DEFRA What is the risk of a cervid TSE being introduced from Norway into
Great Britain? Qualitative Risk Assessment September 2016
Summary
This document is an update of a previous risk assessment carried out in
April 2016 to account for the risk of incursion of CWD from the USA and Canada
and the assessment of a new pathway, deer urine lures. In April 2016, a report
of CWD-like disease was reported in Norway in wild reindeer and later in moose,
and this assessment is to review the risk pathways for this new geographic area.
Therefore any updates which differ from the assessment of April will appear in
red throughout the main text.
The Norwegian Veterinary Institute reported a wild reindeer (Rangifer
tarandus tarandus) found moribund and which later died in March 2016, had tested
positive for the presence of prions. This was the first case of TSE found in a
cervid in Europe and the first ever TSE case in a reindeer or caribou. In
regions where chronic wasting disease is commonly found in native deer, there
have been no reported cases in caribou (related to reindeer), but this is due to
the isolation of the populations, rather than the refractivity of the species.
The following month, two further cases were reported in wild moose (Alces
alces), in a different region and again testing positive for TSE prion protein.
In the last month, a fourth case was detected, again in a reindeer in Nordfjell
region, this time in a healthy bull, shot for disease surveillance.
The new assessment focuses on the potential routes of entry for a cervid
TSE (whether confirmed as chronic wasting disease or another related prion) from
Norway. The main conclusions from this assessment are:
• The likelihood of further cases being found in wild reindeer in Norway is
high, if confirmed as CWD as opposed to a spontaneous mutation event.
• The likelihood of further cases being found in moose is dependent on
whether these are confirmed as a familial case or if related to the TSE in the
reindeer. Moose are generally solitary animals so the risk of spread will depend
on the level of wider environmental contamination, rather than direct contact
with other infected cervids.
• The likelihood of spread of a CWD type disease into the farmed reindeer
herd or into other farmed cervids in Norway is difficult to assess, and depends
on the level of contact between migratory wild reindeer and the semi herded
populations in the north or with other farmed cervid species. In the USA, new
foci are often detected first in farmed herds, before detection in local wild
cervids, so the contact between these two discrete populations is clearly
sufficiently high to facilitate transmission in North America. This should be
assessed for Norwegian / Scandinavian populations.
• The likelihood of spread into other (wild) deer populations in Norway is
medium.
• The possible routes of spread of TSE from Norway to the UK include
movements of live animals, imports of deer-related products (urine lures, meat
used as pet food),
2 contaminated equipment, including clothing and hunting or skiing
equipment and soil surrounding plant imports.
• The likelihood of a reindeer imported from Norway to the UK being
infected with TSE is very low as they are imported from farmed herds, but there
is uncertainty around this level of risk as it is not known if there is disease
in the farmed herds.
• Other cervid species are not generally imported from Norway to the UK and
therefore this is a lower risk pathway. If the pattern of trade changes, or if
disease is detected over a wider area, the risk will also change.
• For other animals, the movement of pet dogs used for hunting or sledging
competitions should be assessed for whether meat of cervid origin is fed to the
animals. Where this occurs, this is considered a low risk of disease
introduction.
• For other pathways, these are a non-negligible risk which is difficult to
evaluate without understanding more on the extent of disease in Norway, but is
likely to be between very low or low, depending on the pathway. For lures made
from natural deer urine, where the provenance of the animal is unknown, the risk
is medium for North American origin urine and Norwegian.
• As a result of the cases in Norway not all the risk levels have increased
in comparison to the same risk pathways with an origin in North America.
• Reindeer in the UK are not commonly kept – there are small herds present
including in the Cairngorms and Staffordshire and some seasonal imports. However
the poor outcome of reindeer kept in captivity in the UK means it is difficult
to ascertain whether any may have been infected with prion disease – a fallen
stock programme does not exist for such animals at present.
• Our previous assessment suggested that of the cervid British species, red
deer (Cervus elaphus elaphus) are susceptible to CWD, fallow deer (Dama dama)
may be less susceptible and the roe deer (Capreolus capreolus) prion gene codes
for susceptibility (and are the most closely related to white-tailed deer). More
recent experimental data suggest Sika deer, Chinese Water deer and Muntjac deer
may also be susceptible. Therefore, it is likely that given exposure to an
infectious dose of CWD or a related prion, deer in GB could become
infected.
Overall, the probability of importing a TSE into the GB deer herds from
Norway and causing infection in British deer is uncertain but likely to be no
greater than very low via movement of deer hunters, other tourists and British
service personnel; at most, low via live animal imports or imported
(non-ruminant) animal feed; very low for the use of lures specifically sourced
in Norway and negligible for plant imports. However, if it was imported and (a)
deer did become infected with CWD, the consequences would be severe as
eradication of the disease is unfeasible, it is clinically indistinguishable
from BSE infection in deer and populations of wild and farmed deer would be
under threat.
3
Acknowledgements
Thanks to members of the APHA wildlife, TSE and Epidemiology teams,
Scottish and Welsh administrations, the Deer Initiative, the Moredun Institute,
the British Deer Society and the British Reindeer Herding Society for comments.
Background
Chronic wasting disease (CWD) is a highly infectious transmissible
spongiform encephalopathy (TSE) that is circulating in the wild and farmed
cervid populations of North America. It is the only TSE maintained in
free-ranging wild animal populations. A feature of CWD is that it is able to
transmit both directly (animal-to-animal) and indirectly via the contaminated
environment. In particular, CWD prions are able to bind to and survive in the
soil in a bio-available form for many years without any decrease in infectivity.
This makes eradication of the disease from a wild population very
unlikely.
Thus far, there have been no reported cases of CWD or other TSE in deer in
Great Britain (GB). This is based on surveys of wild and farmed red deer (Cervus
elaphus elaphus) carried out several years ago (EFSA, 2011). Given the
consequences of CWD observed in North America, it is of high importance that GB
remains free of the disease. Further, as the clinical signs of CWD in deer are
similar to those of deer experimentally infected with bovine spongiform
encephalopathy (BSE), all infected deer would need to be tested to differentiate
if they were infected with CWD or BSE to minimise the risk of BSE entering the
human food chain via affected venison. The public health risk of CWD is not
known but current assessments suggest the risk is very low.
In 2015, the British Deer Society (BDS) carried out an online survey of BDS
and BASC members to gather evidence about the use of deer urine as a lure.
Fifteen percent of respondents (~1,800) answered yes about knowing that deer
urine was used as a lure. Of the respondents, less than 2% responded yes to
using such a product themselves. Of those that use the product, 50% had sourced
the product from the USA, while 20% use more than a litre in volume a year and
~70% is natural (as opposed to synthetic).
***UPDATE: The report of TSE (CWD like) infection in Norwegian free ranging
reindeer and then in European moose has increased the risk to the UK because of
the trade in live animals and the different levels of activity for certain
pathways, therefore we are reviewing those risk pathways.
***In addition, a further pathway was identified by a veterinary colleague
overseas, which is that of plant and soil imports as well as for movement of
hunting dogs so we have included these in the review.
*** Hazard identification
The hazard is identified as TSE in wild European Reindeer and Moose
The current geographic range of the cervid TSE, Chronic Wasting Disease
(CWD) is the USA and Canada (and occasional outbreaks in South Korea following
imports of infected animals).
***A new TSE type infection was identified in Norway, in a wild reindeer in
March 2016 (NVI, 2016). Until the cases in Norway are confirmed to have a source
in USA or Canada, at present we will identify the hazard as a transmissible
spongiform encephalopathy (TSE) affecting wild European reindeer and
moose.
The (found dead) adult reindeer cow showed signs of below-average body
condition and detected in connection with capture for GPS-collaring, when it
died. It was tested as a routine sample for the national surveillance programme
for CWD at the Norwegian Veterinary Institute. Prion disease was confirmed in
mid-March by both biochemical and immunohistochemical tests. According to the
EURL, most of the samples from different organs were strongly positive for TSE
prion protein. Samples were sent to the OIE reference laboratory (Canada) for
confirmation as Chronic Wasting Disease. However, based on the widespread
distribution of PrPCWD in the brain and the case history, the conclusion has
been made that the animal had a spongiform encephalopathy compatible with CWD in
the an early clinical stage (Benestad et al., 2016). The animal was found in the
Nordfjell region (see map below). In a second event, an adult (pregnant) female
moose, (Alces alces) in the Sør-Trøndelag region was found with signs of poor
body condition and lack of response to stimuli. It was culled and samples tested
by both ELISA and Western blot tests. A third case was detected in another
moose, found dead in a river near by a few days later. It also tested positive.
There is approximately 300 km distance between the reindeer and the two elk
cases. In a fourth case, in August 2016, a reindeer bull was shot and tested
positive as part of a surveillance programme, also in the Nordfjell region (Sogn
og Fjordane) and a fifth case, again in a reindeer (cow) shot by hunters in the
same region was detected in September 2016. The North American moose (also Alces
alces) is susceptible to CWD and cases have been found across the moose
populations in both the USA and Canada. Alces alces is different to the North
American elk (Cervus canadensis) which is also susceptible to CWD.
MAP
The passive surveillance system in Norway has been running since 2003 and
involves testing samples from wild native cervid species of which there are
four, red deer (Cervus elaphus), roe deer (Capreolus capreolus), moose (Alces
alces) and reindeer (Rangifer tarandus) and from captive deer (Sviland et al,
2015). Red deer predominate along the west coast, wild reindeer live in high
mountain areas in southern Norway (see map above). In 2013, the numbers of
hunted cervids were nearly 35,000 moose, over 36,000 red deer, over 25,000 roe
deer and nearly 8,000 reindeer. There is also a semi-domestic (herded) reindeer
population of 250,000 which are located in north Norway and managed by the Sami
people, and some of these animals will also be tested. There are 90 deer farms
which mainly keep red deer and some keep fallow deer (Dama dama). Scrapie is
present in sheep in areas where there are free ranging red deer populations. The
number tested each year is very small; in 2014, only 10 deer were tested (all
negative), and none of them reindeer. In 2013, again, just ten animals were
tested (all negative) (Sviland et al, 2014) and in 2012, 21 animals were tested
(all negative) and none were reindeer (Vikoren et al., 2013). This level of
surveillance means that when a single positive sample is recorded, it suggests a
high prevalence level is likely but the statistical confidence in such sampling
is very low. It is not known how many animals have been tested in 2015/2016 for
CWD under
6
the Norwegian programme. The Norwegian Authorities are proposing a large
surveillance programme to start in the autumn of 2016, to test around 15,000
animals (moose, roe deer, red deer and reindeer) for fallen stock, hunted
animals and at game slaughter houses and approved locations.
In Europe and North America, moose or elk (A.alces) are solitary animals,
coming together primarily in the mating season, although young stay with their
mothers for several months until the next offspring is born. There is a wide
level of variation in their movement behaviour with some undertaking very long
range migrations, and others being more sedentary. These movements can be
categorised as migration, dispersal, nomadism or residence. In Scandinavia,
seasonal migration is more likely in northerly populations (regions north of
66oN) than those in the southern regions (regions between 56oN and 66oN) and
mean distances decline from ~100 km to 5 km. Seasonal migration can also change
with time, depending on the environmental changes, climate or urbanisation. A
recent study into the population genetics of Alces alces in Europe suggests
there are genetically distinct populations, with the Scandinavian cluster
showing low genetic diversity and separate to the other European populations
(Niedziałkowska et al. 2016). Nevertheless, the low genetic mixing does not
preclude mixing of animals at common grazing areas and therefore having access
to contaminated land.
The genetic sub-structuring of the A.alces population in Scandinavia could
be partly due to geographic barriers, such as the Scandes mountain range which
separates Sweden and Norway. This supports the understanding that there is a
lower risk of direct disease transmission to other populations of cervids, even
of the same species, which are separated by semi-permeable geographic
boundaries. However, if there has been widespread environmental contamination
over time from a common source of prion, then the risk to other populations will
be more difficult to assess.
Chronic Wasting Disease was first identified as a clinical disease of
captive mule deer in Colorado in 1967 and later classified as a TSE in 1978
(Williams & Miller, 2003). The origin of the disease is unknown and may have
been a spontaneous TSE that arose in deer. Currently, natural infections of CWD
have been reported in the USA and Canada in mule deer (Odocoileus hemionus
hemionus), black-tailed deer (Odocoileus hemionus columbianus), white-tailed
deer (Odocoileus virginianus), Rocky Mountain elk (Cervus elphus nelsoni),
Shira’s moose (Alces alces shirasi) and mule deer and white-tailed deer hybrids
(Hamir et al., 2008).
Caribou (Rangifer tarandus caribou, R.t. granti and R.t. goenlandicus) are
a subspecies of the Eurasian reindeer, Rangifer tarandus and several populations
overlap with the current CWD distribution in Canada. The disease has not been
reported in the scientific literature in caribou as natural infections. However,
experimental infection of six reindeer resulted in TSE in two of the six animals
via oral inoculation (Mitchell et al, 2012). In this study on experimental
infection in reindeer, Mitchell and colleagues showed that the two out of three
reindeer infected with CWD prion protein (PrP) from brain homogenates of
infected white-tailed deer started to show clinical signs between 17 and 18
months after oral inoculation. The same infection route using PrP from infected
elk brains did not result in
7
clinical infection in three further reindeer. Results from histopathology
showed PrP present in peripheral lymphoid tissue, in the kidney, the pituitary
and adrenal glands, in nerves associated with the gastro-intestinal tract and of
course the brain and central nervous system.
The widespread distribution in the USA and two Canadian provinces may be
detected because of enhanced surveillance but may have increased because of
natural movements of cervids and translocation of infected animals by humans
(EFSA, 2011). Within affected areas, the prevalence varies. In the endemic area
of Wyoming, for example, the prevalence of CWD in mule deer has increased from
approximately 11% in 1997 to 36% in 2007 (Almberg et al., 2011). In such areas,
population declines of deer of up to 30 to 50% have been observed (Almberg et
al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA,
2011). However the separation between caribou populations in Canada and affected
cervids is probably the main reason for disease not being detected.
The clinical signs of CWD in affected adults are weight loss and
behavioural changes that can span weeks or months (Williams, 2005). In addition,
signs might include excessive salivation, behavioural alterations including a
fixed stare and changes in interaction with other animals in the herd, and an
altered stance (Williams, 2005). These signs are indistinguishable from cervids
experimentally infected with bovine spongiform encephalopathy (BSE). Given this,
if CWD was to be introduced into countries with BSE such as GB, for example,
infected deer populations would need to be tested to differentiate if they were
infected with CWD or BSE to minimise the risk of BSE entering the human
food-chain via affected venison.
The duration of clinical disease is highly variable and death can occur
within 4 weeks but some infected animals may survive as long as a year
(Williams, 2005). The incubation period is a minimum of approximately 16 months
and is more likely to be between 2 and 4 years (Williams, 2005). In affected
American elk, the incubation period is between 1.5 and 3 years after which they
become clinically affected and may succumb less than 12 months after initial
clinical signs appear (Miller et al., 1998). During the pre-clinical period, the
animal is infectious (Almberg et al., 2011).
The CWD agent or Prion Protein (PrPCWD) in affected animals is distributed
firstly in the gut associated lymphoid tissues, digestive tract (e.g. tonsils,
Peyer’s patches, mesenteric lymph nodes) and then in the brain and spinal cord
as the disease progresses (Sigurdson, 2008). Prions of CWD have also been found
in muscle tissue (Angers et al., 2006) (see Figure 1). The distribution and
levels of PrPCWD in tissues differ between species (e.g. American elk versus
white tailed or mule deer).
Figure 1: Diagram displaying the main organs affected by CWD in infected
cervids (http://www.dnr.state.mn.us/mammals/deer/cwd/index.html)
Given its propensity to colonise the digestive tract, evidence suggests the
prion is excreted in faeces (Safar et al., 2008), urine and saliva potentially
leading to direct and indirect transmission between cervid species. Indeed, the
disease is transmitted horizontally with high efficiency and circumstantial
evidence suggests that environmental contamination with CWD prions contributes
to the maintenance of CWD in affected areas (Safar et al., 2008; Nalls et al.,
2013). The rate of transmission of CWD has been reported to be as high as 30%
and can approach 100% among captive animals in endemic areas (Safar et al.,
2008). The efficiency of CWD transmission is unparalleled among TSE diseases
(EFSA, 2011). Trifilo et al., (2007), using a murine tg mouse model, established
that CWD can be transmitted via the oral route. Indeed, the distribution of
PrPres in the orally infected mice (e.g. in the spleen and lymph nodes) mimicked
what has been reported in deer developing CWD via natural infection (Trifilo et
al., 2007). Modelling studies also support the theory that transmission of CWD
in deer herds is maintained by contact with a prion contaminated environment
(Almberg et al., 2011). Scavenging of CWD-infected carcasses provides another
route of releasing the prion into the environment and exposure of non-cervid
species (Sigurdson, 2008). This indirect transmission route is problematic as it
not only increases the basic reproductive number but also because there are very
few effective mitigation strategies for reducing the risk from indirect
transmission. This is due to the fact that the agent is extremely resistant in
the environment and able to bind to soil particles making eradication and
control of CWD a major obstacle in both farmed and free-ranging cervid
populations.
The hypothesis that disease can be transmitted between cervid species has
been supported by recent experimental studies that have demonstrated that
European red deer become infected with CWD after oral inoculation with brain
tissue from infected Rocky Mountain elk (Balachandran et al., 2010).
Specifically, two of the four 2-month old red deer challenged, showed clinical
signs by 585 days p.i. and all deer had CWD prion in the brain, spinal cord and
other organs at necropsy (Balachandran et al., 2010). Further, Martin et al.,
(2009) demonstrated in a similar study of four European red deer, that red deer
can
9
become infected upon inoculation with 5g of infected brain homogenate from
four CWD elk and hence the species is susceptible to CWD.
Hamir et al., (2008) undertook a study to ascertain if fallow deer (Dama
dama), another British deer species, could be experimentally infected with CWD
brain suspension from infected elk or white-tailed deer. The authors concluded
that it is possible to transmit CWD to fallow deer via the intracerebral route
but the pathological features of CWD in the deer differs from those observed in
white-tailed deer or elk (Hamir et al., 2008). It was further concluded that it
might not be possible to transmit CWD via a more natural route or,
alternatively, a higher dose of inoculum is required leading to a longer
incubation period (Hamir et al., 2008). However it should be noted that these
animals were all sourced from a single breeder therefore genetic diversity would
be low and it cannot be ruled out that other fallow deer sourced from other
breeders with greater heterogeneity would behave differently.
Initial studies into the PRioN Protein (PRNP) gene variability in European
red deer and roe deer suggest that these species have a PRNP genetic background
that is compatible with TSE susceptibility, including CWD (EFSA, 2011). It is
important to note, however, that no experimental studies on roe deer have been
conducted verifying this hypothesis.
***Recent data on the susceptibility of the other free-ranging deer species
present in Britain (muntjac (Muntiacus reevesi), sika (Cervus nippon), Chinese
Water deer (Hydropotes inermis)) to CWD also suggests variability in
susceptibility for these species (Robinson et al., 2012; Nalls et al., 2013).
Further experimental studies would be required to investigate the susceptibility
of these species to CWD. Therefore, on the basis of current scientific
understanding, it is likely that given exposure to an infectious dose to CWD,
most deer species in GB could become infected with CWD.
***Sheep and cattle may be exposed to CWD via common grazing areas with
affected deer but so far, appear to be poorly susceptible to mule deer CWD
(Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed
deer CWD and mule deer CWD in experimental conditions but no natural CWD
infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
It is not known how susceptible humans are to CWD but given that the prion can
be present in muscle, it is likely that humans have been exposed to the agent
via consumption of venison (Sigurdson, 2008). Initial experimental research
suggests that human susceptibility to CWD is low and there may be a robust
species barrier for CWD transmission to humans (Sigurdson, 2008), however the
risk appetite for a public health threat may still find this level unacceptable.
It is apparent, though, that CWD is affecting wild and farmed cervid populations
in endemic areas in the USA with some deer populations decreasing as a
result.
Thus far, CWD is restricted to North America with the exception of imported
infected animals into South Korea from Canada. Surveys of wild and farmed cervid
populations in the European Union between 2006 and 2010 did not identify any
TSEs (EFSA, 2011). As part of this survey, 601 farmed and 598 wild red deer
(Cervus elaphus elaphus) were tested (EFSA, 2010). These included clinical/sick
animals, fallen stock, healthy
10
shot/slaughtered animals and road killed animals. Based on the survey
results, it was concluded that the prevalence of CWD in the EU is less than
0.5%.
Risk Question
This risk assessment considers the risk posed to the Great Britain (GB)
deer population if chronic wasting disease (CWD) is confirmed in Norway. The
specific risk question addressed is:
What is the risk of TSE being introduced into Great Britain (GB) from
Norway and causing infection in deer?
To answer the above question, the risk assessment follows the OIE framework
of release (or entry), exposure and consequence assessment. Specifically, it is
divided into the three key areas:
1. What is the probability of introducing TSE into GB from Norway? [Entry
assessment]
2. What is the probability of a deer species in GB being exposed to the TSE
prion? [Exposure assessment]
3. What is the probability of a GB deer species becoming infected with TSE
upon exposure to the prion? [Consequence assessment]
Risk Assessment
Terminology related to the assessed level of risk
For the purpose of the risk assessment, the following terminology will
apply (OIE, 2004):
(PLEASE NOTE THIS CONSIDERS HOW THE RISK IS PERCEIVED BY BSE MRR POLICY,
AND THE TRUTHFULNESS TO THOSE COUNTRIES DATA THAT IS/WAS PUT FORTH FOR SAID RISK
ASSESSMENT, which in terms of the USA and Canada, is not worth the paper it was
written and submitted on. THE OIE HAS NO AUTHORITY TO MAKE ANY COUNTRY SUPPLY
TRUTHFUL INFORMATION. imo...TSS)
Negligible So rare that it does not merit to be considered
Very low Very rare but cannot be excluded
Low Rare but does occur
Medium Occurs regularly
High Occurs often
Very high Event occurs almost certainly
Entry assessment
The routes by which CWD may be introduced into GB from Norway
include:
• Importation of live deer (including reindeer, other cervids, other
animals)
• Importation of deer urine lures
11
• Importation of meat and other products derived from cervid species (e.g.
trophy items including antlers, semen)
• Importation of animal feed
• Hunters and other tourists (skiers and walkers) and British servicemen
travelling from affected areas to GB with contaminated equipment (e.g. boots,
clothing, knives)
• Importation of plants, shrubs and trees with root balls where the soil
could be contaminated with prion protein
The previous assessments which we carried out concluded the risk of CWD
being imported from the USA in meat or other products of animal origin (skins,
antlers, semen) was very low and for animal feed as non-negligible (but likely
to be very low) because of the requirement for deer entering the food or feed
chain to be tested. For deer urine lures, the risk was considered medium. For
areas where CWD had only recently been detected there was a very low risk of
soil contamination so the risk from movement of equipment of people is
considered to be non-negligible but would depend on the frequency of movement.
The risk from live animals was not evaluated as live deer imports from the USA
and Canada are not allowed under EU Regulation 206/2010. A new pathway is also
considered: for plant imports where root balls may be associated with soil
contaminated with prion protein.
These same controls for meat, products and live animals are not applied to
other countries as CWD was geographically restricted. Therefore, this assessment
focuses on the following:
1) Imports of live animals
2) Imports of reindeer meat or products
3) Importation of animal feed
4) Importation of deer urine lures
5) Importation of CWD prion on contaminated equipment and clothing/footwear
of hunters or other tourists and British servicemen
6) Importation of plants, shrubs and trees
Below is a schematic of the different pathways which could potentially lead
to entry of CWD to the UK. Note, the human exposure pathway is not included
here.
For each pathway, the end point is the possible action which could be put
in place.
SNIP... scheme pathway chart for cwd
Trade in live animals
Cervids
Assuming a maximum incubation period of 2-4 years, the EU Electronic Trade
Notification System (TRACES) was interrogated for consignments of reindeer
(Rangifer tarandus), moose (Alces alces) and other cervids since 2012. During
this period, there have been just two consignments of 28 individual captive
reindeer from Norway, as well as 13 consignments of 347 animals from Sweden and
15 consignments of 266 animals from Finland, all from approved holdings. In the
case of the Norwegian imports, these are from the north of the country,
significantly far from the wild reindeer case and are from semi-domestic herds.
There were no recorded reindeer imports from Norway to the UK between 2011 and
2013 or since 2015. In terms of other deer species, there was a single
consignment of a zoo species (Pudu) from Sweden, but no other deer species were
recorded from the other Nordic or Baltic States. Multiple consignments of deer
were traded from other countries in the EU. The importer of the reindeer from
Norway has been in contact to assure us his animals are still in a healthy
condition.
There is no requirement under EEC/92/65 for the animals to be pre-movement
tested for CWD or for CWD-herd freedom for movement of any cervid species around
the EU or EEA countries, as Europe was believed to be disease free.
Nevertheless, the animals must be moved with a veterinary inspection and health
certificate and TSE infection of cervidae is listed under Annex A as a
notifiable disease of which approved bodies must be free in
13
order to trade. There is no CWD test approved for live animals, therefore
the certifying veterinarian must be confident in signing that the herd is
disease free.
On the basis of the small number of animals legally imported from Norway
and the origin of the reindeer, we consider there is a very low risk of
introduction via this route, but this is based on the high level of uncertainty
around the possible geographic distribution of disease in Norway and the
potential for mixing of wild and captive reindeer and low level of sensitivity
in the surveillance programme. Once more surveillance is undertaken to ascertain
the level of disease in the wild and semi-domestic herds, this risk level and
the uncertainty associated with it can be refined. The level of illegal movement
of reindeer or other cervids is not known and cannot be entirely ruled out, if
there is deliberate attempt to move the animals without declaring them to the
veterinary authorities.
Other animals
Working dogs may travel to Norway for hunting or sledging competitions.
They travel as accompanied animals (under the pet travel scheme) and not with
animal health certification (under EEC/92/65). The risk pathway is these dogs
being fed raw deer meat and defaecating when they return to the UK. The prion
protein would survive the intestine conditions and therefore lead to
environmental contamination. It is difficult to assess the likelihood of this
pathway, and there are no controls over the use of hunted meat for pet food
which is used on farm as opposed to commercially produced. Around 300 dogs are
moved under the pet travel scheme every year from Norway to the UK 1, which is
less than 1% of all pets moving to the UK. Not all will be dogs involved in
hunting or sledging competitions. Therefore we consider this to be a low risk
pathway with high level of uncertainty.
Other animals which could potentially spread prion proteins to the UK would
be from the movements of raptors or other scavenging birds which has fed on a
carcase of an infected animal. We consider this risk pathway to be unlikely,
given the distance between Norway and the UK.
Importation of reindeer meat or products
Products of animal origin destined for human consumption are traded from
Norway to the EU and UK under the same rules as intra-community trade, under the
EEA agreement and are subject to EU Food Law, Regulation (EC) 178/2002. This
means there are no health certification requirements or border checks. However,
there are still rules under the ABP regulations about not allowing the swill
feeding of ruminant material to other ruminants and Food Law covers the general
requirements for only safe food to be placed onto the market. Therefore this
type of product should not be diverted to animal feed for ruminants. However,
poultry and fish feed could contain ruminant material, and this is a
pathway
1 These numbers are based on figures provided voluntarily to the APHA from
pet travel companies and therefore may not be accurate, but are
representative.
14
which may need some further consideration if disease becomes more widely
established or detected in farmed cervids.
At present, we therefore consider this is no greater than a very low risk
pathway, as not only will the product originate in domestic livestock and go
through slaughter house checks, but it will be destined for human consumption
and not animal feed. In the USA, cervids over 12 months old entering a slaughter
house must be tested for CWD, under the USA APHIS Herd Certification Programme,
but this is not applied in Norway, therefore there is uncertainty associated
with this risk estimate for Norway given the lack of data on the amount of deer
or reindeer protein possibly being consigned for human consumption and the lack
of surveillance data for the farmed herds in Norway. Food imported for human
consumption can be reclassified as category 3 material and be composted or
spread as fertiliser, but to understand this pathway better, we consider it
would be beneficial to carry out a quantitative risk assessment on the
infectious dose and availability of prions through this pathway, should disease
be reported more widely.
This assessment is only to cover the risk to animal health if the food
product were to be diverted to animal feed or mistakenly fed to cervids. It is
not the role of this assessment to consider the public health risk associated
with meat or other products from cervids infected with CWD. The European Food
Safety Authority will be looking into this issue, but the current assessment
from the Norwegian Authorities is that it poses a very low risk.
Importation of animal feed
Animal feed encompasses all feed fed to farmed livestock, horses, pets,
farmed fish, zoo and circus animals and also animals living freely in the wild.
Currently, legislation for animal feed relating to production, and labelling and
composition is harmonised at the EU level and, in GB, is the responsibility of
the Food Standards Agency (FSA). In addition, Defra is responsible for ABP
Regulations which includes pet food manufacturing regulation.
Pet food (i.e. feed for non-ruminants) containing material of animal
origin, according to EU Regulation (EC) No. 1069/2009 and its implementing
Regulation (EC) 142/2011 on Animal By-Products, must be derived from animals
inspected and passed as fit for human consumption prior to slaughter (Category 3
– lowest risk - material). Category 1 material (eg from animals in which the
presence of TSE has been confirmed or suspected, or which are derived from
animals killed as part of a TSE eradication programme) must not be used for
animal feed. Furthermore, the category 3 products are subject to strict
microbiological criteria for Enterobacteriaceae and Salmonella. Under the EU
Regulation Category 3 processed animal proteins (PAP) must also adhere to a set
of standards. More specifically, the pet food must satisfy the following
criteria:
• The PAP must have been produced in accordance with requirements for
placing on the market in the EU.
• The PAP must have been sampled and tested to satisfy certain
bacteriological criteria in accordance with the Regulations
15
These requirements apply to canned pet food, processed pet food other than
canned pet food, and to dog chews, raw pet food and flavouring innards.
*** These regulations do cover entire bodies or parts of wild animals which
are carcases and suspected of being diseased, such that they must be disposed of
as Category 1 – high risk – material via rendering and incineration and not
enter the food or feed chain. It will not cover wild animal carcases or parts
from animals not suspected of being diseased or which have been hunted and not
collected for disposal. Indeed, as this is considered EU trade there is no
requirement for veterinary health certificates or TRACES information as this is
part of the European Single Market. Deer antlers are a popular dog chew and deer
velvet may contain a low level of prion (Angers et al., 2009) therefore if the
antlers are collected from wild deer and imported with the velvet still in
place, this could represent a low risk pathway for the pet to consume and
defaecate prion proteins.
*** CWD-like TSE disease in Norway has only been detected to date in the
non-farmed, wild reindeer and moose populations, but there is still uncertainty
over whether there could be undetected disease in the farmed herds in the North
if they had been in contact with diseased animals in the non-herding
areas.
*** Overall, therefore, it is considered there is a very low risk that
(non-ruminant) animal feed and pet food containing TSE-infected cervid protein
is consigned to GB. There is high uncertainty associated with this estimate
given the lack of data on the amount of deer or reindeer protein possibly being
imported in these products and the lack of surveillance data for the farmed
herds in Norway.
Importation of deer urine lures
*** In our previous assessment, the import of deer urine from the USA as
lures from the hunting industry was recognised as a potential route for
introduction of disease to the UK / EU (Defra, 2016). It is well established
that urine from CWD-infected deer contains CWD infectivity. The urine collected
for deer lures has no processing and is immediately refrigerated and bottled
(Anon 2015b). There is no inactivation of the CWD agent in the urine and thus
all infectivity present at the point of bottling in the USA will still be
present at the point of use in the UK. However, under EU rules, (EC Regulation
1069/2009), urine from farmed deer should fall under the definition of “manure”
and therefore the import of such a product, if unprocessed, is not allowed,
according to Regulation (EC) 142/2011. Nevertheless, the processing required for
bottling prior to retail is unlikely to affect the CWD prion and if it did
fulfil the requirements in 142/2011, the active ingredient in the urine would no
longer be effective. It is therefore presumed that the urine is considered
“unprocessed” under EU law. The import and transit of urine from wild deer is
not covered by 1069/2009.
A survey conducted by the British Deer Society (BDS) in July 2015 suggested
small number of hunters in GB were aware of and used deer urine lures (http://www.bds.org.uk/index.php/news-events/135-deer-urine-lure-survey-july-2015
).
16
*** It is not known whether Norway is a source of imported deer urine for
lures. No information has been found to suggest this. Therefore this route for
introduction, while it cannot be discounted, is of no greater risk than for the
import of deer lures from countries like the USA where disease is well
established in certain deer species.
*** Animal urine is not considered a commodity which is subject to animal
by-products legislation for imports. Internet sales are common and although a
license would be required, there are no conditions for the safe sourcing of such
products. Deer urine lures are available in Europe and may be produced from
carcases of hunted deer. The use of deer urine produced from a species such as
reindeer would be questioned for its value in attracting our native GB deer.
This risk is very low, but with a high level of uncertainty, based on the
unknown distribution of disease.
Movement of hunters, other tourists and British servicemen
Probability that the environment in Norway is contaminated with TSE
prions
At present there are just four animals of two different species and in two
different regions which have tested positive for TSE prion proteins in Norway
and it is not known what the wider geographic distribution may be or for how
long the animals had been infected. However, given the incubation period in
experimental infections, the infection was likely to be present for several
months, possibly years. Without knowing the original source of disease it is
difficult to make an assessment of what the environmental contamination would
be. If these were each down to spontaneous mutation events, it may be limited,
but it is unlikely for two unrelated species to each have spontaneous events
within a few weeks of another. The animals in each case may have been ill for
some time, most likely weeks rather than days given the poor condition of the
carcases, therefore it is likely the animals were excreting prion protein in
various bodily fluids, including urine and faeces which can occur during the
pre-clinical phase. This can lead to leaching of prions into the soil and
contamination. Animals with clinical signs may show erratic behaviour which can
include wandering behaviour, so contamination may be wider than normal host
range.
CWD (TSE) is excreted in several different bodily fluids and, as
demonstrated in experimental studies, can be a source for onward transmission to
naïve animals. Infected carcasses decaying naturally in confined areas can also
lead to new CWD infections in naïve deer (Sigurdson, 2008). ***There is no
reason to expect TSE in reindeer or moose to behave differently, given the
experimental infection data and the testing carried out at the EURL and
NVI.
Once in the environment, TSE prions can bind to soil particles and remain
infectious (Saunder et al., 2010). Indeed, Johnson et al., (2006) demonstrated
that the disease-associated form of the prion protein can bind to all soil
mineral surfaces and is preserved in a bioavailable form. Further, in a later
study, Johnson et al., (2007) observed that prions bound to the soil mineral
montmorillonite (Mte) significantly enhanced disease penetrance
17
and reduced the incubation period compared to unbound prions. The reason
why binding to Mte or other soil components enhances transmissibility is unclear
but it may provide some protection for the prion in the gut against denaturation
allowing more agent to be absorbed by the animal (Johnson et al., 2007).
Further, binding to the soil particles maintains prions near the soil surface
increasing the probability of animal exposure (Russo et al., 2009).
In addition to the enhanced infectivity, prions can remain in the soil for
several years as the agents are resistant to inactivation by most chemical
agents, radiation and heat (Johnson et al., 2006). Seidel et al. (2007), for
example, demonstrated that scrapie agent (strain 263K) remains persistent in
soil over a period of at least 29 months and remains highly infectious to Syrian
hamsters in oral inoculation experiments. In Iceland during an epidemiological
investigation of scrapie, a TSE of sheep and goats, Georgsson et al., (2006)
reported that the scrapie agent survived on a farm for at least 16 years.
However, Russo et al., (2009) demonstrated experimentally that reactive soil
components such as manganese oxides may contribute to the inactivation process
of TSE prions in soil. The authors did not study CWD prion specifically but the
study highlights the complexity of the effect the inorganic and organic
constituents in soil may have on prion survival and infectivity.
The extent of the contaminated area is unknown at present as it would
depend on the range of the infected, clinically ill animals and the presence of
undetected infection. However, if there are a larger number of undetected cases
of TSE and if animal carcases have not been picked up as fallen stock, but
allowed to decompose in situ, or been predated on by other animals, the
likelihood of contamination of the land is greater and the risk level increases.
Carcases are only one possible source of contamination, as animals may be
excreting infection in pre-clinical stages which could be for months or even
years. Data from the USA confirm that infection is shed in urine and saliva in
particular. The Norwegians are now withdrawing all salt licks because of this
(http://www.mattilsynet.no/language/english/animals/additional_legal_measures_to_limit_the_spread_of_chronic_wasting_disease_cwd_in_cervids.23275).
Large carnivores, such as lynx, wolves and wolverines may follow herds and prey
on sick and weak members of the herd. Foxes, raptors and crows may also
contribute to the dissemination.
*** In summary, in areas where TSE in cervids has only very recently been
reported, it is certain that the soil would be contaminated with CWD prion, but
the extent and persistence of that contamination is uncertain but we consider is
represents a medium risk in the immediate affected regions and very low to low
risk for other areas in Norway.
Movement of deer hunters, other outdoor tourists and British service
personnel between Norway and GB
The probability a person comes into contact with TSE prions varies
depending upon their place of residence and/or their involvement with outdoor
pursuits (e.g. hunting). In this assessment, focus is given to the following
groups of people:
• Residents in TSE affected areas travelling to GB (particularly the
countryside) and British tourists travelling to TSE affected areas
• Hunters travelling between Norway and GB to hunt/stalk deer
• British service personnel training in and/or near TSE affected
areas
All other people (e.g. city tourists and residents) are considered to pose
a negligible risk of being exposed to TSE in Norway and, therefore, arriving in
GB with contaminated clothing, footwear and/or equipment.
The region where the infected reindeer was found is a relatively poorly
populated area, but nevertheless is an area where walkers and skiers will visit.
Hunting in Norway is a popular sport with many thousand deer shot each year. In
order for a foreign national to hunt in GB with your own rifle, a visitor
firearms permit has to be obtained from the police force in one of the devolved
countries. In 2011, 123 licences were granted by the Scottish Police Force for
non-EU residents (BASC, pers. Comm., 2012). This includes not only individuals
from North America but also Norway and other non-EU countries (BASC, pers.
Comm., 2012). The number of hunters arriving without their own rifle and
participating in an organised hunting package/holiday is unknown. The actual
number of known hunters either visiting Norway or coming from Norway to the UK
is highlighted as a significant data gap. Some of these hunters may also take
their own dogs to Norway as highlighted in previous section on live animal
imports.
As well as tourists, British service personnel frequently move between
Norway and GB for winter sports and for alpine training. Consequently, the
service personnel have the potential to be in close contact with areas where TSE
is present. However data provided by MoD confirm that these affected areas are
not used by the British service personnel and therefore there is very low risk
via this pathway, with a degree of uncertainty around how widespread is the
contamination.
*** In summary, given the volume of tourists, hunters and service personnel
moving between GB and Norway, the probability of at least one person travelling
to/from a TSE affected area and, in doing so, contaminating their clothing,
footwear and/or equipment prior to arriving in GB is considered no greater than
low. For deer hunters, specifically, the risk is likely to be greater given the
increased contact with deer and their environment. However, there is high
uncertainty associated with these estimates, mainly around the level of
environmental contamination in Norway.
Probable amount of CWD prions on contaminated boots and equipment
Given that a hunter or tourist walks in areas which are contaminated with
TSE, it is possible that they will collect soil on their boots and other
equipment. This likelihood will increase if the hunter has shot and handled a
TSE infected carcase resulting in contamination of the hunting equipment (e.g.
knives) and their clothing and they subsequently arrive in GB with this
equipment, footwear and clothing. Furthermore, the soles of hiking boots tend to
retain more soil than those of normal shoes. Wilkinson (2010), for example,
removed 0.1 g of soil from hiking boots after returning to GB from a
2-month
19
research visit to Canada. The amount of TSE prion in this amount of soil
will depend upon the density of TSE-infected animals excreting prions into the
environment and the type of soil; CWD prion binds to clay soil, for example.
Animal mortality sites could also be hotspots of TSE prion given the highly
infectious nervous system matter entering into the environment and soil
(Saunders et al., 2010). Trade in plants, shrubs and trees
Live plants (trees, shrubs etc) are moved around the World in considerable
quantities and many, including large full-grown trees will have intact root
balls which will be covered in soil. As mentioned in the preceding section,
prion proteins will be present in soil for many months / years as a result of
contamination (Johnson et al., 2007).
There are several different categories for imports of stocks of plants,
shrubs and trees. According to Eurostat data for codes beginning 0602 since
January 2014, there have been only two consignments from Norway of “Live trees
and other plants; bulbs, roots and the like; cut flowers and ornamental foliage
// Other live plants (including their roots), cuttings and slips; mushroom
spawn. // -Other”. Further possible commodities would be “plants for planting”
which are generally smaller nursery plants, but we consider these are a very low
risk of being in contact with cervids where they are grown, as there would be
measures to exclude deer from these high value crops. Further interrogation of
the UN COM trade database shows the greatest proportion of imports to the UK of
Live trees, plants, bulbs, roots, flowers etc is from Netherlands, and Norway is
only a tiny proportion of the total value of our trade. The following figure is
a graphical presentation of the imports to the UK of these products. It is also
noted that USA and Canada are similarly low exporters to the UK, with less than
50 tons a year combined (ITC, 2016).
Prospects for diversification of suppliers for a product imported by United
Kingdom in 2015 Product : 06 Live trees, plants, bulbs, roots, cut flowers etc.
snip...chart, graph, etc.
*** Therefore although this is a potential route for introducing prion
proteins into a new area, for this particular situation (Norway to the UK) we
consider this is a very low, if not negligible, risk.
Exposure assessment
Imports of live animals
Reindeer management by the Sami in the north of the Scandinavian countries
provides only two opportunities a year to handle the reindeer: early summer and
autumn. It is these periods which provide many of the non-farmed reindeer for
trade. Farmed reindeer can be drawn off and traded at any time, but it is the
autumn draw which provides many of the reindeer for export across Europe for the
seasonal trade for Christmas markets. In the past they have not thrived
particularly in the UK and often succumb to welfare issues when brought in for
this seasonal trade. There are a few semi-enclosed herds in the UK – including
one in the Cairngorms and one in Staffordshire and there will be plenty of
reindeer kept in small numbers in parks and zoos. The exact number is not known
as there is no requirement for registration of such animals as there would be
for farmed domestic livestock. It is however, estimated that there are around
1,200 – 1,500 reindeer in the UK and there is an intention to start a stud book
for the UK animals in the future (British Reindeer Herders Association, pers.
comm.). Using a combination of Intra Community Health Certification and
performance licencing we have identified several other premises which keep low
numbers of reindeer.
21
Should an infected animal be imported into the resident herds in GB, there
is a high probability disease would spread to other in-contact conspecifics, but
the level of contact with wild deer may not be as high as for other species (as
these are valuable animals). It is nevertheless, difficult to prevent contact
between wild and farmed deer and in the USA, disease is often detected first in
farmed deer where there are more regular inspections. As there is no official
programme of checks on the health status of the reindeer, it is not possible to
ascertain whether disease is already present and CWD has not featured as a
differential diagnosis for any fallen stock which is reported to APHA, because
this was not considered a likely cause of death.
Importation of animal feed or products of animal origin
Once in GB, the use of animal feed is subject to the TSE Feed Ban and ABP
Regulations. The BSE-related feed ban prohibits the feeding of PAP and gelatine
from ruminants to ruminants (including farmed deer) or non-ruminant farmed
animals. Further, ruminants must not be fed any animal protein or feedstuffs
which contain animal protein except for milk, milk-based products and colostrum,
eggs and egg products, gelatine from non-ruminants and hydrolysed proteins
derived from non-ruminants or from ruminant hides and skins. Therefore, in
accordance with the current ban, farmed deer should not be directly exposed to
(i.e. fed) imported animal feed containing any PAP.
The likelihood of non-ruminant feed or cervid origin POAO being fed
accidentally to reindeer or other captive deer in GB is very low.
Therefore, assuming this ban is adhered to correctly the risk of farmed
deer being exposed to animal feed containing deer protein from Norway is
considered negligible but with associated uncertainty.
***However, given that non-ruminant feed produced elsewhere (eg the USA)
may contain deer and moose PAP, it is theoretically possible that wild deer may
be exposed to deer protein in legally imported non-ruminant feed. For this to
occur, wild deer would need to access non-ruminant feed (e.g. pig, fish and
chicken feed) on farms near their habitat. Alternatively, wild deer may be
exposed to TSE prion in the faeces of pets that have consumed and digested
imported, contaminated pet feed. Also to be considered is that food may be
diverted to composting and the resulting effluate spread on pasture. The
frequency in which these routes may occur is unknown and is considered to be a
greater than negligible risk with associated uncertainty.***
Movement of hunters, other tourists and British servicemen
The pathways by which naïve deer can be exposed to CWD contaminated soil
and prions on equipment and clothing from people arriving to GB from North
America or other affected region are variable and highly uncertain. In
principle, in order to expose a deer to CWD prions, the traveller (hunter,
tourist or serviceman) would need to transfer the CWD prion from their clothing
and/or equipment to the environment in which deer habit. The latter will depend
upon the behaviours of returning GB residents or tourists and the probability of
entering into and walking around deer territory. In GB, there are two main deer
populations (wild and farmed or park deer) each of which will have differing
risks of
22
exposure given the type and frequency of contact with people. Each
population type is considered in turn.
Consequence assessment
Wild deer
There are 6 species of wild deer residing in GB including: Red deer (Cervus
elaphus), Roe deer (Capreolus capreolus), fallow deer (Dama dama), muntjac
(Muntiacus reevesi), sika (Cervus nippon), and Chinese Water deer (Hydropotes
inermis). In the UK, enclosed deer herds are principally red deer (Cervus
elaphus) on farms and fallow deer (Dama dama) within parks: currently, only one
commercial fallow deer farm is known to exist in Great Britain. The number of
farmed deer in the UK has grown substantially to about 31,000. The numbers of
park deer are unknown but the most recent assessment in 2005 gave an annual cull
of around 8,000 deer suggesting about 40,000 park deer. The number of wild deer
will be vastly more numerous than the enclosed or captive cervid species,
estimated at around 2 million, with an annual cull of over 300,000.
Deer hunters, particularly, are most likely to be in direct contact with
wild deer and their habitat compared to other tourists and returning GB
residents. During the stalking and/or hunting of deer, there is opportunity for
TSE prion on the hunter’s boots, clothing and/or equipment to be transferred to
the environment. The amount transferred will depend upon the measures taken to
remove soil etc from the equipment prior to stalking. Assuming that TSE prion is
transferred to the environment, there is an uncertain probability that a deer
will come into contact with the TSE prion.
Farmed and park deer
The Deer Initiative recently carried out an informal review of enclosed
deer herds in GB (Deer Initiative, pers comm. Data published in 2015). Current
estimates give the number of extant deer parks or collections as 259. The wild
roe deer population is the most numerous (see maps in Annex 1), while for farmed
deer, fallow deer represent the highest number. Recent estimates provided by the
Deer Initiative are:
Expected number (by species) held in parks and wild population
Species # expected parks Expected population Wild population
Sika spp. (C.nippon) 27 2160 ~35,000
Red (C. elaphus) 111 12386 >350,000
Fallow (D. dama) 196 31849 150-200,000
Roe (C.capreolus) - - ~500,000
Deer farming is a relatively recent enterprise. There are two systems
currently used for managing enclosed deer: park and farm deer systems. In the
park system, deer are raised in a park type setting and allowed to roam freely
and may be provided with some supplemental feed. Farmed deer, in contrast,
following conventional agricultural practices
and may be housed in the winter and nutritional supplements are provided
where necessary. In this farming system, there are several categories including
calf rearers, calf finishers, breeder finishers and producer/processors (
www.bdfpa.org). It is less likely that tourists, deer hunters and British
service personnel will come into contact with conventionally farmed deer
compared to park deer.
*** Reindeer were first introduced in the 1950’s into the Cairngorms, where
there is now an established herd. In the 1990’s the imports of live reindeer
increased with the popularity of Christmas markets. The imports referred to
earlier, from Norway are to one importer where a small herd is maintained for
breeding with occasional imported animals from the Northern farmed /
semi-domestic herds to improve the bloodlines. Reindeer in this particular herd
are fed deer food manufactured in the UK to an adapted Scandinavian recipe. Some
feeds are available for other deer that are used and there are a number of
manufacturers of pellet feed available in the UK now. Reindeer moss may be
imported from a production facility in Norway. This is a dry product which is
rehydrated with tap water prior to feeding. This tends to be harvested from
close to the Finnish Border away from heavy populations of Reindeer otherwise it
wouldn’t be available to pick. A number of people use moss as a treat, training
and supplementary feed. Reindeer moss doesn’t store well wet unless frozen so UK
imports are dried for longevity. Reindeer in parks in England are generally high
fenced and this can reduce contact with local wild deer, particularly
nose-to-nose even across single fencing, although the Cairngorm herd is more
likely to have some level of interaction with local wildlife. However, it may
not be possible to prevent contact with contaminated environment. Reindeer life
expectancy is around 10-12 years and can be as long as 18 years in captivity,
but is more commonly 14-16 years. There is no requirement for registration of
cervidae and their movements, as there is for livestock species.
There are therefore several locations in GB where tourists and returning
residents may come into contact with park deer.
***Nevertheless, there is a relatively low volume of tourists and other
travellers moving between Norway and GB, so there are considerably fewer
opportunities in comparison to the risk from the USA and Canada for CWD / TSE
prions to be transferred from clothing, boots and/or equipment to the
environment.
It has been observed that multiple exposures to low levels of CWD prions in
the environment and increased infectivity of CWD when prions are bound to the
soil are influential factors in transmission (Anger et al., 2009). Given the
nature of their management, there is a restricted area (or environment) in which
park deer inhabit enabling them to have a potentially higher probability of
coming into contact with any CWD transferred to the environment by a tourist or
returning GB resident compared to wild deer in a free-ranging environment.
***Therefore, it is considered that farmed and park deer may have a higher
probability of exposure to CWD transferred to the environment than wild deer
given the restricted habitat range and higher frequency of contact with tourists
and returning GB residents.
***Nevertheless, the risk is not increased by this case in Norway, as to
that posed by visitors from the USA and Canada.
Exposure of UK deer to soil, feed or infected urine
Whether the amount of CWD prion that could be transferred from clothing,
boots and/or other equipment into the deer’s environment is enough to induce
infection given that the infectious dose is extremely small (Saunders et al.,
2010) is uncertain. However, given that the amount of soil ingested is likely to
be very small, the probability of ingesting an infectious dose via this route is
considered no greater than very low. The probability of ingesting an infectious
dose via consumption of non-ruminant feed is likely to be higher and may be very
low, with associated uncertainty.
Although our previous risk assessment considered the risk of importing TSE
through imports of deer urine for lures as medium entry assessment, and the
likely exposure assessment as very low, the risk is not increased as a result of
this case in Norway. The import of unprocessed deer urine is still an illegal
product and should not be imported into the EU, no matter what the source of the
animals.
The CWD agent is relatively dilute in deer urine compared to brain and
spinal cord material with 1 ic LD50 per 10 ml. The LD50 determined by Henderson
et al. (2015) is an intracerebral ID50 in cervidized transgenic mice. The oral
ID50 in deer would be in a much larger volume of urine, because the oral route
may be 100,000-fold less efficient than the intracerebral route in terms of TSE
transmission (Gale et al 1998). Thus, in terms of oral LD50, there may be one in
a 1,000,000 ml i.e. 1 m3 or 1,000 litre volume of deer urine. Therefore a deer
would have to ingest 1,000 litres of urine to have a 50% chance of being
infected through the oral route. Of course the CWD agent would be concentrated
as the urine evaporated from the tree trunk.
The main sources of uncertainty are:-
1. The amount of urine ingested by the deer. A bottle of Tink’s “69
Doe-in-Rut Buck” is about 30 ml and boasts 100% natural doe oestrous urine (Anon
2105d). A bottle from an infected doe would thus contain about 3 i.c. LD50
units. The bottles come with an easy to use squirt top, so it seems relatively
small amounts are used. There are also gel forms which do not freeze as fast,
last longer in the rain, and do not dry out so quickly.
2. The magnitude of oral/i.c. barrier
Assuming a deer drank 10 ml of urine from each 30 ml bottle, then that deer
would ingest 10-5 LD5. It is generally assumed that there is no threshold dose
for TSEs (Gale 2006) and the risk of CWD infection in GB deer per 30 ml bottle
imported is therefore 0.69 x 10-5 (Gale 1998). This is very low.
Risk of infection of deer in GB per 30 ml bottle of deer urine lure
imported from the USA
Step in pathway Risk Uncertainty
Entry (probability a 30-ml bottle contains urine from an infected deer)
Medium Low
Exposure (probability some of 30-ml bottle is ingested by UK deer) Medium
High
Consequence (probability that deer is infected given exposure) Very low
Medium
Overall risk Very low High
*** Overall the risk of a deer in GB being infected per 30 ml bottle of
urine imported from the USA is very low, albeit with high uncertainty.
*** The next question is how much deer urine is imported into GB from the
USA per year. If there are n 30-ml bottles, then the risk is calculated as:-
pn_bottle = 1 - (1 – pone_bottle)n
***Hundreds of gallons of urine are sold every year just by one company in
the USA (Anon 2015b). It is difficult, however, to estimate the volume of deer
urine imported into the UK per year from the USA. That some respondents to the
BDS survey reported they used upwards of 1litre per year, is consistent with
importation of a high number of 30-ml bottles. Assuming that the number, n, of
30-ml bottles imported annually is high, then the risk of CWD infection in at
least one deer in the UK per year will be medium (given the probability, of
infection of a UK deer from one 30-ml bottle is very low (see Table 1)).
***Overall it is concluded that the annual risk of at least one infection
of deer in the UK with CWD from deer urine lures imported from the USA is
medium. This assumes a high number of 30 ml bottles imported per year from all
areas of the USA.
***The case in Norway does not increase this risk at present. A quick
internet search continues to suggest the main source of deer urine lures is the
USA, nevertheless, in the BDS survey, half of respondents sourced deer urine
from North America and a quarter from Europe.
Control and risk management options
The highest level of uncertainty is around the source and level of disease
in Norway and whether it is limited to the wild reindeer herds or if it has
spread into either other species of wild deer or the herder reindeer in the
North. As there is so little by way of surveillance in the EU and surrounding
countries, it is not possible to say whether this is a wider problem.
If these were spontaneous mutations, a form of “atypical CWD”, then these
may be rare and isolated cases. However the animals concerned were in two
regions, of two species and not particularly old, so it may be more likely the
source is an imported prion infection. If this has an origin in the USA or
Canada, it is important to try to understand the source and therefore whether
there are likely to be more cases over a wider area, where the import event may
also have taken place.
If it were to be found in the farmed or herded cervid populations, it will
be necessary to put in place some import controls along the lines of those in
place for imports of live animals and cervid meat from the USA and Canada. As it
is, Norway voluntarily stopped signing trade certificates for all cervid species
and authorisation is required to move cervids
26
between counties within Norway
If the geographic distribution is wider and the environment heavily
contaminated, to reduce the potential amount of TSE prion entering GB on boots
and clothing, it is important to meticulously clean off all adherent material
prior to departing from an affected area and where possible, equipment should be
soaked in a solution of bleach that has 20,000 parts per million of active
chlorine for one hour. However, it is acknowledged it is impractical to soak
hunting boots, clothing or firearms, for example, in strong concentrations of
bleach.
For deer urine lures, the import of unprocessed natural deer urine is not
allowed under the EU Animal By-Product legislation. However the import of such
commodities including internet sales would still require licenses, but it would
be a voluntary action on behalf of the importer to ensure the urine is sourced
from safe herds. One option is to ensure the sourcing is from herds in the USA
which are currently registered under the National CWD Herd Certification
Programme which has recently been introduced in the USA. Otherwise the use of
synthetic or domestic-produced lures should be promoted by the industry and
stakeholder groups.
Areas identified which are not fully understood are those of pets eating
meat from infected animals and of food diverted to Category 3 for composting.
Both would benefit from further investigation if the results of the Norwegian
surveillance suggest wider distribution.
Diagnosis of CWD / TSE in cervids
Conventional immunohistochemistry (IHC) testing for TSE’s involves using
cadavers to remove the brainstem as the most sensitive organ to show the
distribution of prion protein in the nervous and associated tissue is typical of
the pathology associated with the species-specific TSE. The ELISA for CWD has
similar sensitivity and specificity as the IHC test. Both tests use a protease
step which can reduce sensitivity. This means that surveillance cannot be
carried out on live animals. There is a considerable need for a fast, reliable
antemortem test.
There is no current fallen stock scheme for testing deer species in the UK
and there is no European Reference Lab for CWD (although the EURL for TSE’s is
APHA, Weybridge).
Conclusions
There is significant uncertainty associated with estimating the risk of TSE
entering the UK from Norway via imports of live animals, movement of people
(tourists, hunters and British servicemen) and importation of animal feed or
urine lures. This stems from the lack of data on the current distribution of
disease, not only in wild reindeer and moose in Norway, but also in herded
animals and more widely in other wild cervids across the region and
27
neighbouring counties. Notwithstanding this uncertainty, the probability of
importing TSE into GB from Norway and causing infection in British deer is
likely to be greater than negligible via movement of deer hunters, other
tourists and British servicemen and low via live animals, very low via products
of animal origin or imported (non-ruminant) animal feed. However the risk of
natural deer urine lures from Norway is lower than for those products sourced
from the USA, where the risk of containing CWD PrP is considered medium
(reflected by some US States banning the use) and the probability of such a
commodity, if used in significant volumes, leading to CWD infection in GB
populations is considered to be very low (potentially reduced susceptibility in
certain species and limited use by hunters and stalkers in GB) but with a high
level of uncertainty. Nevertheless, the voluntary restrictions on sourcing urine
lures from USA and Canada should be extended to Norwegian sources, as a
precautionary measure.
The consequences of CWD, however, are severe with the minimal possibility
of eradicating the disease from a wild cervid population and populations of both
wild and farmed deer in the UK would be under threat.
Current research indicates that of the six free-ranging deer species in the
UK, red deer, and muntjac are susceptible to CWD, while roe deer, which is the
closest related to white-tailed deer, Japanese sika and Chinese water deer are
likely to also be susceptible. Farmed fallow deer are numerous in the UK and
while those studied to date have lacked the PRNP polymorphisms associated with
higher susceptibility to CWD, our populations are genetically heterogenous so
the risk of infection cannot be ruled out. Wild roe deer are even more numerous,
so again, understanding the susceptibility of this species will be important.
The new case in reindeer in Norway taken alongside existing experimental data
suggests that this species is also at risk.
It is important, therefore, that the risk of these species being exposed to
TSE is minimised by taking appropriate precautionary measures.
Change in risk level for entry assessment (and level of uncertainty) from
previous risk assessment (Defra, 2016)
Change in risk level for entry assessment (and level of uncertainty) from
previous risk assessment (Defra, 2016)
Pathway USA and Canada Norway
Live animals - cervids Not assessed as not possible Very low (high)
Live animal - other Not assessed as new pathway Low (high)
Products of Animal Origin Very low (low) Very low (medium)
Animal Feed Greater than negligible (medium) Very low (high)
Urine lures Medium (low) Medium (medium)
Equipment and people Greater than negligible (medium) Greater than
negligible (medium)
Plants Not assessed as new pathway Negligible (low)
References
snip...see full text here;
March 2016
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
Summary
The previous assessment concentrated on the incursion of disease from North
America through the imports of animal feed or the movement of contaminated
clothing, footwear and equipment. The results suggested that import of pet feed
was a non-negligible risk, but given the unlikely contact of resident deer in GB
with such non-ruminant feed, this was considered overall a negligible to very
low risk. The movement of contaminated clothing, footwear or equipment
(particularly hunting equipment) could pose a very low risk, although the volume
of contaminated soil which would need to be ingested to give rise to an
infection is likely to be higher than would be present. There is a variable
level uncertainty in all these assessments.
The new assessment focuses on an additional potential route of entry: the
importation of natural deer urine lures. The main conclusions from this
assessment are:
***In areas of North America where CWD has been reported, given that CWD is
excreted in faeces, saliva, urine and blood, and survives in the environment for
several years there is a medium probability that the deer urine in North America
contains CWD (high uncertainty; depends on the source of deer used for
production).
***The risk of a deer in GB being infected per 30 ml bottle of urine
imported from the USA is very low, albeit with high uncertainty. Overall it is
concluded that the risk of at least one infection of deer in the UK with CWD per
year from deer urine lures imported from the USA is medium. This assumes a high
number of 30 ml bottles imported per year from all areas of the USA.
***None of the species affected by CWD in North America are present in GB.
For a British species to become infected with CWD following exposure, the dose
and inherent susceptibility of the species will be important. Based on current
scientific evidence Red deer (Cervus elaphus elaphus) are susceptible to CWD,
Fallow deer (Dama dama) are likely to be less susceptible and Roe deer
(Capreolus capreolus) have a gene conferring susceptibility. Therefore, it is
likely that given exposure to an infectious dose of CWD, deer in GB could become
infected with CWD.
Overall, the probability of importing CWD into GB from North America and
causing infection in British deer is uncertain but likely to be negligible to
very low via movement of deer hunters, other tourists and British servicemen and
very low via imported (non-
2
ruminant) animal feed and medium for the use of lures. However, if it was
imported and (a) deer did become infected with CWD, the consequences would be
severe as eradication of the disease is impossible, it is clinically
indistinguishable from BSE infection in deer (Dalgleish et al., 2008) and
populations of wild and farmed deer would be under threat.
The USA has implemented a Herd Certification Programme for farmed and
captive cervids. So far, 29 States are approved for HCP status (APHIS, 2015).
The list includes States such as Colorado, where CWD is present, therefore it is
recommended that any sourcing of such natural urine lures should be not only
from States with an HCP programme, but also from a herd which is registered as
being regularly tested free of CWD.
Animal urine is not considered a commodity which is subject to animal
by-products legislation for imports. Internet sales are common and although a
license would be required, there are no conditions for the safe sourcing of such
products. Deer urine lures are also available in Europe and may be produced from
carcases of hunted deer. The use of deer urine produced from a species not
present in Europe (such as white tailed deer) is questioned for its value with
native GB deer according to the British Deer Society survey.
Background
April 07, 2016
Thursday, April 07, 2016
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
snip...
In the USA, under the Food and Drug Administration’s BSE Feed Regulation
(21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin)
from deer and elk is prohibited for use in feed for ruminant animals. With
regards to feed for non-ruminant animals, under FDA law, CWD positive deer may
not be used for any animal feed or feed ingredients. For elk and deer considered
at high risk for CWD, the FDA recommends that these animals do not enter the
animal feed system. However, this recommendation is guidance and not a
requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD
eradication zones and
2) deer and elk that at some time during the 60-month period prior to
slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive
animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from
the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin
processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible
risk___ that (nonruminant) animal feed and pet food containing deer and/or elk
protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data
on the amount of deer and/or elk protein possibly being imported in these
products.
snip...
36% in 2007 (Almberg et al., 2011). In such areas, population declines of
deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of
Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and
behavioural changes that can span weeks or months (Williams, 2005). In addition,
signs might include excessive salivation, behavioural alterations including a
fixed stare and changes in interaction with other animals in the herd, and an
altered stance (Williams, 2005). These signs are indistinguishable from cervids
experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB,
for example, infected deer populations would need to be tested to differentiate
if they were infected with CWD or BSE to minimise the risk of BSE entering the
human food-chain via affected venison.
snip...
The rate of transmission of CWD has been reported to be as high as 30% and
can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil
and surrounding environment is contaminated with CWD prions and in a
bioavailable form. In rural areas where CWD has not been reported and deer are
present, there is a greater than negligible risk the soil is contaminated with
CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving
between GB and North America, the probability of at least one person travelling
to/from a CWD affected area and, in doing so, contaminating their clothing,
footwear and/or equipment prior to arriving in GB is greater than negligible.
For deer hunters, specifically, the risk is likely to be greater given the
increased contact with deer and their environment. However, there is significant
uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher
probability of exposure to CWD transferred to the environment than wild deer
given the restricted habitat range and higher frequency of contact with tourists
and returning GB residents.
snip...
What is the risk of chronic wasting disease being introduced into Great
Britain? A Qualitative Risk Assessment October 2012
2016
*** Title: Pathological features of chronic wasting disease in reindeer and
demonstration of horizontal transmission ***
Author
item Moore, Sarah item Kunkle, Robert item West greenlee, Mary item
Nicholson, Eric item Richt, Juergen item Hamir, Amirali item Waters, Wade item
Greenlee, Justin
Submitted to: Emerging Infectious Diseases Publication Type: Peer reviewed
journal Publication Acceptance Date: 8/29/2016 Publication Date: N/A Citation:
Interpretive Summary: Chronic wasting disease (CWD) is a fatal
neurodegenerative disease that occurs in farmed and wild cervids (deer and elk)
of North America and was recently diagnosed in a single free-ranging reindeer
(Rangifer tarandus tarandus) in Norway. CWD is a transmissible spongiform
encephalopathy (TSE) that is caused by infectious proteins called prions that
are resistant to various methods of decontamination and environmental
degradation. Little is known about the susceptibility of or potential for
transmission amongst reindeer. In this experiment, we tested the susceptibility
of reindeer to CWD from various sources (elk, mule deer, or white-tailed deer)
after intracranial inoculation and tested the potential for infected reindeer to
transmit to non-inoculated animals by co-housing or housing in adjacent pens.
Reindeer were susceptible to CWD from elk, mule deer, or white-tailed deer
sources after experimental inoculation. Most importantly, non-inoculated
reindeer that were co-housed with infected reindeer or housed in pens adjacent
to infected reindeer but without the potential for nose-to-nose contact also
developed evidence of CWD infection. This is a major new finding that may have a
great impact on the recently diagnosed case of CWD in the only remaining
free-ranging reindeer population in Europe as our findings imply that horizontal
transmission to other reindeer within that herd has already occurred. Further,
this information will help regulatory and wildlife officials developing plans to
reduce or eliminate CWD and cervid farmers that want to ensure that their herd
remains CWD-free, but were previously unsure of the potential for reindeer to
transmit CWD.
Technical Abstract: Chronic wasting disease (CWD) is a naturally-occurring,
fatal prion disease of cervids. Reindeer (Rangifer tarandus tarandus) are
susceptible to CWD following oral challenge, and CWD was recently reported in a
free-ranging reindeer of Norway. Potential contact between CWD-affected cervids
and Rangifer species that are free-ranging or co-housed on farms presents a
potential risk of CWD transmission. The aims of this study were to 1)
investigate the transmission of CWD from white-tailed deer (Odocoileus
virginianus; CWDwtd), mule deer (Odocoileus hemionus; CWDmd), or elk (Cervus
elaphus nelsoni; CWDelk) to reindeer via the intracranial route, and 2) to
assess for direct and indirect horizontal transmission to non-inoculated
sentinels. Three groups of 5 reindeer fawns were challenged intracranially with
CWDwtd, CWDmd, or CWDelk. Two years after challenge of inoculated reindeer,
non-inoculated negative control reindeer were introduced into the same pen as
the CWDwtd inoculated reindeer (direct contact; n=4) or into a pen adjacent to
the CWDmd inoculated reindeer (indirect contact; n=2). Experimentally inoculated
reindeer were allowed to develop clinical disease. At death/euthanasia a
complete necropsy examination was performed, including immunohistochemical
testing of tissues for disease-associated CWD prion protein (PrPcwd).
Intracranially challenged reindeer developed clinical disease from 21 months
post-inoculation (months PI). PrPcwd was detected in 5 out of 6 sentinel
reindeer although only 2 out of 6 developed clinical disease during the study
period (< 57 months PI). We have shown that reindeer are susceptible to CWD
from various cervid sources and can transmit CWD to naïve reindeer both directly
and indirectly.
Monday, September 05, 2016
Pathological features of chronic wasting disease in reindeer and
demonstration of horizontal transmission Major Findings for Norway
Wednesday, September 28, 2016
*** Norway sides with OIE, decides to expose millions of consumers to the
ATYPICAL BSE SRM TSE Prion aka mad cow type disease ***
Thursday, September 22, 2016
NORWAY DETECTS 5TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION
Skrantesjuke
Saturday, September 03, 2016
NORWAY Regulation concerning temporary measures to reduce the spread of
Chronic Wasting Disease (CWD) as 4th case of skrantesjuke confirmed in Sogn og
Fjordane
Wednesday, August 31, 2016
*** NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN
SECOND CARIBOU
Wednesday, August 31, 2016
NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND
CARIBOU
Tuesday, August 02, 2016
Chronic wasting disease of deer – is the battle to keep Europe free already
lost?
Tuesday, June 14, 2016
*** Chronic Wasting Disease (CWD) in a moose from Selbu in Sør-Trøndelag
Norway ***
Thursday, July 07, 2016
Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd
Norwegian moose
14/06/2016 - Norway reports a third case
Saturday, July 16, 2016
Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The
British Deer Society 07/04/2016
Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?
could this have been cwd in the UK back in 1970’S ???
SEE FULL TEXT ;
Tuesday, April 12, 2016
The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging
reindeer from the Nordfjella population in South-Norway.
Saturday, April 9, 2016
The Norwegian Veterinary Institute (NVI, 2016) has reported a case of prion
disease Cervid Spongiform Encephalopathy detected in free ranging wild reindeer
(Rangifer tarandus tarandus)
Department for Environment, Food and Rural Affairs
Wednesday, September 7, 2016
*** An assessment of the long-term persistence of prion infectivity in
aquatic environments
Friday, September 02, 2016
*** Chronic Wasting Disease Drives Population Decline of White-Tailed
Deer
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
Using in vitro prion replication for high sensitive detection of prions and
prionlike proteins and for understanding mechanisms of transmission.
Claudio Soto
Mitchell Center for Alzheimer's diseases and related Brain disorders,
Department of Neurology, University of Texas Medical School at Houston.
Prion and prion-like proteins are misfolded protein aggregates with the
ability to selfpropagate to spread disease between cells, organs and in some
cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m
encephalopathies (TSEs), prions are mostly composed by a misfolded form of the
prion protein (PrPSc), which propagates by transmitting its misfolding to the
normal prion protein (PrPC). The availability of a procedure to replicate prions
in the laboratory may be important to study the mechanism of prion and
prion-like spreading and to develop high sensitive detection of small quantities
of misfolded proteins in biological fluids, tissues and environmental samples.
Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient
methodology to mimic prion replication in the test tube. PMCA is a platform
technology that may enable amplification of any prion-like misfolded protein
aggregating through a seeding/nucleation process. In TSEs, PMCA is able to
detect the equivalent of one single molecule of infectious PrPSc and propagate
prions that maintain high infectivity, strain properties and species
specificity. Using PMCA we have been able to detect PrPSc in blood and urine of
experimentally infected animals and humans affected by vCJD with high
sensitivity and specificity. Recently, we have expanded the principles of PMCA
to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in
Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to
study the utility of this technology to detect Aβ and α-syn aggregates in
samples of CSF and blood from patients affected by these diseases.
=========================
***Recently, we have been using PMCA to study the role of environmental
prion contamination on the horizontal spreading of TSEs. These experiments have
focused on the study of the interaction of prions with plants and
environmentally relevant surfaces. Our results show that plants (both leaves and
roots) bind tightly to prions present in brain extracts and excreta (urine and
feces) and retain even small quantities of PrPSc for long periods of time.
Strikingly, ingestion of prioncontaminated leaves and roots produced disease
with a 100% attack rate and an incubation period not substantially longer than
feeding animals directly with scrapie brain homogenate. Furthermore, plants can
uptake prions from contaminated soil and transport them to different parts of
the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety
of environmentally relevant surfaces, including stones, wood, metals, plastic,
glass, cement, etc. Prion contaminated surfaces efficiently transmit prion
disease when these materials were directly injected into the brain of animals
and strikingly when the contaminated surfaces were just placed in the animal
cage. These findings demonstrate that environmental materials can efficiently
bind infectious prions and act as carriers of infectivity, suggesting that they
may play an important role in the horizontal transmission of the disease.
========================
Since its invention 13 years ago, PMCA has helped to answer fundamental
questions of prion propagation and has broad applications in research areas
including the food industry, blood bank safety and human and veterinary disease
diagnosis.
see ;
with CWD TSE Prions, I am not sure there is any absolute yet, other than
what we know with transmission studies, and we know tse prion kill, and tse
prion are bad. science shows to date, that indeed soil, dirt, some better than
others, can act as a carrier. same with objects, farm furniture. take it with
how ever many grains of salt you wish, or not. if load factor plays a role in
the end formula, then everything should be on the table, in my opinion. see
;
***Recently, we have been using PMCA to study the role of environmental
prion contamination on the horizontal spreading of TSEs. These experiments have
focused on the study of the interaction of prions with plants and
environmentally relevant surfaces. Our results show that plants (both leaves and
roots) bind tightly to prions present in brain extracts and excreta (urine and
feces) and retain even small quantities of PrPSc for long periods of time.
Strikingly, ingestion of prioncontaminated leaves and roots produced disease
with a 100% attack rate and an incubation period not substantially longer than
feeding animals directly with scrapie brain homogenate. Furthermore, plants can
uptake prions from contaminated soil and transport them to different parts of
the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety
of environmentally relevant surfaces, including stones, wood, metals, plastic,
glass, cement, etc. Prion contaminated surfaces efficiently transmit prion
disease when these materials were directly injected into the brain of animals
and strikingly when the contaminated surfaces were just placed in the animal
cage. These findings demonstrate that environmental materials can efficiently
bind infectious prions and act as carriers of infectivity, suggesting that they
may play an important role in the horizontal transmission of the disease.
Since its invention 13 years ago, PMCA has helped to answer fundamental
questions of prion propagation and has broad applications in research areas
including the food industry, blood bank safety and human and veterinary disease
diagnosis.
see ;
Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil
Particles
Author Summary
Transmissible spongiform encephalopathies (TSEs) are a group of incurable
neurological diseases likely caused by a misfolded form of the prion protein.
TSEs include scrapie in sheep, bovine spongiform encephalopathy (‘‘mad cow’’
disease) in cattle, chronic wasting disease in deer and elk, and
Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are
unique among TSEs because they can be transmitted between animals, and the
disease agents appear to persist in environments previously inhabited by
infected animals. Soil has been hypothesized to act as a reservoir of
infectivity and to bind the infectious agent. In the current study, we orally
dosed experimental animals with a common clay mineral, montmorillonite, or whole
soils laden with infectious prions, and compared the transmissibility to unbound
agent. We found that prions bound to montmorillonite and whole soils remained
orally infectious, and, in most cases, increased the oral transmission of
disease compared to the unbound agent. The results presented in this study
suggest that soil may contribute to environmental spread of TSEs by increasing
the transmissibility of small amounts of infectious agent in the
environment.
tse prion soil
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
The sources of dust borne prions are unknown but it seems reasonable to
assume that faecal, urine, skin, parturient material and saliva-derived prions
may contribute to this mobile environmental reservoir of infectivity. This work
highlights a possible transmission route for scrapie within the farm
environment, and this is likely to be paralleled in CWD which shows strong
similarities with scrapie in terms of prion dissemination and disease
transmission. The data indicate that the presence of scrapie prions in dust is
likely to make the control of these diseases a considerable challenge.
>>>Particle-associated PrPTSE molecules may migrate from locations
of deposition via transport processes affecting soil particles, including
entrainment in and movement with air and overland flow. <<<
Fate of Prions in Soil: A Review
Christen B. Smith, Clarissa J. Booth, and Joel A. Pedersen*
Several reports have shown that prions can persist in soil for several
years. Significant interest remains in developing methods that could be applied
to degrade PrPTSE in naturally contaminated soils. Preliminary research suggests
that serine proteases and the microbial consortia in stimulated soils and
compost may partially degrade PrPTSE. Transition metal oxides in soil (viz.
manganese oxide) may also mediate prion inactivation. Overall, the effect of
prion attachment to soil particles on its persistence in the environment is not
well understood, and additional study is needed to determine its implications on
the environmental transmission of scrapie and CWD.
P.161: Prion soil binding may explain efficient horizontal CWD transmission
Conclusion. Silty clay loam exhibits highly efficient prion binding,
inferring a durable environmental reservoir, and an efficient mechanism for
indirect horizontal CWD transmission.
>>>Another alternative would be an absolute prohibition on the
movement of deer within the state for any purpose. While this alternative would
significantly reduce the potential spread of CWD, it would also have the
simultaneous effect of preventing landowners and land managers from implementing
popular management strategies involving the movement of deer, and would deprive
deer breeders of the ability to engage in the business of buying and selling
breeder deer. Therefore, this alternative was rejected because the department
determined that it placed an avoidable burden on the regulated
community.<<<
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4,
Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge,
Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency
Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and
Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary
Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School
of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington,
UK
Classical scrapie is an environmentally transmissible prion disease of
sheep and goats. Prions can persist and remain potentially infectious in the
environment for many years and thus pose a risk of infecting animals after
re-stocking. In vitro studies using serial protein misfolding cyclic
amplification (sPMCA) have suggested that objects on a scrapie affected sheep
farm could contribute to disease transmission. This in vivo study aimed to
determine the role of field furniture (water troughs, feeding troughs, fencing,
and other objects that sheep may rub against) used by a scrapie-infected sheep
flock as a vector for disease transmission to scrapie-free lambs with the prion
protein genotype VRQ/VRQ, which is associated with high susceptibility to
classical scrapie. When the field furniture was placed in clean accommodation,
sheep became infected when exposed to either a water trough (four out of five)
or to objects used for rubbing (four out of seven). This field furniture had
been used by the scrapie-infected flock 8 weeks earlier and had previously been
shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of
23) through exposure to contaminated field furniture placed within pasture not
used by scrapie-infected sheep for 40 months, even though swabs from this
furniture tested negative by PMCA. This infection rate decreased (1 out of 12)
on the same paddock after replacement with clean field furniture. Twelve grazing
sheep exposed to field furniture not in contact with scrapie-infected sheep for
18 months remained scrapie free. The findings of this study highlight the role
of field furniture used by scrapie-infected sheep to act as a reservoir for
disease re-introduction although infectivity declines considerably if the field
furniture has not been in contact with scrapie-infected sheep for several
months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental
contamination.
snip...
Discussion
Classical scrapie is an environmentally transmissible disease because it
has been reported in naïve, supposedly previously unexposed sheep placed in
pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the
vector for disease transmission is not known, soil is likely to be an important
reservoir for prions (2) where – based on studies in rodents – prions can adhere
to minerals as a biologically active form (21) and remain infectious for more
than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in
mule deer housed in paddocks used by infected deer 2 years earlier, which was
assumed to be through foraging and soil consumption (23).
Our study suggested that the risk of acquiring scrapie infection was
greater through exposure to contaminated wooden, plastic, and metal surfaces via
water or food troughs, fencing, and hurdles than through grazing. Drinking from
a water trough used by the scrapie flock was sufficient to cause infection in
sheep in a clean building. Exposure to fences and other objects used for rubbing
also led to infection, which supported the hypothesis that skin may be a vector
for disease transmission (9). The risk of these objects to cause infection was
further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid
tissue after grazing on one of the paddocks, which contained metal hurdles, a
metal lamb creep and a water trough in contact with the scrapie flock up to 8
weeks earlier, whereas no infection had been demonstrated previously in sheep
grazing on this paddock, when equipped with new fencing and field furniture.
When the contaminated furniture and fencing were removed, the infection rate
dropped significantly to 8% of 12 sheep, with soil of the paddock as the most
likely source of infection caused by shedding of prions from the
scrapie-infected sheep in this paddock up to a week earlier.
This study also indicated that the level of contamination of field
furniture sufficient to cause infection was dependent on two factors: stage of
incubation period and time of last use by scrapie-infected sheep. Drinking from
a water trough that had been used by scrapie sheep in the predominantly
pre-clinical phase did not appear to cause infection, whereas infection was
shown in sheep drinking from the water trough used by scrapie sheep in the later
stage of the disease. It is possible that contamination occurred through
shedding of prions in saliva, which may have contaminated the surface of the
water trough and subsequently the water when it was refilled. Contamination
appeared to be sufficient to cause infection only if the trough was in contact
with sheep that included clinical cases. Indeed, there is an increased risk of
bodily fluid infectivity with disease progression in scrapie (24) and CWD (25)
based on PrPSc detection by sPMCA. Although ultraviolet light and heat under
natural conditions do not inactivate prions (26), furniture in contact with the
scrapie flock, which was assumed to be sufficiently contaminated to cause
infection, did not act as vector for disease if not used for 18 months, which
suggest that the weathering process alone was sufficient to inactivate prions.
PrPSc detection by sPMCA is increasingly used as a surrogate for
infectivity measurements by bioassay in sheep or mice. In this reported study,
however, the levels of PrPSc present in the environment were below the limit of
detection of the sPMCA method, yet were still sufficient to cause infection of
in-contact animals. In the present study, the outdoor objects were removed from
the infected flock 8 weeks prior to sampling and were positive by sPMCA at very
low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive
reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay
could not detect PrPSc on any of the objects above the background of the assay.
False positive reactions with sPMCA at a low frequency associated with de novo
formation of infectious prions have been reported (27, 28). This is in contrast
to our previous study where we demonstrated that outdoor objects that had been
in contact with the scrapie-infected flock up to 20 days prior to sampling
harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions
(12)] and was significantly more positive by the assay compared to analogous
samples from the scrapie-free farm. This discrepancy could be due to the use of
a different sPMCA substrate between the studies that may alter the efficiency of
amplification of the environmental PrPSc. In addition, the present study had a
longer timeframe between the objects being in contact with the infected flock
and sampling, which may affect the levels of extractable PrPSc. Alternatively,
there may be potentially patchy contamination of this furniture with PrPSc,
which may have been missed by swabbing. The failure of sPMCA to detect
CWD-associated PrP in saliva from clinically affected deer despite confirmation
of infectivity in saliva-inoculated transgenic mice was associated with as yet
unidentified inhibitors in saliva (29), and it is possible that the sensitivity
of sPMCA is affected by other substances in the tested material. In addition,
sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more
difficult from furniture exposed to weather, which is supported by the
observation that PrPSc was detected by sPMCA more frequently in indoor than
outdoor furniture (12). A recent experimental study has demonstrated that
repeated cycles of drying and wetting of prion-contaminated soil, equivalent to
what is expected under natural weathering conditions, could reduce PMCA
amplification efficiency and extend the incubation period in hamsters inoculated
with soil samples (30). This seems to apply also to this study even though the
reduction in infectivity was more dramatic in the sPMCA assays than in the sheep
model. Sheep were not kept until clinical end-point, which would have enabled us
to compare incubation periods, but the lack of infection in sheep exposed to
furniture that had not been in contact with scrapie sheep for a longer time
period supports the hypothesis that prion degradation and subsequent loss of
infectivity occurs even under natural conditions.
In conclusion, the results in the current study indicate that removal of
furniture that had been in contact with scrapie-infected animals should be
recommended, particularly since cleaning and decontamination may not effectively
remove scrapie infectivity (31), even though infectivity declines considerably
if the pasture and the field furniture have not been in contact with
scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in
furniture that was subjected to weathering, even though exposure led to
infection in sheep, this method may not always be reliable in predicting the
risk of scrapie infection through environmental contamination. These results
suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the
detection of environmentally associated scrapie, and suggest that extremely low
levels of scrapie contamination are able to cause infection in susceptible sheep
genotypes.
Keywords: classical scrapie, prion, transmissible spongiform
encephalopathy, sheep, field furniture, reservoir, serial protein misfolding
cyclic amplification
Wednesday, December 16, 2015
*** Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission ***
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
>>>Another alternative would be an absolute prohibition on the
movement of deer within the state for any purpose. While this alternative would
significantly reduce the potential spread of CWD, it would also have the
simultaneous effect of preventing landowners and land managers from implementing
popular management strategies involving the movement of deer, and would deprive
deer breeders of the ability to engage in the business of buying and selling
breeder deer. Therefore, this alternative was rejected because the department
determined that it placed an avoidable burden on the regulated
community.<<<
Circulation of prions within dust on a scrapie affected farm
Kevin C Gough1, Claire A Baker2, Hugh A Simmons3, Steve A Hawkins3 and Ben
C Maddison2*
Abstract
Prion diseases are fatal neurological disorders that affect humans and
animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk
are contagious prion diseases where environmental reservoirs have a direct link
to the transmission of disease. Using protein misfolding cyclic amplification we
demonstrate that scrapie PrPSc can be detected within circulating dusts that are
present on a farm that is naturally contaminated with sheep scrapie. The
presence of infectious scrapie within airborne dusts may represent a possible
route of infection and illustrates the difficulties that may be associated with
the effective decontamination of such scrapie affected premises.
snip...
Discussion
We present biochemical data illustrating the airborne movement of scrapie
containing material within a contaminated farm environment. We were able to
detect scrapie PrPSc within extracts from dusts collected over a 70 day period,
in the absence of any sheep activity. We were also able to detect scrapie PrPSc
within dusts collected within pasture at 30 m but not at 60 m distance away from
the scrapie contaminated buildings, suggesting that the chance of contamination
of pasture by scrapie contaminated dusts decreases with distance from
contaminated farm buildings. PrPSc amplification by sPMCA has been shown to
correlate with infectivity and amplified products have been shown to be
infectious [14,15]. These experiments illustrate the potential for low dose
scrapie infectivity to be present within such samples. We estimate low ng levels
of scrapie positive brain equivalent were deposited per m2 over 70 days, in a
barn previously occupied by sheep affected with scrapie. This movement of dusts
and the accumulation of low levels of scrapie infectivity within this
environment may in part explain previous observations where despite stringent
pen decontamination regimens healthy lambs still became scrapie infected after
apparent exposure from their environment alone [16]. The presence of sPMCA
seeding activity and by inference, infectious prions within dusts, and their
potential for airborne dissemination is highly novel and may have implications
for the spread of scrapie within infected premises. The low level circulation
and accumulation of scrapie prion containing dust material within the farm
environment will likely impede the efficient decontamination of such scrapie
contaminated buildings unless all possible reservoirs of dust are removed.
Scrapie containing dusts could possibly infect animals during feeding and
drinking, and respiratory and conjunctival routes may also be involved. It has
been demonstrated that scrapie can be efficiently transmitted via the nasal
route in sheep [17], as is also the case for CWD in both murine models and in
white tailed deer [18-20].
The sources of dust borne prions are unknown but it seems reasonable to
assume that faecal, urine, skin, parturient material and saliva-derived prions
may contribute to this mobile environmental reservoir of infectivity. This work
highlights a possible transmission route for scrapie within the farm
environment, and this is likely to be paralleled in CWD which shows strong
similarities with scrapie in terms of prion dissemination and disease
transmission. The data indicate that the presence of scrapie prions in dust is
likely to make the control of these diseases a considerable challenge.
***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.***
***at present, no cervid PrP allele conferring absolute resistance to prion
infection has been identified.
P-145 Estimating chronic wasting disease resistance in cervids using real
time quaking- induced conversion
Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David
Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2
1 Department of Microbiology and Immunology, Midwestern University, United
States; 2Department of Diagnostic Medicine and Pathobiology, Kansas State
University; 3Prion Research Center; Colorado State University; 4U.S. Geological
Survey, Pennsylvania Cooperative Fish and Wildlife Research Unit; 5Agricultural
Research Service, United States Department of Agriculture; 6Canadian Food
Inspection Agency, National and OlE Reference Laboratory for Scrapie and CWO
In mammalian species, the susceptibility to prion diseases is affected, in
part, by the sequence of the host's prion protein (PrP). In sheep, a gradation
from scrapie susceptible to resistant has been established both in vivo and in
vitro based on the amino acids present at PrP positions 136, 154, and 171, which
has led to global breeding programs to reduce the prevalence of scrapie in
domestic sheep. In cervids, resistance is commonly characterized as a delayed
progression of chronic wasting disease (CWD); at present, no cervid PrP allele
conferring absolute resistance to prion infection has been identified. To model
the susceptibility of various naturally-occurring and hypothetical cervid PrP
alleles in vitro, we compared the amplification rates and efficiency of various
CWD isolates in recombinant PrPC using real time quaking-induced conversion. We
hypothesized that amplification metrics of these isolates in cervid PrP
substrates would correlate to in vivo susceptibility - allowing susceptibility
prediction for alleles found at 10 frequency in nature, and that there would be
an additive effect of multiple resistant codons in hypothetical alleles. Our
studies demonstrate that in vitro amplification metrics predict in vivo
susceptibility, and that alleles with multiple codons, each influencing
resistance independently, do not necessarily contribute additively to
resistance. Importantly, we found that the white-tailed deer 226K substrate
exhibited the slowest amplification rate among those evaluated, suggesting that
further investigation of this allele and its resistance in vivo are warranted to
determine if absolute resistance to CWD is possible.
***at present, no cervid PrP allele conferring absolute resistance to prion
infection has been identified.
PRION 2016 CONFERENCE TOKYO
*** Grant Agreement number: 222887 ***
*** Project acronym: PRIORITY ***
*** Project title: Protecting the food chain from prions: shaping European
priorities through basic and applied research Funding ***
Scheme: Large-scale integrating project Period covered: from Oct. 1, 2009
to Sept. 30, 2014
Name of the scientific representative of the project's co-ordinator1, Title
and Organisation: Jesús R. Requena, Ph.D., Associate Professor, Department of
medicine, University of Santiago de Compostela, Spàin. Tel: 34-881815464 Fax:
34-881815403 E-mail: jesus.requena@usc.es
Project website¡Error! Marcador no definido. address: www.prionpriority.eu
PRIORITY, PROJECT FINAL REPORT
*** 14) Concluding that atypical scrapie can transmit to Humans and that
its strain properties change as it transmits between species ***
snip...
Block D: Prion epidemiology
Studies on atypical scrapie were identified as a key element of this block,
given the potential risk associated to this agent. We studied the permeability
of Human, bovine and porcine species barriers to atypical scrapie agent
transmission. Experiments in transgenic mice expressing bovine, porcine or human
PrPC suggest that this TSE agent has the intrinsic ability to propagate across
these species barriers including the Human one. Upon species barrier passage the
biological properties and phenotype of atypical scrapie seem to be altered.
Further experiments are currently ongoing (in the framework of this project but
also in other projects) in order to: (i) characterize the properties of the
prion that emerged from the propagation of atypical scrapie in tg Hu; (ii) to
confirm that the phenomena we observed are also true for atypical scrapie
isolates other than the ones we have studied.
In parallel, studies in shep have concluded that:
*** Atypical scrapie can be transmitted by both oral and intracerebral
route in sheep with various PRP genotypes
*** Low but consistent amount of infectivity accumulates in peripheral
tissue (mammary gland, lymph nodes, placenta, skeletal muscles, nerves) of sheep
incubating atypical scrapie.
*** The combination of data from all our studies leads us to conclude that:
*** Atypical scrapie passage through species barriers can lead to the
emergence of various prions including classical BSE (following propagation in
porcine PRP transgenic mice).
*** Atypical scrapie can propagate, with a low efficacy, in human PrP
expressing mice. This suggests the existence of a zoonotic potential for this
TSE agent.
snip...
We advance our main conclusions and recommendations, in particular as they
might affect public policy, including a detailed elaboration of the evidence
that led to them. Our main recommendations are:
a. The issue of re-introducing ruminant protein into the food-chain The
opinion of the members of Priority is that sustaining an absolute feed ban for
ruminant protein to ruminants is the essential requirement, especially since the
impact of non-classical forms of scrapie in sheep and goats is not fully
understood and cannot be fully estimated. Therefore, the consortium strongly
recommends prohibiting re-introduction of processed ruminant protein into the
food-chain. Arguments in support of this opinion are:
• the large (and still uncharacterized) diversity of prion agents that
circulate in animal populations;
• the uncertainties related to prion epidemiology in animal
populations;
• the unknown efficacy of industrial processes applied to reduce
microbiological risk during processed animal protein (PAP) production on most
prion agents;
• the intrinsic capacity of prions to cross interspecies transmission
barriers;
• the lack of sensitive methodology for identifying cross contamination in
food.
• the evolution of natural food chains in nature (i.e. who eats whom or
what) has generated an efficient barrier preventing, to some extent, novel prion
epidemies and that this naturally evolved ecology should be respected.
The consortium is also hesitant to introduce processed ruminant proteins
into fish food considering the paucity of data on prion infections in fishes and
sea animals including those of mammalian origin, and the risk of establishing an
environmental contamination of the oceans that cannot be controlled.
b. Atypical prion agents and surveillance
Atypical prion agents (see below) will probably continue to represent the
dominant form of prion diseases in the near future, particularly in Europe.
*** Atypical L-type BSE has clear zoonotic potential, as demonstrated in
experimental models.
*** Similarly, there are now some data that seem to indicate that the
atypical scrapie agent can cross various species barriers.
*** Moreover, the current EU policy for eradicating scrapie (genetic
selection in affected flocks) is ineffective for preventing atypical scrapie.
*** The recent identification of cell-to-cell propagation and the
protein-encoded strain properties of human neurodegenerative diseases such as
Alzheimer's disease and Parkinson's disease, suggest that they bear the
potential to be transmissible even if not with the same efficiency as CJD. More
epidemiological data from large cohorts are necessary to reach any conclusion on
the impact of their transmissibility on public health. Re-evaluations of safety
precautions may become necessary depending on the outcome of these studies. In
that context it would appear valuable
• to develop knowledge related to the pathogenesis and inter-individual
transmission of atypical prion agents in ruminants (both intra- and
inter-species)
• to improve the sensitivity of detection assays that are applied in the
field towards this type of agent
• to maintain a robust surveillance of both animal and human populations
c. The need for extended research on prions
Intensified searching for a molecular determinants of the species barrier
is recommended, since this barrier is a key for many important policy areas -
risk assessment, proportional policies, the need for screening of human products
and food. In this respect, prion strain structural language also remains an
important issue for public health for the foreseeable future. Understanding the
structural basis for strains and the basis for adaptation of a strain to a new
host will require continued fundamental research. Prions maintain a complex
two-way relationship with the host cell and fundamental research is needed on
mechanisms for their transmission, replication and cause of nervous system
dysfunction and death.
Early detection of prion infection, ideally at preclinical stage, also
remains crucial for development of effective treatment strategies in humans
affected by the disease.
Position of the Priority consortium
Nearly 30 years ago, the appearance in the UK of Bovine Spongiform
Encephalopathy (BSE) quickly brought the previously obscure “prion diseases” to
the spotlight. The ensuing health and food crises that spread throughout Europe
had devastating consequences. In the UK alone, there were more than 36,000 farms
directly affected by BSE and the transmission of BSE prions to humans via the
food chain has caused over 200 people in Europe to die from variant
Creutzfeldt-Jakob disease (vCJD) (http://www.cjd.ed.ac.uk
Origins of prion epidemies
Classical BSE now appears to be under control, with 18 EU Member States
having achieved the World Organisation for Animal Health (Office International
Epizooties) „negligible risk‟ status (May 2014; http://www.oie.int/en/animal-health-in-the-world/official-disease-status/bse/list-of-bse-risk-status/),
and the remaining MS assessed as „controlled‟ risk. Of note, research, including
EU-funded research, has played a key role in this success: while the origin of
the infection was never defined, the principle driver of the epidemic was
identified as prions in Meat and Bone Meal (MBM). Tests based on prion
protein-specific antibodies were developed, allowing detection of infected
animals, and a better understanding of disease pathogenesis and the distribution
of infectivity in edible tissues; experimental investigation of transmission
barriers between different species allowed a rational estimation of risks, etc.
All of this led to the implementation of rational and effective policies, such
as the MBM ban to protect the animal feed chain, and the Specified Risk Material
(SRM) regulations to protect the human food chain.
In spite of this progress, prions are still a threat. Epidemiological
re-assessment indicates that the ∼10 year incubation period separating the peaks
of the BSE and the vCJD epidemics is probably too short. In addition, results
from a large number of human tonsil and appendix analyses in the UK suggest that
there may be a high number of asymptomatic individuals who are positive for the
disease-associated conformer prion protein PrPSc. While vCJD is the only form of
human prion disease that has been consistently demonstrated to have
lymphoreticular involvement, there has been no systematic investigation of
lymphoid tissue in cases with other prion diseases.
The human prion problem
The clinical cases of vCJD identified to date have all shared a common PrP
genotype (M129M), although one pre-clinical case was confirmed as an M129V
heterozygote, and it has been mooted that perhaps only the M129M proportion of
the population is susceptible. However, in the UK appendix study, PrP
accumulation was described in samples representing every codon 129 genotype,
raising the possibility that genotype does not confer resistance but instead
modulates incubation period. Apart from the two UK studies, the lymphoid tissues
of non-CJD patients have not been examined for the presence of PrPSc, so, these
cases may not solely represent pre-clinical vCJD, but also other forms of prion
disease.
Recent experiments in highly susceptible mouse models indicate the presence
of infectivity in blood or blood components at late disease stages in sporadic
CJD. The significance of this experimental finding for humans has to be explored
in more detail and, at the present time, there is no evidence for the
transmission of prions via blood in sporadic CJD. However a likely scenario is
that all those with signs of infection or abnormal PrP accumulation in
peripheral tissue could have infective blood, posing the risk for transmission
via blood products, which has been clearly demonstrated in experimental models,
and confirmed in several cases of vCJD in man. Altogether, these data clearly
demonstrate the potential risk of a second wave of vCJD, particularly when the
number people identified with lymphoid accumulation of PrPSc (16/32,411) gives a
prevalence estimate in the UK of 493 per million, much higher than the number of
clinical cases seen to date.
The animal prion problem
An increasing number of reports on cases of “atypical” BSE in cattle
throughout the EU and beyond may lead to a new epidemic, particularly since we
still do not understand all factors determining the species barrier. Ovine
scrapie is another concern, because it could mask ovine BSE, presumably
transmissible to humans. Scrapie is endemic and not likely to be eradicated
soon, although current control measures are effective at greatly reducing
disease incidence. Atypical forms, which may be spontaneous, are not affected by
these control measures and these forms of disease will persist in the global
animal population. The low prevalence of these disease forms makes effective
surveillance very challenging. However, there is a clear risk attendant on
ignoring these cases without an understanding of their possible zoonotic
potential, particularly when most forms of human disease have no established
aetiology. In summary, atypical cases of BSE and scrapie presently clearly
outnumber classical cases in cattle and sheep in all member states.
We will highlight the state-of-the-art knowledge and point out scientific
challenges and the major questions for research. Strategic objectives and
priorities in Europe in the future for research that aims to control, eliminate
or eradicate the threat posed by prions to our food and health are also
indicated.
The Priority project has focused on 4 themes, namely the structure,
function, conversion and toxicity of prions; detection of prions; mechanisms of
prion transmission and spreading and epidemiology of prion diseases. This paper
summarizes the opinions/positions reached within these themes at the end of the
project.
WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos,
Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT.
Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas.
France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated
bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD)
disease in human. To date, BSE agent is the only recognized zoonotic prion.
Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that
have been circulating for centuries in farmed ruminants there is no apparent
epidemiological link between exposure to ruminant products and the occurrence of
other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD).
However, the zoonotic potential of the diversity of circulating TSE agents has
never been systematically assessed. The major issue in experimental assessment
of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal forms
of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants,
we study their transmission ability in transgenic mice expressing human PrPC
(HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC
(129Met or 129Val) are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in
HuPrP-Tg mice with 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.
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. ***
O.08: H-type bovine spongiform encephalopathy associated with E211K prion
protein polymorphism: Clinical and pathologic features in wild-type and E211K
cattle following intracranial inoculation
S Jo Moore, M Heather West Greenlee, Jodi Smith, Eric Nicholson, Cathy
Vrentas, and Justin Greenlee United States Department of Agriculture; Ames, IA
USA
In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported
in an animal with an unusual polymorphism (E211K) in the prion protein gene.
Although the prevalence of this polymorphism is low, cattle carrying the K211
allele are predisposed to rapid onset of H-type BSE when exposed. The purpose of
this study was to investigate the phenotype of this BSE strain in wild-type
(E211E) and E211K heterozygous cattle. One calf carrying the wild-type allele
and one E211K calf were inoculated intracranially with H-type BSE brain
homogenate from the US 2006 case that also carried one K211 allelle. In
addition, one wild-type calf and one E211K calf were inoculated intracranially
with brain homogenate from a US 2003 classical BSE case. All animals succumbed
to clinical disease. Survival times for E211K H-type BSE inoculated catttle (10
and 18 months) were shorter than the classical BSE inoculated cattle (both 26
months). Significant changes in retinal function were observed in H-type BSE
challenged cattle only. Animals challenged with the same inoculum showed similar
severity and neuroanatomical distribution of vacuolation and disease-associated
prion protein deposition in the brain, though differences in neuropathology were
observed between E211K H-type BSE and classical BSE inoculated animals. Western
blot results for brain tissue from challenged animals were consistent with the
inoculum strains.
This study demonstrates that the phenotype of E211K H-type BSE remains
stable when transmitted to cattle without the E211K polymorphism, and exhibits a
number of features that differ from classical BSE in both wild-type and E211K
cattle.
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.
P.73: Oral challenge of goats with atypical scrapie
Silvia Colussi1, Maria Mazza1, Francesca Martucci1, Simone Peletto1,
Cristiano Corona1, Marina Gallo1, Cristina Bona1, Romolo Nonno2, Michele Di
Bari2, Claudia D’Agostino2, Nicola Martinelli3, Guerino Lombardi3, and Pier
Luigi Acutis1 1Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e
Valle d’Aosta; Turin, Italy; 2Istituto Superiore di Sanit a; Rome, Italy;
3Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna;
Brescia, Italy
Atypical scrapie transmission has been demonstrated in sheep by
intracerebral and oral route (Simmons et al., Andreoletti et al., 2011) but data
about goats are not available yet. In 2006 we orally challenged four goats, five
months old, with genotype R/H and R/R at codon 154. Animals died starting from
24 to 77 months p.i. without clinical signs. They all resulted negative for
scrapie in CNS and peripheral tissues using Western blot and
immunohistochemistry. Nevertheless these goats could still represent carriers.
This hypothesis was investigated through bioassay in tg338 mice, a sensitive
animal model for atypical scrapie infectivity. By end-point dilution titration,
the starting inoculum contained 106.8 ID50/g. In contrast, all tissues from
challenged goats were negative by bioassay. These negative results could be
explained with the low infectivity of the starting inoculum, which could have
been unable to induce Prion 2015 Poster Abstracts S49 disease or infectivity
within our period of observation. However the challenge conditions could have
been a bias too: as the matter of the fact, while the oral challenge of
classical scrapie is still effective in sheep 6–10 months old (Andreoletti et
al., 2011), Simmons et al. (2011) demonstrated a very short efficacy period for
atypical scrapie (24 hours after birth), hypothesizing that natural transmission
could occur mainly via milk. Our work suggests that this could be true also for
goats and it should be taken into account in oral challenges. However a low
susceptibility of goats to atypical scrapie transmission via oral route cannot
be excluded.
>>> These results suggest that (i) at the level of protein-protein
interactions, CWD adapts to a new species more readily than does BSE and (ii)
the barrier preventing transmission of CWD to humans may be less robust than
estimated.
Accepted manuscript posted online 8 July 2015.
Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy
Species Barriers by Use of Real-Time Conversion
Kristen A. Davenport, Davin M. Henderson, Jifeng Bian, Glenn C. Telling,
Candace K. Mathiason and Edward A. Hoover Prion Research Center, Department of
Microbiology, Immunology and Pathology, College of Veterinary Medicine and
Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA K.
L. Beemon, Editor + Author Affiliations
Next Section ABSTRACT The propensity for transspecies prion transmission is
related to the structural characteristics of the enciphering and new host PrP,
although the exact mechanism remains incompletely understood. The effects of
variability in prion protein on cross-species prion transmission have been
studied with animal bioassays, but the influence of prion protein structure
versus that of host cofactors (e.g., cellular constituents, trafficking, and
innate immune interactions) remains difficult to dissect. To isolate the effects
of protein-protein interactions on transspecies conversion, we used recombinant
PrPC and real-time quaking-induced conversion (RT-QuIC) and compared chronic
wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE)
prions. To assess the impact of transmission to a new species, we studied feline
CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We
cross-seeded fCWD and FSE into each species' full-length, recombinant PrPC and
measured the time required for conversion to the amyloid (PrPRes) form, which we
describe here as the rate of amyloid conversion. These studies revealed the
following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD
was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii)
conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and
CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as
homologous sCJD prions. These results suggest that (i) at the level of
protein-protein interactions, CWD adapts to a new species more readily than does
BSE and (ii) the barrier preventing transmission of CWD to humans may be less
robust than estimated.
IMPORTANCE We demonstrate that bovine spongiform encephalopathy prions
maintain their transspecies conversion characteristics upon passage to cats but
that chronic wasting disease prions adapt to the cat and are distinguishable
from the original prion. Additionally, we showed that chronic wasting disease
prions are effective at seeding the conversion of normal human prion protein to
an amyloid conformation, perhaps the first step in crossing the species barrier.
snip...
Enciphering characteristics of cBSE and cBSE-derived prions are conserved
after transspecies transmission.cBSE and CWD are prion diseases that have been
naturally passaged in their respective species (cattle and deer), whereas feline
spongiform encephalopathy (FSE) and feline chronic wasting disease (fCWD) are
first-passage infections in a new host species (cat). To investigate the
biochemical properties of cBSE and CWD after transspecies transmission to
felines, we compared the amyloidogenicity of fCWD and FSE in the original host
and in feline substrate. We found fCWD to be a more efficient seed for its new
(feline) host, suggesting that adaptation to the new host had occurred (Fig.
4A). In contrast, FSE remained a more efficient seed for its enciphering
(bovine) host, despite its derivation from feline brain PrPC (Fig. 4B). Thereby,
these cross-species seeding experiments in RT-QuIC indicated that the
characteristics of cBSE were maintained upon passage to a new species whereas
CWD had adapted to its new host. These findings in felids suggest that cBSE may
retain its ability to cross species barriers even after transmission to a new
host species and that CWD may change substantially upon transspecies
transmission.
Human rPrPC can be converted by bovine, feline, and cervid prions.The
threat of zoonotic transmission of prion disease is evident and well documented,
yet such transmission is uncommonly observed and incompletely understood. We
thereby explored the propensity of heterologous prions to convert human rPrP. In
these human rPrPC experiments, we used sporadic CJD brain as a positive control
and normal bovine, white-tailed deer, and feline brain as negative controls.
sCJD, as expected, seeded human rPrPC most efficiently, so all other seeds were
normalized to the rate of conversion of sCJD. We found human rPrPC to be a
competent substrate in RT-QuIC for CWD, fCWD, cBSE, and FSE (Fig. 5A).
Interestingly, CWD and fCWD converted human rPrPC more efficiently than did cBSE
and FSE. These data suggest that at the level of PrPC-PrP seed interaction, CWD
has the ability to template the conversion of human rPrPC to ThT-positive
amyloid. In order to assess whether CWD was faster than cBSE due to an increased
concentration of prion seed, we performed Western blotting on the seed inocula.
Western blots indicated that the cBSE sample had a higher concentration of
PrPRes than the CWD sample, indicating that CWD was not a better seed than cBSE
due to PrPRes content (Fig. 5B). Finally, we assessed the behavior of 8 CWD
field isolates, brain samples from white-tailed deer infected naturally and
verified to be positive using full-length white-tailed deer RT-QuIC (Fig. 5C).
All 8 of these isolates converted human rPrPC, confirming that our observations
were not due to the use of experimentally CWD (Fig. 5D). In all, these
experiments suggest that the CWD prions naturally circulating in the western
United States have the capacity to convert human rPrPC in this assay of
protein-protein interactions.
snip...
In summary, real-time conversion demonstrates that CWD and BSE prions
differ in their enciphering rigidity and plasticity across species barriers. One
illustration is the conservation versus adaptation of enciphering prion
characteristics upon passage to cats. These experiments also demonstrate that
human rPrP can be converted to amyloid by both cBSE and CWD prions. These data
point to the importance of deciphering the mechanisms by which prions infect and
adapt to a new species and of prompt continued vigilance regarding indirect
pathways that may facilitate transspecies prion transmission.
Monday, September 19, 2016
Evidence of scrapie transmission to sheep via goat milk
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
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
2015 Annual Report
1a. Objectives (from AD-416): 1. Investigate the pathobiology of atypical
transmissible spongiform encephalopathies (TSEs) in natural hosts. A.
Investigate the pathobiology of atypical scrapie. B. Investigate the
pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate
the horizontal transmission of TSEs. A. Assess the horizontal transmission of
sheep scrapie in the absence of lambing. B. Determine routes of transmission in
chronic wasting disease (CWD) infected premises. C. Assess oral transmission of
CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine
CWD host range using natural routes of transmission. B. Investigate the
pathobiology of CWD.
1b. Approach (from AD-416): The studies will focus on three animal
transmissible spongiform encephalopathy (TSE) agents found in the United States:
bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic
wasting disease (CWD) of deer, elk, and moose. The research will address sites
of accumulation, routes of infection, environmental persistence, and ante mortem
diagnostics with an emphasis on controlled conditions and natural routes of
infection. Techniques used will include clinical exams, histopathology,
immunohistochemistry and biochemical analysis of proteins. The enhanced
knowledge gained from this work will help mitigate the potential for
unrecognized epidemic expansions of these diseases in populations of animals
that could either directly or indirectly affect food animals.
3. Progress Report: Research efforts directed toward meeting objective 1 of
our project plan include work in previous years starting with the inoculation of
animals for studies designed to address the pathobiology of atypical scrapie,
atypical bovine spongiform encephalopathy (BSE), as well as a genetic version of
BSE. Post-mortem examination of the animals inoculated with atypical scrapie has
been initiated and laboratory analysis of the tissues is ongoing. Atypical BSE
animals have developed disease and evaluation of the samples is currently
underway. Animals inoculated with a genetic version of BSE have developed
disease with a manuscript reporting these results was published (2012), and
additional laboratory comparisons of genetic BSE to atypical and classical BSE
are ongoing. In addition, we have investigated the possibility that atypical
scrapie was present earlier than previously detected in the national flock by
analyzing archived field isolates using methods that were unavailable at the
time of original diagnosis. Sample quality was sufficiently degraded that modern
methods, beyond those applied to the tissues at the time the tissues were
archived, were not suitable for evaluation. In research pertaining to objective
2, "Investigate the horizontal transmission of TSEs", we have initiated a study
to determine if cohousing non-lambing scrapie inoculated sheep is sufficient to
transmit scrapie to neonatal lambs. At this time, scrapie free ewes have lambed
in the presence of scrapie inoculated animals and the lambs are cohoused with
these inoculated animals.
4. Accomplishments 1. Changes in retinal function in cattle can be used to
identify different types of bovine spongiform encephalopathy (BSE). BSE belongs
to a group of fatal, transmissible protein misfolding diseases known as
transmissible spongiform encephalopathies (TSEs). Like other protein misfolding
diseases including Parkinson's disease and Alzheimer's disease, TSEs are
generally not diagnosed until the onset of disease after the appearance of
unequivocal clinical signs. As such, identification of the earliest clinical
signs of disease may facilitate diagnosis. The retina is the most accessible
part of the central nervous system. ARS scientist in Ames IA described
antemortem changes in retinal function and thickness that are detectable in BSE
inoculated animals up to 11 months prior to the appearance of any other signs of
clinical disease. Differences in the severity of these clinical signs reflect
the amount of PrPSc accumulation in the retina and the resulting inflammatory
response of the tissue. These results are the earliest reported clinical signs
associated with TSE infection and provide a basis for understanding the
pathology and evaluating therapeutic interventions. Further, this work shows
that High-type BSE and classical BSE can be differentiated by eye examination
alone, the first time BSE strains have been differentiable in a live animal.
2. Sheep genetics influences the susceptibility of sheep to scrapie. Sheep
scrapie is a transmissible spongiform encephalopathy that can be transmitted
between affected animals resulting in significant economic losses in affected
flocks. The prion protein gene (PRNP) profoundly influences the susceptibility
of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in
affected sheep. In this study, sheep of 3 different prion genetic types (denoted
VRQ/VRQ, VRQ/ARR and ARQ/ARR) were inoculated and subsequently euthanized upon
onset of disease. Disease aspects were uniform across genotypes and consistent
with manifestations of classical scrapie. Mean survival time differences were
associated with the genetic type such that VRQ/VRQ sheep survived 18 months,
whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively.
Microscopic evaluation revealed similar accumulations in central nervous system
tissues regardless of host genetic type. PrPSc in lymphoid tissue was
consistently abundant in VRQ/VRQ, present but confined to tonsil or
retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep.
The results of this study demonstrate the susceptibility of sheep with the
ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc
accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in
lymphoid tissue. These results are important for science based policy with
regard to testing of sheep for scrapie where some live animal testing is
conducted using lymphoid tissues which would not detect scrapie in some specific
genetic types which could limit the national scrapie eradication program.
Review Publications Greenlee J.J. 2014. The prion diseases of animals. In:
McManus, L.M., Mitchell, R.N., editors. Pathobiology of Human Disease. San
Diego: Elsevier. p. 1124-1133. Greenlee, J.J., Kunkle, R.A., Richt, J.A.,
Nicholson, E.M., Hamir, A.N. 2014. Lack of prion accumulation in lymphoid
tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of
scrapie. PLoS One. 9(9):e108029. Greenlee, J.J., West Greenlee, M.,H. 2015. The
transmissible spongiform encephalopathies of livestock. ILAR Journal.
56(1):7-25. Munoz-Gutierrez, J.F., Schneider, D.A., Baszler, T.V., Dinkel, K.D.,
Greenlee, J.J., Nicholson, E.M., Stanton, J.J. 2015. hTERT-immortalized ovine
microglia propagate natural scrapie isolates. Virus Research. 198:35-43.
Nicholson, E.M. 2015. Detection of the disease-associated form of the prion
protein in biological samples. Bioanalysis. 7(2):253-261. West Greenlee, M.H.,
Smith, J.D., Platt, E.M., Juarez, J.R., Timms, L.L, Greenlee, J.J. 2015. Changes
in retinal function and morphology are early clinical signs of disease in cattle
with bovine spongiform encephalopathy. PLoS ONE. 10(3):e0119431. 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.
Subject: Wisconsin Governor Scott Walker's DNR et al have floundered again
on taking any actions on CWD TSE Prion disease, decides to put off now until
March 2017
see past history of CWD in Wisconsin here ;
Thursday, September 29, 2016
Wisconsin Governor Scott Walker's DNR et al have floundered again on taking
any actions on CWD TSE Prion disease, decides to put off now until March 2017
Friday, September 30, 2016
Wisconsin CWD-positive white-tailed deer found on Oconto County hunting
preserve Date: September 30, 2016
Saturday, July 09, 2016
Texas Intrastate – within state movement of all Cervid or Trucking Chronic
Wasting Disease CWD TSE Prion Moratorium
Friday, July 01, 2016
*** TEXAS Thirteen new cases of chronic wasting disease (CWD) were
confirmed at a Medina County captive white-tailed deer breeding facility on June
29, 2016***
Monday, July 18, 2016
Texas Parks Wildlife Dept TPWD HIDING TSE (CWD) in Deer Herds, Farmers
Sampling Own Herds, Rapid Testing, False Negatives, a Recipe for Disaster
Wednesday, September 21, 2016
TAHC Passes Authorized Personnel Rule at 396th Commission Meeting
“Certified CWD Sample Collector” to “Certified CWD Postmortem Sample Collector”
Wednesday, September 28, 2016
TPWD CWD Sample Collector Trainings in the Trans Pecos and Panhandle
Thursday, September 22, 2016
TVMDL offers a new, faster CWD testing option
Wednesday, September 21, 2016
TAHC Passes Authorized Personnel Rule at 396th Commission Meeting
“Certified CWD Sample Collector” to “Certified CWD Postmortem Sample Collector”
Monday, July 18, 2016
Texas Parks Wildlife Dept TPWD HIDING TSE (CWD) in Deer Herds, Farmers
Sampling Own Herds, Rapid Testing, False Negatives, a Recipe for Disaster
Wednesday, July 22, 2015
Texas Certified Chronic Wasting Disease CWD Sample Collector, like the Wolf
Guarding the Henhouse
Just got off the phone with TAHC, and I wanted to confirm this. but it
seems true, that in the state of Texas, even if you are a Captive game farmer,
breeder, part of the captive industry at all, if you want to sample your own
cervid for cwd, instead of the TAHC, TPWD, or Doctor, all you have to do is pass
the Certified CWD Sample Collector course, and bingo, you sample your own herd.
...tss
Thursday, May 02, 2013
Chronic Wasting Disease (CWD) Texas Important Update on OBEX ONLY TESTING
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
Friday, February 26, 2016
TEXAS Hartley County Mule Deer Tests Positive for Chronic Wasting Disease
CWD TSE Prion
I understand that the 84th Legislation might have made some terrible
mistakes with regards to Chronic Wasting Disease CWD TSE Prion aka mad cow type
disease, by weakening CWD rules for breeders.
Sunday, December 14, 2014
TEXAS 84th Legislature commencing this January, deer breeders are expected
to advocate for bills that will seek to further deregulate their industry
Tuesday, December 16, 2014
Texas 84th Legislature 2015 H.R. No. 2597 Kuempel Deer Breeding Industry
TAHC TPWD CWD TSE PRION
Monday, February 11, 2013
TEXAS CHRONIC WASTING DISEASE CWD Four New Positives Found in Trans Pecos
Tuesday, July 10, 2012
Chronic Wasting Disease Detected in Far West Texas
Monday, March 26, 2012
Texas Prepares for Chronic Wasting Disease CWD Possibility in Far West
Texas
2011 – 2012
Friday, October 28, 2011
CWD Herd Monitoring Program to be Enforced Jan. 2012 TEXAS
Greetings TAHC et al,
A kind greetings from Bacliff, Texas.
In reply to ;
Texas Animal Health Commission (TAHC) Announcement October 27, 2011
I kindly submit the following ;
***for anyone interested, here is some history of CWD along the Texas, New
Mexico border, and my attempt to keep up with it...terry
snip...
see history CWD Texas, New Mexico Border ;
Monday, March 26, 2012
3 CASES OF CWD FOUND NEW MEXICO MULE DEER SEVERAL MILES FROM TEXAS BORDER
Sunday, October 04, 2009
CWD NEW MEXICO SPREADING SOUTH TO TEXAS 2009 2009 Summary of Chronic
Wasting Disease in New Mexico New Mexico Department of Game and Fish
*** Thursday, September 22, 2016
*** New Mexico CWD confirmed in 5 McGregor Range deer during the 2015-16
hunting season ***
Monday, August 29, 2016
*** NWHC USGS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Thursday, August 18, 2016
*** PROCEEDINGS ONE HUNDRED AND Nineteenth ANNUAL MEETING of the USAHA BSE,
CWD, SCRAPIE, PORCINE TSE PRION October 22 28, 2015 ***
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
***re-DEFRA What is the risk of a cervid TSE being introduced from Norway
into Great Britain? Qualitative Risk Assessment September 2016***
***The likelihood of non-ruminant feed or cervid origin POAO being fed
accidentally to reindeer or other captive deer in GB is very low.
***Therefore, assuming this ban is adhered to correctly the risk of farmed
deer being exposed to animal feed containing deer protein from Norway is
considered negligible but with associated uncertainty.
***However, given that non-ruminant feed produced elsewhere (eg the USA)
may contain deer and moose PAP, it is theoretically possible that wild deer may
be exposed to deer protein in legally imported non-ruminant feed. For this to
occur, wild deer would need to access non-ruminant feed (e.g. pig, fish and
chicken feed) on farms near their habitat. Alternatively, wild deer may be
exposed to TSE prion in the faeces of pets that have consumed and digested
imported, contaminated pet feed. Also to be considered is that food may be
diverted to composting and the resulting effluate spread on pasture. The
frequency in which these routes may occur is unknown and is considered to be a
greater than negligible risk with associated uncertainty.***
================
PLEASE SEE ;
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
___________________________________
PRODUCT
Bulk cattle feed made with recalled Darling’s 85% Blood Meal, Flash Dried,
Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was
cross-contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL
Prot-Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal,
TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY
Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST
POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI – 8# SPECIAL DAIRY
Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J – PROTEIN/LACTATION, ROCK CREEK/GHC
MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR,
V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A-BYPASS ML
W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with
commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm
initiated recall is complete.
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
###
16 years post mad cow feed ban August 1997
2013
Sunday, December 15, 2013
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE
17 years post mad cow feed ban August 1997
Tuesday, December 23, 2014
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION
*** Monday, October 26, 2015 ***
*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015 ***
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
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
SPECIFIED RISK MATERIAL SRM
Monday, June 20, 2016
*** Specified Risk Materials SRMs BSE TSE Prion Program ***
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.
Maximizing profits is all that is going on now, thanks to the OIE BSE MRR
policy, the legal trading of all strains of TSE prion disease globally. ...Terry
S. Singeltary Sr.
atypical BSE spontaneous sporadic ???
Saturday, May 26, 2012
Are USDA assurances on mad cow case 'gross oversimplification'?
SNIP...
*** What irks many scientists is the USDA’s April 25 statement that the
rare disease is “not generally associated with an animal consuming infected
feed.”
*** The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul
Brown, one of the world’s experts on this type of disease who retired recently
from the National Institutes of Health.
*** "(The agency) has no foundation on which to base that statement.”
*** “We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an
official with the USDA during the Clinton Administration now at Mississippi
State.
*** In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows
the origins of atypical cases of BSE,” she said
*** The argument about feed is critical because if feed is the cause, not a
spontaneous mutation, the California cow could be part of a larger outbreak.
SNIP...
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
To further complicate things, we now know that science has shown that
plants and vegetables can uptake the TSE Prion, and that the Scrapie agent can
still be infectious from soil 16 years later. a frightening thought with the CWD
running rampant now in North America (please see source reference materials
below).
IF we don't do this, we have failed, and the TSE Prion agent will continue
to spread, as it is doing as we speak.
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids, as well as non-ruminants such as cats and dogs as
well, as soon as possible for the following reasons...
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
see Singeltary comment ;
Saturday, January 31, 2015
European red deer (Cervus elaphus elaphus) are susceptible to Bovine
Spongiform Encephalopathy BSE by Oral Alimentary route
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids as soon as possible for the following
reasons...
======
In the USA, under the Food and Drug Administrations BSE Feed Regulation (21
CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from
deer and elk is prohibited for use in feed for ruminant animals. With regards to
feed for non-ruminant animals, under FDA law, CWD positive deer may not be used
for any animal feed or feed ingredients. For elk and deer considered at high
risk for CWD, the FDA recommends that these animals do not enter the animal feed
system.
***However, this recommendation is guidance and not a requirement by law.
======
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
see Singeltary comment ;
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
Comment View document:Docket No. FDA-2013-N-0764 for Animal Feed Regulatory
Program Standards. Singeltary Comment,
Greetings FDA et al,
I would kindly like to comment on ;
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards.
I implore that we close the mad cow feed loopholes with cervid, and we must
enforce existing feed regulations against the BSE TSE Prion. we have failed
terribly in this.
the august 1997 mad cow feed ban was nothing but ink on paper, imo. please
see ;
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
see Singeltary comment ;
SEE WHAT DEFRA MAFF ET AL SAID JUST LAST MONTH ABOUT THIS ;
Thursday, April 07, 2016
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
SNIP...
Summary and MORE HERE ;
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
Greetings again FDA and Mr. Pritchett et al,
I would kindly like to comment on ;
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
#158
Guidance for Industry
Use of Material from Deer and Elk in Animal Feed
This version of the guidance replaces the version made available
September15, 2003.
This document has been revised to update the docket number, contact
information, and standard disclosures. Submit comments on this guidance at any
time.
Submit electronic comments to http://www.regulations.gov. Submit written
comments to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments
should be identified with the Docket No. FDA-2003-D-0432 (formerly
03D-0186).
For further information regarding this guidance, contact Burt Pritchett,
Center for Veterinary Medicine (HFV-222), Food and Drug Administration, 7519
Standish Place, Rockville, MD 20855, 240-402-6276, E-mail:
burt.pritchett@fda.hhs.gov.
Additional copies of this guidance document may be requested from the
Policy and Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and
Drug Administration, 7519 Standish Place, Rockville, MD 20855, and may be viewed
on the Internet at either http://www.fda.gov/AnimalVeterinary/default.htm
or http://www.regulations.gov.
U.S. Department of Health and Human Services Food and Drug Administration
Center for Veterinary Medicine March 2016
Contains Nonbinding Recommendations
2
Guidance for Industry Use of Material from Deer and Elk in Animal
Feed
This guidance represents the current thinking of the Food and Drug
Administration (FDA or Agency) on this topic. It does not establish any rights
for any person and is not binding on FDA or the public. You can use an
alternative approach if it satisfies the requirements of the applicable statutes
and regulations. To discuss an alternative approach, contact the FDA office
responsible for this guidance as listed on the title page.
I. Introduction
Under FDA’s BSE feed regulation (21 CFR 589.2000) most material from deer
and elk is prohibited for use in feed for ruminant animals. This guidance
document describes FDA’s recommendations regarding the use in all animal feed of
all material from deer and elk that are positive for Chronic Wasting Disease
(CWD) or are considered at high risk for CWD. The potential risks from CWD to
humans or non-cervid animals such as poultry and swine are not well understood.
However, because of recent recognition that CWD is spreading rapidly in
white-tailed deer, and because CWD’s route of transmission is poorly understood,
FDA is making recommendations regarding the use in animal feed of rendered
materials from deer and elk that are CWD-positive or that are at high risk for
CWD.
In general, FDA’s guidance documents do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s current thinking on a
topic and should be viewed only as recommendations, unless specific regulatory
or statutory requirements are cited. The use of the word should in Agency
guidances means that something is suggested or recommended, but not
required.
II. Background
CWD is a neurological (brain) disease of farmed and wild deer and elk that
belong in the animal family cervidae (cervids). Only deer and elk are known to
be susceptible to CWD by natural transmission. The disease has been found in
farmed and wild mule deer, white-tailed deer, North American elk, and in farmed
black-tailed deer. CWD belongs to a family of animal and human diseases called
transmissible spongiform encephalopathies (TSEs). These include bovine
spongiform encephalopathy (BSE or “mad cow” disease) in cattle; scrapie in sheep
and goats; and classical and variant Creutzfeldt-Jakob diseases (CJD and vCJD)
in humans. There is no known treatment for these diseases, and there is no
vaccine to prevent them. In addition, although validated postmortem diagnostic
tests are available, there are no validated diagnostic tests for CWD that can be
used to test for the disease in live animals.
Contains Nonbinding Recommendations
III. Use in animal feed of material from CWD-positive deer and elk
Material from CWD-positive animals may not be used in any animal feed or
feed ingredients. Pursuant to Sec. 402(a)(5) of the Federal Food, Drug, and
Cosmetic Act, animal feed and feed ingredients containing material from a
CWD-positive animal would be considered adulterated. FDA recommends that any
such adulterated feed or feed ingredients be recalled or otherwise removed from
the marketplace.
IV. Use in animal feed of material from deer and elk considered at high
risk for CWD Deer and elk considered at high risk for CWD include: (1) animals
from areas declared by State officials to be endemic for CWD and/or to be CWD
eradication zones; and (2) deer and elk that at some time during the 60-month
period immediately before the time of slaughter were in a captive herd that
contained a CWD-positive animal.
FDA recommends that materials from deer and elk considered at high risk for
CWD no longer be entered into the animal feed system. Under present
circumstances, FDA is not recommending that feed made from deer and elk from a
non-endemic area be recalled if a State later declares the area endemic for CWD
or a CWD eradication zone. In addition, at this time, FDA is not recommending
that feed made from deer and elk believed to be from a captive herd that
contained no CWD-positive animals be recalled if that herd is subsequently found
to contain a CWD-positive animal.
V. Use in animal feed of material from deer and elk NOT considered at high
risk for CWD FDA continues to consider materials from deer and elk NOT
considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal
feeds in accordance with current agency regulations, 21 CFR 589.2000. Deer and
elk not considered at high risk include: (1) deer and elk from areas not
declared by State officials to be endemic for CWD and/or to be CWD eradication
zones; and (2) deer and elk that were not at some time during the 60-month
period immediately before the time of slaughter in a captive herd that contained
a CWD-positive animal.
3
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
Greetings again FDA and Mr. Pritchett et al,
MY comments and source reference of sound science on this very important
issue are as follows ;
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
I kindly wish to once again submit to Docket No. FDA-2003-D-0432 (formerly
03D-0186) Use of Material from Deer and Elk in Animal Feed.
Thank you kindly for allowing me to comment again, ...and again...and
again, on a topic so important, why it is ‘NON-BINDING’ is beyond me.
this should have been finalized and made ‘BINDING’ or MANDATORY OVER A
DECADE AGO.
but here lay the problem, once made ‘BINDING’ or ‘MANDATORY’, it is still
nothing but ink on paper.
we have had a mad cow feed ban in place since August 1997, and since then,
literally 100s of millions of pounds BANNED MAD COW FEED has been sent out to
commerce and fed out (see reference materials).
ENFORCEMENT OF SAID BINDING REGULATIONS HAS FAILED US TOO MANY TIMES.
so, in my opinion, any non-binding or voluntary regulations will not work,
and to state further, ‘BINDING’ or MANDATORY regulations will not work unless
enforced.
with that said, we know that Chronic Wasting Disease CWD TSE Prion easily
transmits to other cervid through the oral route.
the old transmission studies of BSE TSE floored scientist once they figured
out what they had, and please don’t forget about those mink that were fed 95%+
dead stock downer cow, that all came down with TME. please see ;
It is clear that the designing scientists must also have shared Mr Bradleys
surprise at the results because all the dose levels right down to 1 gram
triggered infection.
it is clear that the designing scientists must have also shared Mr Bradleys
surprise at the results because all the dose levels right down to 1 gram
triggered infection.
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...
To further complicate things, we now know that science has shown that
plants and vegetables can uptake the TSE Prion, and that the Scrapie agent can
still be infectious from soil 16 years later. a frightening thought with the CWD
running rampant now in North America (please see source reference materials
below).
IF we don’t not do this, we have failed, and the TSE Prion agent will
continue to spread, as it is doing as we speak.
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids, as well as non-ruminants such as cats and dogs as
well, as soon as possible for the following reasons...
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
see Singeltary comment ;
please see further ;
REFERENCE MATERIALS
snip...
Terry S. Singeltary Sr.
Sunday, March 20, 2016
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer
and Elk in Animal Feed Singeltary Submission
-------- Original Message --------
Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material
From Deer and Elk in Animal Feed; Availability
Date: Fri, 16 May 2003 11:47:37 –0500
From: "Terry S. Singeltary Sr." mailto:flounder@wt.net
To: fdadockets@oc.fda.gov
Greetings FDA, i would kindly like to comment on; Docket 03D-0186FDA Issues
Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability
Several factors on this apparent voluntary proposal disturbs me greatly, please
allow me to point them out;
snip...
Oral transmission and early lymphoid tropism of chronic wasting
diseasePrPres in mule deer fawns (Odocoileus hemionus ) These results indicate
that CWD PrP res can be detected in lymphoid tissues draining the alimentary
tract within a few weeks after oral exposure to infectious prions and may
reflect the initial pathway of CWD infection in deer. The rapid infection of
deer fawns following exposure by the most plausible natural route is consistent
with the efficient horizontal transmission of CWD in nature and enables
accelerated studies of transmission and pathogenesis in the native species.
snip...
now, just what is in that mad deer feed?
_ANIMAL PROTEIN_
Subject: MAD DEER/ELK DISEASE AND POTENTIAL SOURCES
Date: Sat, 25 May 2002 18:41:46 –0700
From: "Terry S. Singeltary Sr."
Reply-To: BSE-L
To: BSE-L
8420-20.5% Antler DeveloperFor Deer and Game in the wildGuaranteed Analysis
Ingredients / Products Feeding Directions snip... _animal protein_
snip...
DEPARTMENT OF HEALTH & HUMAN SERVICES
PUBLIC HEALTH SERVICEFOOD AND DRUG ADMINISTRATION
April 9, 2001
WARNING LETTER
01-PHI-12CERTIFIED MAILRETURN RECEIPT REQUESTED
Brian J. Raymond, Owner Sandy Lake Mills 26 Mill Street P.O. Box 117 Sandy
Lake, PA 16145 PHILADELPHIA DISTRICT Tel: 215-597-4390
Dear Mr. Raymond:
Food and Drug Administration Investigator Gregory E. Beichner conducted an
inspection of your animal feed manufacturing operation, located in Sandy Lake,
Pennsylvania, on March 23,2001, and determined that your firm manufactures
animal feeds including feeds containing prohibited materials.
The inspection found significant deviations from the requirements set forth
in Title 21, code of Federal Regulations, part 589.2000 - Animal Proteins
Prohibited in Ruminant Feed. The regulation is intended to prevent the
establishment and amplification of Bovine Spongiform Encephalopathy (BSE) . Such
deviations cause products being manufactured at this facility to be misbranded
within the meaning of Section 403(f), of the Federal Food, Drug, and Cosmetic
Act (the Act).
Our investigation found failure to label your swine feed with the required
cautionary statement "Do Not Feed to cattle or other Ruminants" The FDA suggests
that the statement be distinguished by different type-size or color or other
means of highlighting the statement so that it is easily noticed by a purchaser.
In addition, we note that you are using approximately 140 pounds of cracked
corn to flush your mixer used in the manufacture of animal feeds containing
prohibited material. This flushed material is fed to wild game including deer, a
ruminant animal.
Feed material which may potentially contain prohibited material should not
be fed to ruminant animals which may become part of the food chain.
The above is not intended to be an all-inclusive list of deviations from
the regulations. As a manufacturer of materials intended for animal feed use,
you are responsible for assuring that your overall operation and the products
you manufacture and distribute are in compliance with the law.
We have enclosed a copy of FDA's Small Entity Compliance Guideto assist you
with complying with the regulation...
snip...end...full text ;
2003D-0186 Guidance for Industry: Use of Material From Deer and Elk In
Animal Feed EMC 1 Terry S. Singeltary Sr. Vol #: 1
see my full text submission here ;
>>> We can prevent, effectively treat, and make an Alzheimer’s
cure possible by 2025.
PREVENT
this must be on the forefront of research i.e. ‘iatrogenic’ transmission.
Alzheimer’s disease, iatrogenic, and Transmissible Spongiform
Encephalopathy TSE Prion disease, that is the question ???
>>> The only tenable public line will be that "more research is
required’’ <<<
>>> possibility on a transmissible prion remains
open<<<
O.K., so it’s about 23 years later, so somebody please tell me, when is
"more research is required’’ enough time for evaluation ?
http://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf
SWISS MEDICAL WEEKLY
Alzheimer-type brain pathology may be transmitted by grafts of dura mater
26/01/2016 Singeltary comment ;
re-Evidence for human transmission of amyloid-β pathology and cerebral
amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26
April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated
online 11 September 2015 Erratum (October, 2015)
snip...see full Singeltary Nature comment here;
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Sunday, November 22, 2015
*** Effect of heating on the stability of amyloid A (AA) fibrils and the
intra- and cross-species transmission of AA amyloidosis Abstract
Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by
extracellular deposition of AA fibrils. AA fibrils are found in several tissues
from food animals with AA amyloidosis. For hygienic purposes, heating is widely
used to inactivate microbes in food, but it is uncertain whether heating is
sufficient to inactivate AA fibrils and prevent intra- or cross-species
transmission. We examined the effect of heating (at 60 °C or 100 °C) and
autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western
blot analysis, transmission electron microscopy (TEM), and mouse model
transmission experiments. TEM revealed that a mixture of AA fibrils and
amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at
135 °C produced large amorphous aggregates. AA fibrils retained antigen
specificity in Western blot analysis when heated at 100 °C or autoclaved at 121
°C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and
bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly
stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA
fibrils at 121 °C or 135 °C significantly decreased amyloid deposition.
Moreover, amyloid deposition in mice injected with murine AA fibrils was more
severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils
autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These
results suggest that AA fibrils are relatively heat stable and that similar to
prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA
fibrils. These findings may contribute to the prevention of AA fibril
transmission through food materials to different animals and especially to
humans.
Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD
54.00
*** 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
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!
Monday, August 22, 2016
CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES
HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES
*** 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.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
Human Prion Diseases in the United States Robert C. Holman ,
Ermias D. Belay, Krista Y. Christensen, Ryan A. Maddox, Arialdi M. Minino,
Arianne M. Folkema, Dana L. Haberling, Teresa A. Hammett, Kenneth D. Kochanek,
James J. Sejvar, Lawrence B. Schonberger
PLOS
Published: January 1, 2010 • http://dx.doi.org/10.1371/journal.pone.0008521
re-Human Prion Diseases in the United States
Posted by flounder on 01 Jan 2010 at 18:11 GMT
I kindly disagree with your synopsis for the following reasons ;
The Pathological Protein:
Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
Philip Yam
*** ''Answering critics like Terry Singeltary, who feels that the US
undercounts CJD, Schonberger _conceded_ that the current surveillance system has
errors but stated that most of the errors will be confined to the older
population'' ***
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003
doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is
one of a number of people who have remained largely unsatisfied after being told
that a close relative died from a rapidly progressive dementia compatible with
spontaneous Creutzfeldt—Jakob ...
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
Sent: Monday, January 08,2001 3:03 PM
TO: freas@CBS5055530.CBER.FDA.GOV
FDA CJD BSE TSE Prion Scientific Advisors and Consultants Staff January
2001 Meeting Singeltary Submission
2001 FDA CJD TSE Prion Singeltary Submission
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
2001 FDA CJD TSE Prion Singeltary Submission TSEAC
Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net
Thursday, September 29, 2016
A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom
of Saudi Arabia
======================END...TSS==================
Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon.net
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.