From: TSS (216-119-163-95.ipset45.wt.net)
Subject: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (Williams et al) (rebuttal, TSS et me;-)
Date: March 6, 2003 at 9:47 am PST
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
ELIZABETH S. WILLIAMS, JAMES K. KIRKWOOD,
AND MICHAEL W. MILLER
INTRODUCTION. The transmissible spongiform
encephalopathies (TSEs) comprise an unusual group of
neurologic diseases of humans and animals. They are
apparently caused by proteinaceous agents called pri-
ons that are devoid of nucleic acids (Prusiner 1982).
Although debate continues (Chesebro 1998; Farquhar
et al. 1998), there is now a great deal of evidence sup-
porting the hypothesis that TSEs are caused by abnor-
mal, protease-resistant forms (PrPres) of cellular pro-
teins (PrPc) coded for and normally synthesized in
central nervous system (CNS) and lymphoid tissues
(Prusiner 1991). It is thought that these abnormal pro-
teins arise through posttranslational modifications in
tertiary structure of PrPc, resulting in decreased a-heli-
cal content and increased amounts of p-sheet (Prusiner
1997). In humans, PrPres may arise sporadically through
somatic mutations or spontaneous conversion of PrPc to
PrPres as a result of germline mutations in the PrP gene
resulting in familial disease; or they may be acquired
by infection (Prusiner 1997). In animals, TSEs are
infectious; spontaneous and familial forms have not
been identified, though they may occur.
On entering a susceptible host by some natural or
experimental process, PrPres promotes production of
species-specific PrPres from PrPc in lymphoid and CNS
tissues. The finding that PrPres catalyzes production of
PrPres from PrPc in vitro added weight to the hypothesis
that this is its mode of action in vivo (Kocisko et al.
1994; Raymond et al. 1997).
Thus, although the TSEs behave like infectious dis-
eases, the agents appear to have no inherent genetic
identity, and if this is so, the disease is more correctly
perceived and classified as a special type of toxicity.
Prions have remarkable resistance to environmental
conditions and a range of treatments that typically kill
or inactivate conventional infectious agents (Millison et
al. 1976; Taylor et al. 1995).
Prior to 1980, naturally occurring TSEs had been
reported in four species: scrapie in domestic sheep Ovis
aries and goats Capra hircus (Dickinson 1976); trans-
missible mink encephalopathy (TME) in mink Mustela
vison (Hartsough and Burger 1965); and kuru,
Creutzfeldt-Jakob disease (CJD), and Gerstmann-
Straussler-Scheinker syndrome of humans (Prusiner
and Hadlow 1979; Collnge and Palmer 1997). More
recently, chronic wasting disease (CWD) was reported
in deer Odocoileus spp. and Rocky Mountain elk
Cervus elaphus nelsoni in the United States (Williams
and Young 1980, 1982). Bovine spongiform
encephalopathy (BSE) was diagnosed in cattle Bos tau-
rus (Wells et al. 1987), in domestic cats Felis catus
(Pearson et al. 1992), and in wild mammals in or from
Great Britain (Jeffrey and Wells 1988; Kirkwood and
Cunningham 1994a) or in France (Bons et al. 1996,
1999). Bovine spongiform encephalopathy was associ-
ated with a variant of CJD (vCJD) in a few humans
beginning in 1996 (Will et al. 1996).
A disease indistinguishable from scrapie occurred In
mouflon Ovis musimon in the United Kingdom (Wood
et al. 1992). In addition, several suspect cases of TSE
were reported in albino tigers Panthera tigris (Kelly et
al. 1980) and ostriches Struthio camelus (Schoon et al.
1991), but these were not confirmed and probably were
not prion diseases.
Recent studies draw somewhat conflicting conclu-
sions about the pathogenesis of the TSEs. In part, this
may be due to variation in the different agents, differ-
ent doses and routes of exposure, and different animal
models used to study these diseases; natural hosts are
seldom employed in these studies.
Substantial evidence exists for genetic variation in
susceptibility to some prion diseases among and within
species. For example, there are differences in suscepti-
bility to scrapie among breeds of sheep (Hunter et al.
1992; O'Rourke et al. 1997b) and differences in incu-
bation period associated with genotype in mice (Bruce
et al. 1994). Genetic variation in susceptibility to spo-
radic and iatrogenic prion disease in humans is recog-
nized (Collnge and Palmer 1994). In contrast, there is
no evidence for variation in susceptibility to BSE
among cattle (Wilesmith 1994).
Studies of the pathogenesis of scrapie after intragas-
tric inoculation of mice suggested neural spread of the
agent from the gastrointestinal tract to thoracic spinal
cord via the sympathetic nervous system (Kimberlin
and Walker 1989). In hamsters orally infected with
scrapie, the route to the CNS was hypothesized to be
the vagus nerve to the parasympathetic vagal nucleus
(dorsal motor nucleus of the vagus) in the medulla
oblongata, the initial site of detection of PrPres in the
CNS (Beekes et al. 1998). Evidence of infectivity in
cattle orally infected with large doses of BSE agent was
found first in the CNS in thoracic and lumbar spinal
cord (Wells et al. 1998). Neuroinvasion in scrapie-
infected mice was linked to B lymphocytes (Klein et al
1997). There is no known immune response to TSE
292
Chapter 17 TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
agents in affected hosts; however, the lymphoreticular
system plays a role in pathogenesis of disease in rodent
models.
Histopathologic changes in animals and humans
with TSEs are qualitatively similar and confined to the
CNS. Lesions include vacuolation of neuronal
perikarya and neurites, neuronal degeneration and loss,
gliosis (mainly astrocytic), and accumulation of PrPres
(Wells and McGill 1992; McGill and Wells 1993). The
pathogenetic mechanisms of neurodegeneration are not
understood but are under study (Sakaguchi et al. 1996;
Tobler et al. 1996; Jeffrey et al. 1997; Williams et al.
1997; Hegde et al. 1998). Scrapie-associated fibrils
(SAFs), which are fibrillar aggregates of PrPres may be
revealed by electron-microscopic examination of deter-
gent extracts of brain from affected animals (Merz et al.
1984; Hope et al. 1988; Wells and McGill 1992).
With the importance of BSE and scrapie in domestic
livestock, and the heightened concern about the rela-
tionship of these diseases and human health, more
attention will certainly be focused on the TSEs in the
future.
CHRONIC WASTING DISEASE
History and Distribution. Chronic wasting disease
(CWD) was first recognized in 1967 as a clinical syn-
drome of unknown etiology among captive mule deer
Odocoileus hemionus at wildlife research facilities in
Colorado (Williams and Young 1992). The disease was
diagnosed in 1978 as a spongiform encephalopathy by
histopathologic examination of CNS from affected ani-
mals. Shortly afterward CWD was recognized among
captive deer in Wyoming (Williams and Young 1980).
Diagnosis of CWD in Rocky Mountain elk from these
same facilities quickly followed (Williams and Young
1982). Deer and elk in a few zoological gardens in the
United States and Canada were identified with CWD in
subsequent years (Williams and Young 1992). Appar-
ently it did not persist in these locations. Chronic wast-
ing disease has recently become a concern to the game
farm industry following its diagnosis in elk in
Saskatchewan, Canada, and in South Dakota,
Nebraska, Montana, Colorado, and Oklahoma.
In 1981, CWD was recognized in a free-ranging elk
in Colorado (Spraker et al. 1997). Subsequently, it was
found in free-ranging elk in Wyoming, and in free-
ranging mule deer [1985 (M.W. Miller unpublished)]
and white-tailed deer Odocoileus virginianus [1990
(E.S. Williams unpublished)] in both states. The known
distribution of CWD currently includes captive and
free-ranging cervids in southeast Wyoming and north-
central and northeast Colorado (Miller et al. 2000) and
several game farms in the United States and Canada.
Host Range. Only three species of Cervidae are
known to be naturally susceptible to CWD: mule deer,
white-tailed deer, and Rocky Mountain elk. Subspecies
of these cervids probably are also naturally susceptible.
Pronghorn Antilocapra americanus. Rocky Moun-
tain bighorn sheep Ovis canadensis, mouflon, moun-
tain goats Oreamnos americana, moose Alces alces,
and a blackbuck Antilope cervicapra have been in con-
tact with CWD-affected deer and elk or resided in
premises where CWD had occurred but have not devel-
oped the disease. Domestic livestock are not known to
be naturally susceptible to CWD, and a few cattle,
sheep, and goats have resided in research facilities with
CWD for prolonged periods without developing the
disease.
Many species are experimentally susceptible to
CWD by intracerebral inoculation, an unnatural but
commonly used route for the study of prion disease.
Mink, domestic ferret Mustela putorius furo, squirrel
monkey Saimiri sciureus, mule deer, domestic goat
(Williams and Young 1992), and laboratory mice
(Bruce et al. 1997) are susceptible to CWD by this
route on primary passage.
Etiology. The origin of CWD is not known. Sponta-
neous development of PrPres might have occurred in
deer, with subsequent transmission to other deer and
elk. An alternate explanation is that CWD is actually
scrapie occurring in cervids. Chronic wasting disease
could also have originated by infection with an as-yet-
unrecognized prion.
Characteristics of the agent causing CWD are poorly
understood, but the agent is presumed to be a prion.
Based on mouse strain typing, it appears to differ from
the BSE agent (Bruce et al. 1997), many strains of
scrapie, and the TME agent (M.E. Bruce personal com-
munication). The marked similarity of CNS lesions and
epidemiology strongly suggests CWD agent is the
same in captive and free-ranging deer and elk.
Transmission and Epidemiology. The mode of trans-
mission of CWD is unknown. There is no evidence that
CWD is a food-borne disease associated with rendered
ruminant meat and bonemeal as was the case in BSE
(Wilesmith et al. 1988). Occurrence of the disease
among captive deer and elk, many of which were
acquired as neonates, fawns, or adults, provides strong
evidence of lateral transmission (Williams and Young
1992; Miller et al. 1998; Miller et al. 2000). Maternal
transmission may also occur; however, this has not
been definitively determined. It is likely transmission
occurred from mule deer to elk.
The scrapie agent is found in many lymphoid tissues,
including those of the digestive tract (Hadlow et al. 1980,
1982), suggesting the agent may be shed through the ali-
mentary tract. Lymphoid tissues of affected deer and elk
contain PrPres; thus, alimentary tract shedding may also
occur in CWD. The TSE agents are extremely resistant in
the environment (Brown and Gajdusek 1991); pasture
contamination has been suspected of being the source of
scrapie agent in some outbreaks of sheep scrapie (Greig
1940; Palsson 1979). Concentration of deer and elk a
captivity or by artificial feeding may increase the likeli-
hood of transmission between individuals.
293
The youngest animal diagnosed with natural CWD
was 17 months of age, suggesting this as an approxi-
mate minimum incubation period; however, without
knowledge of when the animal was infected, it is impos-
sible to accurately determine the incubation period.
Maximum incubation periods are not known. Most
cases of CWD among deer and elk residing in facilities
with a long history of CWD are in 3-7-year-old ani-
mals. The age of onset of clinical signs is variable in
animals brought into facilities as adults or among ani-
mals in herds newly recognized to have CWD. For
example, one elk in a presumed newly infected herd
was more than 15 years old. It is not known when dur-
ing the course of infection an animal may be infectious.
In one study, more than 90% of mule deer residing
on a premises for more than 2 years died or were eu-
thanized due to CWD (Williams and Young 1980).
Chronic wasting disease was the primary cause of adult
mortality [5 (71%) of 7 and 4 (23%) of 23] in two cap-
tive elk herds (Miller et al. 1998).
Relatively little is known about the epidemiology of
CWD in free-ranging cervids. In addition to necropsy
and examination of brains from animals showing clini-
cal signs suggestive of CWD to determine its distribu-
tion (targeted surveillance), brains from deer and elk
harvested by hunters in the CWD-endemic area have
been used to estimate prevalence. Within endemic
areas, prevalence of preclinical CWD, based on
histopathology and/or immunohistochemistry for
PrPres, is estimated at less than 1%-8% (Miller et al.
2000). Chronic wasting disease has not been found in
cervids outside the endemic areas.
Preliminary modeling suggested lateral transmission
is necessary to maintain CWD at the prevalence
observed in surveillance programs. Maternal transmis-
sion may occur, but in the model this route of trans-
mission alone was not adequate to maintain the disease
at observed levels (Miller et al. 2000).
Clinical Signs. The most striking clinical features of
CWD in deer and elk are loss of body condition and
changes in behavior. Clinical signs of CWD may be
more subtle and prolonged in elk than in mule deer.
Affected animals may increase or decrease their inter-
action with handlers or other members of the herd.
They may show repetitive behaviors, such as walking
set patterns in their pens or pastures, show periods of
somnolence or depression from which they are easily
roused, and may carry their head and ears lowered.
Affected animals continue to eat, but they consume
reduced amounts of feed, leading to gradual loss of
body condition. As the disease progresses, many
affected animals display polydipsia and polyuria;
increased salivation with resultant slobbering or drool-
ing; and incoordination, particularly posterior ataxia,
fine head tremors, and wide-based stance. Esophageal
dilatation, hyperexcitability, and syncope are, rarely
seen. Death is inevitable.
In captive herds newly experiencing CWD, sporadic
cases of prime-aged animals losing condition, being
unresponsive to symptomatic treatment, and death
from pneumonia are common. Aspiration pneumonia,
presumably from difficulty swallowing and hypersali-
vation, may lead to misdiagnosis of the condition if the
brain is not examined.
The clinical course of CWD varies from a few days
to a year, with most animals surviving a few weeks to
3-4 months. Although a protracted clinical disease is
typical, occasionally acute death may occur in white-
tailed deer (M.W. Miller unpublished). Caretakers
familiar with individual animals often recognize subtle
changes in behavior well before those not familiar with
the particular animal detect abnormalities or serious
weight loss occurs. Also, those who have seen clini-
cally affected animals are more astute at detecting early
behavioral changes than naive observers.
The clinical course of CWD in free-ranging deer and
elk is probably shorter than in captivity. Wild cervids
must forage, find water, and are susceptible to preda-
tion, all factors affecting longevity of sick animals in
the wild.
Pathogenesis. The pathogenesis of CWD is not specif-
ically known, though considerable research is currently
under way to better understand the dynamics of the dis-
ease in deer and elk. Based on similarities in clinical
course, neuropathology, and distribution of PrPres, patho-
genesis of CWD is likely similar to scrapie (Hadlow et
al. 1980,1982) The CWD agent probably enters the ani-
mal by ingestion, perhaps from environmental contami-
nation or direct interaction with animals shedding the
agent. In mule deer fawns experimentally infected with
CWD, PrPres was detected in retropharyngeal and ileoce-
cal lymph nodes, tonsil, and Peyer's patches by 42 days
after inoculation (Sigurdson et al. 1999).
The parasympathetic vagal nucleus in the medulla
oblongata is the site of the most severe and consistent
lesions in deer (Williams and Young 1993) and is the site
of PrPres accumulation, prior to development of spongi-
form changes (E.S. Williams unpublished; T.R. Spraker
personal communication). Distribution of lesions in the
brain (Williams and Young 1993) may explain clinical
signs. Emaciation may be associated with hypothalamic
damage, and polydipsia may reflect damage to the par-
aventricular and supraoptic nuclei and subsequent dia-
betes insipidus (Williams and Young 1992).
Pathology. Alterations in clinical chemistry and
hematology may occur in CWD-affected animals, but
the alterations are not diagnostic. In captive deer, low
urine specific gravity (1.002-1.010) reflects polydipsia
and possibly inability to concentrate urine (Williams
and Young 1980). In free-ranging animals, urine spe-
cific gravity may not be as low because they may not
have ready access to water and may be dehydrated at
death. Other nonspecific changes in clinical pathology
reflect emaciation or intercurrent diseases.
The gross lesions of CWD are nonspecific. Car-
casses may be in poor nutritional state or emaciated
but may be in fair condition if the animal died of aspi-
294
ration pneumonia or after only a short clinical course.
Aspiration pneumonia with or without fibrinous pleuri-
tis may be present in some animals. Rumen contents
contain excessive water in those animals displaying
polydipsia; sometimes the contents appear frothy. Sand
and gravel are often abundant in the forestomachs.
Microscopic lesions of CWD have been described in
mule deer and elk (Williams and Young 1993; Hadlow
1996). The lesions are qualitatively typical of TSEs.
Distribution of lesions is similar in deer and elk, with
some minor differences in degree. In all cases of clini-
cal CWD, lesions are in the parasympathetic vagal
nucleus in the dorsal portion of the medulla oblongata
at the obex, in hypothalamus and thalamus, and in
olfactory tracts and cortex. Other regions of the brain,
in particular, thalamus and cerebellum, show typical
spongiform changes with varying degrees of severity.
Lesions are usually mild in the cerebral cortex, hip-
pocampus, and basal ganglia.
Plaques composed of PrPres can be appreciated on
routine hematoxylin-eosin staining in most clinically
affected white-tailed deer and in a few mule deer but
are not obvious in elk (Bahmanyar et al. 1985;
Williams and Young 1992). In white-tailed deer,
plaques are often surrounded by vacuoles in the neu-
ropil, which allows them to be easily visualized. The
plaques stain strongly on immunohistochemistry for
PrPres by using a variety of polyclonal and monoclonal
antibodies (Guiroy et al. 1991a,b; Williams and Young
1992; Liberski et al. 1993; O'Rourke et al. 1998b). Pat-
terns of immunostaining in CWD include granularity
and amorphous clumps on neuronal membranes,
perivascular aggregates, and large, apparently extracel-
lular accumulations of PrPres.
Scrapie-associated fibrils are found in brains and
spleen of deer and elk with CWD (Williams and Young
1992; Spraker et al. 1997). The ultrastructural lesions
of CWD are typical of lesions found in the other TSEs
(Guiroy et al. 1993, 1994; Liberski et al. 1993).
Diagnosis. Clinical signs of CWD are not specific, and
currently diagnosis is based on examination of the brain
for spongiform lesions and/or accumulation of PrPres.
The parasympathetic vagal nucleus in the dorsal portion
of the medulla oblongata at the obex is the most impor-
tant site to be examined for diagnosis of CWD
(Williams and Young 1993) and should be submitted for
histopathologic examination on every animal suspected
of having CWD. The whole head or whole brain can be
submitted to the diagnostic laboratory to ensure that the
correct portion of the brain is examined. Supplemental
tests include negative-stain electron microscopy for
SAP or Western blotting for detection of PrPres in brain
(Williams and Young 1992; Spraker et al. 1997).
Demonstration of PrPres in lymph nodes, tonsil, and
conjunctival lymphoid tissues is useful in antemortem
diagnosis of sheep scrapie (Ikegami et al. 1991;
Schreuder et al. 1996, 1998; O'Rourke et al. 1998a).
These techniques are currently being tested in deer and
elk to determine their sensitivity and specificity.
Differential Diagnoses. Differential diagnoses of
CWD in deer and elk include a wide variety of diseases
that cause CNS disease and emaciation. Animals with
brain abscesses, traumatic injuries, encephalitis,
meningitis, peritonitis, pneumonia, arthritis, starvation,
nutritional deficiencies, and dental attrition have been
submitted to laboratories as CWD suspects. Aspiration
pneumonia is often seen as a terminal event in deer and
elk with CWD and, when it is recognized in a prime-
aged cervid, CWD should be considered.
Immunity. There is no known immune response to the
CWD agent. In sheep and mice, PrP genotype plays a
major role in development of scrapie. There is marked
homology between mule deer, white-tailed deer, and
elk PrP gene sequences (Cervenakova et al. 1997; K.
O'Rourke personal communication). Polymorphism
was detected in mule deer (codon 138, serine or
asparagine) (Cervenakova et al. 1997; O'Rourke et al.
1997a), white-tailed deer (K. O'Rourke personal com-
munication), and elk [codon 132 (129), methionine or
leucine] (Cervenakova et al. 1997; Schatzl et al. 1997;
O'Rourke et al. 1998b). It is not yet known whether
particular PrP genotypes confer resistance or increase
susceptibility to CWD; however, codon 132 methio-
nine homozygotes were overrepresented in free-rang-
ing and captive CWD-affected elk when compared to
unaffected elk (O'Rourke et al. 1999).
Control and Treatment There is no known treatment
for animals affected with CWD, and it is considered
100% fatal once clinical signs develop. If an affected
animal develops pneumonia, treatment with antibiotics
might prolong the course of illness but will not alter the
fatal outcome.
Control of CWD is problematic. In the face of long
incubation periods, subtle early clinical signs, absence of
reliable antemortem diagnostic tests, extremely resistant
infectious agent, possible environmental contamination,
and lack of understanding of transmission, designing
methods for control or eradication of CWD is extremely
difficult. Management currently involves quarantine or
depopulation of CWD-affected herds. Two attempts to
eradicate CWD from captive cervid facilities failed,
though the cause of the failure was not determined;
residual environmental contamination following facility
cleanup was possible (Williams and Young 1992).
Management of CWD in free-ranging animals is
even more problematic. Long-term active surveillance
to determine distribution and prevalence of CWD has
been instituted to assist in evaluating changes over time
and effect of management intervention. Translocation
and artificially feeding cervids in the endemic areas has
been banned in an attempt to limit range expansion and
to decrease transmission of CWD. Localized popula-
tion reduction in areas of high CWD prevalence is
being considered.
Public Health Concerns. No cases of human disease
have been associated with CWD. There is a long history
295
of human exposure to scrapie through handling and
eating sheep tissues, including brain, yet there is no
evidence that this presents a risk to human health.
However, in the absence of complete information and
in consideration of the similarities of animal and
human TSEs, hunters harvesting deer and elk in the
endemic areas or meat processors and taxidermists
handling cervid carcasses should take some common-
sense measures to avoid exposure to the agent and to
other zoonotic pathogens. Sick animals should not be
harvested for consumption; hunters, game-meat
processors, and taxidermists should wear latex or rub-
ber gloves when dressing a deer or elk from these
areas; and the brain, spinal cord, lymph nodes, spleen,
tonsils, and eyes should be discarded and not con-
sumed, because these organs probably contain the
greatest amount of CWD agent. Since TSE agents have
never been demonstrated in skeletal muscle, boning
game meat is an effective way to reduce the potential
for exposure.
Management Implications. The presence of CWD in
captive and free-ranging cervids is a serious manage-
ment problem. Captive populations are quarantined,
which limits usefulness and value of the animals for
research or commerce. Indemnity for depopulated
cervids currently is not available. Guidelines for man-
agement of captive herds with CWD are being devel-
oped by federal, state, and provincial animal health
officials.
Implications for free-ranging populations of deer
and elk are significant. Deer and elk are not translo-
cated from CWD-endemic areas, surveillance pro-
grams are expensive for wildlife management agencies,
and the impact of the disease on the population dynam-
ics of deer and elk is not currently known. Preliminary
modeling suggests that CWD could detrimentally
affect populations in endemic areas (M.W. Miller
unpublished). Public and agency concerns and percep-
tions about human health risks associated with all the
TSEs may ultimately influence management of herds
of free-ranging cervids in the endemic areas.
BOVINE SPONGIFORM ENCEPHALOPATHY
IN NONDOMESTIC SPECIES
Distribution and Host Range. Cases of TSE, now rec-
ognized as caused by the BSE agent, were diagnosed in
ten species of Bovidae and Felidae (Table 17.1) at or
from zoological collections in the British Isles (Kirk-
wood and Cunningham 1994a). Cases occurred in
cheetah Acinonyx jubatus exported to Australia (Peel
and Curran 1992) and France (Baron et al. 1997). A
possible case of TSE associated with BSE agent was
reported in a rhesus macaque Macaco mulatto (Bons et
al. 1996); however, this diagnosis has been questioned
(Baker et al. 1996). Recently, spongiform encephalopa-
thy associated with oral exposure to the BSE agent was
confirmed in captive brown lemurs Eulemurfluvus and
TABLE 17.1—Wild mammals reported with naturally occurring transmissible
spongiform encephalopathies
Scientific name Common Name Disease(a) References
Bovidae
Taurotragus oryx Eland(b) BSE Fleetwood and Furley 1990; Kirkwood and Cunningham 1994a
Tragelaphus strepsiceros Greater kudu' BSE Kirkwood et al. 1990; Kirkwood and and Cunningham 1994a
Tragelaphus angasii Nyala(b) BSE Jeffrey and Wells 1988
Oryx dammah Scimitar-homed oryx(b) BSE Kirkwood and Cunningham 1994a
Oryx gazella Gemsbok(b) BSE Jeffrey and Wells 1988
Oryx leucoryx Arabian oryx(b) BSE Kirkwood et al. 1990
Bison bison Bison BSE R. Bradley, personal communication
Ovis musimon Mouflon(b) Scrapie Wood et al. 1992
Cervidae
Odocoileus hemionus Mule deer(b,c) CWD Williams and Young 1980
Odocoileus virginianus White-tailed deer(b,c) CWD Spraker et al. 1997
Cervus elaphus nelsoni Rocky Mountain elk(b,c) CWD Williams and Young 1982
Felidae
Felis concolor Cougar(b) BSE Willoughby et al. 1992
Felis pardalis Ocelot(b) BSE Kirkwood and Cunningham 1994b
Panthera tigris Tiger(b) BSE Kirkwood and Cunningham 1999
Acinonyx jubatus Cheetah(b) BSE Peet and Curran 1992; Kirkwood and Cunningham 1994b; Kirkwood et al. 1995; Baron et al. 1997
Mustelidae
Mustela vison Mink (b) TME Hartsough and Burger 1965; Hadlow and Karstad 1968; Hartung et al. 1970
(a) BSE, bovine spongiform encephalopathy; CWD, chronic wasting disease;
TME, transmissible mink encepalopathy.
(b) Captive animals.
(c) Free-ranging animals.
296
a mongoose lemur Eulemur mongw in France (Bons et
al. 1999).
Transmission and Epidemiology. The epidemiology
of BSE in zoo animals in Great Britain is similar to that
of BSE in cattle. The epidemic in cattle arose through
the practice of including ruminant-derived protein in
cattle feeds (Wilesmith et al. 1988, 1991). It was
thought that changes in rendering procedures used in
preparing this material resulted in failure to inactivate
the agent, which was hypothesized to be a strain of
scrapie from sheep. The first clinical cases were diag-
nosed in cattle in 1986. Subsequent analysis of the epi-
demic in cattle revealed there must have been wide-
spread exposure to the agent via proprietary feeds
starting during the winter of 1980-81 (Wilesmith et al.
1988,1991).
The cases in zoo animals are thought to have been
caused by the BSE agent for three reasons: their tem-
poral and geographic coincidence with the BSE epi-
demic in cattle; affected zoo animals were either
known, or suspected, to have been exposed to contam-
inated feeds; and the pathology and incubation period
of the disease in various strains of mice inoculated with
brain homogenates from an affected nyala Tragelaphus
angasii and a greater kudu Tragelaphus strepsicems
were nearly identical to those occurring when mice
were inoculated with BSE from cattle (Jeffrey et al.
1992; Bruce et al. 1994). The ungulates were exposed
to feeds containing ruminant-derived protein, and the
carnivores were exposed to tissues, probably including
CNS, from cattle incubating BSE that were considered
unfit for human consumption (Kirkwood and Cunning-
ham 1994a,b).
The question of whether BSE is laterally or mater-
nally transmissible in cattle has received vigorous
investigation. At present, there is some indication that
it is transmissible vertically or by other routes at a low
rate (Donnelly et al. 1997a; Wilesmith et al. 1997). The
occurrence of cases in greater kudu that were born after
the July 1988 ban on inclusion of ruminant-derived
protein in ruminant feeds [Her Majesty's Stationery
Office (HMSO) 1988] and that were not thought to
have been exposed via the diet raised the possibility
that lateral transmission might have occurred in this
species (Kirkwood et al. 1992, 1994; Cunningham et
al. 1993; Kirkwood and Cunningham 1994a). How-
ever, the pattern of the epidemic in cattle has since
revealed that some degree of feed contamination was
present for a considerable period after the July 1988
ban, and the possibility that the kudu were exposed to
these feeds cannot be excluded. Because of this, and
the fact that no further cases have occurred in this
species since 1992, which exceeds the apparent aver-
age incubation period of 31 months, it is possible that
all the kudu cases could, as in cattle, have been due to
ingestion of contaminated feeds.
It seems reasonable that the cases in eland Taurotra-
gus oryx (Fleetwood and Furley 1990) and scimitar-
homed orvx Orvx dammah, bom, like some of the
kudu, quite long after the July 1988 feed ban, were due
to exposure to contaminated feeds. Measures to ensure
the exclusion of ruminant-derived protein from feeds
were subsequently tightened in the United Kingdom,
and there has been a marked decline in the number of
cases among cattle, indicating the efficacy of these
measures (Donnelly et al. 1997b). Decline in the num-
ber of new cases in zoo ungulates during recent years
supports this and, although no firm conclusions can be
drawn at this stage, provides no evidence for natural
transmission between antelope.
Because dates of infection of affected zoo animals
were not known, incubation periods of the disease
could not be determined precisely. However, data on
age at death suggest that incubation periods vary
between species, and they are clearly longer in Felidae
(62-84 months) than in Bovidae (28-48 months).
Clinical Signs. Clinical signs in zoo animals have
been reviewed by Kirkwood and Cunningham (1994a),
and a detailed description of clinical signs in one
greater kudu has been published (Kirkwood et al.
1994). These include various signs of CNS dysfunc-
tion, including ataxia, abnormal head and ear posture,
fine muscle tremors, myoclonus, dullness, behavioral
changes, excessive lip and tongue movements, and
weight loss. In most cases, the disease progressed over
weeks, and there was gradual progression of severity
but, in some cases, the disease appeared to have a rapid
onset and a course of only a few days.
Pathogenesis. The specific pathogenesis of BSE in
zoo animals has not been studied. The route of spread
of the agent after oral exposure to central nervous and
other tissues remains unclear. Although infectivity has
been detected in several tissues other than CNS in
sheep with scrapie and cattle with BSE, lesions have
been observed only in the CNS.
Pathology. The comparative pathology of BSE and the
recent cases of spongiform encephalopathy in greater
kudu and domestic cats have been reviewed (Wells et al.
1993). In cheetah, spongiform changes involved the
entire brain axis, and vacuolation of tha neuropil was
the most prominent feature (Kirkwood et al. 1995). All
the zoo animals that were examined for SAP were pos-
itive (Kirkwood and Cunningham 1994a).
Diagnosis. Clinical signs are not specific, but the dis-
ease may be strongly suspected in animals that show
progressive behavioral changes or ataxia, postural
abnormalities, and abnormal muscle movements; the
suspect animals reside in or were imported from the
United Kingdom or other European countries with
endemic BSE; and where there is potential exposure to
BSE-contaminated feeds. The disease cannot be con-
firmed during life, and diagnosis depends on detection
of characteristic histopathologic changes and other
analyses of CNS material collected at postmortem
examination. In addition to detection of SAP, these
297
analyses include immunostaining and immunoblotting
techniques for PrPres (Scott et al. 1990). Further confir-
mation and, possibly, some information about strain
type can be obtained by inoculating brain homogenates
into panels of various genotypes of mice and studying
the incubation periods and lesion profiles (Jeffrey et al.
1992; Bruce et al. 1994, 1997).
Immunity. There is no known immune response to
TSE agents. Patchiness of the distribution of cases
among taxa in zoo animals suggested variation in sus-
ceptibility to the BSE agent among species (Kirkwood
and Cunningham 1994a; Kirkwood et al. 1995). How-
ever, this remains to be confirmed.
Treatment and Control. No treatment is available to
halt, reverse, or delay the development of these dis-
eases. Control of BSE in zoo animals has been dis-
cussed (Cunningham 1991; Kirkwood and Cunning-
ham 1992, 1994a). Measures to prevent inclusion of
rendered products in feeds (HMSO 1988) for zoo rumi-
nants should effectively control the disease unless ver-
tical or horizontal transmission occurs.
Since September 1990, there has been a statutory
ban in the United Kingdom on feeding specified offal
(brain, spinal cord, spleen, thymus, tonsils, and intes-
tines) from cattle older than 6 months to any animals
(HMSO 1990). This legislation did not preclude feed-
ing tissues from zoo ungulates, but Kirkwood and Cun-
ningham (1994a) considered it advisable not to feed to
animals the offals of any species that could have been
exposed to BSE. Furthermore, in the absence of infor-
mation about tissue distribution of the agent in zoo
animals, they considered that it would be prudent to
avoid using any tissues of zoo animals in BSE-endemic
countries as food for others.
Public Health Concerns. There is no known human
health risk from zoo ungulates or felids with BSE,
because these animals are not part of the human food
chain. Contact with clinically affected animals is not
considered a health risk, but appropriate protective mea-
sures should be taken during postmortem examinations.
Management Concerns. Management implications
depend on whether BSE is naturally transmissible among
zoo animals. If it is, then introduction of an incubating
animal into a population of captive or free-living wild
animals is likely to have serious consequences (Cunning-
ham 1991; Kirkwood and Cunningham 1994a). The dis-
ease may therefore severely compromise movements
between zoological collections for breeding management
or for rcintroduction to the wild. Animals that could have
been exposed to the BSE agent, their offspring, or con-
tacts should not be moved into populations that have not
been exposed, unless the damage that this would cause to
a conservation breeding program outweighs the risk of
introduction of a TSE (Kirkwood and Cunningham
1994a). However, even if there is no risk of spread to con-
specifics during life, tissues from affected or carrier ani-
mals could present a risk if eaten by other animals. For
this reason, it has been recommended that no animal
that could have been exposed to the BSE or other TSE
agent should be used in reintroduction programs (Cun-
ningham 1991; Kirkwood and Cunningham 1994a).
TRANSMISSIBLE MINK ENCEPHALOPATHY.
Transmissible mink encephalopathy is a rare TSE of
ranched mink (Marsh and Hanson 1979); it has never
been diagnosed in free-ranging mink. Only a few out-
breaks have occurred in North America and Europe
(Marsh 1976). The disease is thought to be associated
with inadvertently incorporating sheep with scrapie into
mink feed (Marsh and Hanson 1979); however, several
TME outbreaks were associated with feeding cattle and
not sheep (Marsh et al. 1991). This has led to the hypoth-
esis that an unidentified spongiform encephalopathy
may be circulating in cattle in the United States (Marsh
et al. 1991; Robinson 1996). Neither BSE nor any other
bovine TSE has been identified in the United States.
Transmissible mink encephalopathy causes 60%-
100% morbidity within a population and 100% mortal-
ity of affected mink during outbreaks (Robinson 1996).
Animals show behavioral changes and become aggres-
sive, ataxic, and carry their tail over their backs, until
they become somnolent, moribund, and die. The dis-
ease is not transmissible among affected animals
except occasionally by bite wounds or cannibalism
(Marsh and Hanson 1979). The microscopic lesions are
qualitatively typical of the TSEs, but the lesions tend to .
be more severe in the rostral portions of the brain in
comparison to the distribution of lesions in ruminants
(Eckroade et al. 1979). Transmissible mink enceph-
alopathy has been experimentally transmitted by
intracerebral inoculation to cattle (Robinson et al.
1995) and to sheep, goats, and a variety of laboratory
species, including primates (Marsh 1976; Hadlow et al.
1987). Striped skunks Mephitis mephitis and raccoons
Procyon lotor were also experimentally susceptible to
TME (Eckroade et al. 1973). Transmissible mink
encephalopathy, may be considered of greatest impor-
tance as a model of the TSEs, primarily through the
carefully crafted studies of Marsh, Hadlow, and col-
leagues, rather than as a significant disease of domestic
animals or humans. It is of potential management con-
cern to those raising mink but is of no known concern
to free-ranging species.
LITERATURE CITED
Bahmanyar, S., E.S. "Williams, F.B. Johnson, S. Young, and
D.C. Gajdusek. 1985. Amyloid plaques in spongiform
encephalopathy of mule deer. Journal of Comparative
Pathology 95:1-5.
Baker, H.F., R.M. Ridley, G.A. Wells, and J.W. Ironside. 1996.
Spontaneous spongiform encephalopathy in a monkey.
Lancet 348:955-956.
Baron, T., P. Belli, J.Y. Madec, P. Moutou, C. Vitaud, and M.
Savey. 1997. Spongiform encephalopathy in an imported
cheetah in France. Veterinary Record 141:270-271.
298
Beekes, M., P.A. McBride, and E. Baldauf. 1998. Cerebral tar-
geting indicates vagal spread of infection in hamsters fed
with scrapie. Journal of General Virology 79:601-607.
Bons, N., N. Mestre-Frances, Y. Chamay, and F. Tagliavini.
1996. Spontaneous spongifonn encephalopathy in a
young adult rhesus monkey. Lancet 348:55.
Bons, N., N. Mestre-Frances, P. Belli, P. Cathala, D.C. Gaj-
dusek, and P. Brown. 1999. Natural and experimental
oral infection of nonhuman primates by bovine spongi-
fonn encephalopathy agents. Proceedings of the National
Academy of Sciences USA 96:4046-4051.
Brown, P., and D.C. Gajdusek. 1991. Survival of scrapie virus
after 3 years' interment. Lancet 337:269-70.
Bruce, M.E., A. Chree, I. McConnell, J. Foster, G. Pearson,
and H. Praser. 1994. Transmission of bovine spongifonn
encephalopathy and scrapie to mice: Strain variation and
species barrier. Philosophical Transactions of the Royal
Society of London [B] 343:405^11.
Bruce, M.E., R.G. Will, J.W. Ironside, I. McConnell, D.
Drummond, A. Suttie, L. McCardle, A. Chree, J. Hope,
C. Birkett, S. Cousens, H. Fraser, and C.J, Bostock. 1997.
Transmission to mice indicate that 'new variant' CJD is
caused by the BSE agent. Nature 389:498-501.
Cervenakova, L., R. Rohwer, E.S. Williams, P. Brown, and
D.C. Gajdusek. 1997. High sequence homology of the
PrP gene in mule deer and Rocky Mountain elk. Lancet
350:219-220.
Chesebro, B. 1998. BSE and prions: Uncertainties about the
agent. Science 279:42-43.
Collinge, J., and M.S. Palmer. 1994. Molecular genetics of
human prion diseases. Philosophical Transactions of the
Royal Society of London [B] 343:371-378.
———. 1997. Human prion diseases. In Prion diseases, ed. J.
Collinge and M.S. Palmer. New York: Oxford University
Press, pp. 18-56.
Cunningham, A.A. 1991. Bovine spongifonn encephalopathy
and British zoos. Journal of Zoo and Wildlife Medicine
11:605-634.
Cunningham, A.A., G.A.H. Wells, A.C. Scott, J.K. Kirkwood,
and J.E.F. Bamett. 1993. Transmissible spongifonn
encephalopathy in greater kudu (Tragelaphus strep-
siceros). Veterinary Record 132:68.
Dickinson, A.G. 1976. Scrapie in sheep and goats. In Slow
virus diseases of animals and man, ed. R.H. Kimbcrlin.
Amsterdam: North Holland, pp. 209-241.
Donnelly, C.A., N.M. Perguson, A.C. Ghani, J.W. Wilesmith,
. and R.M. Anderson. 1997a. Analysis of dam-calf pairs of
BSE cases: Confirmation of a maternal risk enhance-
ment. Proceedings of the Royal Society of London [B]
264:1647-1656.
Donnelly, C.A., A.C. Ghani, N.M. Ferguson, and R.M. Ander-
son. 1997b. Recent trends in the BSE epidemic. Nature
389:903.
Eckroade, R.J., G.M. Zu Rhein, and R.P. Hanson. 1973. Trans-
missible mink encephalopathy in carnivores: Clinical,
light and electron microscopic studies in raccoons, skunks
and ferrets. Journal of Wildlife Diseases 9:229-240.
•———. 1979. Experimental transmissible mink encephalopa-
thy: Brain lesions and their sequential development. In
Slow transmissible diseases of the nervous system, vol. I,
ed. S.B. Prusiner and W.J. Hadlow. New York: Academic,
pp.409-449.
Farquhar, C.F., R.A. Somerville, and M.E. Bruce. 1998.
Straining the prion hypothesis. Nature 391:345-346.
Fleetwood, A.J., and C.W. Purley. 1990. Spongiform
encephalopathy in an eland. Veterinary Record
126:408-409.
Greig, J.R. 1940. Scrapie: Observations on the transmission of
the disease by mediate contact. Veterinary Journal
96:203-206.
Guiroy, D.C., E.S. Williams, R. Yanagihara, and D.C. Gaj-
dusek. 199 la. Immunolocalization of scrapie amyloid
(PrP27-30) in chronic wasting disease of Rocky Moun-
tain elk and hybrids of captive mule deer and white-tailed
deer. Neuroscience Letters 126:195-198.
———. 199 1b. Topographic distribution of scrapie amyloid-
immunoreactive plaques in chronic wasting disease in
captive mule deer (Odocoileus hemionus hemionus).
Acta Neuropathologica (Berlin) 81:475-478.
Guiroy, D.C., E.S. Williams, P.P. Liberski, I. Wakayama, and
D.C. Gajdusek. 1993. Ultrastructural neuropathology of
chronic wasting disease in captive mule deer. Acta Neu-
ropathologica (Berlin) 85:437-444.
Guiroy, D.C., P.P. Liberski, E.S. Williams, and D.C. Gajdusek.
1994. Electron microscopic findings in brain of Rocky
Mountain elk with chronic wasting disease. Folia Neu-
ropathology 32:171-173.
Hadlow, W.J. 1996. Differing neurohistologic images of
scrapie, transmissible spongifonn encephalopathy, and
chronic wasting disease of mule deer and elk. In
Bovine spongifonn encephalopathy: The BSE dilemma,
ed. C.J. Gibbs Jr. New York: Springer-Verlag,
pp. 122-137.
Hadlow, W.J., and L. Karstad. 1968. Transmissible
encephalopathy of mink in Ontario. Canadian Veterinary
Journal 9:193-196.
Hadlow, W.J., R.C. Kennedy, R.E. Race, and C.M. Ekiund.
1980. Virologic and neurohistologic findings in dairy
goats affected with natural scrapie. Veterinary Pathology
17:187-199.
Hadlow, W.J., R.C. Kennedy, and R.E. Race. 1982. Natural
infection of Suffolk sheep with scrapie virus. Journal of
Infectious Disease 146:657-664.
Hadlow, W.J., R.E. Race, and R.C. Kennedy. 1987. Experi-
mental infection of sheep and goats with transmissible
mink encephalopathy virus. Canadian Journal of Veteri-
nary Research 51:135-144.
Hartsough, G.R., and D. Burger. 1965. Encephalopathy of
mink: I. Epizootiologic and clinical observations. Jour-
nal of Infectious Diseases 115:387-392.
Hartung, J., H. Zimmermann, and U. Johannsen. 1970. Infec-
tious encephalopathy in the mink: I. Clinical, epizootio-
logical and experimental studies. Monatshefte fur Veteri-
narmedivn 15:385-388.
Hegde, R.S., J.A. Mastrianni, M.R. Scott, K.A. de Fea, P.
Tremblay, M. Torctua, S.J. de Annond, S.B. Prusiner,
and V.R. Lingappa. 1998. A transmembrane form of the
prion protein in neurodegenerative disease. Science
279:827-834.
Her Majesty's Stationery Office (HMSO). 1988. The bovine
spongifonn encephalopathy order 1988. Statutory Instru-
ment Number 1039. London: HMSO.
————. 1990. Bovine spongifonn encephalopathy (No. 2).
Amendment Order 1990. London: HMSO.
Hope, J., L.J. Reekie, N. Hunter, G. Multhaup, K. Beyreuther,
H. White, A.C. Scott, M.J. Stack, M. Dawson, and G.A.
Wells. 1988. Fibrils from brains of cows with new cattle
disease contain scrapie-associated protein. Nature
336:390-392.
Hunter, N., J.D. Foster, and J. Hope. 1992. Natural scrapie in
British sheep: Breeds, ages and PrP gene polymor-
phisms. Veterinary Record 130:389-392.
Ikegami. Y., M. Ito, H. Isomura, E. Momotani, K. Sasaki, Y.
Muramatsu, N. Ishiguro, and M. Shinagawa. 1991. Pre-
clinical and clinical diagnosis of scrapie by detection of
PrP protein in tissues of sheep. Veterinary Record
128:271-275.
Jeffrey, M., and G.A.H. Wells. 1988. Spongiform
encephalopathy in a nyala (Tragelaphus angasi). Veteri-
nary Pathology 25:398-399.
299
Jeffrey, M., J.R. Scott, A. Williams, and H. Fraser. 1992.
Ultrastructural features of spongifonn encephalopathy
transmitted to mice from three species of Bovidae. Ada
Neuropalhologica (Berlin) 84:559-569.
Jeffrey, M., C.M. Goodsir, M.E. Bruce, P.A. McBride, and
J.R. Fraser. 1997. In vivo toxicity of prion protein in
murine scrapie: Ultrastructural and immunogold stud-
ies. Neuropathology and Applied Neurobiology
23:93-101.
Kelly, D.F, H. Pearson, A.I. Wright, and L.W. Greenham.
1980. Morbidity in captive white tigers. In The compar-
ative pathology of zoo animals, ed. RJ. Montali and G.
Migaki. Front Royal, VA: Smithsonian Institution, pp.
183-188.
Kimberiin, R.H., and C.A. Walker. 1989. Pathogenesis of
scrapie in mice after intragastric infection. Virus
Research 12:213-220.
Kirkwood, J.K., and A.A. Cunningham. 1992. Spongifonn
encephalopathy in zoo ungulates: Implications for
translocation and reintroduction. In Proceedings of the
conference'of the American Association of Zoo Veteri-
narians and the American Association of Wildlife Veteri-
narians, Oakland, California, ed. R.E. Junge. Oakland,
CA: American Association of Zoo Veterinarians, pp.
26-27.
————. 1994a. Epidemiological observations on spongiform
encephalopathies in captive wild animals in the British
Isles. Veterinary Record 135:296-303.
——. 1994b. Patterns of incidence of spongiform
encephalopathy in captive wild animals in the British
Isles. In Wildlife Disease Association, European Divi-
sion, Symposium. Paris, pp. 28.
1999. Scrapie-like spongiform encephalopathies
(prion diseases) in nondomesticated species. In Zoo and
wild animal medicine, ed. M.E. Fowler and R.E. Miller.
Philadelphia: W.B. Saunders, pp. 662-668.
Kirkwood, J.K., G.A.H. Wells, J.W. Wilesmith, A.A. Cun-
ningham, and S.I. Jackson. 1990. Spongiform
encephalopathy in an Arabian oryx (Oryx leucoryx) and
a greater kudu (Tragelaphus strepsiceros). Veterinary
Record 127:418-420.
Kirkwood, J.K., G.A.H. Wells, A. A. Cunningham, S.I. Jack-
son, A.C. Scott, M. Dawson, and J.W. Wilesmith. 1992.
Scrapie-like encephalopathy in a greater kudu (Tragela-
phus strepsiceros) which had not been fed ruminant-
derived protein. Veterinary Record 130:365-367.
Kirkwood, J.K., A.A. Cunningham, A.R. Austin, G.A.H.
Wells, and A.W. Sainsbury. 1994. Spongiform
encephalopathy in a greater kudu (Tragelaphus strep-
siceros) introduced into an affected group. Veterinary
Record 134:167-168.
Kirkwood, J.K., A.A. Cunningham, E.J. Flach, S.M. Thorn-
ton, and G.A.H. Wells. 1995. Spongiform encephalopa-
thy in another captive cheetah (Acinonyx jubatus): Evi-
dence for variation in susceptibility or incubation periods
between species? Journal of Zoo and Wildlife Medicine
26:577-582.
Klein, M.A., R. Prigg, E. Flechsig, A.J. Raeber, U. Kalinke, H.
Bluethmann, F. Bootz, M, Suter, R.M. Zinkemagel, and
A. Aguzzi. 1997. A crucial role for B cells in neuroinva-
sive scrapie. Nature 390:687-690.
Kocisko, D.A., J.H. Come, S.A. Priola, B. Chesebro, G.J.
Raymond, P.T. Lansbury, and B. Caughley. 1994. Cell-
free formation of protease-resistant prion protein. Nature
370:471-474.
Liberski, P.P., D.C. Guiroy, E.S. Williams, R. Yangihara, P.
Brown, and D.C. Gajdusek. 1993. The amyloid plaque.
In Light and microscopic neuropathology of slow virus
disorders, ed. P.P. Uberski. Boca Raton, FL: CRC, pp.
295-347.
Marsh, R.F. 1976. The subacute spongiform encepha-
lopathies. Frontiers of Biology 44:359-380.
Marsh, R.F, and R.P. Hanson. 1979. On the origin of trans-
missible mink encephalopathy. In Slow transmissible dis-
eases of the nervous system, vol. 1, ed. S.B. Prusiner and
W.J. Hadlow. New York: Academic, pp. 451-460.
Marsh, R.F., R.A. Bessen, S. Lehmann, and G.R. Hartsough.
1991. Epidemiological and experimental studies on a
new incident of transmissible mink encephalopathy.
Journal of General Virology 72:589-594.
McGill, I.S., and G.A. Wells. 1993. Neuropathological find-
ings in cattle with clinically suspect but histologically
unconfirmed bovine spongifonn encephalopathy (BSE).
Journal of Comparative Pathology 108:241-260.
Merz, P.A., R.G. Rohwer, K. Kascsak, H.M. Wisniewiski,
R.A. Somerville, C.J. Gibbs Jr., and D.C. Gajdusek.
1984. Infection-specific particle from the unconventional
slow virus diseases. Science 225:437-440.
Miller, M.W, M.A. Wild, and E.S. Williams. 1998. Epidemi-
ology of chronic wasting disease in Rocky Mountain elk.
Journal of Wildlife Diseases 34:532-538.
Miller, M.W., E.S. Williams, C.W. McCarty, T.R. Spraker, T.J.
Kreeger, C.T. Larsen, and E.T. Thoroe. 2000. Epidemiol-
ogy of chronic wasting disease in free-ranging cervids.
Journal of Wildlife Diseases. 36:676-690.
Millison, G.C., G.D. Hunter, and R.H. Kimberiin. 1976. The
physico-chemical nature of the scrapie agent. In Slow
virus diseases of animals and man, ed. R.H. Kimberiin.
Amsterdam: North Holland, pp. 243-266.
O'Rourke, K., T.R. Spraker, M.W. Miller, and E.S. Williams.
1997a. Three alleles of the prion protein gene in mule
deer (Odocoileus hemionus hemionus) with chronic
wasting disease. GenBank, Accession nos. 2213811,
2213938, 2213936, http://www.ncbi.nlm.gov/Entrez/
protein.html.
O'Rourke, K., G.R. Holyoak, W.W. dark, J.R. Mickelson, S.
Wang, R.P. Meico, T.E. Besser, and W.C. Foote. 1997b.
PrP genotypes and experimental scrapie in orally inocu-
lated Suffolk sheep in the United States. Journal of Gen-
eral Virology 78:975-978.
O'Rourke, K., TV. Baszler, S.M. Parish, and D.P. Knowles.
1998a. Preclinical detection of PrPsc in nictitating mem-
brane lymphoid tissue of sheep. Veterinary Record
142:489-491.
O'Rourke, K., TV. Baszler, J.M. Miller, T.R. Spraker, I.
Sadler-Riggleman, and D.P. Knowles. 1998b. Mono-
clonal antibody F89/160.1.5 defines a conserved epitope
on the ruminant prion protein. Journal of Clinical Micro-
biology 36:1750-1755.
O'Rourke, K.I;, T.E. Besser, M.W. Miller, T.P. Cline, T.R.
Spraker, A.L. Jenny, M.A. Wild, G.L. Zebarth, and E.S.
Williams. 1999. PrP genotypes of captive and free-rang-
ing Rocky Mountain elk (Cervus elaphus nelsoni) with
chronic wasting disease. Journal of General Virology
80:2765-2769.
Palsson, P.A. 1979. Rida (scrapie) in Iceland and its epidemi
ology. In Slow transmissible diseases of the nervous system,
vol. 1, ed. S.B. Prusiner and W.J. Hadlow. New
York: Academic, pp. 357-366.
Pearson, G.R., J.M. Wyatt, T.J. Gruffydd-Jones, J. Hope, A
Chong, R.J. Higgins, A.C. Scott, and G.A. Wells. 1992
Feline spongifonn encephalopathy: Fibril and PrP stud
ies. Veterinary Record 131:307-310.
Peet, R.L., and J.M. Curran. 1992. Spongiform encephalopathy
in an imported cheetah (Acinonyx jubatus). Australian
Veterinary Journal 69:117.
Prusiner, S.B. 1982. Novel proteinaceous infectious particle
cause scrapie. Science 216:136-144.
————. 1991. Molecular biology of prion diseases. Selene
252:1515-1522.
300
1997. Prion diseases and the BSE crisis. Science
278:245-251.
Prusiner, S.B., and W.J. Hadlow, eds. 1979. Slow transmissi-
ble diseases of the nervous system, vol. 1. New York:
Academic, 472 pp.
Raymond, G.J., J. Hope, D.A. Kocisko, S.A. Priola, L.D. Ray-
mond, A. Bossers, J. Ironside, R.G. Will, S.G. Chen, R.B.
Petersen, P. Gambetti, R. Rubenstein, M.A. Smits, P.T.
Lansbury Jr., and B. Caughey. 1997. Molecular assess-
ment of the potential transmissibilities of BSE and
scrapie to humans. Nature 388:285-288.
Robinson, M.M. 1996. An assessment of transmissible mink
encephalopathy as an indicator of bovine scrapie in U.S.
cattle. In Bovine spongiform encephalopathy: The BSE
dilemma, ed. C.J. Gibbs Jr. New York: Springer-Verlag,
pp. 97-107.
Robinson, M.M., W.J. Hadlow, D.P. Knowles, T.P. Huff, P.A.
Lacy, R.F. Marsh, and J.R. Gorham. 1995. Infection of
cattle with the agents of TME and scrapie. Journal of
Comparative Pathology 113:241-251.
Sakaguchi, S., S. Katamine, N. Nishida, R. Moriuchi, K.
Shigematsu, T. Sugimoto, A. Nakatani, Y. Kataoka, T.
Houtani, S. Shirabe, H. Okada, S' Hasegawa, T.
Miyamoto, and T. Noda. 1996. Loss of cerebellar Purk-
inje cells in aged mice homozygous for a disrupted PrP
gene. Nature 380:528-531.
Schatzl, H.M., F. Wopmer, S. Gilch, A. von Brunn, and G.
Jager. 1997. Is codon 129 of prion protein polymorphic
in human beings but not in animals? Lancet
349:219-220.
Schoon, H.-A., D. Brunckhorst, and J. Pohlenz. 1991. Spongi-
form encephalopathy in a red-necked ostrich [in Ger-
man]. Tierwritliche Praxis 19:263-265. Abstract.
Schreuder, B.E.C., L.J.M. van Keulen, M.E.W. Vromans,
J.P.M. Langeveld, and M.A. Smits. 1996. Preclinical test
for prion diseases. Nature 381:563.
————. 1998. Tonsillar biopsy and PrPsc detection in the pre-
clinical diagnosis of scrapie. Veterinary Record
142:564-568.
Scott, A.C., G.A.H. Wells, M.J. Stack, H. White, and M. Daw-
son. 1990. Bovine spongiform encephalopathy: Detec-
tion and quantitation of fibrils, fibril protein (PrP) and
vacuolation in brain. Veterinary Microbiology
23:295-305.
Sigurdson, C.J., E.S. Williams, M.W. Miller, T.R. Spraker,
K.I. O'Rouike, and E.A. Hoover. 1999. Oral transmis-
sion and early lymphoid tropism of chronic wasting dis-
ease PrPres in mule deer fawns (Odocoileus hemionus).
Journal of General Virology 80:2757-2764.
Spraker, T.R., M.W. Miller, E.S. Williams, D.M. Getzy, W.J.
Adrian, G.G. Schoonveld, R.A. Spowart, K.I. O'Rourke,
J.M. Miller, and P.A. Merz. 1997. Spongiform
encephalopathy in free-ranging mule deer (Odocoileus
hemionus), white-tailed deer (Odocoileus virginianus),
and Rocky Mountain elk (Cervus elaphus nelsoni) in
northcentral Colorado. Journal of Wildlife Diseases
33:1-6.
Taylor, D.M., S.L. Woodgate, and M.J. Atkinson. 1995. Inac-
tivation of the bovine spongiform encephalopathy agent
by rendering procedures. Veterinary Record
137-605-610.
Tobler, I., S.E. Gaus, T. Deboer, P. Achermann, M. Fischer, T.
Rulicke, M. Moser, B. Oesch, P.A. McBride, and J.C.
Manson. 1996. Altered circadian activity rhythms and
sleep in mice devoid of prion protein. Nature
380:639-642.
Wells, G.A., and I.S. McGill. 1992. Recently described
scrapie-like encephalopathies of animals: Case defini-
tions. Research in Veterinary Science 53:1-10.
Wells, G.A., A.C. Scott, C.T. Johnson, R.F. Gunning, R.D.
Hancock, M. Jeffrey, M. Dawson, and R. Bradley. 1987.
A novel progressive spongiform encephalopathy in cat-
tle. Veterinary Record 121:419-420.
Wells, G.A., S.A.C. Hawkins, A.A. Cunningham, W.H.
Blamire, J.W. Wilesmith, A.R. Sayers, and P. Hams.
1993. Comparative pathology of the new transmissible
spongiform encephalopathies. In Transmissible spongi-
form encephalopathies, ed. R. Bradley and B. Marchant.
Brussels: European Commission, pp. 327—345.
Wells, G.A., S.A.C. Hawkins, R.B. Green, A.R. Austin, I.
Dexter, Y.I. Spencer, M.J. Chaplin, M.J. Stack, and M.
Dawson. 1998. Preliminary observations on the patho-
genesis of experimental bovine spongiform encephalopa-
thy (BSE): An update. Veterinary Record 142:103-106.
Wilesmith, J.W. 1994. An epidemiologist's view of bovine
spongiform encephalopathy. Philosophical Transactions
of the Royal Society of London [B] 343:357-361.
Wilesmith, J.W, G.A.H. Wells, M.P. Cranwell, and J.B.M.
Ryan. 1988. Bovine spongiform encephalopathy: Epi-
demiological studies. Veterinary Record 123:638-644.
Wilesmith, J.W., J.B.M. Ryan, and M.J. Atkinson. 1991.
Bovine spongiform encephalopathy: Epidemiological
studies on the origin. Veterinary Record 128:199-203.
Wilesmith, J.W, G.A. Wells, J.B. Ryan, D. Gavier-Widen, and
M.M. Simmons. 1997. A cohort study to examine mater-
nally-associated risk factors for bovine spongiform
encephalopathy. Veterinary Record 141:239-43.
Will, R.G., J.W. Ironside, M. Zeidler, S.N. Cousens, K.
Estibeiro, A. Alperovitch, S. Poser, M. Pocchiari, A. Hof-
man, and P.G. Smith. 1996. A new variant of Creutzfeldt-
Jakob disease in the UK. Lancet 347:921-925.
Williams, A., P.J. Lucassen, D. Ritchie, and M. Bruce. 1997.
PrP deposition, microglial activation, and neuronal apop-
tosis in murine scrapie. Experimental Neurology
144:433-438.
Williams, E.S., and S. Young. 1980. Chronic wasting disease
of captive mule deer: A spongiform encephalopathy.
Journal of Wildlife Diseases 16:89-98.
————. 1982. Spongiform encephalopathy of Rocky Moun-
tain elk. Journal of Wildlife Diseases 18:465-471.
——. 1992. Spongiform encephalopathies of Cervidae. Sci-
entific and Technical Review Office of International Epi-
wotics 11:551-567.
-. 1993. Neuropathology of chronic wasting disease of
mule deer (Odocoileus hemionus) and elk (Cervus ela-
phus nelsoni). Veterinary Pathology 30:36-45.
Willoughby, K., D.F. Kelly, D.G. Lyon, and G.A.H. Wells.
1992. Spongiform encephalopathy in a captive puma
(Felis concolor). Veterinary Record 131:431-434.
Wood, J.L.N., L.J. Lund, and S.H. Done. 1992. The natural
occurrence of scrapie in moufflon. Veterinary Recora
130:25-27.
====================
a few things to ponder...TSS
What state officials aren't telling you about chronic wasting disease -- the politics and blunders behind its spread and the true dangers.
snip...
No case of mad cow disease has ever been confirmed in the United States,
but Marsh urged the USDA to ban the practice of feeding processed bone
and blood meal made from rendered sheep, cows and deer to other
ruminants. His suggestion would have cost the agricultural industry
dearly in substitute protein, and the USDA took no action. Frustrated,
in 1993, Marsh repeated his concern in the state Ag Review, warning
Wisconsin dairy farmers they were feeding cattle to cattle. He also
talked to The New York Times. Marsh's published comments ignited such a
torrent of complaints from the state's agri-business industry, which
underwrites much of the UW Agriculture School's research, that the
college's dean tried to silence Marsh. Marsh was harassed and threatened
with lawsuits, and the university sponsored a symposium "whose only
purpose seemed to be arguing there was no need to change animal feeding
patterns," recalls Aiken, then a Marsh colleague, as was Olander. (Both
joined Marsh in pushing for a broad ruminant-to-ruminant feeding ban.)
Marsh was "not allowed to speak, while everyone discredited his work,"
says John Stauber, executive director of the Madison-based Center for
Media and Democracy, who dedicated his book, Mad Cow, USA, to Marsh.
Despite the humiliation inflicted by the university, Marsh would be
vindicated. When protein feed from rendered downer cows and scrapie
sheep was identified as the cause of mad cow disease in Britain in 1996,
the university lionized Marsh in its Wisconsin Alumni Magazine as the
scientist who'd predicted the disaster and tried to stop it.
"We were inundated. We had over 200 phone messages from CBS, NBC and
other people in the media who wanted to talk to Dick," remembers
professor Bruce Christenson, Marsh's successor as chair of the
department of animal health and biomedical sciences. But by then, Marsh,
58, had cancer, recalls Christenson. "He was a warrior even when he knew
he was dying."
snip...
http://www.milwaukeemagazine.com/122002/cwd.html
ROUND TABLE ON BSE -- WASHINGTON -- 27-28 JUNE 1989
snip...
The summary does tend to give a particular slant to the epidemiology of
BSE which is not totally sound. It is a possibility that the agent of
BSE may be in the cattle population in a number of countries already
apart from the USA and that clinical cases are occurring on rare
occasions. It is also important to off the possibility of the
relationship between BSE and certain low-temperature rendering systems.
For that reason a number of other countries apart from the USA and
France are at risk and, in particular, the Netherlands, Denmark,
Germany and Belgium. For these reasons it would be wise to move to an
international ban on the feeding of ruminant protein to ruminants.
Clearly the summary also needs to refer to the incidence of BSE in the
UK and not solely to Great Britain. No doubt this has been tidied up
in your comments on the summary conclusions. It is a pity that more of
the comments put forward by Dr. Kimberlin have not been included in the
summary since his views on page 13 are succinct and valuable...
snip...
http://www.bseinquiry.gov.uk/files/yb/1989/08/29003001.pdf
Is there a Scrapie-like disease in cattle ?
IN CONFIDENCE
R.F. MARSH
snip...
re-mink rancher 'Wisconsin' dead stock feeder using >95%
downer or dead dairy and a few horses...
http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf
Part of the Proceedings of an International Roundtable on Bovine
Spongiform Encephalopathy, Bethesda, Maryland, USA, June 27-28, 1989.
The possibility of infection with BSE in the United States, as defined
by studies on the disease in Great Britain, is judged to be low on the
basis of the following: (1) meat and bonemeals imported into the United
States from Great Britain between 1980 and 1988 were used mainly in
poultry, not ruminant feed; (2) the Scrapie Eradication Program had
reduced the prevalence of scrapie in the United States compared with
that in Great Britain; and (3) little, if any, rendered animal products
are used for protein supplements in cattle feed in the United States.
However, there is some evidence that there may already be a scrapie-like
disease in cattle in the United States. This evidence comes from
epidemiologic studies on an incident of transmissible mink
encephalopathy (TME) in Stetsonville, Wis, in 1985. This mink farmer
used no commercially available animal by-product mixtures in his feed,
but instead slaughtered all animals going into the mink diet, which
included mostly (>95%) "downer" dairy cows, a few horses, but never
sheep. To examine the possibility that cattle may have been the source
of this incident of TME, two 6-week-old Holstein bull calves were
inoculated intracerebrally with mink brain from the affected farm. The
bulls developed neurologic disease 18 and 19 months after inoculation.
Both brains had spongiform degeneration at necropsy and both were
transmissible back to mink by either intracerebral (incubation period of
4 months) or oral (incubation period of 7 months) inoculation
Whereas TME has been thought to be caused by feeding scrapie-infected
sheep to mink, this theory has no conclusive evidence. Experimental oral
inoculation of mink with several different sources of sheep scrapie has
never been successful, and an incubation period of less than 12 months
has never (sic) produced by intracerebral inoculation. Transmissible
mink encephalopathy can develop naturally by infection with incubation
periods of less than 12 months.
There is reason to believe that scrapie has not been transmitted in the
United States from sheep to cattle by rendered protein concentrates as
it was in Great Britain. However, some circumstantial evidence exists
that cattle may be a source of some TME infections. It is recommended
that we increase our surveillance for a BSE-like disease in American
cattle by encouraging state diagnostic laboratories to formalin-fix
specimens of midbrain and brain stem from bovine brains submitted for
rabies testing. If results of these tests are negative, these fixed
tissues can then be examined for evidence of spongiform degeneration of
the gray matter.
-Comments on bovine spongiform encephalopathy
J Am Vet Med Assoc 197 (4): (1990)
Letter to the Editor, Journal of the American Veterinary Medical
Association, August 15, 1990
In my article, "Bovine spongiform encephalopathy in the United States"
(JAVMA, May 15, 1990, p 1677), I stated that "little, if any, rendered
animal products are used for protein supplements in cattle feed in the
United States." I have since learned that this is incorrect, because of
the recent trend of using less assimilated "by-pass" proteins in cattle
feed. A large amount of meat-and-bone meal is being fed to American
cattle, and this change in feeding practice has greatly increased the
risk of bovine spongiform encephalopathy (BSE) developing in the United
States.
Epidemiologic studies on BSE in Great Britain have indicated that the
disease originated in cattle by exposure to the heat-resistant
transmissible agent in compounded feed containing rendered animal
protein. The most likely source of infection was assumed to be
meat-and-bone meal prepared from scrapie-infected sheep, but it is also
possible that a heretofore unrecognized scrapie-like infection of cattle
could have been spread in the same manner.
Because of concern for the possible development of BSE in the United
States, the American rendering industry discontinued the processing of
fallen and sick sheep last December. In my opinion, this was a prudent
policy, but one that will not prevent the possible transmission of BSE
from cattle to cattle. As emphasized in my article, there is some
evidence that BSE-like infection may already exist in American cattle.
The current practice of feeding meat-and-bone meal to cattle solidifies
the most important means to perpetuate and amplify the disease cycle.
In Great Britain, BSE has produced a great economic and emotional
burden. We must take all reasonable measures to prevent BSE from
developing in the United States. Therefore, the practice of using animal
protein in cattle feed should be discontinued as soon as possible.
Waiting until the first case of BSE is diagnosed in the United States
will certainly be "closing the barn door after the horse is gone." With
a disease having a 3- to 6-year incubation period, thousands of animals
would be exposed before we recognize the problem and, if that happens,
we would be in for a decade of turmoil.
R. F. Marsh, DVM, PhD
Madison, Wis
=============
UCSF-LED TEAM REPORTS NEW TEST IMPROVES DETECTION OF PRIONS IN ANIMALS
snip...
(more)
This finding is of concern because
early on in the BSE epidemic in Great Britain decisions on what precautions to take were
UCSF led team reports new test improves detection of prions in animals -- Page 3
based on titrations in normal mice. Thus, says Safar, they underestimated the likely threat of
infectivity in many organs.
“This finding indicates that previous attempts to quantify BSE and scrapie prions in
milk or non-neural tissues, such as muscle, may have underestimated infectious titers by as
much as a factor of 10,000, raising the possibility that prions could be present in these
products in sufficient quantities to pose risk to humans,” says Safar.
The new transgenic mice, developed in the Prusiner lab, provide information about
infectivity within 220 to 400 days, thus accelerating the accumulation of data. The Prusiner
lab is now using the mouse model to test tissue samples for the UK Department of
Environment, Food and Rural Affairs.
“At present, we have no data on the frequency of sub-clinical prion infections in
livestock,” says Safar. “Because most livestock destined for human consumption are
slaughtered by two years of age, many animals may be infected but never show clinical
signs of central nervous system dysfunction since incubation periods generally exceed three
years.”
snip...
http://www.vegsource.com/talk/madcow/messages/9911841.html
or
http://media.ucsf.edu/ucsf/newsitem.nsf/20cb52fe59c7e8c288256a540001ac1b/5AE0A95B09E6962B88256C5900678EAC/$FILE/jo.prusiner.natbiotech.2002.pdf
Medical Sciences
Prions in skeletal muscle
Patrick J. Bosque*,dagger ,Dagger, Chongsuk Ryou*, Glenn Telling*,§, David Peretz*,dagger , Giuseppe Legname*,dagger , Stephen J. DeArmond*,dagger ,¶, and Stanley B. Prusiner*,dagger ,||,**
* Institute for Neurodegenerative Diseases and Departments of dagger Neurology, ¶ Pathology, and || Biochemistry and Biophysics, University of California, San Francisco, CA 94143
Contributed by Stanley B. Prusiner, December 28, 2001
Abstract
Top
Abstract
Introduction
Materials and Methods
Transgene Constructs
Results
Discussion
References
Considerable evidence argues that consumption of beef products from cattle infected with bovine spongiform encephalopathy (BSE) prions causes new variant Creutzfeldt-Jakob disease. In an effort to prevent new variant Creutzfeldt-Jakob disease, certain "specified offals," including neural and lymphatic tissues, thought to contain high titers of prions have been excluded from foods destined for human consumption [Phillips, N. A., Bridgeman, J. & Ferguson-Smith, M. (2000) in The BSE Inquiry (Stationery Office, London), Vol. 6, pp. 413-451]. Here we report that mouse skeletal muscle can propagate prions and accumulate substantial titers of these pathogens. We found both high prion titers and the disease-causing isoform of the prion protein (PrPSc) in the skeletal muscle of wild-type mice inoculated with either the Me7 or Rocky Mountain Laboratory strain of murine prions. Particular muscles accumulated distinct levels of PrPSc, with the highest levels observed in muscle from the hind limb. To determine whether prions are produced or merely accumulate intramuscularly, we established transgenic mice expressing either mouse or Syrian hamster PrP exclusively in muscle. Inoculating these mice intramuscularly with prions resulted in the formation of high titers of nascent prions in muscle. In contrast, inoculating mice in which PrP expression was targeted to hepatocytes resulted in low prion titers. Our data demonstrate that factors in addition to the amount of PrP expressed determine the tropism of prions for certain tissues. That some muscles are intrinsically capable of accumulating substantial titers of prions is of particular concern. Because significant dietary exposure to prions might occur through the consumption of meat, even if it is largely free of neural and lymphatic tissue, a comprehensive effort to map the distribution of prions in the muscle of infected livestock is needed. Furthermore, muscle may provide a readily biopsied tissue from which to diagnose prion disease in asymptomatic animals and even humans.
snip...
Discussion
Top
Abstract
Introduction
Materials and Methods
Transgene Constructs
Results
Discussion
References
Our studies demonstrate that mouse skeletal muscle is intrinsically capable of propagating prions, that titers at least as high as 107 ID50 units/g can accumulate in muscle, and most surprisingly, that the efficiency of this accumulation varies markedly among groups of muscles taken from different regions of the body. Our finding of prion accumulation in skeletal muscle seems unambiguous, in that we obtained similar results with two different prion strains in wt mice and in Tg mice expressing PrPC almost exclusively in skeletal muscle. Why prions accumulate more efficiently in certain muscles than in others is not clear. However, different skeletal muscle groups demonstrate differential susceptibility to a number of disease processes, a property that presumably reflects biochemical differences in skeletal muscles of different body regions (45).
Studies in Tg mice (46) and cultured cells (43, 44) have implicated a cellular factor other than PrP, provisionally termed "protein X," that is needed for the efficient propagation of prions. Perhaps only some skeletal muscles have sufficient amounts of protein X to enable the accumulation of high titers of prions. Similarly, the inefficient accumulation of prions in hepatic tissue demonstrated by our studies is further evidence of a role for an auxiliary factor such as protein X in prion propagation.
That high prion titers may be found in skeletal muscle even if central nervous system and lymphatic tissues are carefully excluded from the muscle raises the concern that humans consuming meat from prion-infected animals are at risk for acquiring infection. However, several caveats must be considered when assessing the risk of humans developing disease from prion-tainted meat. First, the efficiency of prion accumulation in muscle may vary with either the host species or the prion strain involved. Indeed, mouse RML prions seem to have accumulated more efficiently in muscle than did hamster Sc237 prions. Second, oral transmission is inefficient compared with the i.c. inoculations used for the bioassays reported in this study. In hamsters, oral exposure is 105- to 109-fold less efficient that the i.c. route (47, 48). Finally, the species barrier must be considered. In many cases, efficient transmission of prions from one species to another requires a high degree of homology in the amino acid sequence of PrP between the two species. However, the degree to which amino acid sequence influences the efficiency of transmission depends on the strain of prion. In the case of new variant Creutzfeldt-Jakob disease (nvCJD) prions, Tg mice expressing bovine PrPC are much more susceptible to nvCJD prions, derived from human brain, than are Tg mice expressing either human or chimeric human-mouse PrPC (refs. 10 and 49; C. Korth and S.B.P., unpublished data).
Previous studies have generally reported low prion titers in muscle tissue. Some of these studies used inefficient cross-species transmissions, which might be responsible for their failure to detect prions in muscle (19). Our investigations reveal another potential explanation for this failure. Because muscle prion accumulation varies between muscle groups or perhaps between specific muscles, previous studies may have failed to sample the muscles bearing the highest prion titers. If prions accumulate in certain muscles of humans with prion disease to levels near those that we found in mice with prion disease, it should be possible to definitively diagnose all forms of CJD and related disorders by using muscle tissue for biopsy. This approach would offer significant advantages over the relatively difficult and morbid brain biopsy procedure, which is currently the only way to definitively diagnose prion disease in humans.
Whether prions accumulate in skeletal muscle of cattle with BSE, of sheep with scrapie, or of deer and elk with chronic wasting disease remains to be established. However, our findings indicate that a comprehensive and systematic effort to determine the distribution of prions in the skeletal muscle of animals with prion disease is urgently needed. The distribution of prions in muscle may vary with the animal species, perhaps even with breeds, varieties, and lines within a species as well as with the strain of prions. Such assays need to be carried out by using sensitive and quantitative techniques, such as bioassays in Tg mice and quantitative immunoassays adapted to PrPSc detection in muscle tissue.
full text;
http://www.pnas.org/cgi/content/full/99/6/3812?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=prusiner&author2=prusiner&titleabstract=prions+meat+tissue+mice&fulltext=prions+meat+tissue+mice&searchid=1024347192881_6049&stored_search=&FIRSTINDEX=0&fdate=1/1/2002
prions in ass muscle, Hadlow et al figured this out long ago;
http://www.bseinquiry.gov.uk/files/yb/1990/01/19009001.pdf
Call for national CJD tests
snip...
He also indicated muscle and flesh of cattle and sheep could harbour prions - raising the prospect that today's meat could still be infected.
Prions can lie dormant in the body for up to 40 years, so estimates of the scale of the epidemic vary.
But there is some opposition to human testing because some fear the knowledge can only bring misery and maybe spark huge compensation claims.
snip...
http://www.vegsource.com/talk/madcow/messages/9912131.html
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.
http://www.fda.gov/foi/warning_letters/g1115d.pdf
full text on this feeding practice RAP;
http://www.vegsource.com/talk/madcow/messages/9912024.html
i also question a comment in this article about no known
human risk from ungulates or felids with BSE. what's this?
In October 1998 the simultaneous occurrence of spongiform encephalopathy in a man and his pet cat was reported. The report from Italy noted that the cat did not display the same clinical features as FSE cases previously seen. Indeed, the presence of a new type of FSE was suggested. The man was diagnosed as having sporadic CJD, and neither case (man nor cat) appeared to be affected by a BSE-related condition.
http://www.defra.gov.uk/animalh/bse/bse-science/level-4-othertses.html
The Lancet
The Lancet is Copyright. The Lancet Ltd, 1998.
Volume 352(9134) October 3, 1998 pp 1116-1117
Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy
[Research Letters]
Zanusso, Gianluigi; Nardelli, Ettore; Rosati, Anna; Fabrizi, GianMaria; Ferrari, Sergio; Carteri, Antonella; De Simone, Franco; Rizzuto, Nicola; Monaco, Salvatore
Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e della Visione, Universita di Verona, Policlinico Borgo Roma, 37134 Verona, Italy (S Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia, Brescia
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Outline
* REFERENCES
Graphics
* Figure 1
Transmissible spongiform encephalopathies (TSE) encompass inherited, acquired, and sporadic mammalian neurological disorders, and are characterised by the conversion of the cellular prion protein (PrP) in an insoluble and protease-resistant isoform (PrP sup res). In human TSE, four types of PrP sup res have been identified according to size and glycoform ratios, which may represent different prion strains. Type-1 and type-2 PrP sup res are associated with sporadic Creutzfeldt-Jakob disease (CJD), type 3 with iatrogenic CJD, and type 4 with variant CJD. (1,2) There is evidence that variant CJD is caused by the bovine spongiform encephalopathy (BSE)-prion strain. (2-4 ) The BSE strain has been identified in three cats with feline spongiform encephalopathy (FSE), a prion disease which appeared in 1990 in the UK. (5) We report the simultaneous occurrence of sporadic CJD in a man and a new variety of FSE in his cat.
A 60-year-old man, with no unusual dietary habits, was admitted in November, 1993, because of dysarthria, cerebellar ataxic gait, visual agnosia, and myoclonus. An electroencephalogram (EEG) showed diffuse theta-delta activity. A brain magnetic resonance imaging scan was unremarkable. 10 days later, he was speechless and able to follow only simple commands. Repeat EEGs showed periodic triphasic complexes. 2 weeks after admission, he was mute, akinetic, and unable to swallow. He died in early January, 1994.
His 7-year-old, neutered, female shorthaired cat presented in November, 1993, with episodes of frenzy, twitching of its body, and hyperaesthesia. The cat was usually fed on canned food and slept on its owner's bed. No bites from the cat were recalled. In the next few days, the cat became ataxic, with hindquarter locomotor dysfunction; the ataxia got worse and there was diffuse myoclonus. The cat was killed in mid-January, 1994.
No pathogenic mutations in the patient's PrP gene were found. The patient and the cat were methionine homozygous at codon 129. Histology of the patient's brain showed neocortical and cerebellar neuronal loss, astrocytosis, and spongiosis (* Figure 1*A). PrP immunoreactivity showed a punctate pattern and paralleled spongiform changes (* Figure 1*B). The cat's brain showed mild and focal spongiosis in deeper cortical layers of all four lobes (* Figure 1*C), vacuolated cortical neurons (* Figure 1 *D), and mild astrogliosis. The cerebellar cortex and the dentate nucleus were gliosed. Immunoreactive PrP showed a punctate pattern in neocortex, allocortex, and caudate nucleus (* Figure 1 *E). Western blot analysis of control and affected human and cat brain homogenates showed 3 PrP bands of 27-35 kDa. After digestion with proteinase K and deglycosylation, only samples from the affected patient and cat showed type-1 PrP sup res, with PrP glycoform ratios cornparable to those observed in sporadic CJD (1) (details available from author).
[Graphic]
[Help with image viewing]
*Figure 1. Microscopic sections of patient and cat brains: A: Occipital cortex of the patient showing moderate spongiform degeneration and neuronal loss (haematoxylin and eosin) and B: punctate perineuronal pattern of PrP immunoreactivity; peroxidase immunohistochemistry with monoclonal antibody 3F4. C: cat parietal cortex showing mild spongiform degeneration (haematoxylin and eosin). D: vacuolated neurons (arrow, haematoxylin and eosin), E: peroxidase immunohistochemistry with antibody 3F4 shows punctate perineuronal deposition of PrP in temporal cortex.*
This study shows a spatio-temporal association between human and feline prion diseases. The clinical features of the cat were different from previously reported cases of FSE which were characterised by gradual onset of behavioural changes preceding locomotor dysfunction and ataxia. (5 ) Neuropathological changes were also at variance with the diffuse spongiosis and vacuolation of brainstem neurons, seen in FSE. (5 ) The synaptic pattern of PrP deposition, similar in the cat and in the patient, was atypical for a BSE-related condition. Evidence of a new type of FSE was further provided by the detection of a type-1 PrP sup res, other than the BSE-associated type 4. (2) Taken together, our data suggest that the same agent strain of sporadic CJD was involved in the patient and in his cat.
It is unknown whether these TSE occurred as the result of horizontal transmission in either direction, infection from an unknown common source, or the chance occurrence of two sporadic forms.
REFERENCES
1. Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic variablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39: 767-78. [Medline Link] [Context Link]
2. Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90. [Fulltext Link] [Medline Link] [Context Link]
3. Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501. [Fulltext Link] [Medline Link] [Context Link]
4. Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJD and BSE. Nature 1997; 389: 448-50. [Fulltext Link] [Medline Link] [Context Link]
5. Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiform encephalopathy: a review. Vet Annual 1993; 33: 1-10. [Context Link]
http://cloud.prohosting.com/lzambeni/prions/italianmanandcat.htm
and what about that MAD Red Neck Ostrich;
THE AUTOPSY
ate: Mon, 11 Jun 2001 16:24:51 -0700
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: The Red-Neck Ostrich & TSEs 'THE AUTOPSY'######## Bovine Spongiform Encephalopathy #########TRANSLATION
F437/91
A CONTRIBUTION TO THE NEUROPATHOLOGY OF THE RED-NECKED OSTRICH (STRUTHIO CAMELUS) - SPONGIFORM ENCEPHALOPATHY -
H A Schoon, Doris Brunckhorst and J Pohienz Institute of Pathology, Veterinary University of Hannover
Introduction
Since the first appearance of BSE in Great Britain in l985 {review in TRUYEN & KAADEN, l990), research into the incidence, diagnosis, differential diagnosis and epidemiology of spongiform encephalopathies in humans and animals has been a focus of medical and public interest. In view of the growing number of reports of "new" spontaneously or experimentally susceptible species (cats: WYATT et al, l990; pigs: DAWSON et al, 1990), and of the associated questions with regard to the causal agent and in particular its transmissibility, it seems essential that agnopathogenetic individual cases should also be described. We therefore report below the preliminary findings of morphological examinations of three red-necked ostriches in 1986, 1988 and 1989, taking account of differential diagnostic factors.
History/subjects
The three ostriches (Flock A: Ostrich 1, female, adult, 150 kg; Flock B: Ostrich 2, female, adult, 80 kg; Ostrich 3: male, juvenile, 60 kg) came from two zoos in North West Germany and were euthenised because of their hopeless prognosis. Preliminary reports indicated that all three birds had presented protracted central nervous symptoms with ataxia, disturbance of balance and discoordinated feeding behaviour. Ostrich 2 had also exhibited pronounced lameness of the left lower limbs and the juvenile bird was suffering from perosis. The birds were fed on vegetable material, supplemented by commercial compound poultry feed and ''raw meat'', some of which was ''obtained from local small emergency slaughterers''. Comparable clinical pictures with fatal outcome in individual birds had occurred in both flocks: in a male bird at the same time (Flock A) and in several ostriches over recent years (Flock B).
Methods
Autopsy was followed in all three cases by histopathological examination of the following tissues: heart (several locations including coronary arteries and aorta), right and left pulmonary lobes, liver, kidneys, limb musculature, peripheral nerves (brachial plexus, sciatic nerve, in each case both left and right) and brain (left and right cerebral hemispheres, two samples each from the cranial/caudal third, two sagittal sections of the cerebellum, two cross-sections of the brain stem at the level of the optical lobes, four cross-sections from the medulla oblongata). The tissue material was fixed in formalin and embedded in Paraplast by the conventional method and the sections were evaluated using the following staining techniques and histochemical reactions: all organs: haematoxylin eosin staining; brain: PAS reaction (McManus), Ziehl/Neelsen staining (mod. Pearse), iron method (Lillie) for detection of neuromelanin, Turnbull's reaction (Bancroft & Stevens), alkaline Congo red method (Puchtler) (of SCOON & SCHINKEL, 1986), myelin sheath staining (Spielmeyer) (ROMEIS, 1968). In addition, unstained sections were examined by fluorescence microscopy (to detect autofluorescing lipofuscin granula) and the following lipid stains were applied to cryostat sections of liver, and of heart and skeletal musculature: Sudan III, Sudan black, oil red.
Findings
Ostrich 1
Brain: whilst only middle grade oedematisation of the neuropil was noted in the cerebral and cerebellar region, major changes were detected in the brain stem and medulla oblongata (Figures 1-3): in addition to pronounced vacuolation of the grey matter, optically vacant, ovoid to spherical vacuoles of differing sizes occurred bilaterally symmetrically in numerous neurons of the brain centres nucleus ruber, vestibular nucleus and reticular formation, in certain cases compressing the Nissl substance into a narrow fringe. In addition, fine granular pigments were found in the perikaryon of the neurons (with and without vacuoles), which showed a golden brown coloration in the haematoxylin eosin specimen, gave positive reactions to both PAS and Ziehl-Neelsen and also exhibited a yellowish-green spontaneous autofluorescence. Lillie staining to detect neuromelanin gave a negative result. The pigments thus exhibited the characteristics of lipofuscin (SCHOON & SCHINKEL, 1986). Ferruginous pigments and histochemically detectable amyloids were absent. Mild gliosis, isolated necrotic neurons and neuronophagia were observed only in the cranial locations of the brain stem.
Other findinqs: The ostrich exhibited marked adiposity and multiple pressure sores of both lower limbs. Moderate steatosis was found in the heart and skeletal musculature and in the liver. Multifocal arteriosclerotic plaques were also noted in the coronary and limb arteries.
Ostrich 2
Brain: Histopathological changes in the brain of this ostrich were limited to the medulla oblongata and were qualitatively consistent with those found in Ostrich 1, although confined, bilaterally symmetrically, to small localised areas and affecting only individual neurons. Gliosis reaction was almost entirely absent.
Other findinqs: The carcase was moderately well nourished and exhibited multifocal dermal and muscular necroses on both lower limbs in conjunction with lateral chronically destructive tarsitis and coxitis. In the internal organs, parenchymatous degeneration of the liver and kidneys and multifocal arteriosclerotic plaques in the coronary arteries were noted.
Ostrich 3
Brain: Whilst no histopathological changes were found in the cerebrum and cerebellum of this ostrich, a high grade spongious dispersion of the neuropil existed in all locations examined in the brain stem and medulla oblongata (status spongiosus, Figure 4). Individual neurons contained optically vacant vacuoles of varying size, whilst numerous nerve cells exhibited clear signs of nuclear degeneration, in particular in the form of nuclear pyknosis. Low grade gliosis was also noted in all locations.
Other findinqs: The left lower limb of this bird exhibited defective positioning of the tarsal joint resulting from axial distortion of the long bones with applanation of the lateral [Rollkamm - word not found] and resultant instability of the tendons and inward turning of the tarsus.
Discussion
Although ostriches are widely kept in zoos, there are virtually no detailed descriptions of central nervous disorders with associated locomotor disfunction in this species. Neurological symptoms have been reported in connection with an outbreak of Newcastle Disease (KLOPPEL, 1969) and bacterial meningitis has been described (GRZIMEK, 1953), whilst other, sporadic cases have remained etiologically unexplained (ZUKOWSKY, 1959; LANDOWSKI, 1965). Disfunctions of the locomotor system of extracerebral origin occur predominantly in juvenile ostriches, emus and rheas in connection with muscular disease, perosis and trauma (FROIKA, 1982, 1983; MIHALIK & SRANK, 1982; SCHRODER & SEIDEL0 1989). One of the ostriches we examined was suffering from perosis, another from unilateral tarsitis and coxitis. All three, however, exhibited neuropathological findings consisting of a gradual, bilaterally symmetrical, spongiform encephalopathy of varying degree in the brain stem and medulla oblongata. No descriptions of such findings in this species appear in any of the literature we have been able to obtain.
These histopathologically confirmed brain changes are not consistent either with those caused by the classic viral infections in domesticated and wild birds or with those described by GRATZL & KOHLER (1957) and CHEVILLE (1966) as typical of Vitamin E deficiency-related encephalopathy in chicks. Instead, at the light microscopy level, both in qualitative terms and in the pattern of distribution in the central nervous system, there is a high degree of coincidence with findings which occur in transmissible spongiform encephalopathies in mammals (scrapie, BSE, transmissible mink encephalopathy, chronic wasting disease of captive mule deer and elk) (HADLOW, 1961; BURGER & HARTSOUGH, 1965; HARTSOUGH & BURGER, 1965; WILLIAMS & YOUNG, 1980; WELLS et al, 1987, 1989).
The sporadic occurrence of vacuoles in individual neurons of the nucleus ruber in cattle was interpreted species-specifically as an artefact by FRANKHAUSER et al (1972). We are unable to judge whether a similar conclusion is also appropriate in the case of the ostrich, since our experience is based on only a small number of neuropathologically investigated cases. However, examination of the brains of twelve other ostriches which came to autopsy after death from extracerebral causes did not reveal any such findings. FRANKENHAUSER et al (1972) also emphasise that none were observed by them either in small ruminants or in the horse or the dog.
It is not possible at this time to determine whether and to what extent our neuropathological findings in an omnivorous bird, the ostrich, are etiopathogenetically consistent with those of the spongiform encephatopathies of mammals. There are no indications whatever in the relevant literature of even a hypothetical susceptibility in birds, although it must be said by way of qualification that clinical manifestations would be most unlikely in short-lived farm poultry, given the long incubation period. Moreover, Germany was officially free of scrapie and BSE at the time the condition appeared in the ostriches. The question of possible contamination of carcase meal is discussed in the work of TRUYEN & KAADEN (1990).
Conclusive diagnosis, especially in these cases, and in spite of the certainty ascribed by WELLS et al (1989) to histopathological diagnosis in cattle, also requires electron microscopic detection of so-called scrapie-associated fibrils (SCOTT et al, 1987; HOPE et al, 1988) and attempts, by inoculation of suspect brain material, to transmit the disease to the mouse (TRUYEN & KAADEN, 1990). Both of these procedures are normally carried out using fresh material, whereas we now have only tissue fixed in formalin and embedded in Paraplast.
Etiological consideration must also be given retrospectively to unidentified toxic influences, unknown species-specific deficiency diseases and unexplained predisposing metabolic conditions.
The etiologically unexplained neuropathological findings reported here, together with the multitude of unanswered questions in this connection, underline the need for further, systematic, standardised studies in this species, based on a larger sample of birds.
Summary and Literature
[Not translated]
Figures
Figure 1: Spongiform encephalopathy with oedematisation and vacuolation of the neuropil and "ballooning" degeneration of virtually all neurons in this area of the brain - brain stem. (H,-E.-Frgb., magnification x 120)
Figure 2: Detail of Figure 1. In 'addition to oedematisation of the neuropil, numerous, optically vacant vacuoles in the neurons, with partial displacement of the Nissl substance - brain stem. (H.-E.-Frgb., magnification x 480)
Figure 3: Medulla oblongara with high grade spongiform dissociation of the neuropil. (H.-E.-Frgb., magnification x 300)
Figure 4: Medulla oblongata. Status spongiosus with neuron degeneration. (H.-E.-Frgb., magnification x 300).
TSS
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
and again, this is about more than just the 132 or so victims
of nv/v CJD. the nv/v CJD only theory has been shot to hell;
Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD
Date: Thu, 28 Nov 2002 10:23:43 -0000
From: "Asante, Emmanuel A"
To: "'flounder@wt.net'" Dear Terry,
I have been asked by Professor Collinge to respond to your
request. I am a Senior Scientist in the MRC Prion Unit and the lead
author on the paper. I have attached a pdf copy of the paper for your
attention. Thank you for your interest in the paper.
In respect of your first question, the simple answer is, yes. As you
will find in the paper, we have managed to associate the alternate
phenotype to type 2 PrPSc, the commonest sporadic CJD.
It is too early to be able to claim any further sub-classification in
respect of Heidenhain variant CJD or Vicky Rimmer's version. It will
take further studies, which are on-going, to establish if there are
sub-types to our initial finding which we are now reporting. The main
point of the paper is that, as well as leading to the expected new
variant CJD phenotype, BSE transmission to the 129-methionine genotype
can lead to an alternate phenotype which is indistinguishable from type
2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I
can be of any further assistance please to not hesitate to ask. Best wishes.
Emmanuel Asante
<>
____________________________________Dr. Emmanuel A Asante
MRC Prion Unit & Neurogenetics Dept.
Imperial College School of Medicine (St. Mary's)
Norfolk Place, LONDON W2 1PG
Tel: +44 (0)20 7594 3794
Fax: +44 (0)20 7706 3272
PLEASE SEE FULL TEXT OF THIS ARTICLE;
http://www.vegsource.com/talk/madcow/messages/9912118.html
Subject: Re: hello Dr. Manuelidis...TSS ''BSE as another phenotype of sporadic CJD''
Date: Fri, 17 Jan 2003 17:38:00 -0500
From: laura manuelidis
Reply-To: laura.manuelidis@yale.edu
Organization: Yale University Medical School
To: "Terry S. Singeltary Sr."
References: <3E286F2F.6060700@wt.net>Dear Terry,
Many thanks for the references, a rather late recognition of lots of
experimental data that showed PrP was not predictive of disease. Nobody wanted
to listen when I said years ago that vCJD should be able to transmit to people
regardless of host PrP sequence differences. I also warned the CDC ~5 years ago
that people infected by BSE strain might well show classic rather than vCJD
lesions, and that their narrow sampling for vCJD by young age and PrP band
pattern was based on preconceptions of Prion theory.
Additionally, Dickinson showed many years ago that scrapie could be subclinical
in mice dying of old age, (and we showed transmissions of CJD that lacked PrP
but had many vacuoles in the 1980s, also now conveniently ignored. Our Science
paper further showed a typical sporadic CJD strain could evolve into one that
provoked vCJD plaques. So really, there is not much new here except the
authorship.
I also do not believe the glycosylation story since in 1987 we showed
deglycosylation of PrP in infected brain samples yielded no differences from
unglycosylated parallel samples in terms of incubation time, PrP band patterns
or lesion profiles.
best,
laura
=========
FULL TEXT OF GOA REPORT BELOW (takes a while to load)
2. Mad Cow Disease: Improvements in the Animal Feed Ban and Other
Regulatory Areas Would Strengthen U.S. Prevention Efforts. GAO-02-183,
January 25.
http://www.gao.gov/cgi-bin/getrpt?GAO-02-183
=============================================
Subject: SCRAPIE 'USA' ANNUAL REPORT (105 newly infected flocks 2002) &
CWD IN USA
Date: Tue, 10 Dec 2002 08:17:17 -0600
From: "Terry S. Singeltary Sr."
To: flounder@wt.netDate: Mon, 9 Dec 2002 21:21:10 -0600
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: SCRAPIE 'USA' ANNUAL REPORT (105 newly infected flocks
2002) & CWD IN USAAs of September 30, 2002, there were 45 scrapie infected and source
flocks (figure 3). There were 105 newly infected flocks, reported in
FY2002 (figure 4). In addition, 379 scrapie cases were confirmed and
reported by the National Veterinary Services Laboratories (NVSL) in FY
2002 (figure 5) and (figure 6). Five cases of scrapie in goats were
reported in FY 2002 (figure 7), the last of which was confirmed in
August 2002. New infected and source flocks numbers and the number of
these flocks released in FY 2002 are depicted in chart 4. One hundred
(100) flocks which is 67 percent of the scrapie infected and source
flocks present in FY 2002 were released or put on clean-up plans in FY2002.
Slaughter Surveillance
Slaughter Surveillance is currently in Phase II which is intended to
determine the prevalence of scrapie in the US culled sheep population.
Through September 2002 samples from 3,269 sheep were submitted to NVSL
for testing. Samples from a total of 6,795 sheep have been submitted
since the beginning of Phase II on April 1, 2002. Surveillance regions
are depicted in (figure 8).
Scrapie Testing
During FY 2002 11,751 animals have been tested for scrapie which
includes: 2,711 regular necropsy cases, 1,343 third eyelid biopsies for
the test validation project, 546 third eyelid biopsies for the
regulatory program, and approximately 7,151 animals for Phase I & II of
SOSS (chart 5). Laboratory testing has been taking 10 - 11 days on
average with a range of 3 - 34 days.
Ear Tag Orders
During FY 2002 9.9 million plastic and 6.0 million metal tags were
distributed by APHIS (chart 6).
http://www.aphis.usda.gov/vs/nahps/scrapie/annual_report/annual-report.html
NEW SCRAPIE INFECTED AND SOURCE FLOCKS
http://www.aphis.usda.gov/vs/nahps/scrapie/annual_report/figure04.gif
DISTRIBUTION OF CHRONIC WASTING DISEASE THROUGHOUT THE STATES (as of
Oct. 2002)
http://www.aphis.usda.gov/vs/nahps/cwd/cwd-distribution.html
CWD USA surveillance
http://www.aphis.usda.gov/vs/nahps/cwd/cwd-state.html
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT]
Date: February 22, 2003 at 7:38 am PST
plus TSS rebuttal and submission to Neurology with CONFIDENTIAL
data
http://www.vegsource.com/talk/madcow/messages/9912538.html
Cattlemen to finalize BSE research contracts (WHAT'S THE RUSH, LET'S
WAIT ANOTHER 30 YEARS) - TSS 1/17/03 (0)
http://www.vegsource.com/talk/madcow/messages/9912336.html
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy BSE-Lhttp://vegancowboy.org/TSS-part1of8.htm
#Docket No. 01-068-1 Risk Reduction Strategies for Potential BSE
Pathways Involving Downer Cattle and Dead Stock of Cattle and Other
Species - TSS 1/21/03 (2)
http://www.vegsource.com/talk/madcow/messages/9912348.html
In Reply to: Docket No. 01-068-1 Risk Reduction Strategies for Potential
BSE Pathways Involving Downer Cattle and Dead Stock of Cattle and Other
Species [TSS SUBMISSION] January 21, 2003
http://www.vegsource.com/talk/madcow/messages/9912358.html
Re: Docket No. 01-068-1 -- (200,000 USA DOWNERS ANNUALLY) TSS 1/21/03
http://www.vegsource.com/talk/madcow/messages/9912360.html
Re: Docket No. 02N-0273 – Substances Prohibited From Use In Animal Food
Or Feed;
http://www.vegsource.com/talk/madcow/messages/9912338.html
# Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of
2002; [TSS SUBMISSION ON POTENTIAL FOR BSE/TSE & FMD 'SUITCASE BOMBS'] -
TSS 1/27/03 (0)
http://www.vegsource.com/talk/madcow/messages/9912395.html
# Re: [Docket No. 99-017-2] Blood and Tissue Collection at Slaughtering
Establishments [TSS SUBMISSION]
http://www.vegsource.com/talk/madcow/messages/9912402.html
# Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of
2002; [TSS SUBMISSION ON POTENTIAL FOR BSE/TSE & FMD 'SUITCASE BOMBS'] -
TSS 1/27/03 (0)
http://www.vegsource.com/talk/madcow/messages/9912395.html
TSS Submission will be on the 'slides' of the Jan. 19, meeting...tss
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2.htm
CJD WATCH
http://www.fortunecity.com/healthclub/cpr/349/part1cjd.htm
CJD Watch/NEWS message board
http://disc.server.com/Indices/167318.html
TSS MAD COW NEWS
http://www.vegsource.com/talk/madcow/index.html
USA GBR risk assessment on BSE _MUST_ be changed to
include all animal TSEs ASAP.
GBR BSE risk assessment of the USA should be changed to
GBR III immediately.
http://www.testcowsnow.com
USA MAD COW cover-up
http://www.vegsource.com/talk/lyman/messages/9558.html
thank you,
kindest regards,
terry
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, TEXAS USA 77518
