Date: 30 Aug 2016 J-STAGE Advance Published Date: 11 Sep 2016 1 Note Public
Health 2 3
Identification of the first case of atypical scrapie in Japan
4 5 Morikazu IMAMURA, Kohtaro MIYAZAWA*, Yoshifumi IWAMARU, Yuichi 6
MATSUURA, Takashi YOKOYAMA and Hiroyuki OKADA* 7 8 National Institute of Animal
Health, National Agriculture and Food Research Organization 9 (NARO), Tsukuba,
Ibaraki 305-0856, Japan 10 11 *CORRESPONDENCE TO: MIYAZAWA, K. or OKADA, H.,
National Institute of Animal 12 Health, 3-1-5 Kan-nondai, Tsukuba, Ibaraki
305-0856, Japan 13 E-mail: miyazawak@affrc.go.jp; okadahi@affrc.go.jp 14 15
Running head: Atypical Scrapie in Japan
ABSTRACT.
A Corriedale ewe was confirmed as the first atypical scrapie case during an
active surveillance program for transmissible spongiform encephalopathies in
small ruminants in Japan. The animal was homozygous for the AF141RQ haplotype of
PRNP. The animal showed clinical neurological signs possibly due to listeriosis
before culling. Western blot analysis showed an unusual multiple banded pattern
with a low-molecular fragment at ~7 kDa. Histopathology revealed suppurative
meningoencephalitis caused by listeriosis in the brainstem. Fine granular to
globular immunostaining of disease-associated prion proteins was mainly detected
in the neuropil of the spinal tract of the trigeminal nerve and in the white
matter of the spinocerebellar tract. Based on these results, this case was
conclusively diagnosed as atypical scrapie with encephalitic listeriosis.
KEY WORDS: atypical scrapie, coinfection, listeriosis, PRNP genotype,
surveillance
From: TSS
Subject: PrPSc distribution of a natural case of bovine spongiform
encephalopathy
Date: August 8, 2005 at 12:28 pm PST
PrPSc distribution of a natural case of bovine spongiform
encephalopathy
Yoshifumi Iwamaru, Yuka Okubo, Tamako Ikeda, Hiroko Hayashi, Mori- kazu
Imamura, Takashi Yokoyama and Morikazu Shinagawa Priori Disease Research Center,
National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba 305-0856 Japan
gan@affrc.go.jp
Abstract
Bovine spongiform encephalopathy (BSE) is a disease of cattle that causes
progressive neurodegeneration of the central nervous system. Infectivity of BSE
agent is accompanied with an abnormal isoform of prion protein (PrPSc). The
specified risk materials (SRM) are tissues potentially carrying BSE infectivity.
The following tissues are designated as SRM in Japan: the skull including the
brain and eyes but excluding the glossa and the masse- ter muscle, the vertebral
column excluding the vertebrae of the tail, spinal cord, distal illeum. For a
risk management step, the use of SRM in both animal feed or human food has been
prohibited. However, detailed PrPSc distribution remains obscure in BSE cattle
and it has caused controversies about definitions of SRM. Therefore we have
examined PrPSc distribution in a BSE cattle by Western blotting to reassess
definitions of SRM.
The 11th BSE case in Japan was detected in fallen stock surveillance. The
carcass was stocked in the refrigerator. For the detection of PrPSc, 200 mg of
tissue samples were homogenized. Following collagenase treatment, samples were
digested with proteinase K. After digestion, PrPSc was precipitated by sodium
phosphotungstate (PTA). The pellets were subjected to Western blotting using the
standard procedure. Anti-prion protein monoclonal antibody (mAb) T2 conjugated
horseradish peroxidase was used for the detection of PrPSc.
PrPSc was detected in brain, spinal cord, dorsal root ganglia, trigeminal
ganglia, sublingual ganglion, retina. In addition, PrPSc was also detected in
the peripheral nerves (sciatic nerve, tibial nerve, vagus nerve). Our results
suggest that the currently accepted definitions of SRM in BSE cattle may need to
be reexamined.
9/13/2005 179 Page 10 of 17
T. Kitamoto (Ed.)
PRIONS
Food and Drug Safety
================
ALSO from the International Symposium of Prion Diseases held in Sendai,
October 31, to November 2, 2004;
Bovine spongiform encephalopathy (BSE) in Japan
snip...
"Furthermore, current studies into transmission of cases of BSE that are
atypical or that develop in young cattle are expected to amplify the BSE prion"
NO. Date conf. Farm Birth place and Date Age at diagnosis
8.
2003.10.6. Fukushima Tochigi 2001.10.13. 23
9.
2003.11.4. Hiroshima Hyogo 2002.1.13. 21
Test results
# 8b, 9c cows Elisa Positive, WB Positive, IHC negative, histopathology
negative
b = atypical BSE case
c = case of BSE in a young animal
b,c, No PrPSc on IHC, and no spongiform change on histology
International Symposium of Prion Diseases held in Sendai, October 31, to
November 2, 2004.
Tetsuyuki Kitamoto Professor and Chairman Department of Prion Research
Tohoku University School of Medicine 2-1 SeiryoAoba-ku, Sendai 980-8575, JAPAN
TEL +81-22-717-8147 FAX +81-22-717-8148 e-mail; kitamoto@mail.tains.tohoku.ac.jp
Symposium Secretariat Kyomi Sasaki TEL +81-22-717-8233 FAX +81-22-717-7656
e-mail: kvomi-sasaki@mail.tains.tohoku.ac.ip
=================================
9/13/2005
--------------------------------------
Page 11 of 17 From: TSS
Subject: Atypical Proteinase K-Resistant Prion Protein (PrPres) observed in
an Apparently Healthy 23-Month-Old Holstein Steer
Date: August 26, 2005 at 10:24 am PST
Atypical Proteinase K-Resistant Prion Protein (PrPres) observed in an
Apparently Healthy 23-Month-Old Holstein Steer
Jpn. J. Infect. Dis., 56, 221-222, 2003
Laboratory and Epidemiology Communications
Atypical Proteinase K-Resistant Prion Protein (PrPres) Observed in an
Apparently Healthy 23-Month-Old Holstein Steer
Yoshio Yamakawa*, KenÕichi Hagiwara, Kyoko Nohtomi, Yuko Nakamura, Masahiro
Nishizima ,Yoshimi Higuchi1, Yuko Sato1, Tetsutaro Sata1 and the Expert
Committee for BSE Diagnosis, Ministry of Health, Labour and Welfare of Japan2
Department of Biochemistry & Cell Biology and 1Department of Pathology,
National Institute of Infectious Diseases, Tokyo 162-8640 and 2Miistry of
Health, Labour and Welfare, Tokyo 100-8916 Communicated by Tetsutaro Sata
(Accepted December 2, 2003)
*Corresponding author: Mailing address: Department of Biochemistry and Cell
Biology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku,
Tokyo 1628640, Japan. Tel: +81-3-5285-1111, Fax: +81-3-5285-1157, E-mail:
yamakawa@nih.go.jp
Since October 18, 2001, 'bovine spongiform encephalopathy (BSE) examination
for all cattle slaughtered at abattoirs in the country' has been mandated in
Japan by the Ministry of Health, Labour and Welfare (MHLW). 'Plateria' ELISA-kit
(Bio-Rad Laboratories, Hercules, Calif., USA) is routinely used at abattoirs for
detecting proteinase K (PK)-resistant prion protein (PrPSc) in the obex region.
Samples positive according to the ELISA screening are further subjected to
Western blot (WB) and histologic and immunohistochemical examination (IHC) at
the National Institute of Infectious Diseases (NIID) or Obihiro University. If
PrPSc is detected either by WB or by IHC, the cattle are diagnosed as BSE. The
diagnosis is approved by the Expert Committee for BSE Diagnosis, MHLW. From
October 18, 2001 to September 30, 2003, approximately 2.5 million cattle were
screened at abattoirs. A hundred and ten specimens positive according to ELISA
were subjected to WB/IHC. Seven showed positive by both WB and IHC, all
exhibiting the typical electrophoretic profile of a high content of the
di-glycosylated molecular form of PrPSc (1-3) and the distinctive granular
deposition of PrPSc in neuronal cells and neuropil of the dorsal nucleus of
vagus.
An ELISA-positive specimen from a 23 month-old Holstein steer slaughtered
on September 29, 2003, in Ibaraki Prefecture (Ibaraki case) was sent to the NIID
for confirmation. The animal was reportedly healthy before slaughter. The OD
titer in ELISA was slightly higher than the 'cut-off' level given by the
manufacturer. The histology showed no spongiform changes and IHC revealed no
signal of PrPSc accumulation typical for BSE. However, WB analysis of the
homogenate that was prepared from the obex region and used for ELISA revealed a
small amount of PrPSc with an electrophoretic profile different from that of
typical BSE-associated PrPSc (1-3). The characteristics were (i) low content of
the di-glycosylated molecular form of PrPSc, (ii) a faster migration of the
non-glycosylated form of PrPSc on SDS-PAGE, and (iii) less resistance against PK
digestion as compared with an authentic PrPSc specimen derived from an
83-month-old Holstein (Wakayama case) (Fig. 1). Table 1 summarizes the relative
amounts of three distinctive glycoforms (di-, mono, non-glycosylated) of PrPSc
calculated by densitometric analysis of the blot shown in Fig. 1. As 2.5 mg wet
weight obex-equivalent homogenate of the Ibaraki case (Fig. 1, lane 4) gave
slightly stronger band intensities of PrPSc than an 8 mg wet weight
obex-equivqlent homogenate of a typical BSE-affected Wakayama case (Fig. 1, lane
2), the amount of PrPSc accumulated in the Ibaraki case was calculated to be
1/500 - 1/1000 of the Wakayama case. In the Ibaraki case, the PrPSc bands were
not detectable in the homogenates of the proximal surrounding region of the
obex. These findings were consistent with the low OD value in ELISA, i.e., 0.2
-0.3 for the Ibaraki case versus over 3.0 for the Wakayama case. The DNA
sequence of the PrP coding region of the Ibaraki case was the same as that
appearing in the database (GenBank accession number: AJ298878). More recently,
we encountered another case that resembled the Ibaraki case. It was a
21-monthold Holstein steer from Hiroshima Prefecture. WB showed typical
BSE-specific PrPSc deposition though IHC did not detect positive signals of
PrPSc (data not shown).
Though the clinical onset of BSE is usually at around 5 years of age or
later, a 20-month-old case showing the clinical signs has been reported (4).
Variant forms of BSE similar to our cases, i.e., with atypical histopathological
and/or biochemical phenotype, have been recently reported in Italy (5) and in
France (6). Such variant BSE was not associated with mutations in the prion
protein (PrP) coding region as in our case (5,6). The Ministry of Agriculture,
Forestry and Fisheries of Japan (MAFF) announced a ban of feeding ruminants with
meat bone meal (MBM) on September 18, 2001, and a complete ban was made on
October 15 of the same year. According to the recent MAFF report, the previous
seven cases of BSE in Japan were cattle born in 1995 - 1996 and possibly fed
with cross-contaminated feed. However, the two cattle in this report were born
after the complete ban. Whether contaminated MBM was implicated in the present
cases remains to be investigated.
REFERENCES
Collinge, J., Sidle, K. C. L., Meads, J., Ironside, J. and Hill, A. F.
(1996): Molecular analysis of prion strain variation and the aetiology of 'new
variant' CJD. Nature, 383, 685690. Bruce, M. E., Will, R. G., Ironside, J. W.,
McConnell, I., Drummond, D., Suttie, A., McCardle, L., Chree, A., Hope, J.,
Birkett, C., Cousens, S., Fraser, H. and Bostock, C. J. (1997): Transmissions to
mice indicate that 'new variant' CJD is caused by the BSE agent. Nature, 389,
498-501. Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C. L., Gowland, I.
and Collinge, J. (1997): The same prion strain causes vCJD and BSE. Nature, 389,
448-450. Matravers, W., Bridgeman, J. and Smith, M.-F. (ed.)(2000): The BSE
Inquiry. p. 37. vol. 16. The Stationery Office Ltd., Norwich, UK. Casalone, C.,
Zanusso, G., Acutis, P. L., Crescio, M. I., Corona, C., Ferrari, S., Capobianco,
R., Tagliavini, F., Monaco, S. and Caramelli, M. (2003): Identification of a
novel molecular and neuropathological BSE phenotype in Italy. International
Conference on Prion Disease: from basic research to intervention concepts.
Gasreig, Munhen, October 8-10. Bicaba, A. G., Laplanche, J. L., Ryder, S. and
Baron, T. (2003): A molecular variant of bovine spongiform encephalopatie.
International Conference on Prion Disease: from basic research to intervention
concepts. Gasreig, Munhen, October 8-10. Asante, E. A., Linehan, J. M.,
Desbruslais, M., Joiner, S., Gowland, I., Wood, A. L., Welch, J., Hill, A. F.,
Lloyd, S. E., Wadsworth, J. D. F. and Collinge, J. (2002). BSE prions propagate
as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice
expressing human prion protein. EMBO J., 21, 6358-6366.
9/13/2005 Page 12 of 17
SEE SLIDES IN PDF FILE;
Published online January 27, 2005
Risk of oral infection with bovine spongiform encephalopathy agent in
primates
Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog,
Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie
Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe
Deslys The uncertain extent of human exposure to bovine spongiform
encephalopathy (BSE)—which can lead to variant Creutzfeldt-Jakob disease
(vCJD)—is compounded by incomplete knowledge about the ef.ciency of oral
infection and the magnitude of any bovine-to-human biological barrier to
transmission. We therefore investigated oral transmission of BSE to non-human
primates. We gave two macaques a 5 g oral dose of brain homogenate from a
BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months
after exposure, whereas the other remained free of disease at 76 months. On the
basis of these .ndings and data from other studies, we made a preliminary
estimate of the food exposure risk for man, which provides additional assurance
that existing public health measures can prevent transmission of BSE to
man.
snip...
BSE bovine brain inoculum
100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg
Primate (oral route)* 1/2 (50%)
Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%)
1/15 (7%)
RIII mice (ic�ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)
PrPres biochemical detection ���
The comparison is made on the basis of calibration of the bovine inoculum
used in our study with primates against a bovine brain inoculum with a similar
PrPres concentration that was inoculated into mice and cattle.8 *Data are number
of animals positive/number of animals surviving at the time of clinical onset of
disease in the .rst positive animal (%).
The accuracy of bioassays is generally judged to be about plus or minus 1
log. ic ip=intracerebral and intraperitoneal.
Table 1: Comparison of transmission rates in primates and cattle infected
orally with similar BSE brain inocula
snip...end
www.thelancet.com Published online January 27, 2005
Epidemiology and Infection, Volume 144, Issue 10 July 2016, pp. 2107-2116
Epidemiological investigations on the potential transmissibility of a rare
disease: the case of atypical scrapie in Great Britain
A. ORTIZ-PELÁEZ (a1), M. E. ARNOLD (a1) and A. VIDAL-DIEZ (a2) (a1)
1Department of Epidemiological Sciences, Animal and Plant Health Agency, New
Haw, Addlestone, Surrey, UK (a2) 2Population Health Research Institute, St
Georgés University of London, Tooting, London, UK DOI: http://dx.doi.org/10.1017/S0950268816000303
Published online: 15 March 2016
Abstract
Multiple cases of atypical scrapie in the same holding and co-existence
with classical scrapie have been reported in Great Britain. A two-stage
simulation tool was developed by combining a sampling algorithm and a
hierarchical Bayesian model to simulate the number of positive cases of atypical
scrapie from: (i) random sampling and (ii) using the actual sampled population
in Great Britain, being the output probability of detection of flocks with one
and more cases. Cluster analysis was conducted to assess the level of
geographical over- and under-sampling over the years. The probability of
detecting at least two cases of atypical scrapie in the same holding is much
lower in simulated random data than in simulated actual data for all scenarios.
Sampling bias in the selection of sheep for testing led to multiple sampling
from fewer but larger holdings, Scotland, and areas of Wales were under-sampled
and the South-West and East of England oversampled. The pattern of atypical
scrapie cases observed is unlikely to be explained by a multi-case event
epidemiologically linked. The co-existence of classical and atypical scrapie is
a rare event with 19 holdings detected in GB and does not suggest an
epidemiological link between the two types of disease.
Journal of Veterinary Medical Science Article ID: 16-0259
Language: English Japanese Previous Article | Next Article
Advance Publication Transmission of atypical scrapie to homozygous ARQ
sheep
Hiroyuki OKADA1), Kohtaro MIYAZAWA1), Morikazu IMAMURA1), Yoshifumi
IWAMARU1), Kentaro MASUJIN1), Yuichi MATSUURA1), Takashi YOKOYAMA1) 1) National
Institute of Animal Health, National Agriculture and Food Research Organization
(NARO)
[Advance Publication] Released 2016/06/20
Keywords: ARQ allele, atypical scrapie, prion, sheep, transmission
Two Cheviot ewes homozygous for the A136L141R154Q171 (AL141RQ) prion
protein (PrP) genotype were exposed intracerebrally to brain pools prepared
using four field cases of atypical scrapie from the United Kingdom. Animals were
clinically normal until the end of the experiment, when they were culled 7 years
post-inoculation. Limited accumulation of disease-associated PrP (PrPSc) was
observed in the cerebellar molecular layer by immunohistochemistry, but not by
western blot or enzyme-linked immunosorbent assay. In addition, PrPSc was
partially localized in astrocytes and microglia, suggesting that these cells
have a role in PrPSc processing, degradation or both. Our results indicate that
atypical scrapie is transmissible to AL141RQ sheep, but these animals act as
clinically silent carriers with long incubation times.
snip...
following considerations: (1) even regarding atypical scr 132 apie to be
contagious, each animal 133 was reared separately in a single pen; and (2)
according to epidemiological studies, the 134 incidence of this disease among
AL141RQ sheep in the field is far too low for this to be a 135 concern, with
atypical scrapie naturally occurring as a single case in a flock [1, 2, 6, 26,
31, 136 39, 42, 48]. Therefore, the likelihood of two ewes contracting this
condition at the same time 137 during the investigation in a manner unrelated to
the experiment seems negligible. It can thus 138 be concluded that the natural
occurrence of atypical scrapie during this study can be excluded 139 for these
reasons.
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National
Veterinary Insitute, Sweden; 2National Veterinary Institute,
Norway Nor98 is a prion disease of old sheep and goats. This atypical form
of scrapie was first described in Norway in 1998. Several features of Nor98 were
shown to be different from classical scrapie including the distribution of
disease associated prion protein (PrPd) accumulation in the brain. The
cerebellum is generally the most affected brain area in Nor98. The study here
presented aimed at adding information on the neuropathology in the cerebellum of
Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A
panel of histochemical and immunohistochemical (IHC) stainings such as IHC for
PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers
for phagocytic cells were conducted. The type of histological lesions and tissue
reactions were evaluated. The types of PrPd deposition were characterized. The
cerebellar cortex was regularly affected, even though there was a variation in
the severity of the lesions from case to case. Neuropil vacuolation was more
marked in the molecular layer, but affected also the granular cell layer. There
was a loss of granule cells. Punctate deposition of PrPd was characteristic. It
was morphologically and in distribution identical with that of synaptophysin,
suggesting that PrPd accumulates in the synaptic structures. PrPd was also
observed in the granule cell layer and in the white matter. The pathology
features of Nor98 in the cerebellum of the affected sheep showed similarities
with those of sporadic Creutzfeldt-Jakob disease in humans.
***The pathology features of Nor98 in the cerebellum of the affected sheep
showed similarities with those of sporadic Creutzfeldt-Jakob disease in
humans.
PR-26
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B.
Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto
Superiore di Sanità, Department of Food Safety and Veterinary Public Health,
Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna,
Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo,
Norway
Molecular variants of PrPSc are being increasingly investigated in sheep
scrapie and are generally referred to as "atypical" scrapie, as opposed to
"classical scrapie". Among the atypical group, Nor98 seems to be the best
identified. We studied the molecular properties of Italian and Norwegian Nor98
samples by WB analysis of brain homogenates, either untreated, digested with
different concentrations of proteinase K, or subjected to enzymatic
deglycosylation. The identity of PrP fragments was inferred by means of
antibodies spanning the full PrP sequence. We found that undigested brain
homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11),
truncated at both the C-terminus and the N-terminus, and not N-glycosylated.
After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and
N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11.
Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are
mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at
the highest concentrations, similarly to PrP27-30 associated with classical
scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment
of 17 kDa with the same properties of PrP11, that was tentatively identified as
a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in
2% sodium laurylsorcosine and is mainly produced from detergentsoluble,
full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a
sample with molecular and pathological properties consistent with Nor98 showed
plaque-like deposits of PrPSc in the thalamus when the brain was analysed by
PrPSc immunohistochemistry. Taken together, our results show that the
distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids
~ 90-155. This fragment is produced by successive N-terminal and C-terminal
cleavages from a full-length and largely detergent-soluble PrPSc, is produced in
vivo and is extremely resistant to PK digestion.
*** Intriguingly, these conclusions suggest that some pathological features
of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
119
A newly identified type of scrapie agent can naturally infect sheep with
resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne
Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?,
Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author
Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et
Cytogénétique, Institut National de la Recherche Agronomique, 78350
Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la
Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte
Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire
des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon,
France; **Pathologie Infectieuse et Immunologie, Institut National de la
Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology,
National Veterinary Institute, 0033 Oslo, Norway
***Edited by Stanley B. Prusiner, University of California, San Francisco,
CA (received for review March 21, 2005)
Abstract Scrapie in small ruminants belongs to transmissible spongiform
encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative
disorders that affect humans and animals and can transmit within and between
species by ingestion or inoculation. Conversion of the host-encoded prion
protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP
(PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified
surveillance of scrapie in the European Union, together with the improvement of
PrPSc detection techniques, has led to the discovery of a growing number of
so-called atypical scrapie cases. These include clinical Nor98 cases first
identified in Norwegian sheep on the basis of unusual pathological and PrPSc
molecular features and "cases" that produced discordant responses in the rapid
tests currently applied to the large-scale random screening of slaughtered or
fallen animals. Worryingly, a substantial proportion of such cases involved
sheep with PrP genotypes known until now to confer natural resistance to
conventional scrapie. Here we report that both Nor98 and discordant cases,
including three sheep homozygous for the resistant PrPARR allele (A136R154R171),
efficiently transmitted the disease to transgenic mice expressing ovine PrP, and
that they shared unique biological and biochemical features upon propagation in
mice. *** These observations support the view that a truly infectious TSE agent,
unrecognized until recently, infects sheep and goat flocks and may have
important implications in terms of scrapie control and public health.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Authors
Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon
S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J.
M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France;
ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex,
France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway,
INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.
Content
Atypical scrapie is a TSE occurring in small ruminants and harbouring
peculiar clinical, epidemiological and biochemical properties. Currently this
form of disease is identified in a large number of countries. In this study we
report the transmission of an atypical scrapie isolate through different species
barriers as modeled by transgenic mice (Tg) expressing different species PRP
sequence.
The donor isolate was collected in 1995 in a French commercial sheep flock.
inoculation into AHQ/AHQ sheep induced a disease which had all
neuro-pathological and biochemical characteristics of atypical scrapie.
Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate
retained all the described characteristics of atypical scrapie.
Surprisingly the TSE agent characteristics were dramatically different
v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and
biochemical characteristics similar to those of atypical BSE L in the same mouse
model. Moreover, whereas no other TSE agent than BSE were shown to transmit into
Tg porcine mice, atypical scrapie was able to develop into this model, albeit
with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed
similar biological and biochemical characteristics than BSE adapted to this
porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross
species barriers
(ii) the possible capacity of this agent to acquire new characteristics
when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on
the origin of the diversity of the TSE agents and could have consequences on
field TSE control measures.
RESEARCH
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A.
Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins,
Melanie J. Chaplin, and John Spiropoulos
To investigate the possibility of oral transmission of atypical scrapie in
sheep and determine the distribution of infectivity in the animals’ peripheral
tissues, we challenged neonatal lambs orally with atypical scrapie; they were
then killed at 12 or 24 months. Screening test results were negative for
disease-specifi c prion protein in all but 2 recipients; they had positive
results for examination of brain, but negative for peripheral tissues.
Infectivity of brain, distal ileum, and spleen from all animals was assessed in
mouse bioassays; positive results were obtained from tissues that had negative
results on screening. These fi ndings demonstrate that atypical scrapie can be
transmitted orally and indicate that it has the potential for natural
transmission and iatrogenic spread through animal feed. Detection of infectivity
in tissues negative by current surveillance methods indicates that diagnostic
sensitivity is suboptimal for atypical scrapie, and potentially infectious
material may be able to pass into the human food chain.
SNIP...
Although we do not have epidemiologic evidence that supports the effi cient
spread of disease in the fi eld, these data imply that disease is potentially
transmissible under fi eld situations and that spread through animal feed may be
possible if the current feed restrictions were to be relaxed. Additionally,
almost no data are available on the potential for atypical scrapie to transmit
to other food animal species, certainly by the oral route. However, work with
transgenic mice has demonstrated the potential susceptibility of pigs, with the
disturbing fi nding that the biochemical properties of the resulting PrPSc have
changed on transmission (40). The implications of this observation for
subsequent transmission and host target range are currently unknown.
How reassuring is this absence of detectable PrPSc from a public health
perspective? The bioassays performed in this study are not titrations, so the
infectious load of the positive gut tissues cannot be quantifi ed, although
infectivity has been shown unequivocally. No experimental data are currently
available on the zoonotic potential of atypical scrapie, either through
experimental challenge of humanized mice or any meaningful epidemiologic
correlation with human forms of TSE. However, the detection of infectivity in
the distal ileum of animals as young as 12 months, in which all the tissues
tested were negative for PrPSc by the currently available screening and confi
rmatory diagnostic tests, indicates that the diagnostic sensitivity of current
surveillance methods is suboptimal for detecting atypical scrapie and that
potentially infectious material may be able to pass into the human food chain
undetected.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Tuesday, April 28, 2009
Nor98-like Scrapie in the United States of America
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
*** Canada Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what
otherwise would have been unreported findings of atypical scrapie in sheep. In
2009, five new cases have been reported in Quebec, Ontario, Alberta, and
Saskatchewan. With the exception of Quebec, all cases have been diagnosed as
being the atypical form found in older animals. Canada encourages producers to
join its voluntary surveillance program in order to gain scrapie-free status.
The World Animal Health will not classify Canada as scrapie-free until no new
cases are reported for seven years. The Canadian Sheep Federation is calling on
the government to fund a wider surveillance program in order to establish the
level of prevalence prior to setting an eradication date. Besides long-term
testing, industry is calling for a compensation program for farmers who report
unusual deaths in their flocks.
2016 PRION CONFERENCE
SCRAPIE ZOONOSIS
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.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of scrapie prions to primate after an extended silent
incubation period
Authors
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire,
Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item
Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item
Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron,
Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item
Deslys, Jean-Philippe -
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015
Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E.,
Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C.,
Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J.
2015. Transmission of scrapie prions to primate after an extended silent
incubation period. Scientific Reports. 5:11573.
Interpretive Summary: The transmissible spongiform encephalopathies (also
called prion diseases) are fatal neurodegenerative diseases that affect animals
and humans. The agent of prion diseases is a misfolded form of the prion protein
that is resistant to breakdown by the host cells. Since all mammals express
prion protein on the surface of various cells such as neurons, all mammals are,
in theory, capable of replicating prion diseases. One example of a prion
disease, bovine spongiform encephalopathy (BSE; also called mad cow disease),
has been shown to infect cattle, sheep, exotic undulates, cats, non-human
primates, and humans when the new host is exposed to feeds or foods contaminated
with the disease agent. The purpose of this study was to test whether non-human
primates (cynomologous macaque) are susceptible to the agent of sheep scrapie.
After an incubation period of approximately 10 years a macaque developed
progressive clinical signs suggestive of neurologic disease. Upon postmortem
examination and microscopic examination of tissues, there was a widespread
distribution of lesions consistent with a transmissible spongiform
encephalopathy. This information will have a scientific impact since it is the
first study that demonstrates the transmission of scrapie to a non-human primate
with a close genetic relationship to humans. This information is especially
useful to regulatory officials and those involved with risk assessment of the
potential transmission of animal prion diseases to humans. Technical Abstract:
Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease
that also causes variant Creutzfeldt-Jakob disease in humans. Over the past
decades, c-BSE's zoonotic potential has been the driving force in establishing
extensive protective measures for animal and human health.
*** 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.
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.
==============
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
see more here ;
***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.***
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
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides further
grounds for concern that scrapie-infected meat may occasionally give rise in
humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is
transmissible to man. This has followed reports that the disease has been
transmitted to primates. One particularly lurid speculation (Gajdusek 1977)
conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and
transmissible encephalopathy of mink are varieties of a single "virus". The U.S.
Department of Agriculture concluded that it could "no longer justify or permit
scrapie-blood line and scrapie-exposed sheep and goats to be processed for human
or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is
emphasised by the finding that some strains of scrapie produce lesions identical
to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be
transmissible to man raises two considerations. First, the safety of laboratory
personnel requires prompt attention. Second, action such as the "scorched meat"
policy of USDA makes the solution of the acrapie problem urgent if the sheep
industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the time
of intracerebral inoculation of scrapie-infected mouse brain. The animal
developed a chronic central nervous system degeneration, with ataxia, tremor and
myoclonus with associated severe scrapie-like pathology of intensive astroglial
hypertrophy and proliferation, neuronal vacuolation and status spongiosus of
grey matter. The strain of scrapie virus used was the eighth passage in Swiss
mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral
passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton,
Berkshire).
USDA OIE AND THE DUMBING DOWN OF THE TSE PRION DISEASE SCRAPIE AND ATYPICAL
SCRAPIE, just spreading the love around $$$
Proposed Rules Planned for Publication:
• VS published revisions to 9 CFR parts 54 and 79. The proposed changes are
intended to improving the effectiveness and cost efficiency of surveillance and
to increase animal identification compliance by addressing gaps in
identification and by requiring States to meet reasonable surveillance targets
to remain consistent States. States must meet these targets for VS to
demonstrate geographically appropriate surveillance to meet the criteria for
freedom and have confidence that all of the remaining cases have been
found.
• The rule would propose to:
o Give the APHIS Administrator authority to relieve requirements for sheep
and goats exposed to scrapie types, such as Nor98-like, that do not pose a
significant risk of transmission;
o Increase flexibility in how investigations can be conducted and allow the
epidemiology in a specific flock to be given more consideration in determining
flock and animal status;
o Add a genetic-based approach to regulation;
o Make goat identification requirements similar to those for sheep to
support ongoing slaughter surveillance in goats (no changes will be made in the
consistent State requirements regarding identification of goats in intrastate
commerce);
o Tighten the definition of slaughter channels;
o Expand the individual identification requirement to all sexually intact
animals unless moving as a group/lot (allows mixed-source groups moving in
slaughter channels at under 18 months);
o Limit the use of tattoos and implants to animals not moving through
markets and not in slaughter channels; and
o Reduce recordkeeping requirements by making them similar to the current
uniform methods and rules compliance guidance.
• APHIS is also revising its scrapie import regulations to bring them more
in line with the OIE scrapie chapter. This will ensure that we meet OIE criteria
for free status and prevent the reintroduction of scrapie after free status is
achieved.
snip...
Regarding our studies on modes of prion transmission, we very recently
completed and are finalizing analyses for a 7-year study on Nor98-like scrapie
in breeding ewes. Ewes were experimentally inoculated with brain homogenate
obtained from a US sheep with clinical Nor98-like scrapie. Recipient ewes were
bred annually to examine the placenta for evidence of a transmissible agent. One
recipient ewe developed an unrelated disease in her 5th year of scrapie
incubation. At postmortem examination, a Nor98-like pattern of misfolded prion
protein, PrP-Sc, accumulation was observed. Similar findings were recently
confirmed through postmortem examination of the other three ewes in the 7th year
of scrapie incubation. These results confirm that inoculation of these ewes was
successful. Not all placental tissue analyses have yet been completed, but there
has been no evidence of placental accumulation of PrP-Sc out to the 6th year of
infection. We have recently confirmed that the classical scrapie prions which
accumulate in the placenta of goats are infectious to sheep. Similarly,
transmission to sheep has also occurred via the milk of infected goats. Thus,
both the placenta and milk of infected goats are significant transmission risks
to sheep.
Finally, we are nearing the completion of a study to determine if
transgenic mice can be used to differentiate the origin of prions in new cases
of scrapie disease in sheep and goats raised in regions with endemic chronic
wasting disease (CWD) in cervids. The results show that transgenic mice bearing
a susceptible prion protein are readily susceptible to classical scrapie prions
derived from naturally infected sheep and goats but not to CWD prions derived
from naturally infected cervids. The converse was true for transgenic mice
bearing a susceptible cervid prion protein. Both types of mice were only
intermediately susceptible to CWD prions derived from experimentally infected
sheep. Thus, to date, the results suggest this bioassay model can discriminate
between these sources of prions in new cases of prion disease in small ruminants
from regions in which CWD is endemic in cervid populations.
Evidence of scrapie transmission to sheep via goat milk
Timm KonoldEmail author, Leigh Thorne, Hugh A. Simmons, Steve A. C.
Hawkins, Marion M. Simmons and Lorenzo González
BMC Veterinary ResearchBMC series – open, inclusive and
trusted201612:208
DOI: 10.1186/s12917-016-0807-4
© Crown copyright; licensee BioMed Central Ltd. 2016
Received: 29 April 2016
Accepted: 19 August 2016
Published: 17 September 2016
Abstract
Background
Previous studies confirmed that classical scrapie can be transmitted via
milk in sheep. The current study aimed to investigate whether scrapie can also
be transmitted via goat milk using in vivo (new-born lambs fed milk from
scrapie-affected goats due to the unavailability of goat kids from guaranteed
scrapie-free herds) and in vitro methods (serial protein misfolding cyclic
amplification [sPMCA] on milk samples).
Results
In an initial pilot study, new-born lambs of two different prion protein
gene (PRNP) genotypes (six VRQ/VRQ and five ARQ/ARQ) were orally challenged with
5 g brain homogenate from two scrapie-affected goats to determine susceptibility
of sheep to goat scrapie. All sheep challenged with goat scrapie brain became
infected based on the immunohistochemical detection of disease-associated PrP
(PrPsc) in lymphoid tissue, with an ARQ/ARQ sheep being the first to succumb.
Subsequent feeding of milk to eight pairs of new-born ARQ/ARQ lambs, with each
pair receiving milk from a different scrapie-affected goat, resulted in scrapie
in the six pairs that received the largest volume of milk (38–87 litres per
lamb), whereas two pairs fed 8–9 litres per lamb, and an environmental control
group raised on sheep milk from healthy ewes, did not show evidence of infection
when culled at up to 1882 days of age. Infection in those 12 milk recipients
occurred regardless of the clinical status, PrPsc distribution, caprine
arthritis-encephalitis virus infection status and PRNP polymorphisms at codon
142 (II or IM) of the donor goats, but survival time was influenced by PRNP
polymorphisms at codon 141. Serial PMCA applied to a total of 32 milk samples
(four each from the eight donor goats collected throughout lactation) detected
PrPsc in one sample each from two goats.
Conclusions
The scrapie agent was present in the milk from infected goats and was able
to transmit to susceptible species even at early preclinical stage of infection,
when PrPsc was undetectable in the brain of the donor goats. Serial PMCA as a
PrPsc detection method to assess the risk of scrapie transmission via milk in
goats proved inefficient compared to the bioassay.
Keywords Transmissible spongiform encephalopathy – Scrapie – Goat – Sheep –
Milk – Colostrum – Transmission – Protein misfolding cyclic amplification –
Prion protein – Genotype
see full text ;
Monday, September 19, 2016
Evidence of scrapie transmission to sheep via goat milk
Thursday, December 20, 2012
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED, WISHES TO
CONTINUE SPREADING IT AROUND THE GLOBE
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE, DOES NOT SURPRISE ME $
Wednesday, August 31, 2016
NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND
CARIBOU
Monday, September 05, 2016
*** Pathological features of chronic wasting disease in reindeer and
demonstration of horizontal transmission Major Findings for Norway
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
Saturday, September 17, 2016
*** Texas Parks Wildlife Chronic Wasting Disease CWD Management and
Regulations for Hunters 2016 – 2017
Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base
Scrapie Experiment 1964
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 TSE Prion (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 ;
Thursday, June 09, 2016
Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base
Scrapie TSE Prion Experiment 1964
How Did CWD Get Way Down In Medina County, Texas?
Friday, April 22, 2016
*** Texas Scrapie Confirmed in a Hartley County Sheep where CWD was
detected in a Mule Deer
Monday, August 29, 2016
*** NWHC USGS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
1-14 of 14 2012
Terry S. Singeltary Sr. 9/3/12
JAPAN BANS DEER AND ELK MEAT AND ALLOWS SOME BEEF PRODUCTS, what about TSE
prion concerns ?
Terry S. Singeltary Sr. 1/5/12
Importation of Whole Cuts of Boneless Beef from Japan [Docket No.
05-004-1] RIN 0579-AB93
Terry S. Singeltary Sr. 10/15/10
U.S. Beef Talks May Progress as Japan Gathers Mad-Cow Disease Risk Data
about U.S.A.
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!
Saturday, December 12, 2015
NOTICE: Environmental Impact Statement on Large Livestock Carcasses TSE
Prion REPORT December 14, 2015
Friday, August 14, 2015
Carcass Management During a Mass Animal Health Emergency Draft Programmatic
Environmental Impact Statement—August 2015
food for thought, specified risk materials srm’s, TSE Prions
anyone...
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
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.
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
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.***
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
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
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.
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).***
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.***
================
*** 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.
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
***********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 ;
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 ***
*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD
*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent
*** Here we report that a human prion strain that had adopted the cervid
prion protein (PrP) sequence through passage in cervidized transgenic mice
efficiently infected transgenic mice expressing human PrP,
*** indicating that the species barrier from cervid to humans is prion
strain-dependent and humans can be vulnerable to novel cervid prion strains.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
*** Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD Isolates
*** The data presented here substantiate and expand previous reports on the
existence of different CWD strains.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from
CWD-infected cervids suggests prevention of such tissue in the human diet as a
precautionary measure for food safety, pending on further clarification of
whether CWD may be transmissible to humans.
>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO
CONVERSION OF THE HUMAN PRION PROTEIN<<<
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
Wednesday, January 01, 2014
Molecular Barriers to Zoonotic Transmission of Prions
*** 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.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from
CWD-infected cervids suggests prevention of such tissue in the human diet as a
precautionary measure for food safety, pending on further clarification of
whether CWD may be transmissible to humans.
Yet, it has to be noted that our assessments of PrPTSE levels in skeletal
muscles were based on findings in presumably pre- or subclinically infected
animals. Therefore, the concentration of PrPTSE in skeletal muscles of WTD with
clinically manifest CWD may possibly exceed our estimate which refers to
clinically inconspicuous animals that are more likely to enter the human food
chain. Our tissue blot findings in skeletal muscles from CWD-infected WTD would
be consistent with an anterograde spread of CWD prions via motor nerve fibres to
muscle tissue (figure 4A). Similar neural spreading pathways of muscle infection
were previously found in hamsters orally challenged with scrapie [28] and
suggested by the detection of PrPTSE in muscle fibres and muscle-associated
nerve fascicles of clinically-ill non-human primates challenged with BSE prions
[29]. Whether the absence of detectable PrPTSE in myofibers observed in our
study is a specific feature of CWD in WTD, or was due to a pre- or subclinical
stage of infection in the examined animals, remains to be established. In any
case, our observations support previous findings suggesting the precautionary
prevention of muscle tissue from CWD-infected WTD in the human diet, and
highlight the need to comprehensively elucidate of whether CWD may be
transmissible to humans. While the understanding of TSEs in cervids has made
substantial progress during the past few years, the assessment and management of
risks possibly emanating from prions in skeletal muscles of CWD-infected cervids
requires further research.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Rachel C.
Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡,
Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ + Author
Affiliations
1 Department of Microbiology, Immunology and Molecular Genetics, University
of Kentucky, Lexington, KY 40536, USA. 2 Sanders Brown Center on Aging,
University of Kentucky, Lexington, KY 40536, USA. 3 Department of Neurology,
University of Kentucky, Lexington, KY 40536, USA. 4 Department of Microbiology,
Immunology and Pathology, Colorado State University, Fort Collins, CO 80523,
USA. 5 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO
80526, USA. ↵§ To whom correspondence should be addressed. E-mail:
gtell2@uky.edu ↵* These authors contributed equally to this work.
↵† Present address: Department of Infectology, Scripps Research Institute,
5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA.
↵‡ Present address: Institute of Neuropathology, University of Zurich,
Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
Abstract The emergence of chronic wasting disease (CWD) in deer and elk in
an increasingly wide geographic area, as well as the interspecies transmission
of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt
Jakob disease, have raised concerns about the zoonotic potential of CWD. Because
meat consumption is the most likely means of exposure, it is important to
determine whether skeletal muscle of diseased cervids contains prion
infectivity. Here bioassays in transgenic mice expressing cervid prion protein
revealed the presence of infectious prions in skeletal muscles of CWD-infected
deer, demonstrating that humans consuming or handling meat from CWD-infected
deer are at risk to prion exposure.
Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin
Because It May Contain Meat Derived From An Elk Confirmed To Have Chronic
Wasting Disease
Contact: Exotic Meats USA 1-800-680-4375
FOR IMMEDIATE RELEASE -- February 9, 2009 -- Exotic Meats USA of San
Antonio, TX is initiating a voluntary recall of Elk Tenderloin because it may
contain meat derived from an elk confirmed to have Chronic Wasting Disease
(CWD). The meat with production dates of December 29, 30 and 31, 2008 was
purchased from Sierra Meat Company in Reno, NV. The infected elk came from Elk
Farm LLC in Pine Island, MN and was among animals slaughtered and processed at
USDA facility Noah’s Ark Processors LLC.
Chronic Wasting Disease (CWD) is a fatal brain and nervous system disease
found in elk and deer. The disease is caused by an abnormally shaped protein
called a prion, which can damage the brain and nerves of animals in the deer
family. Currently, it is believed that the prion responsible for causing CWD in
deer and elk is not capable of infecting humans who eat deer or elk contaminated
with the prion, but the observation of animal-to-human transmission of other
prion-mediated diseases, such as bovine spongiform encephalopathy (BSE), has
raised a theoretical concern regarding the transmission of CWD from deer or elk
to humans. At the present time, FDA believes the risk of becoming ill from
eating CWD-positive elk or deer meat is remote. However, FDA strongly advises
consumers to return the product to the place of purchase, rather than disposing
of it themselves, due to environmental concerns.
Exotic Meats USA purchased 1 case of Elk Tenderloins weighing 16.9 lbs. The
Elk Tenderloin was sold from January 16 – 27, 2009. The Elk Tenderloins was
packaged in individual vacuum packs weighing approximately 3 pounds each. A
total of six packs of the Elk Tenderloins were sold to the public at the Exotic
Meats USA retail store. Consumers who still have the Elk Tenderloins should
return the product to Exotic Meats USA at 1003 NE Loop 410, San Antonio, TX
78209. Customers with concerns or questions about the Voluntary Elk Recall can
call 1-800-680-4375. The safety of our customer has always been and always will
be our number one priority.
Exotic Meats USA requests that for those customers who have products with
the production dates in question, do not consume or sell them and return them to
the point of purchase. Customers should return the product to the vendor. The
vendor should return it to the distributor and the distributor should work with
the state to decide upon how best to dispose. If the consumer is disposing of
the product he/she should consult with the local state EPA office.
#
COLORADO: Farmer's market meat recalled after testing positive for CWD
24.dec.08 9News.com Jeffrey Wolf
Elk meat that was sold at a farmer's market is being recalled because tests
show it was infected with chronic wasting disease. The Boulder County Health
Department and Colorado Department of Public Health and Environment issued the
recall Wednesday after the meat was sold at the Boulder County Fairgrounds on
Dec. 13. Although there isn't any human health risk connected with CWD, the
recalled was issued as a precaution. About 15 elk were bought from a commercial
ranch in Colorado in early December and processed at a licensed plant. All 15
were tested for CWD and one came up positive. The labeling on the product would
have the following information: *Seller: High Wire Ranch *The type of cut:
"chuck roast," "arm roast," "flat iron," "ribeye steak," "New York steak,"
"tenderloin," "sirloin tip roast," "medallions" or "ground meat." *Processor:
Cedaredge Processing *The USDA triangle containing the number "34645" People
with questions about this meat can contact John Pape, epidemiologist at the
Colorado Department of Public Health and Environment at 303-692-2628.
COULD NOT FIND any warning or recalls on these two sites confirming their
recall of CWD infected meat. ...TSS
Wednesday, April 06, 2011
Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in
Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease
Prion Infectivity in Fat of Deer with Chronic Wasting Disease
Brent Race,# Kimberly Meade-White,# Richard Race, and Bruce Chesebro* Rocky
Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840
Received 2 June 2009/ Accepted 24 June 2009
ABSTRACT Top ABSTRACT TEXT REFERENCES
Chronic wasting disease (CWD) is a neurodegenerative prion disease of
cervids. Some animal prion diseases, such as bovine spongiform encephalopathy,
can infect humans; however, human susceptibility to CWD is unknown. In
ruminants, prion infectivity is found in central nervous system and lymphoid
tissues, with smaller amounts in intestine and muscle. In mice, prion
infectivity was recently detected in fat. Since ruminant fat is consumed by
humans and fed to animals, we determined infectivity titers in fat from two
CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD
infectivity and might be a risk factor for prion infection of other species.
snip...
The highest risk of human contact with CWD might be through exposure to
high-titer CNS tissue through accidental skin cuts or corneal contact at the
time of harvest and butchering. However, the likelihood of a human consuming fat
infected with a low titer of the CWD agent is much higher. It is impossible to
remove all the fat present within muscle tissue, and fat consumption is
inevitable when eating meat. Of additional concern is the fact that meat from an
individual deer harvested by a hunter is typically consumed over multiple meals
by the same group of people. These individuals would thus have multiple
exposures to the CWD agent over time, which might increase the chance for
transfer of infection.
In the Rocky Mountain region of North America, wild deer are subject to
predation by wolves, coyotes, bears, and mountain lions. Although canines such
as wolves and coyotes are not known to be susceptible to prion diseases, felines
definitely are susceptible to BSE (9) and might also be infected by the CWD
agent. Deer infected with the CWD agent are more likely to be killed by
predators such as mountain lions (11). Peripheral tissues, including lymph
nodes, muscle, and fat, which harbor prion infectivity are more accessible for
consumption than CNS tissue, which has the highest level of infectivity late in
disease. Therefore, infectivity in these peripheral tissues may be important in
potential cross-species CWD transmissions in the wild.
The present finding of CWD infectivity in deer fat tissue raises the
possibility that prion infectivity might also be found in fat tissue of other
infected ruminants, such as sheep and cattle, whose fat and muscle tissues are
more widely distributed in both the human and domestic-animal food chains.
Although the infectivity in fat tissues is low compared to that in the CNS,
there may be significant differences among species and between prion strains.
Two fat samples from BSE agent-infected cattle were reported to be negative by
bioassay in nontransgenic RIII mice (3, 6). However, RIII mice are
10,000-fold-less sensitive to BSE agent infection than transgenic mice
expressing bovine PrP (4). It would be prudent to carry out additional
infectivity assays on fat from BSE agent-infected cattle and scrapie
agent-infected sheep using appropriate transgenic mice or homologous species to
determine the risk from these sources.
0C7.04
North American Cervids Harbor Two Distinct CWD Strains
Authors
Angers, R. Seward, T, Napier, D., Browning, S., Miller, M., Balachandran
A., McKenzie, D., Hoover, E., Telling, G. 'University of Kentucky; Colorado
Division of Wildlife, Canadian Food Inspection Agency; University Of Wisconsin;
Colorado State University.
Content
Despite the increasing geographic distribution and host range of CWD,
little is known about the prion strain(s) responsible for distinct outbreaks of
the disease. To address this we inoculated CWD-susceptible Tg(CerPrP)1536+/·
mice with 29 individual prion samples from various geographic locations in North
America. Upon serial passage, intrastudy incubation periods consistently
diverged and clustered into two main groups with means around 210 and 290 days,
with corresponding differences in neuropathology. Prion strain designations were
utilized to distinguish between the two groups: Type I CWD mice succumbed to
disease in the 200 day range and displayed a symmetrical pattern of vacuolation
and PrPSc deposition, whereas Type II CWD mice succumbed to disease near 300
days and displayed a strikingly different pattern characterized by large local
accumulations of florid plaques distributed asymmetrically. Type II CWD bears a
striking resemblance to unstable parental scrapie strains such as 87A which give
rise to stable, short incubation period strains such as ME7 under certain
passage conditions. In agreement, the only groups of CWD-inoculated mice with
unwavering incubation periods were those with Type I CWD. Additionally,
following endpoint titration of a CWD sample, Type I CWD could be recovered only
at the lowest dilution tested (10-1), whereas Type II CWD was detected in mice
inoculated with all dilutions resulting in disease. Although strain properties
are believed to be encoded in the tertiary structure of the infectious prion
protein, we found no biochemical differences between Type I and Type II CWD. Our
data confirm the co·existence of two distinct prion strains in CWD-infected
cervids and suggest that Type II CWD is the parent strain of Type I CWD.
see page 29, and see other CWD studies ;
Sunday, November 23, 2008
PRION October 8th - 10th 2008 Book of Abstracts
ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A
WISCONSIN STRAIN OF CWD
Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of
Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2
Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary
Research Institute, 4.Center for Prions and Protein Folding Diseases, 5
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
T6G 2P5
The identification and characterization of prion strains is increasingly
important for the diagnosis and biological definition of these infectious
pathogens. Although well-established in scrapie and, more recently, in BSE,
comparatively little is known about the possibility of prion strains in chronic
wasting disease (CWD), a disease affecting free ranging and captive cervids,
primarily in North America. We have identified prion protein variants in the
white-tailed deer population and demonstrated that Prnp genotype affects the
susceptibility/disease progression of white-tailed deer to CWD agent. The
existence of cervid prion protein variants raises the likelihood of distinct CWD
strains. Small rodent models are a useful means of identifying prion strains. We
intracerebrally inoculated hamsters with brain homogenates and phosphotungstate
concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD
endemic area) and experimentally infected deer of known Prnp genotypes. These
transmission studies resulted in clinical presentation in primary passage of
concentrated CWD prions. Subclinical infection was established with the other
primary passages based on the detection of PrPCWD in the brains of hamsters and
the successful disease transmission upon second passage. Second and third
passage data, when compared to transmission studies using different CWD inocula
(Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin
white-tailed deer population is different than the strain(s) present in elk,
mule-deer and white-tailed deer from the western United States endemic region.
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a
middle aged woman with progressive dementia were previously implicated in the
accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger
patients. The diagnoses of CJD have been confirmed for all three cases. More
than two years after their last use in humans, after three cleanings and
repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were
implanted in the cortex of a chimpanzee. Eighteen months later the animal became
ill with CJD. This finding serves to re-emphasise the potential danger posed by
reuse of instruments contaminated with the agents of spongiform
encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
Wednesday, September 07, 2016
Michigan Launches an investigation into the Detroit Medical Center dirty,
broken and missing surgical instruments, what about the CJD TSE PRION iatrogenic
threat past and present therefrom?
Tuesday, July 05, 2016
Michigan DNR announces expansion of Chronic Wasting Disease Core Area and
Management Zone
Thursday, August 18, 2016
*** PROCEEDINGS ONE HUNDRED AND Nineteenth ANNUAL MEETING of the USAHA BSE,
CWD, SCRAPIE, PORCINE TSE PRION October 22 28, 2015 ***
Tuesday, August 9, 2016
*** Concurrence with OIE Risk Designations for Bovine Spongiform
Encephalopathy [Docket No. APHIS-2015-0055]
Saturday, July 23, 2016
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING,
AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY
2016
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, June 20, 2016
*** Specified Risk Materials SRMs BSE TSE Prion Program ***
Thursday, October 22, 2015
*** Former Ag Secretary Ann Veneman talks women in agriculture and we talk
mad cow disease USDA and what really happened those mad cows in Texas ***
Tuesday, July 26, 2016
*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY
2016
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
Saturday, July 23, 2016
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING,
AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, August 9, 2016
$$$ Concurrence with OIE Risk Designations for Bovine Spongiform
Encephalopathy [Docket No. APHIS-2015-0055] $$$
*** Evidence That Transmissible Mink Encephalopathy Results from Feeding
Infected Cattle ***
Over the next 8-10 weeks, approximately 40% of all the adult mink on the
farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or
dead dairy cattle...
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to
accord it a very low profile indeed. Dr. A Thiermann showed the picture in the
''Independent'' with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. ...
”The occurrence of CWD must be viewed against the contest of the locations
in which it occurred. It was an incidental and unwelcome complication of the
respective wildlife research programmes. Despite it’s subsequent recognition as
a new disease of cervids, therefore justifying direct investigation, no specific
research funding was forthcoming. The USDA veiwed it as a wildlife problem and
consequently not their province!” ...page 26.
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
snip...
1979
SILENCE ON CJD AND SCRAPIE
1980
SILENCE ON CJD AND SCRAPIE
*** 1981 NOVEMBER
snip...see full text ;
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
Tuesday, July 12, 2016
Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE,
TSE, Prion Zoonosis Science History see history of NIH may destroy human brain
collection
Saturday, December 12, 2015
CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015
Monday, August 22, 2016
CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES
HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES
Terry S. Singeltary Sr.
