibited the inclusion of mammalian protein in feed for cattle and other ruminants since 1997 and have also prohibited high risk tissue materials in all animal feed since 2009.''

FALSE!

oh what webs of deceit we weave, when all we do is practice to deceive $$$

LET'S REVIEW RECENT AND PAST SCIENCE THAT SHOWS THE ABOVE TWO STATEMENTS ARE FAR FROM TRUE;

PRION 2018 CONFERENCE

P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge 

Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States. 

reading up on this study from Prion 2018 Conference, very important findings ;

***> This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. 

***> These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.

PRION 2018 CONFERENCE ABSTRACT



WEDNESDAY, OCTOBER 24, 2018 

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



MONDAY, JANUARY 09, 2017 

Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle 

CDC Volume 23, Number 2—February 2017 

*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.

*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.


TUESDAY, AUGUST 28, 2018 

USDA finds BSE infection in Florida cow 08/28/18 6:43 PM


WEDNESDAY, AUGUST 29, 2018 

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT


WEDNESDAY, AUGUST 29, 2018 

Transmissible Spongiform Encephalopathy TSE Prion Atypical BSE Confirmed Florida Update USA August 28, 2018


WEDNESDAY, AUGUST 29, 2018 

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

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

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

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


THURSDAY, AUGUST 30, 2018 

Florida Department of Agriculture and Consumer Services announced it is working closely with U.S. Department of Agriculture regarding an atypical case of Bovine Spongiform Encephalopathy BSE


THURSDAY, AUGUST 30, 2018 

TRACKING HERD MATES USDA MAD COW DISEASE, TRACE FORWARD, TRACE BACK RECORDS, WHO CARES, NOT THE OIE


USDA ONLY TESTING 20k HEAD OF CATTLE A YEAR FOR MAD COW DISEASE ...LOL!

WEDNESDAY, AUGUST 29, 2018 

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT





WEDNESDAY, AUGUST 29, 2018 

***> USDA DROPS MAD COW TESTING FROM 40K A YEAR TO JUST 20K A YEAR, IMPOSSIBLE TO FIND BSE, BUT THEY DID, IN FLORIDA!


Saturday, July 23, 2016

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


Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016


Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program


THURSDAY, NOVEMBER 01, 2018 

***> National Scrapie Eradication Program September 2018 Monthly Report Fiscal Year 2018 October 15, 2018


***> P.108: Successful oral challenge of adult cattle with classical BSE

Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge; Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology Laboratory; Truro, Nova Scotia, Canada

Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and food-borne fatal neurological disease which can be orally transmitted to cattle and humans. Due to the presence of contaminated milk replacer, it is generally assumed that cattle become infected early in life as calves and then succumb to disease as adults. Here we challenged three 14 months old cattle per-orally with 100 grams of C-type BSE brain to investigate age-related susceptibility or resistance. During incubation, the animals were sampled monthly for blood and feces and subjected to standardized testing to identify changes related to neurological disease. At 53 months post exposure, progressive signs of central nervous system disease were observed in these 3 animals, and they were euthanized. Two of the C-BSE animals tested strongly positive using standard BSE rapid tests, 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. 

***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. 

We are further examining explanations for the unusual disease presentation in the third challenged animal.


***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.

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama

National Institute of Animal Health; Tsukuba, Japan

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, 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.


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

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

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

Keywords: Atypical BSE, oral transmission, RT-QuIC

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

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

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





Detection of PrPBSE and prion infectivity in the ileal Peyer’s patch of young calves as early as 2 months after oral challenge with classical bovine spongiform encephalopathy 

Ivett Ackermann1 , Anne Balkema‑Buschmann1 , Reiner Ulrich2 , Kerstin Tauscher2 , James C. Shawulu1 , Markus Keller1 , Olanrewaju I. Fatola1 , Paul Brown3 and Martin H. Groschup1* 

Abstract 

In classical bovine spongiform encephalopathy (C-BSE), an orally acquired prion disease of cattle, the ileal Peyer’s patch (IPP) represents the main entry port for the BSE agent. In earlier C-BSE pathogenesis studies, cattle at 4–6 months of age were orally challenged, while there are strong indications that the risk of infection is highest in young animals. In the present study, unweaned calves aged 4–6 weeks were orally challenged to determine the earli‑ est time point at which newly formed PrPBSE and BSE infectivity are detectable in the IPP. For this purpose, calves were culled 1 week as well as 2, 4, 6 and 8 months post-infection (mpi) and IPPs were examined for BSE infectivity using a bovine PrP transgenic mouse bioassay, and for PrPBSE by immunohistochemistry (IHC) and protein misfolding cyclic amplifcation (PMCA) assays. For the frst time, BSE prions were detected in the IPP as early as 2 mpi by transgenic mouse bioassay and PMCA and 4 mpi by IHC in the follicular dendritic cells (FDCs) of the IPP follicles. These data indi‑ cate that BSE prions propagate in the IPP of unweaned calves within 2 months of oral uptake of the agent.

In summary, our study demonstrates for the frst time PrPBSE (by PMCA) and prion infectivity (by mouse bioassay) in the ileal Peyer’s patch (IPP) of young calves as early as 2 months after infection. From 4 mpi nearly all calves showed PrPBSE positive IPP follicles (by IHC), even with PrPBSE accumulation detectable in FDCs in some animals. Finally, our results confrm the IPP as the early port of entry for the BSE agent and a site of initial propagation of PrPBSE and infectivity during the early pathogenesis of the disease. Terefore, our study supports the recommendation to remove the last four metres of the small intestine (distal ileum) at slaughter, as designated by current legal requirements for countries with a controlled BSE risk status, as an essential measure for consumer and public health protection.


A study comparing preclinical cattle infected naturally with BSE to clinically affected cattle either naturally or experimentally infected with BSE by the oral route found the most abundant PrPSc in the brainstem area (39), which is consistent with ascension to the brain from the gut by sympathetic and parasympathetic projections (40). In our experiment, abundant prions were observed in the brainstem of cattle with clinical signs of BSE, which is similar to the amount in their thalamus or midbrain regions. Interestingly, prions in the brainstem of cattle with clinical evidence of BSE seeded the RT-QuIC reactions faster than any other brain region despite the brainstem area having lower EIA OD values (Table 2) in comparison to other brain regions. This suggests that higher concentrations of prions do not necessarily seed the reaction faster. Perhaps prions of the brainstem exist in a preferred conformation for better conversion despite being present in lower concentrations.

snip... 


TUESDAY, NOVEMBER 02, 2010 

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992


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


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

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

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

see page 176 of 201 pages...tss


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



ZOONOSIS OF SCRAPIE TSE PRION

 O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

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

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

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

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

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

=============== 

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

=============== 

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

============== 



***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. 


PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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

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

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

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

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

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

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

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

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

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

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

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

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

snip...

R. BRADLEY



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. 



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

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

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

Abstract 

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

SNIP...

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

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

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

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

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

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

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

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

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

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


Singeltary on Scrapie and human transmission way back, see;


FRIDAY, NOVEMBER 30, 2018 

The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSEs) in 2017


***> 2018 URGENT DATA <***


***2018***

Cervid to human prion transmission 

Kong, Qingzhong 

Case Western Reserve University, Cleveland, OH, United States

Abstract 

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

We hypothesize that: 

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

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

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

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

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

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

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

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

Public Health Relevance

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

 Funding Agency

Agency

National Institute of Health (NIH)

Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Type

Research Project (R01)

Project #

5R01NS088604-04

Application #

9517118

Study Section

Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

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

 Related projects

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

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

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

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


ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

here is the latest;

PRION 2018 CONFERENCE 

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

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

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

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

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

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

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

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


READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ; 

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

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

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

AND ANOTHER STUDY; 

P172 Peripheral Neuropathy in Patients with Prion Disease 

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

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

AND 

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

AND 

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

snip...see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below...terry 



just out CDC...see;

Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions 

Marcelo A. Barria

Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell) M. A. Barria et al. 

ABSTRACT 

Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. 

We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted. 


Molecular Barriers to Zoonotic Transmission of Prions 

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

snip... 

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

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

snip... 

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

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


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 



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

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

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

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

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

also, see; 

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

snip... 

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


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

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


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

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

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

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

Summary and Recommendation: 

snip...

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

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


*** 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 


THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update


FRIDAY, DECEMBER 28, 2018 

Chronic Wasting Disease CWD TSE Prion 2019 Where The Rubber Meets The Road 


SUNDAY, DECEMBER 09, 2018 

Creutzfeldt Jakob Disease CJD, BSE, Scrapie, CWD, TSE Prion Annual Report December 14, 2018


Sunday, December 9, 2018 

Variable Protease-Sensitive Prionopathy Transmission to Bank Voles CDC Volume 25, Number 1—January 2019


Saturday, December 15, 2018

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


TUESDAY, JANUARY 1, 2019 

CHILDHOOD EXPOSURE TO CADAVERIC DURA 



Terry S. Singeltary Sr.

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