Thursday, November 22, 2018

Nebraska NEFGA Chronic Wasting Disease CWD TSE Prion 02106-19-40 North Platte River 279 NPR279 Lymph node sample Positive

CWD testing results

Elk season testing results from the Nebraska Veterinary Diagnostic Laboratory (NVDL) can be viewed below. Future results will be updated here as they become available.

02106-19-40 North Platte River 279 NPR279 Lymph node sample Positive 11/19/18

***> Cervid to human prion transmission 5R01NS088604-04 Update

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;


Volume 24, Number 8—August 2018

 
Research
 
Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
 
Marcelo A. BarriaComments to Author , 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.
 
snip...see;
 



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. 


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884726/


THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update



SATURDAY, NOVEMBER 10, 2018 

cwd, bse, scrapie, cjd, tse prion updated November 10 2018



THURSDAY, OCTOBER 25, 2018 

***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion



MONDAY, FEBRUARY 05, 2018 

Nebraska Chronic Wasting Disease CWD TSE Prion 2017 Survey Confirms 203 Positives From 1,807 Deer Sampled



FRIDAY, MARCH 10, 2017 

Nebraska Tests confirm spread of CWD to Lancaster County



WEDNESDAY, JANUARY 11, 2017 

Nebraska Four positives for CWD found in recent testing of deer



TUESDAY, AUGUST 30, 2016 

NEBRASKA CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT



Wednesday, January 04, 2012

CWD NEBRASKA NGPC 26 DEER CARCASSES TESTED POSITIVE BUFFALO, CUSTER AND HOLT COUNTIES DURING NOVEMBER HUNT



WEDNESDAY, MARCH 02, 2011 

CWD IN NEBRASKA IS INCREASING WITH 51 POSITIVE CASES IN 2010



WEDNESDAY, JANUARY 25, 2012 

Nebraska Fish and Game Association Censors Singeltary from speaking about Chronic Wasting Disease (CWD) again




***> Mineral licks as environmental reservoirs of chronic wasting disease prions <***

Published: May 2, 2018

Ian H. Plummer,Chad J. Johnson,Alexandra R. Chesney,Joel A. Pedersen ,Michael D. Samuel 

Abstract 

Chronic wasting disease (CWD) is a fatal neurodegenerative disease of deer, elk, moose, and reindeer (cervids) caused by misfolded prion proteins. The disease has been reported across North America and recently discovered in northern Europe. Transmission of CWD in wild cervid populations can occur through environmental routes, but limited ability to detect prions in environmental samples has prevented the identification of potential transmission “hot spots”. We establish widespread CWD prion contamination of mineral licks used by free-ranging cervids in an enzootic area in Wisconsin, USA. We show mineral licks can serve as reservoirs of CWD prions and thus facilitate disease transmission. Furthermore, mineral licks attract livestock and other wildlife that also obtain mineral nutrients via soil and water consumption. Exposure to CWD prions at mineral licks provides potential for cross-species transmission to wildlife, domestic animals, and humans. Managing deer use of mineral licks warrants further consideration to help control outbreaks of CWD.

Snip...

DISCUSSION

Our results demonstrate that CWD-infected white-tailed deer deposit prions at mineral licks they visit. Although the mechanism of prion deposition is unknown, we suspect deposition of saliva by infected deer during ingestion of soil and water at mineral licks has the highest potential to facilitate indirect transmission to susceptible deer. Saliva from white-tailed deer infected with CWD contains on the order of 1–5 infectious doses (ID50) per 10 mL as quantified by real-time quaking-induced conversion, where an ID50 is the dose of CWD prions capable of infecting half of the transgenic mice expressing cervid prion protein [48]. Frequent visitation by infected cervids could allow mineral licks to become potential “hot spots” for indirect transmission of CWD [49]. Currently, little is known about the relative importance of direct contact and environmental routes of CWD transmission in free-ranging cervids [10]. Thus, how artificial and natural mineral licks contribute to current and future CWD infection in cervids and whether licks should be managed to control cervid use are important questions for further research.

Despite the relatively recent detection of CWD in Wisconsin (2001) and the moderate incidence of infection (6–19% prevalence in adult deer in the area sampled at the time of sample collection), our results suggest contamination of mineral licks in the CWD outbreak zone is widespread. This finding suggests that mineral licks may serve as reservoirs of CWD prions that contribute to disease transmission to susceptible animals. Although the levels of CWD prions in the samples analyzed appears low, we note that the association of prions with clay minerals often present at mineral licks can dramatically enhance disease transmission via the oral route of exposure [30–31]. For hamster-adapted scrapie prions binding to montmorillonite clay particles enhanced transmission by a factor of 680, however, an upper bound on the enhancement factor could not be assigned [30–31]. At present, the degree to which binding to clay mineral particles enhances CWD transmission to deer via the oral (or nasal) route of exposure is not known. Furthermore, repeated oral exposure to prions is associated with increased likelihood of disease transmission [50]. Differences in the sialyation status of N-linked glycans between brain-derived and secreted/excreted PrPCWD may impact oral infectivity [51]. Cervid species that avoid interspecific contact make use of the same mineral lick sites [49], potentially leading to interspecies transmission. Mineral licks also attract livestock and other wildlife that supplement mineral intake via soil and water consumption, exposing these animals to CWD prions. Exposure of predators and scavengers to CWD prions via consumption of infected tissue has been previously documented [23]; our results suggest that environmental exposure of non-cervid animal groups can also occur via environmental routes. We also detected CWD prions in fecal samples collected in proximity to a mineral lick, indicating that fecal excretion represents a route of CWD deposition into the environment with potential transmission to susceptible cervids [19]. Deposition of fecal pellets by white-tailed deer near bait sites increases with higher deer visitation [52] and similar patterns probably occur at mineral licks. Thus, increased local fecal deposition by CWD-infected deer likely contributes to increased environmental concentrations of prions in and around mineral licks. Deer generally avoid consumption of feces [52]; however, the apparent long-term duration of prion infectivity in the environment [27–29], the enhanced disease transmission by soil-bound prions combined with the repeated visitation, long-term existence of and multi-generational use of mineral licks suggest the impact of concentrated environmental contamination on the dynamics of disease transmission warrants further investigation. Recent laboratory research indicates plants grown in prion-contaminated soil can accumulate prions [53]. Our data suggest that plants growing near contaminated mineral licks may warrant investigation as a source of prions for foraging animals. Areas where cervids congregate for mineral consumption, feeding and baiting sites, winter yarding, wallows [54] or other activities where CWD prions are deposited in the environment may also provide potential long-term reservoirs for transmission to cervid and non-cervid species. 

CONCLUSIONS

We used mb-PMCA to detect CWD in soil and water from mineral licks naturally contaminated with prions and used by free-ranging deer, livestock, and non-cervid wildlife species. Detection of prions in environmental reservoirs represents an important first step in understanding the contribution of environmental transmission to CWD epizootics and potential for cross-species transmission. The present study characterized an environmental prion reservoir by (1) identifying an apparent “hot spot” of deposition and potential exposure to both cervid and non-cervid species; (2) indicating CWD prions shed by free-ranging cervids are present in areas of frequent use leading to environmental contamination and potentially plant uptake; and (3) motivating investigation of the exposure and susceptibility of non-cervid species to CWD contaminated soil, water, and plant materials. Future research should be directed at quantifying CWD prion concentrations at mineral licks and other areas where cervids congregate, determining the persistence of prion infectivity at these sites, delineating spatial-temporal patterns of environmental prion deposition and accumulation, and assessing consumption by susceptible animals. Identifying additional environmental reservoirs of CWD prions and determining the contributions of direct and indirect transmission over the course of CWD outbreaks represent key aims in advancing understanding of long-term CWD infection dynamics.



Subject: Nebraska NEFGA cwd ban on singeltary


You have been permanently banned by DingerFlinger for the following reason:
Voted to ban..



WEDNESDAY, JANUARY 25, 2012

Nebraska Fish and Game Association Censors Singeltary from speaking about Chronic Wasting Disease (CWD) again

Nebraska Fish and Game Association Censors Singeltary from speaking about Chronic Wasting Disease (CWD) again

You have been banned for the following reason: Voted to ban.

Date the ban will be lifted: Never



The director and the moderators of this forum came together and voted to ban you from this forum. We had a lot of members complain about the way you wet about posting your threads.

I personally would like to say thanks for helping some of our members realize the importance of CWD and the affects. Thank you for your time.

Best regards, xxxx


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


Terry,

First off, I would like to apologize for the harsh manner in which you have been greeted on this site. As you said, I'm sure you are used to it but that is no excuse. I know there have been problems in the past of people registering on this forum to simply blow their own horn and promote their own cause. One guy was trying to convince people common carp were the best game fish and threatened to stock them into every public body of water he could reach! Notwithstanding, the greeting you received was unnecessarily harsh and a poor representation of the majority of people on this site.

Regarding CWD, I am not too familiar with the disease but I do try to keep up on the current state it. I too am puzzled why the people with the largest interest in deer are so resistant to learn more about this major issue. It certainly seems like you know what you are talking about and as you have said you have spent many years learning about and researching this topic.

One small piece of advice I may offer you is to introduce yourself and give some background information about yourself. Where are you from? Do you hunt or fish? Why are you interested in CWD/TSE? Do you work professionally with this topic? Just some ideas. I understand you are trying to provide a large amount of information and are unable to post links to articles, but the large blocks of text pasted in your posts comes off as impersonal and abrasive to some, especially from a new member.

I hope you stick around, I am always eager to learn especially when the issue is something as large as this.

Regards xxxxxxx


***************


WEDNESDAY, JANUARY 25, 2012

Nebraska Fish and Game Association Censors Singeltary from speaking about Chronic Wasting Disease (CWD) again



Terry S. Singeltary Sr.

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