Classical Scrapie Diagnosis in ARR/ARR Sheep in Brazil
Acta Scientiae Veterinariae, 2015. 43(Suppl 1): 69.
CASE REPORT Pub. 69
ISSN 1679-9216
1
Received: 4 August 2014 Accepted: 19 December 2014 Published: 6 February
2015
1Programa de Pós-graduação em Ciências Veterinárias (PPGCV), Faculdade de
Veterinária (FaVet), Universidade Federal do Rio Grande do Sul (UFRGS), Porto
Alegre, RS, Brazil. 2Setor de Patologia Veterinária (SPV), Departamento de
Patologia Clínica Veterinária (DPCV), FAVET, UFRGS, Porto Alegre, RS, Brazil.
3Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde
(ICBS), UFRGS, Porto Alegre, RS. CORRESPONDENCE: J.S. Leal [julianoob@gmail.com
- Tel.: +55 (51) 3308 3631]. Setor de Patologia Veterinária, FAVET, UFRGS. Av.
Bento Gonçalves n. 9090, Bairro Agronomia. CEP 91540-000 Porto Alegre, RS,
Brazil.
Classical Scrapie Diagnosis in ARR/ARR Sheep in Brazil
Juliano Souza Leal1,2, Caroline Pinto de Andrade2, Gabriel Laizola Frainer
Correa2, Gisele Silva Boos2, Matheus Viezzer Bianchi2, Sergio Ceroni da Silva2,
Rui Fernando Felix Lopes3 & David Driemeier2
ABSTRACT
Background: Scrapie is a transmissible spongiform encephalopathy (TSE) that
affects sheep flocks and goat herds. The transfer of animals or groups of these
between sheep farms is associated with increased numbers of infected animals and
with the susceptibility or the resistance to natural or classical scrapie form.
Although several aspects linked to the etiology of the natural form of this
infection remain unclarified, the role of an important genetic control in
scrapie incidence has been proposed. Polymorphisms of the PrP gene (prion
protein, or simply prion), mainly in codons 136, 154, and 171, have been
associated with the risk of scrapie. Case: One animal from a group of 292 sheep
was diagnosed positive for scrapie in the municipality of Valparaíso, state of
São Paulo, Brazil. The group was part of a flock of 811 free-range, mixed-breed
Suffolk sheep of the two genders and ages between 2 and 7 years from different
Brazilian regions. Blood was collected for genotyping (for codons 136, 141, 154
and 171), and the third lid and rectal mucosa were sampled for
immunohistochemistry (IHC) for scrapie, from all 292 animals of the group. IHC
revealed that seven (2.4%) animals were positive for the disease. Collection of
samples was repeated for 90 animals, among which the seven individuals diagnosed
positive and 83 other animals that had some degree of kinship with those. These
90 sheep were sacrificed and necropsied, when samples of brain (obex),
cerebellum, third eyelid, rectal mucosa, mesenteric lymph node, palatine tonsil,
and spleen were collected for IHC. The results of IHC analyses carried out after
necropsy of the seven positive animals submitted to the second collection of
lymphoreticular tissue and of the 83 animals with some degree of kinship with
them confirmed the positive diagnosis obtained in the first analysis, and
revealed that three other sheep were also positive for scrapie. Samples of 80
animals (89%) were negative for the disease in all organs and tissues analyzed.
In turn, 10 sheep (11%) were positive, presenting immunoreactivity in one or
more tissues. Genotyping revealed the presence of four of the five alleles of
the PrP gene commonly detected in sheep: ARR, ARQ, VRQ and ARH. These allele
combinations formed six haplotypes: ARR/ARR, ARR/ARQ, ARH/ARH, ARQ/ARH, ARQ/ARQ
and ARQ/VRQ. Animals were classified according to susceptibility to scrapie,
when 8.9% of the genotyped sheep were classified into risk group R1 (more
resistant, with no restriction to breeding). In turn, 40% of the animals tested
ranked in groups R4 and R5 (genetically very susceptible, cannot be used for
breeding purposes). Discussion: The susceptibility of sheep flocks depends on
the genetic pattern of animals and is determined by the sequence of the gene
that codifies protein PrP. Additionally, numerous prion strains are
differentiated based on pathological and biochemical characteristics, and may
affect animals differently, depending on each individual’s genotype. Most
epidemiologic data published to date indicate that animals that carry the
ARR/ARR genotype are less susceptible to classical scrapie. However, in the
present study, the fact that two scrapie-positive sheep presented the haplotype
ARR/ARR indicates that this genotype cannot always be considered an indicator of
resistance to the causal agent of the classical manifestation of the disease.
The coexistence in the same environment of several crossbred animals from
different flocks and farms, which characterizes a new heterogeneous flock, may
have promoted a favorable scenario to spread the disease, infecting animals in
the most resistant group.
Keywords: biopsy, scrapie, TSEs, immunohistochemistry.
DISCUSSION
The susceptibility of sheep flocks to scrapie depends largely on the
genetic pattern of the animal, and is determined mainly by the sequence of the
gene that codifies the PrP protein, since there are several polymorphisms that
affect the conversion of the cell protein PrPC to its pathological form, PrPSc
[8, 9]. Nevertheless, it is not possible to consider the occurrence of only one
form of ovine prion, since there are numerous prion strains with different
pathological and biochemical characteristics that may affect animals
distinctively, depending on their genotypes [1, 30]. In the present study, the
frequency of codon VRQ was very low (2.2%), confirming previous findings, which
revealed that the alleles ARR and ARQ prevail in Suffolk sheep, and that the
allele ARH sometimes is detected [12, 32]. The high sensitivity of homozygous
VRQ carriers or of individuals with ARQ haplotypes has also been reported in the
literature [24]. This condition raises concerns about susceptibility from the
epidemiological perspective, since the allele VRQ, which is rare or absent in
breeds like Suffolk, was present in two animals, one of which was positive for
scrapie. Most epidemiological and genetic data published indicate that sheep
carrying the haplotype ARR/ ARR are less susceptible to classical form, while
animals with the haplotype VRQ in homozygosis or with ARQ haplotypes are highly
susceptible [24]. This hypothesis is supported by genotyping data for thousands
of sheep with the disease around the world. For example, a study carried out in
Japan described a classical scrapie case in one ARR/ARR sheep [16]. Sensitivity
of ARR/ARR sheep in a scenario of oral exposure to the disease has also been
reported [3]. Atypical cases were observed in ARR/ARR animals [11, 42].
Polymorphisms at codon positions 136, 154 and 171 are not the only ones
associated with resistance or susceptibility to scrapie [33]. An analysis of the
variation of codon positions 136 and 171, for instance, showed that each has
several adjacent polymorphic sites and may codify up to four amino acids [7,
50]. The atypical scrapie form, characterized by strain Nor98 [6], is more
frequently detected in AHQ animals that carry a polymorphism in codon 141, and
has not been described in Suffolk sheep in Brazil [2]. This atypical form
expresses phenylalanine (F), instead of leucine (L) in the form L141F [6, 37,
46].
However, although it is generally acceptable that classical scrapie is an
infectious and contagious disease [14], contagion with the atypical form is
questionable in light of the fact that the specific marker for the atypical
manifestation of the disease is detected outside the central nervous system [5,
20, 29], even in cases experimentally transmitted to transgenic mice [35] and
sheep [47]. Several studies have demonstrated that susceptibility to the
atypical form is consistently associated with PrP codons 141 (L/F) and 154 (R/H)
[6, 42]. In fact, studies have proposed the hypothesis that this form may evolve
when the animal is not exposed to the infectious agent [5, 18, 29, 48], given
the limited knowledge of the physiopathology of this manifestation of the
disease [19].
In the present study, two (2/8) positive animals presented the haplotype
ARR/ARR, which is considered to be the least susceptible and therefore
responsible for the lowest risk of scrapie. However, like all sheep that were
genotyped, these animals did not present any change in lysine in codon position
141. This change (that is, when lysine is replaced by phenylalanine) has been
associated with atypical scrapie in Suffolk sheep [6]. Therefore, these two
ARR/ARR sheep do not fit in the genotypic characteristics of sheep that may
commonly present the atypical form. It is possible that the presence of several
crossbred animals of different flocks and farms in the same environment, which
characterizes an heterogeneous flock, has created the favorable conditions for
the disease to evolve and spread, infecting the more susceptible animals.
The variation in the frequency of the PrP genotype between flocks has been
identified as a real risk factor for the disease [4]. The introduction of adult
sheep free of scrapie in contaminated flocks is believed to allow lateral
transmission, even between adult animals with less susceptible genotypes [40,
45], although young sheep are more predisposed [43]. Other reasons behind
differences in occurrence include the stress caused during husbandry and large
population numbers [26]. Additionally, the lack of a defined epidemiological
pattern and the different strains of the causal agent play an important role in
inter-flock variability [40]. Several models were based on the assumption that
outbreak duration is influenced by flock size and by the frequency of the PrP
genotype in one flock [25, 26, 38, 51]. Commercial flocks with high genetic
diversity, mainly in codons other than 136, 154 and 171, are more consistently
affected. In these animals, the onset of clinical manifestations occurs at
significantly different ages, with means varying from 2 to 5.7 years, due to
noteworthy dissimilarities in age and PrP genotype profiles [40]. The purchase
of infected animals has been pointed out as the main scrapie infection mechanism
in flocks [27, 41].
*** The diagnosis of scrapie in two homozygous ARR/ARR sheep indicates that
the resistance of this genotype to the classical form of the disease is
debatable. Although scrapie in these animals is rare, the cases presented in
this case report lend strength to the notion that its occurrence depends on a
combination of infectious factors, including differences in biological and
biochemical properties in the natural hosts to this prion.
MANUFACTURERS 1VMRD Pullman Albion Road. Pullman, WA, USA. 2Qiagen. Hilden,
Germany. 3InvitrogenTM. São Paulo, Brazil. 4Life TechnologiesTM. Gaithersburg,
MD, USA. 5InvitrogenTM. Carlsbad, CA, USA. 6Applied Biosystems Inc. Foster City,
CA, USA. Declaration of interest. The authors report no conflicts of interest.
The authors alone are responsible for the content and writing of the
paper.
Monday, May 5, 2014 Brazil 2nd BSE Mad Cow disease confirmed OIE 02/05/2014
http://bovineprp.blogspot.com/2014/05/brazil-bse-mad-cow-disease-confirmed.html
Thursday, April 24, 2014
Brazil investigates possible BSE mad cow case
http://bovineprp.blogspot.com/2014/04/brazil-investigates-possible-bse-mad.html
Thursday, September 26, 2013
Brazil evaluate the implementation of health rules on animal by-products
and derived products SRM BST TSE PRION aka MAD COW DISEASE http://bse-atypical.blogspot.com/2013/09/brazil-evaluate-implementation-of.html
Friday, December 07, 2012
ATYPICAL BSE BRAZIL 2010 FINALLY CONFIRMED OIE 2012 http://bse-atypical.blogspot.com/2012/12/atypical-bse-brazil-2010-finally.html
Wednesday, December 19, 2012
Scientific Report of the European Food Safety Authority on the Assessment
of the Geographical BSE Risk (GBR) of Brazil http://bse-atypical.blogspot.com/2012/12/scientific-report-of-european-food.html
Assessment of the PrPc amino-terminal domain in prion species barriers
Kristen A. Davenporta, Davin M. Hendersona, Candace K. Mathiasona and
Edward A. Hoovera# + Author Affiliations
Prion Research Center, Department of Microbiology, Immunology and
Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado
State University, Fort Collins, CO 80523a ABSTRACT Chronic wasting disease (CWD)
in cervids and bovine spongiform encephalopathy (BSE) in cattle are prion
diseases that are caused by the same protein-misfolding mechanism, but appear to
pose different risks to humans. We are interested in understanding the
differences between the species barriers of CWD and BSE. We used real-time,
quaking-induced conversion (RT-QuIC) to model the central molecular event in
prion disease, the templated misfolding of the normal prion protein, PrPc, to a
pathogenic, amyloid isoform, PrPSc. We examined the role of the PrPc
amino-terminal domain (NTD, aa23-90) in cross-species conversion by comparing
the conversion efficiency of various prion seeds in either full-length
(aa23-231) or truncated (aa90-231) PrPc. We demonstrate that the presence of
white-tailed deer and bovine NTDs hindered seeded conversion of PrPc, but human
and bank vole NTDs did the opposite. Additionally, full-length human and bank
vole PrPc were more likely to be converted to amyloid by CWD prions than were
their truncated forms. A chimera with replacement of the human NTD by the bovine
NTD resembled human PrPc. The requirement for an NTD, but not for the specific
human sequence, suggests that the NTD interacts with other regions of the human
PrPc to increase promiscuity. These data contribute to the evidence that, in
addition to primary sequence, prion species barriers are controlled by
interactions of the substrate NTD with the rest of the substrate PrPc molecule.
Importance We demonstrate that the amino-terminal domain of the normal
prion protein, PrPc, hinders seeded conversion of bovine and white-tailed deer
PrPc to the prion form, but it facilitates conversion of the human and bank vole
PrPc to the prion form. Additionally, we demonstrate that the amino-terminal
domain of human and bank vole PrPc requires interaction with the rest of the
molecule to facilitate conversion by CWD prions. These data suggest that
interactions of the amino-terminal domain with the rest of the PrPc molecule
play an important role in the susceptibility of humans to CWD prions.
snip...
We found that human rPrPc can be readily converted to an amyloid state by
CWD prions, and that the NTD facilitates this conversion. As there is little
evidence for the susceptibility of humans to CWD, the biologic significance of
our observation remains to be determined. However, the role of the NTD in this
in vitro phenomenon may be important to the in vivo mechanism as well. RT-QuIC,
transgenic mouse bioassay, and PMCA measure different outcomes. This manuscript
compares the efficiency of initial amyloid formation, while bioassay and PMCA
reflect total accumulation of protease-resistant PrPSc, which may explain the
difference in the apparent susceptibility of full-length human rPrPc in these
models. The molecular underpinnings for species barriers and trans-species prion
conversion remain a complex, yet important problem in prion biology. We propose
that an interaction between the amino terminal
FOOTNOTES
↵#Address correspondence to Edward A. Hoover, edward.hoover@colostate.edu
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
‘’We demonstrate that the presence of white-tailed deer and bovine NTDs
hindered seeded conversion of PrPc, but human and bank vole NTDs did the
opposite. Additionally, full-length human and bank vole PrPc were more likely to
be converted to amyloid by CWD prions than were their truncated forms. ‘’
***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.***
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
SCRAPIE AND CWD ZOONOSIS
PRION 2016 CONFERENCE 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
Saturday, September 24, 2016
Assessment of the PrPc amino-terminal domain in prion species barriers
Transmission of scrapie prions to primate after an extended silent
incubation period
***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
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion
disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD)
in humans and having guided protective measures for animal and human health
against animal prion diseases. Recently, partial transmissions to humanized mice
showed that the zoonotic potential of scrapie might be similar to c-BSE. We here
report the direct transmission of a natural classical scrapie isolate to
cynomolgus macaque, a highly relevant model for human prion diseases, after a
10-year silent incubation period, with features similar to those reported for
human cases of sporadic CJD. Scrapie is thus actually transmissible to primates
with incubation periods compatible with their life expectancy, although fourfold
longer than BSE. Long-term experimental transmission studies are necessary to
better assess the zoonotic potential of other prion diseases with high
prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98
scrapie.
snip...
In addition to previous studies on scrapie transmission to primate1,8,9 and
the recently published study on transgenic humanized mice13, our results
constitute new evidence for recommending that the potential risk of scrapie for
human health should not be dismissed. Indeed, human PrP transgenic mice and
primates are the most relevant models for investigating the human transmission
barrier. To what extent such models are informative for measuring the zoonotic
potential of an animal TSE under field exposure conditions is unknown. During
the past decades, many protective measures have been successfully implemented to
protect cattle from the spread of c-BSE, and some of these measures have been
extended to sheep and goats to protect from scrapie according to the principle
of precaution. Since cases of c-BSE have greatly reduced in number, those
protective measures are currently being challenged and relaxed in the absence of
other known zoonotic animal prion disease. We recommend that risk managers
should be aware of the long term potential risk to human health of at least
certain scrapie isolates, notably for lymphotropic strains like the classical
scrapie strain used in the current study. Relatively high amounts of infectivity
in peripheral lymphoid organs in animals infected with these strains could lead
to contamination of food products produced for human consumption. Efforts should
also be maintained to further assess the zoonotic potential of other animal
prion strains in long-term studies, notably lymphotropic strains with high
prevalence like CWD, which is spreading across North America, and atypical/Nor98
scrapie (Nor98)50 that was first detected in the past two decades and now
represents approximately half of all reported cases of prion diseases in small
ruminants worldwide, including territories previously considered as scrapie
free. Even if the prevailing view is that sporadic CJD is due to the spontaneous
formation of CJD prions, it remains possible that its apparent sporadic nature
may, at least in part, result from our limited capacity to identify an
environmental origin.
***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.***
2015
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.
==============
CWD TSE PRION HUMAN ZOONOSIS POTENTIAL, has it already happened, and being
masked as sporadic CJD? and what about iatrogenic, or the pass if forward,
friendly fire mode of transmission of cwd to humans, same thing, sporadic cjd
?
*** 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
Ms. Alyssa Wetterau1, Dr. Krysten Schuler1, Dr. Elizabeth Bunting1, Dr.
Hussni Mohammed1 1Cornell University
Chronic wasting disease (CWD) is a fatal disease of North American
Cervidae. New York State (NYS, USA) successfully managed an outbreak of CWD in
2005 in both captive and wild white-tailed deer (Odocoileus virginianus) with no
reoccurrence of the disease as of 2015. To attain maximum compliance and
efficacy of management actions for prevention of CWD entry, understanding the
varied risk perceptions will allow for targeted, proactive communication efforts
to address divergences between expert-derived risk assessments and stakeholder
risk perceptions. We examined perceived risks associated with CWD introduction
and exposure among agricultural and wildlife agency professionals within and
outside of NYS, as well as stakeholder groups (e.g., hunters and captive cervid
owners). We measured perceived risk using a risk assessment questionnaire online
via Qualtrics survey software and evaluated similarities within, as well as
differences in, perception among participant groups. New York State biologists
employed by the Department of Environmental Conservation and independent non-NYS
wildlife and agricultural professionals thought CWD risks associated with
captive cervids were high; captive cervid owners thought risks for wild and
captive cervids were low. Agriculture and wildlife professional groups agreed on
general risk perceptions. We ranked 15 individual risk hazards into high and low
medium categories based on all responses. Differences between groups were most
evident in hypothetical disease pathways. Any pathway involving inter-state
import of live cervids received high ranking for all groups except captive
cervid owners. Comparatively low risk perceptions by captive cervid operators
may stem from misinformation, lack of understanding of testing programs, and
indemnity payments for animal depopulation. Communication and education directed
at areas of disagreement may facilitate effective disease prevention and
management.
* No evaluation of determination of CWD risk is required for alternative
livestock or captive wildlife shipped directly to slaughter or to a biosecure
facility approved by the Division and the Dept. of Agriculture.
*** 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. ***
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
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier
Andréoletti1, Affiliations Contributions Corresponding author Journal name:
Nature Communications Volume: 5, Article number: 5821 DOI:
doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014
Published 16 December 2014 Article tools Citation Reprints Rights &
permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
*** 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.
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.
2016
SCRAPIE AND CWD ZOONOSIS
PRION 2016 CONFERENCE 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
Transmission of scrapie prions to primate after an extended silent
incubation period
***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
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion
disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD)
in humans and having guided protective measures for animal and human health
against animal prion diseases. Recently, partial transmissions to humanized mice
showed that the zoonotic potential of scrapie might be similar to c-BSE. We here
report the direct transmission of a natural classical scrapie isolate to
cynomolgus macaque, a highly relevant model for human prion diseases, after a
10-year silent incubation period, with features similar to those reported for
human cases of sporadic CJD. Scrapie is thus actually transmissible to primates
with incubation periods compatible with their life expectancy, although fourfold
longer than BSE. Long-term experimental transmission studies are necessary to
better assess the zoonotic potential of other prion diseases with high
prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98
scrapie.
snip...
In addition to previous studies on scrapie transmission to primate1,8,9 and
the recently published study on transgenic humanized mice13, our results
constitute new evidence for recommending that the potential risk of scrapie for
human health should not be dismissed. Indeed, human PrP transgenic mice and
primates are the most relevant models for investigating the human transmission
barrier. To what extent such models are informative for measuring the zoonotic
potential of an animal TSE under field exposure conditions is unknown. During
the past decades, many protective measures have been successfully implemented to
protect cattle from the spread of c-BSE, and some of these measures have been
extended to sheep and goats to protect from scrapie according to the principle
of precaution. Since cases of c-BSE have greatly reduced in number, those
protective measures are currently being challenged and relaxed in the absence of
other known zoonotic animal prion disease. We recommend that risk managers
should be aware of the long term potential risk to human health of at least
certain scrapie isolates, notably for lymphotropic strains like the classical
scrapie strain used in the current study. Relatively high amounts of infectivity
in peripheral lymphoid organs in animals infected with these strains could lead
to contamination of food products produced for human consumption. Efforts should
also be maintained to further assess the zoonotic potential of other animal
prion strains in long-term studies, notably lymphotropic strains with high
prevalence like CWD, which is spreading across North America, and atypical/Nor98
scrapie (Nor98)50 that was first detected in the past two decades and now
represents approximately half of all reported cases of prion diseases in small
ruminants worldwide, including territories previously considered as scrapie
free. Even if the prevailing view is that sporadic CJD is due to the spontaneous
formation of CJD prions, it remains possible that its apparent sporadic nature
may, at least in part, result from our limited capacity to identify an
environmental origin.
***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.***
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
1978 SCRAPIE IN CONFIDENCE SCJD
1979
SILENCE ON CJD AND SCRAPIE
1980
SILENCE ON CJD AND SCRAPIE
*** 1981 NOVEMBER
Thursday, August 04, 2016
*** MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON
CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL
SCJD
Sunday, August 28, 2016
CONFIDENTIAL
Transmissible Spongiform Encephalopathy TSE Prion and how Politics and
Greed by the Industry spread madcow type diseases from species to species and
around the globe
TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!
Please be assured, the USA does NOT have any clue as to what the real
perspective on the TSE prion disease in domestic feline and canine, much less
our big wild cats, OR any other species including humans for that matter, but
one thing for sure, the studies and history of the mad cow debacle below are
deeply concerning with regards, to humans and wild big cats like mountain lions,
cougars, lynx, Jaguar, and such, that feed on cervids that are infected with
CWD. one thing for sure, don’t kid yourselves, all are very much susceptible to
the TSE Prion disease, and if you don’t look, you don’t find, problems
solved$$$
Tuesday, September 06, 2016
A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation
Tuesday, July 26, 2016
Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND
SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
*** Calling Canadian beef unsafe is like calling your twin sister ugly,"
Dopp said. ***
Thursday, August 25, 2016
*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible
Specified Risk Materials Contamination the most high risk materials for BSE TSE
PRION AKA MAD COW TYPE DISEASE ***
Monday, June 20, 2016
Specified Risk Materials SRMs BSE TSE Prion Program
Friday, August 26, 2016
*** Journal Journal of Toxicology and Environmental Health, Part A Volume
79, 2016 - Issue 16-17 Prion Research in Perspective IV CANADA BSE CWD SCRAPIE
CJD TSE Prion Disease
Saturday, July 16, 2016
Importation of Sheep, Goats, and Certain Other Ruminants [Docket No.
APHIS-2009-0095]RIN 0579-AD10
WITH great disgust and concern, I report to you that the OIE, USDA, APHIS,
are working to further legalize the trading of Transmissible Spongiform
Encephalopathy TSE Pion disease around the globe.
THIS is absolutely insane. it’s USDA INC.
Monday, September 19, 2016
Evidence of scrapie transmission to sheep via goat milk
Saturday, April 16, 2016
*** APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on
Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission
***
Wednesday, January 20, 2016
Exportation of Live Animals, Hatching Eggs, and Animal Germplasm From the
United States [Docket No. APHIS-2012-0049] RIN 0579-AE00 2016-00962
Thursday, January 14, 2016
EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address
Future Risks Report to the Chairman, Committee on Energy and Commerce, House of
Representatives December 2015 GAO-16-132
GAO
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND
SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Wednesday, May 2, 2012
ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND
ANIMAL HEALTH
Saturday, June 12, 2010
PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05
Study of Atypical Bse
Wednesday, July 28, 2010
re-Freedom of Information Act Project Number 3625-32000-086-05, Study of
Atypical BSE UPDATE July 28, 2010
Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net
posted by Terry S. Singeltary Sr. | 12:20 PM
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