Vet Res. 2015; 46: 126.
Published online 2015 Oct 28. doi: 10.1186/s13567-015-0269-x
PMCID: PMC4625529
Dynamics of the natural transmission of bovine spongiform encephalopathy
within an intensively managed sheep flock
Martin Jeffrey, Janey P. Witz, Stuart Martin, Steve A. C. Hawkins, Sue J.
Bellworthy, Glenda E. Dexter, Lisa Thurston, and Lorenzo Gonzálezcorresponding
author
Abstract
Sheep are susceptible to the bovine spongiform encephalopathy (BSE) agent
and in the UK they may have been exposed to BSE via contaminated meat and bone
meal. An experimental sheep flock was established to determine whether ovine BSE
could be naturally transmitted under conditions of intensive husbandry. The
flock consisted of 113 sheep of different breeds and susceptible PRNP genotypes
orally dosed with BSE, 159 sheep subsequently born to them and 125 unchallenged
sentinel controls. BSE was confirmed in 104 (92%) orally dosed sheep and natural
transmission was recorded for 14 of 79 (18%) lambs born to BSE infected dams,
with rates varying according to PRNP genotype. The likelihood of natural BSE
transmission was linked to stage of incubation period of the dam: the attack
rate for lambs born within 100 days of the death of BSE infected dams was
significantly higher (9/22, 41%) than for the rest (5/57, 9%). Within the group
of ewes lambing close to death, those rearing infected progeny (n = 8, for 9/12
infected lambs) showed a significantly greater involvement of lymphoid tissues
than those rearing non-infected offspring (n = 8, for 0/10 infected lambs).
Horizontal transmission to the progeny of non-infected mothers was recorded only
once (1/205, 0.5%). This low rate of lateral transmission was attributed, at
least partly, to an almost complete absence of infected placentas. We conclude
that, although BSE can be naturally transmitted through dam-lamb close contact,
the infection in this study flock would not have persisted due to low-efficiency
maternal and lateral transmissions.
snip...
Discussion
This study provides compelling evidence that sheep BSE is naturally
transmissible and contagious. This is in contrast to the report by Foster et al.
[28], who did not find evidence of maternal transmission in nine susceptible
offspring from four BSE-infected dams. In the present study, 14 lambs born to
BSE infected dams and another born to a non-infected dam either developed
clinical BSE or were positive for PrPd when culled. Moreover, since the relative
risk of infection was much higher (around 35 times) for the progeny of infected
dams (~18%) than for the offspring of non-infected ewes (~0.5%), we conclude
that, within the context of the experimental design of this study, natural BSE
transmission occurs mostly from dam to offspring, that is, through a maternal or
vertical route. The importance of maternal transmission as a means of
maintaining endemic infection has previously been well documented for classical
scrapie [20, 29–31], but there is neither epidemiological nor experimental
evidence for maternal transmission of cattle BSE [32, 33].
It has recently been suggested that sheep foetuses may be infected with
classical scrapie in utero [12–14]. In the present experiment, the lack of PrPd
detection in the placentas of the offspring that went on to develop BSE (Figure
4) and the fact that in some twin births only one lamb became infected (Table
3), do not suggest that maternal transmission occurred in utero. However, the
relatively small SDs in the ST of the infected Suffolk and Romney F1 progeny,
which were comparable to that in the corresponding orally dosed parental stock
(Table 1; Figure 2), suggest that all those offspring became infected with
similar infectious doses and at a similar time. Since STs of the offspring did
not differ from that of the parental stock (Table 1; Figure 2), it is likely
that infection occurred shortly after birth, and certainly before 3 months of
age when lambs were separated from their dams. The precise maternal source of
infectious agent for the progeny cannot be determined in this study. By
comparison with classical scrapie, blood and other birth fluids, saliva [34] and
milk [18, 19] are all potential sources of BSE agent. Infectivity in the last
two secretions most probably reflects presence of the infectious agent in blood
(prionaemia) rather than true replication of the agent in the salivary and
mammary glands. This possibility is further suggested by the higher levels of
PrPd found in the LRS of dams with infected progeny compared to those with
uninfected offspring (Table 3) and by the increased probability of infection in
lambs born to ewes that lambed close to their death from BSE (Figure 3), that
is, in advanced stages of the incubation period. This late preclinical disease
stage is when dissemination of the infectious agent throughout the LRS is at its
peak, as shown by studies on sheep BSE [7, 8, 10] and on sheep scrapie [35–38]
and when prionaemia reaches highest levels, as demonstrated by blood transfusion
experiments [39].
Lambs that were naturally infected from their dams, survived significantly
longer than lambs receiving 1 g oral dose at 6–10 days of age (Figure 2). On one
hand, this could be due to natural infection occurring at an older age than 10
days but still before weaning. On the other hand, it could suggest that the
infection passed from dams to lambs was less that the equivalent titre
represented by a 1 g oral infectious dose. This relatively low maternal
infectious dose would also be in agreement with the significantly lower AR
observed in the offspring compared to the orally dosed dams and with the fact
that in some twin parturitions one lamb became infected and the other did not
(Figure 4). However, a low infectious maternal dose may be difficult to
reconcile with the fact that the survival times of the naturally infected
progeny were actually no longer than those observed in their dams, which were
given a 5 g dose. The explanation may lie in the age difference at infection
between naturally infected offspring (pre-weaning) and their dams (average 5
months for Suffolk and 10 months for Romney sheep), which would make young lambs
significantly more susceptible to BSE than weaned lambs and young adults, as has
already been shown in a different study [9].
The results of this study thus show that BSE infected dams can transmit
infection to their progeny. However, the excretion of the infectious agent is
either discontinuous and/or its level variable. Thus, only some lambs
–particularly those born at late preclinical stage of the dams—would receive an
efficient dose and develop disease with relatively short incubation periods,
while others would remain uninfected (at least as shown by PrPd detection within
the context of the study). Husbandry factors may also be important to explain
the lack of transmission to some of the uninfected offspring. Dams incubating
BSE were often poor mothers and, as is common practice in commercial farming,
poorly mothered newborn lambs were often reared by other ewes, including
sentinel controls and ewes at early BSE incubation stages. Efforts to trace back
information about each individual lamb were unsuccessful because of the large
scale of the study and its duration.
One sheep that was the progeny of a non-infected Romney F1 ewe was found to
be BSE-infected. Assuming that there were no confounding management factors
(e.g. that this lamb suckled from an infected ewe), this finding is indicative
of the occurrence of horizontal or lateral BSE transmission. However, despite
the flock being kept indoors for the duration of the study, the level of true
horizontal transmission found in this study was very low (~0.5%) and certainly
much lower than that observed for classical scrapie, where a high proportion of
sheep of susceptible genotypes born to non-infected dams can become infected in
a heavily contaminated environment [20]. A possible explanation for the
difference between scrapie and sheep BSE in this respect lies in placental
infectivity. In classical scrapie, a high proportion of placentas from infected
ewes harbouring foetuses of susceptible genotype are infectious and/or contain
detectable PrPd/PrPres [16, 17, 40–43] and such infected placentas are regarded
as one of the most important, if not the main, sources of environmental
contamination and horizontal transmission [20, 44]. In contrast, in this study,
where BSE infected dams had foetuses and placentas of the same susceptible
genotypes, only one placenta was found to be PrPd positive. This was despite
many placentas corresponding to lambs that went on to develop BSE or others
being collected once the dam had shown peripheral prion replication as
demonstrated by PrPd positive biopsy. Arrival of infectivity in the placenta is
most likely through the haematogenous route and, since a high number of BSE
infected dams showed LRS involvement around gestation, their placentas are
likely to have been exposed to the infectious agent. This would therefore
suggest that there is a difference between the scrapie and BSE agents’ ability
to replicate in the placenta, although without proper comparative kinetics data
between scrapie and BSE infected sheep such a possibility cannot be ascertained.
Nevertheless, regardless of the pathogenetic mechanism, the almost complete lack
of placental PrPd detected in this study is probably a significant factor in the
low rate of horizontal transmission observed.
In addition to placentas, environmental contamination at lambing time may
be due to birth excreta such as blood and amniotic fluid from infected dams,
which were not tested in the course of this study. Even if those fluids were
infectious, the level of environmental contamination would have been low, since
only a few (50 in 7 years) BSE infected dams lambed each year and even fewer
(between 0 and 4 per year for a total of 13 in 7 years) lambed offspring that
went on to develop BSE. In other words, pressure of infection at lambing time,
which has been recognised as an important factor for sheep scrapie [20], would
have been low in the experimental set up of this study. This would have
contributed to low environmental contamination and negligible horizontal
transmission, as observed.
In order to achieve endemic BSE within a flock, horizontal and/or maternal
transmission of infection must be efficient. This was not the case in the
present study. Only a single lamb became infected by putative horizontal
transmission. Of 99 BSE orally infected ewes, 49 succumbed to BSE before lambing
or had progeny that died at young age (without having lambed) and 50 lambed
viable offspring. Thirty-seven of these dams, most of which lambed only once
before succumbing to BSE, had an uninfected progeny. Of the remaining 13, one
(C1 in Figure 4) had multiple parturitions with only one of six lambs becoming
infected, one (R5) had two parturitions with only one of two lambs becoming
infected and the remaining 11 ewes had only one lambing, with 12/14 lambs
developing BSE. Only one of these ewes (R7) produced a set of twins both of
which developed infection; the rest only reared single infected progeny.
Moreover, of the 14 F1 progeny that developed BSE, only 6 sheep (2 each of ARQ
Suffolk, ARQ Romney and VRQ Cheviot sheep) were females. In other words, out of
almost a hundred infected ewes of the parental stock only slightly more than 6%
of the sheep of the F1 generation were in a situation of transmitting infection
to the next generation and the only one that lambed did not transmit. Thus,
although the results of this study clearly indicate that natural transmission of
BSE can occur, they do not provide strong evidence for multigenerational
maintenance of infection. This conclusion would agree with the absence of any
BSE-like case in a retrospective study on more than 2000 natural ovine TSEs
diagnosed between 1998 and 2004 [45]. However, a perhaps important caveat of the
present experiment is the rapidity with which orally dosed dams succumbed to
BSE. In a different scenario, perhaps with a lower oral dose, infected dams
could have had the opportunity to lamb in several successive seasons and this
could have led to a higher opportunity to raise infected progeny and/or to
increase environmental contamination at lambing time. Therefore, the possibility
that ovine BSE may show greater trans-generational spread of infectivity under
conditions of high infectivity pressure, which was not the case in this
experiment, cannot be ruled out.
This study has also provided some additional information regarding the
pathogenesis of sheep BSE after oral infection. Firstly, the resistance of M112T
ARQ Suffolk sheep to oral BSE, which confirms previous reports [10, 22]; in this
respect BSE differs from oral scrapie, for which the threonine polymorphism at
codon 112 confers only partial resistance, both in terms of AR and ST [23].
Secondly, the poor correlation between clinical disease, magnitude of PrPd in
the brain and survival time (Figure 5A); this is in agreement with previous
reports on experiments done by the oral [10] and the intracerebral [25] routes.
Thirdly, that non-PrP genetics may be involved in the relative proportion of
PrPd in the brain and LRS tissues. Thus, when pooling data from parental stock
and F1 together, ARQ Romney sheep showed higher brain PrPd for lower LRS PrPd
compared with Suffolk sheep of the same genotype, which showed the reverse
pattern (results not shown but can be inferred from Figures 5A and B); this is
in agreement with the findings of other sheep BSE experiments [10, González et
al., unpublished observations). Fourthly, that VRQ sheep appear to be, in terms
of survival time, less susceptible to cattle BSE than to some forms of classical
sheep scrapie, which might be related to low replication of the agent in the LRS
(Figure 5B) of BSE- compared to scrapie-infected sheep (for review see [46]);
however, long incubation periods in VRQ sheep have also been reported for sheep
scrapie, when the infectious source is of a heterologous ARQ genotype [23].
Finally, that both in terms of truncation site of intracellular PrPd and of
brain PrPd profile, BSE in the naturally infected animals is indistinguishable
from that in the donor ewes; this finding is in agreement with those obtained on
serial experimental passage of BSE in sheep [47].
In conclusion, the results of the present study show that transmission of
BSE from dam to offspring may occur. However, the low efficiency of maternal
transmission and the almost complete lack of horizontal transmission do not
suggest that BSE infectivity is likely to be self-sustaining within sheep
flocks, at least within the context of the experimental design reported here and
the caveats already expressed.
Go to: Authors’ contributions MJ participated in the design of the study,
in the immunohistochemical (IHC) examinations, in data analysis and
interpretation and drafted the manuscript. JPW carried out statistical analyses.
SM coordinated IHC processing and quality control and participated in the IHC
examinations. SACH coordinated and participated in post-mortems and sample
collection. SJB conceived and designed the study. GED carried out biopsies and
participated in post-mortems and sample collection. LT participated in
post-mortems and sample collection. LG participated in data analysis and
interpretation and helped in drafting the manuscript. All authors read and
approved its final manuscript.
Acknowledgements This study was funded under Defra project SE1946. The
authors wish to thank H. Simmons and the staff at the ARSU (APHA) for provision
and husbandry of New Zealand-derived, TSE-free sheep, Y. Spencer and the
histology laboratory (APHA-Weybridge) for tissue sample preparation, L. Algar,
A. Dunachie and M. Oliva (APHA-Lasswade) for technical support with
immunohistochemistry. J. Hope’s (APHA) appraisal of the manuscript is also
acknowledged.
Competing interests The authors declare that they have no competing
interests.
*** This study provides compelling evidence that sheep BSE is naturally
transmissible and contagious
Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr.
Submission
Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats
SUMMARY: We are reopening the comment period for our proposed rule that
would revise completely the scrapie regulations, which concern the risk groups
and categories established for individual animals and for flocks, the use of
genetic testing as a means of assigning risk levels to animals, movement
restrictions for animals found to be genetically less susceptible or resistant
to scrapie, and recordkeeping requirements. This action will allow interested
persons additional time to prepare and submit comments.DATES: The comment period
for the proposed rule published on September 10, 2015 (80 FR 54660-54692) is
reopened. We will consider all comments that we receive on or before December 9,
2015. ...
COMMENT SUBMISSION TERRY S. SINGELTARY SR.
WITH regards to Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats, I
kindly submit the following ;
>>>The last major revision of the scrapie regulations occurred on
August 21, 2001, when we published in theFederal Register(66 FR 43964, Docket
No. 97-093-5) a final rule amending part 79 by imposing additional restrictions
on the interstate movement of sheep and goats.<<<
Indeed, much science has changed about the Scrapie TSE prion, including
more science linking Scrapie to humans. sadly, politics, industry, and trade,
have not changed, and those usually trump sound science, as is the case with all
Transmissible Spongiform Encephalopathy TSE Prion disease in livestock producing
animals and the OIE. we can look no further at the legal trading of the Scrapie
TSE prion both typical and atypical of all strains, and CWD all stains. With as
much science of old, and now more new science to back this up, Scrapie of all
types i.e. atypical and typical, BSE all strains, and CWD all strains, should be
regulated in trade as BSE TSE PRION. In fact, I urge APHIS et al and the OIE,
and all trading partners to take heed to the latest science on the TSE prion
disease, all of them, and seriously reconsider the blatant disregards for human
and animal health, all in the name of trade, with the continued relaxing of TSE
Prion trade regulations through the ‘NEGLIGIBLE BSE RISK’ PROGRAM, which was set
up to fail in the first place. If the world does not go back to the ‘BSE RISK
ASSESSMENTS’, enhance, and or change that assessment process to include all TSE
prion disease, i.e. ‘TSE RISK ASSESSMENT’, if we do not do this and if we
continue this farce with OIE and the USDA et al, and the ‘NEGLIGIBLE BSE RISK’
PROGRAM, we will never eradicate the TSE prion aka mad cow type disease, they
will continue to mutate and spread among species of human and animal origin, and
they will continue to kill. ...
please see ;
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 longe 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***
===============
***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.
***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.
Monday, November 16, 2015
Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr.
Submission
Friday, April 24, 2015
The placenta shed from goats with classical scrapie is infectious to goat
kids and lambs
*** PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS ***
THANK YOU PRION 2015 TAYLOR & FRANCIS, Professor Chernoff, and
Professor Aguzzi et al, for making these PRION 2015 Congressional Poster and
Oral Abstracts available freely to the public. ...Terry S. Singeltary Sr.
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, Val erie 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 longe 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...
===============
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.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of the agent of sheep scrapie to deer results in PrPSc
with two distinct molecular profiles Authors
item Greenlee, Justin item Moore, Sarah - item Smith, Jodi item West
Greenlee, Mary - item Kunkle, Robert
Submitted to: Prion Publication Type: Abstract Only Publication Acceptance
Date: March 31, 2015 Publication Date: May 25, 2015 Citation: Greenlee, J.,
Moore, S.J., Smith, J.., West Greenlee, M.H., Kunkle, R. 2015.
Scrapie transmits to white-tailed deer by the oral route and has a
molecular profile similar to chronic wasting disease and distinct from the
scrapie inoculum. Prion 2015. p. S62. Technical Abstract: The purpose of this
work was to determine susceptibility of white-tailed deer (WTD) to the agent of
sheep scrapie and to compare the resultant PrPSc to that of the original
inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route
of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie
isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc
was detected in lymphoid tissues at preclinical time points, and deer necropsied
after 28 months post-inoculation had clinical signs, spongiform encephalopathy,
and widespread distribution of PrPSc in neural and lymphoid tissues. Western
blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral
cortex had a profile similar to the original scrapie inoculum, whereas WB of
brainstem, cerebellum, or lymph nodes reveal PrPSc with a higher profile
resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical
scrapie were further passaged to mice expressing cervid prion protein and
intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct
incubation times. Sheep inoculated intranasally with WTD derived scrapie
developed disease, but only after inoculation with the inoculum that had a
scrapie-like profile. The WTD study is ongoing, but deer in both inoculation
groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work
demonstrates that WTD are susceptible to the agent of scrapie, two distinct
molecular profiles of PrPSc are present in the tissues of affected deer, and
inoculum of either profile type readily passes to deer.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Scrapie transmits to white-tailed deer by the oral route and has a
molecular profile similar to chronic wasting disease Authors
item Greenlee, Justin item Moore, S - item Smith, Jodi - item Kunkle,
Robert item West Greenlee, M -
Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015
Publication Date: N/A
Technical Abstract: The purpose of this work was to determine
susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to
compare the resultant PrPSc to that of the original inoculum and chronic wasting
disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral
and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer
had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at
preclinical time points, and deer necropsied after 28 months post-inoculation
had clinical signs, spongiform encephalopathy, and widespread distribution of
PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with
2 distinct molecular profiles. WB on cerebral cortex had a profile similar to
the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph
nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the
2 distinct profiles from WTD with clinical scrapie were further passaged to mice
expressing cervid prion protein and intranasally to sheep and WTD. In cervidized
mice, the two inocula have distinct incubation times. Sheep inoculated
intranasally with WTD derived scrapie developed disease, but only after
inoculation with the inoculum that had a scrapie-like profile. The WTD study is
ongoing, but deer in both inoculation groups are positive for PrPSc by rectal
mucosal biopsy. In summary, this work demonstrates that WTD are susceptible to
the agent of scrapie, two distinct molecular profiles of PrPSc are present in
the tissues of affected deer, and inoculum of either profile readily passes to
deer.
***Our study demonstrates susceptibility of adult cattle to oral
transmission of classical BSE. ***
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. ***
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, ***our findings suggest that possible transmission risk of
H-type BSE to sheep and human. Bioassay will be required to determine whether
the PMCA products are infectious to these animals.
================
==========================================
***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.
==========================================
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.***
================
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of
infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical
BSE investigations
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67
PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in
unusual brain location and PrPsc detection by PMCA only.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
Singeltary et al
31 Jan 2015 at 20:14 GMT
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
*** It also suggests a similar cause or source for atypical BSE in these
countries. ***
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan.
*** This supports the theory that the importation of BSE contaminated
feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these
countries. ***
see page 176 of 201 pages...tss
Monday, October 26, 2015
*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q
(AAQQ) and the disease phenotype is similar to that seen with experimental
strain CH1641.
4.2.9 A further hypothesis to explain the occurrence of BSE is the
emergence or selection of a strain or strains of the scrapie agent pathogenic
for cattle. Mutations of the scrapie agent. which can occur after a single
passage in mice. have been well documented (9). This phenomenon cannot be
dismissed for BSE. but given the form of the epidemic and the geographically
widespread occurrence of BSE, such a hypothesis" would require the emergence of
a mutant scrapie strain simultaneously in a large . number of sheep flocks, or
cattle. throughout the country. Also. if it resulted "from a localised chance
transmission of the scrapie strain from sheep to cattle giving rise , . to a
mutant. a different pattern of disease would have been expected: its range would
'. have increased with time. Thus the evidence from Britain is against the
disease being due to a new strain of the agent, but we note that in the United
States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to
have Increased markedly. now being nearly 3 times as high as during any previous
period (18).
If the scrapie agent is generated from ovine DNA and thence causes disease
in other species, then perhaps, bearing in mind the possible role of scrapie in
CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the
notifiable disease. ...
EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE
This is provided by the statistically significant increase in the incidence
of sheep scrape from 1985, as determined from analyses of the submissions made
to VI Centres, and from individual case and flock incident studies.
........
RISK OF BSE TO SHEEP VIA FEED
OPII-1
Disease incidence and incubation period of BSE and CH1641 in sheep is
associated with PrP gene polymorphisms.
Goldman WI, Hunter N., Benson G., Foster J. and Hope J. AFRC&MRC
Neuropathogenesis Unit, Institute for Animal Health, West Mains Rd. Edinburgh
EH9 3JF. U.K.
The relative survival periods of mice with different Sine genotype have
long been used for scrapie strain typing. The PrP protein. a key molecule in the
pathogenesis of scrapie and related diseases, is a product of the Sine locus and
homologous proteins are also linked to disease-incidence loci in sheep and man.
In sheep alleles of this locus (Sip) encode several PrP protein variants, of
which one has been associated with short incubation periods of Cheviot sheep
infected with SSBP/1 scrapie. Other isolates, i.e. BSE or CH1641. cause a
different pattern of incubation periods and a lower disease incidence in the
same flock of Cheviot sheep. Using transmission to sheep of known PrP genotype
as our criterion for agent strain typing. we have found a link between BSE and
CH1641. a C-group strain of scrapie. Disease susceptibility of sheep to these
isolates is associated with different PrP genotypes compared to SSBP/1 scrapie.
OPII –2
Transmission of Bovine Spongiform Encephalopathy in sheep, goats and mice.
Foster J., Hope J., McConnell I. and Fraser H. Institute for Animal Health,
AFRC and MRC Neuropathogenesis Unit, Kings Buildings, West Mains Road, Edinburgh
EH9 3JF
Bovine Spongiform Encephalopathy (BSE) has been transmitted in two lines of
genetically selected sheep [differing in their susceptibilities to the SSBP/1
source of scrapie), and to goats by intracerebral injection and by oral dosing.
Incubation periods in sheep for both routes of challenge ranged from 440-994
days. In goats this range was 506-1508 days. Both routes of infection in sheep
and goats were almost equally efficient. In mice, primary transmission of BSE
identified a sinc-independant genetic control of incubation period. Also,
intermediate passage of BSE in sheep or goats did not alter these primary
transmission properties. Hamsters were susceptible to BSE only after intervening
passage through mice.
RESEARCH ARTICLE
Phenotype Shift from Atypical Scrapie to CH1641 following Experimental
Transmission in Sheep
Marion M. Simmons*, S. Jo Moore¤a, Richard Lockey¤b, Melanie J. Chaplin,
Timm Konold, Christopher Vickery, John Spiropoulos
Animal and Plant Health Agency—Weybridge, Woodham Lane, Addlestone, Surrey,
KT15 3NB, United Kingdom
¤a Current address: School of Veterinary and Biomedical Sciences, Murdoch
University, South Street, Murdoch, Western Australia, 6150, Australia
¤b Current address: University of Southampton, Southampton, SO17 1BJ,
United Kingdom * marion.simmons@apha.gsi.gov.uk
Abstract
The interactions of host and infecting strain in ovine transmissible
spongiform encephalopathies are known to be complex, and have a profound effect
on the resulting phenotype of disease. In contrast to classical scrapie, the
pathology in naturally-occurring cases of atypical scrapie appears more
consistent, regardless of genotype, and is preserved on transmission within
sheep homologous for the prion protein (PRNP) gene. However, the stability of
transmissible spongiform encephalopathy phenotypes on passage across and within
species is not absolute, and there are reports in the literature where
experimental transmissions of particular isolates have resulted in a phenotype
consistent with a different strain. In this study, intracerebral inoculation of
atypical scrapie between two genotypes both associated with susceptibility to
atypical forms of disease resulted in one sheep displaying an altered phenotype
with clinical, pathological, biochemical and murine bioassay characteristics all
consistent with the classical scrapie strain CH1641, and distinct from the
atypical scrapie donor, while the second sheep did not succumb to challenge. One
of two sheep orally challenged with the same inoculum developed atypical scrapie
indistinguishable from the donor. This study adds to the range of transmissible
spongiform encephalopathy phenotype changes that have been reported following
various different experimental donor-recipient combinations. While these
circumstances may not arise through natural exposure to disease in the field,
there is the potential for iatrogenic exposure should current disease
surveillance and feed controls be relaxed. Future sheep to sheep transmission of
atypical scrapie might lead to instances of disease with an alternative
phenotype and onward transmission potential which may have adverse implications
for both public health and animal disease control policies.
snip...
Despite naturally-occurring atypical scrapie being observed in a range of
genotypes, successful experimental transmissions of clinical disease have so far
only been reported within a particular homologous donor-recipient genotype model
using sheep which are AHQ/AHQ homozygous [8,15,16]. These published
transmissions represent part of a large study at APHA which has been running
since 2004, investigating the potential transmissibility of atypical scrapie in
a range of both homologous and cross-genotype combinations. Here we describe an
unexpected and interesting finding from that study where one experimental
challenge in which atypical scrapie from an ARR/ARR donor was inoculated
intracerebrally into two AHQ/AHQ recipient sheep, and in one of them the
resulting disease had a phenotype that was indistinguishable from CH1641 [29], a
classical scrapie strain which has some BSE-like Western blot properties.
Subject: more on scrapie/BSE strain CH1641
From: tom
Reply-To: Bovine Spongiform Encephalopathy
Date: Sun, 10 Jan 1999 21:52:05 -0800
Content-Type: text/plain
Parts/Attachments: Parts/Attachments text/plain (37 lines) Reply Reply
Recall a forthcoming J Gen Virol Jan 1999 v80:1 - 4 says there are
similarities between BSE and an experimental isolate of natural scrapie, CH1641.
This might then be the long-sought missing scrapie strain that could have given
rise to the BSE epidemic. It would raise additional questions about the
harmlessness to humans of scrapie.
On the other hand, CH1641 happened to be one of the scrapie strains studied
very recently by Collinge's group, Neurosci Lett. 1998 Oct 23;255(3):159-62. It
did not have the prp-sc type identical to BSE passaged in sheep.
The CH1641 strain is mentioned only twice before in Medline abstracts
(though there could be many fulltext mentions), one of these being the original
naming of the strain in 1988:
The unusual properties of CH1641, a sheep-passaged isolate of
scrapie.
Foster JD, Dickinson AG Vet Rec 1988 Jul 2;123(1):5-8
An isolate of scrapie designated CH1641 was identified from a natural case
of scrapie in a Cheviot sheep by passage in sheep and goats. It has not been
possible to transmit scrapie to mice from this source. The Sip gene which
controls the incubation periods of experimental scrapie in Cheviot sheep has two
alleles; sA which shortens and pA which lengthens the incubation periods of most
strains of scrapie after the first experimental injection in sheep (the A group
of strains). The CH1641 isolate differs from them in that the alleles of Sip act
in the opposite way, with incubation being shorter in the pA homozygotes. There
is some evidence that one or more genes, in addition to Sip, may be implicated
in the control of scrapie incubation in sheep and the possibility of a carrier
infection with CH1641 is also discussed.
Novel polymorphisms in the caprine PrP gene: a codon 142 mutation
associated with scrapie incubation period.
J Gen Virol 1996 Nov;77 ( Pt 11):2885-91 Published erratum appears in J Gen
Virol 1997 Mar;78(Pt 3):697 Goldmann W, Martin T, Foster J, Hughes S, Smith G,
Hughes K, Dawson M, Hunter N
Age at disease onset and rate of progression of transmissible spongiform
encephalopathies in man, sheep and mice are modulated by the host genome, in
particular by the PrP gene and its allelic forms. Analysis of the caprine PrP
gene revealed several different alleles. Four PrP protein variants were found,
three of which were goat specific with single amino acid changes at codons 142,
143 and 240. The fourth was identical to the most common sheep PrP protein
variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met)
appeared to be associated with differing disease incubation periods in goats
experimentally infected with isolates of bovine spongiform encephalopathy, sheep
scrapie CH1641 or sheep-passaged ME7 scrapie.
######## Bovine Spongiform Encephalopathy
#########
JOURNAL OF VIROLOGY, June 2004, p. 6243–6251 Vol. 78, No.
120022-538X/04/$08.00 0 DOI: 10.1128/JVI.78.12.6243–6251.2004
Copyright © 2004, American Society for Microbiology. All Rights
Reserved.Molecular Analysis of the Protease-Resistant Prion Protein in
Scrapieand Bovine Spongiform Encephalopathy Transmitted toOvine Transgenic and
Wild-Type MiceThierry Baron,1* Carole Crozet,1† Anne-Gae¨lle Biacabe,1
SandrinePhilippe,2 Je´re´mie Verchere,1Anna Bencsik,1 Jean-Yves Madec,1 Didier
Calavas,2 and Jacques Samarut3Unite´ Agents Transmissibles Non Conventionnels1
and Unite´Epide´miologie,2 Agence Franc¸aise de Se´curite´ Sanitairedes
Aliments—Lyon, and Laboratoire de Biologie, Ecole Normale Supe´rieure de Lyon,3
Lyon, France Received 27 October 2003/Accepted 4 February 2004
The existence of different strains of infectious agents involved in
scrapie, a transmissible spongiform encephalopathy (TSE) of sheep and goats,
remains poorly explained. These strains can, however, be differentiated by
characteristics of the disease in mice and also by the molecular features of the
protease-resistant prion protein (PrPres) that accumulates into the infected
tissues. For further analysis, we first transmitted the disease from brain
samples of TSE-infected sheep to ovine transgenic[Tg(OvPrP4)] and to
wild-type(C57BL/6) mice. We show that, as in sheep, molecular differences
ofPrPres detected by Western blotting can differentiate, in both ovine
transgenic and wild-type mice, infection bythe bovine spongiform
encephalopathy(BSE) agent from most scrapie sources. Similarities of an
experimental scrapie isolate (CH1641) with BSE were also likewise found
following transmission in ovine transgenic mice. Secondly, we transmitted the
disease to ovine transgenic mice by inoculation of brain samples of wild-type
mice infected with different experimental scrapie strains (C506M3, 87V, 79A, and
Chandler) or with BSE. Features of these strains in ovine transgenic mice were
reminiscent of those previously described for wild-type mice,by both ratios and
by molecular masses of the different PrPres glycoforms. Moreover, these studies
revealed the diversity of scrapie strains and their differences with BSE
according to labeling by a monoclonal antibody(P4). These data, in an
experimental model expressing the prion protein of the host of natural
scrapie,further suggest a genuine diversity of TSE infectious agents and
emphasize its linkage to the molecular features of the abnormal prion protein.
snip...
######### http://mailhost-alt.rz.uni-karlsruhe.de/warc/bse-l.html
##########
BSE and Scrapie
TSE PRION UPDATE USA 2012
re-BSE in goats can be mistaken for scrapie
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
February 1, 2012
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
Saturday, September 19, 2015
*** An interview with Professor John Collinge: VIDEO Director of the MRC
Prion Unit Part of the Hayward Gallery's History Is Now ***
Saturday, September 12, 2015
The Canadian Management of Bovine Spongiform Encephalopathy in Historical
and Scientific Perspective, 1990-2014
>>>We propose that Canadian policies largely ignored the implicit
medical nature of BSE, treating it as a purely agricultural and veterinary
issue. In this way, policies to protect Canadians were often delayed and
incomplete, in a manner disturbingly reminiscent of Britain’s failed management
of BSE. Despite assurances to the contrary, it is premature to conclude that BSE
(and with it the risk of variant Creutzfeldt-Jakob disease) is a thing of
Canada’s past: BSE remains very much an issue in Canada’s present.
<<<
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. ...
Wednesday, September 23, 2015
NIH Availability for Licensing AGENCY: [FR Doc. 2015–24117 Filed 9–22–15;
8:45 am] Detection and Discrimination of Classical and Atypical L-Type BSE
Strains by RT-QuIC
Thursday, October 1, 2015
H-type bovine spongiform encephalopathy associated with E211K prion protein
polymorphism: clinical and pathologic features in wild-type and E211K cattle
following intracranial inoculation
Wednesday, May 27, 2015
BSE Case Associated with Prion Protein Gene Mutation
spontaneous atypical BSE ???
don’t let anyone fool you. spontaneous TSE prion disease is a hoax in
natural cases, never proven.
all one has to do is look at France. France is having one hell of an
epidemic of atypical BSE, probably why they stopped testing for BSE, problem
solved $$$ same as the USA, that’s why they stopped testing for BSE mad cow
disease in numbers they could find any with, after those atypical BSE cases
started showing up. shut down the testing to numbers set up by OIE that are so
low, you could only by accident find a case of BSE aka mad cow disease. and this
brilliant idea by the WHO et al, to change the name of mad cow disease, thinking
that might change things is preposterous. it’s all about money now folks, when
the OIE, USDA and everyone else went along and made the TSE prion disease aka
mad cow type disease a legal trading commodity by the BSE MRR policy, I would
say everyone bit off more then they can chew, and they will just have to digest
those TSE Prions coming from North America, and like it, and just prey you don’t
get a mad cow type disease i.e. Transmissible Spongiform Encephalopathy TSE
prion disease in the decades to come, and or pass it to some other poor soul via
the iatrogenic medical surgical tissue friendly fire mode of transmission i.e.
second hand transmission. it’s real folks, just not documented much, due to lack
of trace back efforts. all iatrogenic cjd is, is sporadic cjd, until the
iatrogenic event is tracked down and documented, and put into the academic and
public domain, which very seldom happens. ...
As of December 2011, around 60 atypical BSE cases have currently been
reported in 13 countries, *** with over one third in France.
FRANCE STOPS TESTING FOR MAD COW DISEASE BSE, and here’s why, to many
spontaneous events of mad cow disease $$$
so 20 cases of atypical BSE in France, compared to the remaining 40 cases
in the remaining 12 Countries, divided by the remaining 12 Countries, about 3+
cases per country, besides Frances 20 cases. you cannot explain this away with
any spontaneous BSe. ...TSS
Sunday, October 5, 2014
France stops BSE testing for Mad Cow Disease
Saturday, June 14, 2014
Rep. Rosa DeLauro (D-CT) Calls for Briefing on Beef Recalled for Mad Cow
Potential Rep. Rosa DeLauro (D-CT)
Sunday, October 25, 2015
USAHA Detailed Events Schedule – 119th USAHA Annual Meeting CAPTIVE
LIVESTOCK CWD SCRAPIE TSE PRION
Thursday, October 22, 2015
Former Ag Secretary Ann Veneman talks women in agriculture and we talk mad
cow disease USDA and what really happened
Sunday, October 18, 2015
World Organisation for Animal Health (OIE) and the Institut Pasteur
Cooperating on animal disease and zoonosis research
Friday, May 29, 2015
GAO FEDERAL VETERINARIANS US Federal Government Is Unprepared for a
Large-Scale Animal Disease Outbreak
Thursday, September 10, 2015
25th Meeting of the Transmissible Spongiform Encephalopathies Advisory
Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015
Terry S. Singeltary Sr.
