Thursday, December 08, 2016

TEXAS TAHC confirmed Chronic Wasting Disease (CWD) in a free-ranging elk Dallam County

Media Contacts: Callie Ward, Texas Animal Health Commission, 512-719-0743, callie.ward@tahc.texas.gov; Steve Lightfoot, Texas Parks & Wildlife Department, 512-389-4701, steve.lightfoot@tpwd.texas.gov


FOR IMMEDIATE RELEASE December 8, 2016

    Dallam County Elk Tests Positive for  Chronic Wasting Disease

Austin, TX – Texas Animal Health Commission (TAHC) officials confirmed Chronic Wasting Disease (CWD) in a free-ranging elk, harvested in Dallam County, on December 6, 2016. This is the first known elk in Texas to test positive for CWD.

TAHC and Texas Parks and Wildlife Department (TPWD) discovered the CWD positive elk while conducting enhanced surveillance of cervids at TPWD Panhandle Containment Zone check stations. The National Veterinary Services Laboratory in Ames, Iowa confirmed the presence of CWD prions in the tissue samples taken from the elk. Dallam County is located in the Texas Panhandle and borders Oklahoma and New Mexico. 

“We commend all hunters and land owners who are submitting samples in the surveillance zone,” said Dr. Andy Schwartz, TAHC Executive Director. “Surveillance is critical in detecting and preventing the inadvertent spread of CWD.”

Hunters who harvest mule deer or white-tailed deer within the Trans-Pecos and Panhandle CWD Containment and Surveillance Zones are required by TPWD to bring their animals to a TPWD check station within 24 hours of harvest. You can find a check station near you at http://tpwd.texas.gov/huntwild/wild/diseases/cwd/#checkMap.

CWD has been found in free-ranging elk across the United States, including the neighboring states of New Mexico and Colorado.

CWD was first recognized in 1967 in captive mule deer in Colorado. The first case of CWD in Texas was discovered in 2012 in free-ranging mule deer in an isolated area of far West Texas. The disease has since been detected in a total of 8 mule deer in that West Texas population located in the Hueco Mountains and 1 mule deer in Hartley County. CWD has also been confirmed in white-tailed deer breeding operations located in Medina and Lavaca counties.
 CWD is a progressive, fatal disease of cervids that commonly results in altered behavior as a result of microscopic changes made to the brain of affected animals. An animal may carry the disease for years without outward indication, but in the latter stages, signs may include listlessness, lowering of the head, weight loss, repetitive walking in set patterns, and a lack of responsiveness. To date there is no evidence that CWD poses a risk to humans or non-cervids. However, as a precaution, the U.S. Centers for Disease Control and the World Health Organization recommend not to consume meat from infected animals. 
###

Saturday, December 03, 2016


TEXAS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE 35 CASES TO DATE


Wednesday, December 07, 2016


Student Assistant (Temporary) – Chronic Wasting Disease: Texas A&M Veterinary Medical Diagnostic Laboratory


http://chronic-wasting-disease.blogspot.com/2016/12/student-assistant-temporary-chronic.html


 *** 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

http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf


PRION 2016 TOKYO

Zoonotic Potential of CWD Prions: An Update

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

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

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

http://prion2016.org/dl/newsletter_03.pdf


Cervid to human prion transmission

Kong, Qingzhong

Case Western Reserve University, Cleveland, OH, United States

Abstract

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

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

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

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

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

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

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

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

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

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

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Neurological Disorders and Stroke (NINDS)

Type Research Project (R01)

Project # 1R01NS088604-01A1

Application # 9037884

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

Project Start 2015-09-30

Project End 2019-07-31

Budget Start 2015-09-30

Budget End 2016-07-31

Support Year 1

Fiscal Year 2015

Total Cost $337,507

Indirect Cost $118,756

Institution

Name Case Western Reserve University

Department Pathology

Type Schools of Medicine

DUNS # 077758407

City Cleveland

State OH

Country United States

Zip Code 44106

http://grantome.com/grant/NIH/R01-NS088604-01A1

Monday, May 02, 2016

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

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

 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

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf


http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160


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

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

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html

Wednesday, November 09, 2016
Norway and Finland Rule Changes for importation and exportation of deer to limit the spread of skrantesjuke (CWD)
Title: Pathological features of chronic wasting disease in reindeer and demonstration of horizontal transmission


Monday, September 05, 2016

Pathological features of chronic wasting disease in reindeer and demonstration of horizontal transmission Major Findings for Norway


Thursday, September 22, 2016

NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke


SUNDAY, OCTOBER 02, 2016

*** What is the risk of a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk Assessment September 2016


Wednesday, September 7, 2016

*** An assessment of the long-term persistence of prion infectivity in aquatic environments


Friday, September 02, 2016

*** Chronic Wasting Disease Drives Population Decline of White-Tailed Deer


*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3


Monday, December 5, 2016

Prion Institute protein folding and misfolding; pathobiology of TSEs; surveillance, control; and TSEs


Thursday, December 1, 2016

PRION2017 DECIPHERING NEURODEGENERATIVE DISORDERS 23 – 26 May 2017 Edinburgh



kind regards, terry

Wednesday, December 07, 2016

Student Assistant (Temporary) – Chronic Wasting Disease: Texas A&M Veterinary Medical Diagnostic Laboratory

Student Assistant (Temporary) – Chronic Wasting Disease: Texas A&M Veterinary Medical Diagnostic Laboratory


Agency

Texas A&M Veterinary Medical Diagnostic Laboratory

Location

College Station, TX

Job Category

Student Employment at A&M

Website

http://tvmdl.tamu.edu/

Salary

$7.25/hour

Start Date

12/05/2016

Last Date to Apply

12/16/2016

Description

Texas A&M Veterinary Medical Diagnostic Laboratory (TVMDL), a global leader in providing innovative and state-of-the-art veterinary diagnostic services, is looking for a Student Worker to join its team. TVMDL’s Serology section in College Station is looking for an individual with a passion for performing bench-top laboratory work as part of state-wide surveillance efforts to assess wildlife health. The incumbent will have the opportunity to learn how to process tissues harvested from cervid species (e.g. deer and elk) as part of ongoing chronic wasting disease (CWD) surveillance efforts in Texas. This position is temporary (up to 6 months), and will provide a meaningful boost to TVMDL’s CWD testing capabilities during the peak Texas hunting season. Student worker hours are capped at part-time during the semester; however additional hours (up to full-time) are available during the winter break. Immediate availability for the maximum number of hours is preferred. Rabies vaccination is required for work with fresh mammalian tissue (vaccination series will be provided by TVMDL, though previous vaccination is a plus).
TVMDL’s Serology section performs a high volume of tests and offers over 50 different assays to provide valuable diagnostic services to veterinary clients around the world. The incumbent will be part of a specialized team whose goal is to provide high-volume testing for CWD surveillance programs conducted by various state and federal agencies. This will involve precise processing of fresh lymph node and/or obex tissues for testing via an enzyme-linked immunosorbent assay (ELISA) that has been well-validated for detection of CWD. Performance of this task in adherence to standard operating procedures is of utmost importance, and thorough training will be provided. Safe operation and maintenance of laboratory equipment is paramount to this position, as is maintaining a safe, clean, and professional working environment. As such, the incumbent will actively participate in quality assurance, safety, and training programs, and communicate well to foster a cooperative, teamwork-oriented environment. This opportunity is ideal for someone who is a quick learner and has a passionate interest in veterinary/wildlife medicine. In addition to the specific techniques listed above, the incumbent may also have the opportunity to learn additional assays and techniques with the goal of providing continued service to TVMDL clientele when other technicians are absent.

THIS IS A SECURITY SENSITIVE POSITION; THEREFORE, A CRIMINAL BACKGROUND CHECK WILL BE PERFORMED ON THE FINAL CANDIDATE.

*** TAMU Parking hangtags are required to park in the TVMDL lot. If you do not have a parking hangtag or only have a night permit, you will need to find an alternate method of getting to work; i.e., walking, taking the bus, riding a bike, etc.***

Qualifications

High school diploma or equivalent. Must be quick thinking, decisive, punctual, and dependable. Candidate will be required to take pre-exposure rabies vaccination series (TVMDL will cover all costs).

Apply at http://jobsforaggies.tamu.edu/ or email resume to Carlos Rodriguez, Veterinary Diagnostic Laboratory Supervisor, at crodriguez@tvmdl.tamu.edu.

Start date below is approximate; we are looking to fill this position ASAP (i.e. over the winter break).

Contact Person

Carlos Rodriguez

Contact Phone

979-458-9130

Contact eMail


Saturday, December 03, 2016

TEXAS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE 35 CASES TO DATE

CWD Positives in Texas

CWD Positive
Year Confirmed
CWD Positve
Confirmation Date
Free Range / CaptiveCountySourceSpeciesSexAge
20169/21/2016Breeder Deer - ReleasedMedinaFacility #3white-tailed deerM3.5
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF1
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerM1
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF1
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerM1
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20166/29/2016Breeder DeerMedinaFacility #4white-tailed deerF4
20164/13/2016Breeder DeerLavacaFacility #2white-tailed deerM3
20164/13/2016Breeder DeerLavacaFacility #2white-tailed deerM3
20164/13/2016Breeder DeerLavacaFacility #2white-tailed deerM3
20164/13/2016Breeder DeerLavacaFacility #2white-tailed deerM3
20164/1/2016Breeder DeerMedinaFacility #4white-tailed deerF4.5
20163/29/2016Breeder DeerMedinaFacility #3white-tailed deerM3
20153/25/2016Free RangeHartleyMule DeerM3.5
20153/18/2016Free RangeHudspethMule DeerM5.5
20162/4/2016Breeder Deer - ReleasedMedinaFacility #3white-tailed deerM3



CWD Positive
Year Confirmed
CWD Positve
Confirmation Date
Free Range / CaptiveCountySourceSpeciesSexAge
20159/14/2015Breeder DeerLavacaFacility #2white-tailed deerM3
20158/12/2015Breeder DeerMedinaFacility #1white-tailed deerM2.5
20158/6/2015Breeder DeerMedinaFacility #1white-tailed deerM2.5
20158/6/2015Breeder DeerMedinaFacility #1white-tailed deerM2.5
20156/30/2015Breeder DeerMedinaFacility #1white-tailed deerM2.5
201412/4/2014Free RangeHudspethMule DeerM4.5
201212/28/2012Free RangeHudspethMule DeerM3.5
201212/1/2012Free RangeHudspethMule DeerM4.5
201212/2/2012Free RangeHudspethMule DeerM5.5
201212/10/2012Free RangeHudspethMule DeerM4.5
20127/12/2012Free RangeHudspethMule DeerF6.5
20127/12/2012Free RangeHudspethMule DeerF4.5



CWD National Map



Horizontal Transmission of Chronic Wasting Disease in Reindeer CDC Volume 22, Number 12—December 2016


Sunday, November 13, 2016

Horizontal Transmission of Chronic Wasting Disease in Reindeer CDC Volume 22, Number 12—December 2016


Wednesday, November 09, 2016

Norway and Finland Rule Changes for importation and exportation of deer to limit the spread of skrantesjuke (CWD)



Wednesday, November 09, 2016

Chronic Wasting Disease (CWD) Program Standards - Review and Comment By Terry S Singeltary Sr. November 9, 2016



Friday, November 18, 2016

IMPORTANT: SAWCorp CWD Test is NOT APHIS Approved


Monday, July 18, 2016

Texas Parks Wildlife Dept TPWD HIDING TSE (CWD) in Deer Herds, Farmers Sampling Own Herds, Rapid Testing, False Negatives, a Recipe for Disaster


http://chronic-wasting-disease.blogspot.com/2016/07/texas-parks-wildlife-dept-tpwd-hiding.html

Friday, July 01, 2016



TEXAS Thirteen new cases of chronic wasting disease (CWD) were confirmed at a Medina County captive white-tailed deer breeding facility on June 29, 2016

http://chronic-wasting-disease.blogspot.com/2016/07/texas-thirteen-new-cases-of-chronic.html

Wednesday, May 04, 2016
TPWD proposes the repeal of §§65.90 -65.94 and new §§65.90 -65.99 Concerning Chronic Wasting Disease - Movement of Deer Singeltary Comment Submission


Saturday, April 02, 2016

TEXAS TAHC BREAKS IT'S SILENCE WITH TWO MORE CASES CWD CAPTIVE DEER BRINGING TOTAL TO 10 CAPTIVES REPORTED TO DATE

http://chronic-wasting-disease.blogspot.com/2016/04/texas-tahc-breaks-its-silence-with-two.html
Friday, February 26, 2016

TEXAS Hartley County Mule Deer Tests Positive for Chronic Wasting Disease CWD TSE Prion

http://chronic-wasting-disease.blogspot.com/2016/02/texas-hartley-county-mule-deer-tests.html

Friday, April 22, 2016

*** Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer


Friday, February 05, 2016

TEXAS NEW CHRONIC WASTING DISEASE CWD CASE DISCOVERD AT CAPTIVE DEER RELEASE SITE

http://chronic-wasting-disease.blogspot.com/2016/02/texas-new-chronic-wasting-disease-cwd.html



Tuesday, June 07, 2016

How Did CWD Get Way Down In Medina County, Texas?

How Did CWD Get Way Down In Medina County, Texas?

Confucius ponders...

Could the Scrapie experiments back around 1964 at Moore Air Force near Mission, Texas, could this area have been ground zero for CWD (besides the CWD cases that have waltzed across the Texas, New Mexico border near WSMR Trans Pecos region since around 2001)?

Epidemiology of Scrapie in the United States 1977

snip...

Scrapie Field Trial Experiments Mission, Texas

A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission, Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.

The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas: (1) a series of pastures and-pens occupied by male animals only, and (2) a series of pastures and pens occupied by females and young progeny of both sexes. ...

snip...see full text ;



Mission, Texas Scrapie transmission to cattle study

Wilbur Clarke (reference the Mission, Texas scrapie transmission transmission to cattle study) is now the State Veterinarian for Montana based at Helena.

I was given confidential access to sections from the Clarke scrapie-cattle transmission experiment. Details of the experimental design were as supplied previously by...SNIP...SEE FULL TEXT ;


TEXAS TAHC OLD STATISTICS BELOW FOR PAST CWD TESTING; 
Subject: CWD testing in Texas
Date: Sun, 25 Aug 2002 19:45:14 –0500
From: Kenneth Waldrup

snip...see ;



Wednesday, September 28, 2016
TPWD CWD Sample Collector Trainings in the Trans Pecos and Panhandle

CHRONIC WASTING DISEASE CWD AND SCRAPIE TSE PRION ZOONOSIS UPDATE


 *** 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

http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf


PRION 2016 TOKYO

Zoonotic Potential of CWD Prions: An Update

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

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

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

http://prion2016.org/dl/newsletter_03.pdf


Cervid to human prion transmission

Kong, Qingzhong

Case Western Reserve University, Cleveland, OH, United States

Abstract

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

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

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

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

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

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

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

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

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

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

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Neurological Disorders and Stroke (NINDS)

Type Research Project (R01)

Project # 1R01NS088604-01A1

Application # 9037884

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

Project Start 2015-09-30

Project End 2019-07-31

Budget Start 2015-09-30

Budget End 2016-07-31

Support Year 1

Fiscal Year 2015

Total Cost $337,507

Indirect Cost $118,756

Institution

Name Case Western Reserve University

Department Pathology

Type Schools of Medicine

DUNS # 077758407

City Cleveland

State OH

Country United States

Zip Code 44106

http://grantome.com/grant/NIH/R01-NS088604-01A1


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

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.

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

Key Molecular Mechanisms of TSEs

Zabel, Mark D.

Colorado State University-Fort Collins, Fort Collins, CO, United States Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative diseases affecting humans, cervids, bovids, and ovids. The absolute requirement of PrPC expression to generate prion diseases and the lack of instructional nucleic acid define prions as unique infectious agents. Prions exhibit species-specific tropism, inferring that unique prion strains exist that preferentially infct certain host species and confront transmission barriers to heterologous host species. However, transmission barriers are not absolute. Scientific consensus agrees that the sheep TSE scrapie probably breached the transmission barrier to cattle causing bovine spongiform encephalopathy that subsequently breached the human transmission barrier and likely caused several hundred deaths by a new-variant form of the human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease of cervids, overcoming similar human transmission barriers. A groundbreaking discovery made last year revealed that mice infected with heterologous prion strains facing significant transmission barriers replicated prions far more readily in spleens than brains6. Furthermore, these splenic prions exhibited weakened transmission barriers and expanded host ranges compared to neurogenic prions. These data question conventional wisdom of avoiding neural tissue to avoid prion xenotransmission, when more promiscuous prions may lurk in extraneural tissues. Data derived from work previously funded by NIH demonstrate that Complement receptors CD21/35 bind prions and high density PrPC and differentially impact prion disease depending on the prion isolate or strain used. Recent advances in live animal and whole organ imaging have led us to generate preliminary data to support novel, innovative approaches to assessing prion capture and transport. We plan to test our unifying hypothesis for this proposal that CD21/35 control the processes of peripheral prion capture, transport, strain selection and xenotransmission in the following specific aims. 1. Assess the role of CD21/35 in splenic prion strain selection and host range expansion. 2. Determine whether CD21/35 and C1q differentially bind distinct prion strains 3. Monitor the effects of CD21/35 on prion trafficking in real time and space 4. Assess the role of CD21/35 in incunabular prion trafficking

Public Health Relevance Transmissible spongiform encephalopathies, or prion diseases, are devastating illnesses that greatly impact public health, agriculture and wildlife in North America and around the world. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease (CWD) of cervids, overcoming similar human transmission barriers. Early this year Canada reported its first case of BSE in over a decade audits first case of CWD in farmed elk in three years, underscoring the need for continued vigilance and research. Identifying mechanisms of transmission and zoonoses remains an extremely important and intense area of research that will benefit human and other animal populations.

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Allergy and Infectious Diseases (NIAID)

Type High Priority, Short Term Project Award (R56)

Project # 1R56AI122273-01A1

Application # 9211114

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Beisel, Christopher E

Project Start 2016-02-16

Project End 2017-01-31

Budget Start 2016-02-16

Budget End 2017-01-31

Support Year 1

Fiscal Year 2016

Total Cost

Indirect Cost Institution Name Colorado State University-Fort Collins

Department Microbiology/Immun/Virology

Type Schools of Veterinary Medicine

DUNS # 785979618 City Fort Collins

State CO

Country United States

Zip Code 80523

http://grantome.com/grant/NIH/R56-AI122273-01A1


PMCA Detection of CWD Infection in Cervid and Non-Cervid Species

Hoover, Edward Arthur

Colorado State University-Fort Collins, Fort Collins, CO, United States

Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly transmissible prion disease now recognized in 18 States, 2 Canadian provinces, and Korea. We have shown that Infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces, and in the tissues generating those body fluids and excreta, thereby leading to facile transmission by direct contact and environmental contamination. We have also shown that CWD can infect some non-cervid species, thus the potential risk CWD represents to domestic animal species and to humans remains unknown. Whether prions borne in blood, saliva, nasal fluids, milk, or excreta are generated or modified in the proximate peripheral tissue sites, may differ in subtle ways from those generated in brain, or may be adapted for mucosal infection remain open questions. The increasing parallels in the pathogenesis between prion diseases and human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, add relevance to CWD as a transmissible protein misfolding disease. The overall goal of this work is to elucidate the process of CWD prion transmission from mucosal secretory and excretory tissue sites by addressing these questions: (a) What are the kinetics and magnitude of CWD prion shedding post-exposure? (b) Are excreted prions biochemically distinct, or not, from those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the source of excreted prions? and (d) Are excreted prions adapted for horizontal transmission via natural/trans-mucosal routes? The specific aims of this proposal are: (1) To determine the onset and consistency of CWD prion shedding in deer and cervidized mice; (2); To compare the biochemical and biophysical properties of excretory vs. CNS prions; (3) To determine the capacity of peripheral tissues to support replication of CWD prions; (4) To determine the protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To compare the mucosal infectivity of excretory vs. CNS prions. Understanding the mechanisms that enable efficient prion dissemination and shedding will help elucidate how horizontally transmissible prions evolve and succeed, and is the basis of this proposal. Understanding how infectious misfolded proteins (prions) are generated, trafficked, shed, and transmitted will aid in preventing, treating, and managing the risks associated with these agents and the diseases they cause.

Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an emergent highly transmissible prion disease now recognized throughout the USA as well as in Canada and Korea. We have shown that infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces thereby leading to transmission by direct contact and environmental contamination. In that our studies have also shown that CWD can infect some non-cervid species, the potential risk CWD may represents to domestic animal species and humans remains unknown. The increasing parallels in the development of major human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and prion diseases add relevance to CWD as a model of a transmissible protein misfolding disease. Understanding how infectious misfolded proteins (prions) are generated and transmitted will aid in interrupting, treating, and managing the risks associated with these agents and the diseases they cause.

Funding Agency Agency National Institute of Health (NIH)

Institute National Institute of Neurological Disorders and Stroke (NINDS)

Type Research Project (R01)

Project # 4R01NS061902-07

Application # 9010980

Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May Project Start 2009-09-30

Project End 2018-02-28

Budget Start 2016-03-01

Budget End 2017-02-28

Support Year 7

Fiscal Year 2016

Total Cost $409,868

Indirect Cost $134,234 Institution Name Colorado State University-Fort Collins

Department Microbiology/Immun/Virology

Type Schools of Veterinary Medicine

DUNS # 785979618 City Fort Collins

State CO

Country United States

Zip Code 80523

http://grantome.com/grant/NIH/R01-NS061902-07


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

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

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

O18

Zoonotic Potential of CWD Prions

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

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

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

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

P.105: RT-QuIC models trans-species prion transmission

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

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

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

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

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf


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

Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

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

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

http://wwwnc.cdc.gov/eid/article/20/1/13-0858_article.htm


http://chronic-wasting-disease.blogspot.com/2014/01/molecular-barriers-to-zoonotic.html


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

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249


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

http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf


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

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss)

These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

Table 9 presents the results of an analysis of these data.

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf


CJD9/10022

October 1994

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

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

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

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

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

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

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

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf


Monday, May 02, 2016

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

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html


*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD


http://chronic-wasting-disease.blogspot.com/2014/06/prion-2014-chronic-wasting-disease-cwd.html


http://chronic-wasting-disease.blogspot.com/2016/07/colorado-chronic-wasting-disease-cwd.html


http://chronic-wasting-disease.blogspot.com/


Monday, May 02, 2016

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

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html


 Saturday, April 23, 2016

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

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20


 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

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf


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

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

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

 http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160


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

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

 Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

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

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

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

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

 ===============

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

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

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

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

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

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html


Saturday, July 23, 2016

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

http://bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html

Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

http://bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html
 
Tuesday, November 29, 2016
Transmissibility of Gerstmann–Sträussler–Scheinker syndrome in rodent models: new insights into the molecular underpinnings of prion infectivity
Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

*** Singeltary comment PLoS ***

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic,
what if ?

Posted by flounder on 05 Nov 2014 at 21:27 GMT

http://www.plosone.org/annotation/listThread.action?root=82860

Sunday, November 22, 2015

*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis Abstract

Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00

http://www.tandfonline.com/doi/abs/10.3109/13506129.2015.1095735?journalCode=iamy20

http://betaamyloidcjd.blogspot.com/2015/11/effect-of-heating-on-stability-of.html
SWISS MEDICAL WEEKLY

Alzheimer-type brain pathology may be transmitted by grafts of dura mater 26/01/2016 Singeltary comment ;

http://blog.smw.ch/alzheimer-type-brain-pathology-may-be-transmitted-by-grafts-of-dura-mater/#comment-89016

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

Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)

snip...see full Singeltary Nature comment here;

http://www.nature.com/nature/journal/v525/n7568/full/nature15369.html#/comments
Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

http://jama.jamanetwork.com/article.aspx?articleid=1031186

26 March 2003

Terry S. Singeltary, retired (medically) CJD WATCH

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

http://www.neurology.org/content/60/2/176/reply#neurology_el_535

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

2 January 2000

British Medical Journal

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

http://www.bmj.com/rapid-response/2011/10/28/us-scientist-should-be-concerned-cjd-epidemic-us-well

15 November 1999

British Medical Journal

vCJD in the USA * BSE in U.S.

http://www.bmj.com/rapid-response/2011/10/28/re-vcjd-usa-bse-us ;;
Terry S. Singeltary Sr.
Bacliff, Texas USA 77518