Subject: SEAC 96th MEETING ON TUESDAY 20 FEBRUARY 2007 AGENDA (HIGH SUSCEPTIBILITY OF A PRIMATE SPECIES TO THE BASE)
Date: February 13, 2007 at 2:46 pm PST
Agenda
96th meeting on Tuesday 20 February 2007
http://www.seac.gov.uk/minutes/95.pdf
CONFERENCE ON PRION DISEASES OF NEUROPRION, NETWORK OF EXCELLENCE, TURIN, ITALY, 3-6 OCTOBER 2006
BASE
OUR OBSERVATIONS UNDERLINE THE HIGH SUSCEPTIBILITY OF A PRIMATE SPECIES TO THE BASE PRION STRAIN AND PROVIDE A BIOCHEMICAL BASIS FOR THE IDENTIFICATION OF A POTENTIAL OCCURRENCE IN MAN. ...page 9...tss
http://www.seac.gov.uk/papers/96-2.pdf
UPDATE ATYPICAL SCRAPIE IN A TSE RESEARCH FLOCK
http://www.seac.gov.uk/papers/96-4.pdf
> Some unofficial information from a source on the inside looking out -
>
> Confidential!!!!
>
> As early as 1992-3 there had been long studies conducted on small
> pastures containing scrapie infected sheep at the sheep research station
> associated with the Neuropathogenesis Unit in Edinburgh, Scotland.
> Whether these are documented...I don't know. But personal recounts both
> heard and recorded in a daily journal indicate that leaving the pastures
> free and replacing the topsoil completely at least 2 feet of thickness
> each year for SEVEN years....and then when very clean (proven scrapie
> free) sheep were placed on these small pastures.... the new sheep also
> broke out with scrapie and passed it to offspring. I am not sure that TSE
> contaminated ground could ever be free of the agent!!
> A very frightening revelation!!!
>
http://www.microbes.info/forums/index.php?showtopic=306
Science 24 September 2004:
Vol. 305. no. 5692, pp. 1918 - 1921
DOI: 10.1126/science.1103581
Perspectives
BIOMEDICINE:
A Fresh Look at BSE
Bruce Chesebro*
Mad cow disease, or bovine spongiform encephalopathy (BSE), is the cattle
form of a family of progressive brain diseases. These diseases include
scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and chronic
wasting disease (CWD) in deer and elk. They are also known as either "prion
diseases" because of the association of a misfolded cellular prion protein
in pathogenesis or "transmissible spongiform encephalopathies" (TSEs)
because of the spongelike nature of the damaged brain tissue (1).
The recent discovery of two BSE-infected cows, one in Canada and one in the
United States, has dramatically increased concern in North America among
meat producers and consumers alike over the extent to which BSE poses a
threat to humans as well as to domestic and wild animals. The European BSE
epidemic of the late-1980s seems to have been initiated a decade earlier in
the United Kingdom by changes in the production of meat and bone meal (MBM)
from rendered livestock, which led to contamination of MBM with the BSE
infectious agent. Furthermore, the fact that UK farmers fed this rendered
MBM to younger animals and that this MBM was distributed to many countries
may have contributed to the ensuing BSE epidemic in the United Kingdom and
internationally (2).
Despite extensive knowledge about the spread of BSE through contaminated
MBM, the source of BSE in Europe remains an unsolved mystery (2). It has
been proposed that BSE could be derived from a cross-species infection,
perhaps through contamination of MBM by scrapie-infected sheep tissues (see
the figure). Alternatively, BSE may have been an endemic disease in cattle
that went unnoticed because of its low level of horizontal transmission.
Lastly, BSE might have originated by "spontaneous" misfolding of the normal
cellular prion protein into the disease-associated abnormal isoform (3),
which is postulated to be the infectious agent or "prion."
Five possible sources of BSE in North American cattle. Sheep, deer, and elk
could spread prion diseases (TSEs) to cattle through direct animal contact
or contamination of pastures. Endemic BSE has not been proven to exist
anywhere in the world, but it is difficult to exclude this possibility
because of the inefficient spread of BSE infectivity between individual
animals (2). BSE caused by spontaneous misfolding of the prion protein has
not been proven.
CREDIT: KATHARINE SUTLIFF/SCIENCE
Spontaneous protein misfolding is not a new phenomenon as proteins are known
to sometimes misfold after synthesis. Cells in turn have devised ingenious
ways to deal with this problem. These include molecular chaperone proteins
that bind to misfolded proteins and help them to unfold, and organelles
called proteosomes that degrade misfolded or unwanted proteins. However,
although misfolded prion proteins have been generated in test tubes as well
as in cultured cells, it has been difficult to demonstrate that such
misfolded abnormal prion proteins are infectious (4, 5). Even the most
recent data do not prove conclusively that infectivity has been generated in
vitro because misfolded synthetic prion proteins were not able to transfer
disease directly to wild-type mice (6). To obtain infectivity and subsequent
prion disease, the misfolded proteins had to be inoculated and incubated for
1 to 2 years in transgenic mice that overexpressed a mutant version of the
prion protein. Previous data from this group showed that transgenic mice
expressing high amounts of prion protein developed neurological disease
without inoculation of misfolded prion protein (7). Thus, at the biochemical
level, the critical attributes of the misfolded prion protein required for
infectivity are not known, and misfolding of prion protein alone may not be
sufficient to generate an infectious agent (.
Nevertheless, the idea that BSE might originate due to the spontaneous
misfolding of prion proteins has received renewed interest in the wake of
reports suggesting the occurrence of atypical BSE (9-11). These results
imply that new strains of cattle BSE might have originated separately from
the main UK outbreak. Where and how might such strains have originated?
Although such rare events cannot be studied directly, any number of sources
of the original BSE strain could also explain the discovery of additional
BSE strains in cattle (see the figure). However, it would be worrisome if
spontaneous BSE were really a valid etiology because such a mechanism would
be impossible to prevent--unlike other possible scenarios that could be
controlled by large-scale eradication of TSE-positive animals.
Another way to look at this problem is to examine evidence for possible
spontaneous TSE disease in other animals besides cattle. Spontaneous BSE
would be extremely difficult to detect in cattle, where horizontal spread is
minimal. However, in the case of the sheep TSE disease, scrapie, which
spreads from ewes to lambs at birth as well as between adults, spontaneous
disease should be detectable as new foci of clinical infection. In the early
1950s scrapie was eradicated in both Australia and New Zealand, and the
mainland of both these countries has remained scrapie-free ever since. This
scrapie-free status is not the result of selection of sheep resistant to
scrapie because sheep from New Zealand are as susceptible as their UK
counterparts to experimental scrapie infection (12). These experiments of
man and nature appear to indicate that spontaneous clinical scrapie does not
occur in sheep. Similarly, because CWD is known to spread horizontally, the
lack of CWD in the deer or elk of eastern North America but its presence in
western regions would also argue against a spontaneous disease mechanism.
This is particularly noteworthy in New Zealand, where there are large
numbers of deer and elk farms and yet no evidence of spontaneous CWD. If
spontaneous scrapie does not occur in sheep or deer, this would suggest that
spontaneous forms of BSE and sporadic Creutzfeldt-Jakob disease (sCJD) are
unlikely to be found in cattle or humans. The main caveat to this notion is
that spontaneous disease may arise in some animal species but not others. In
humans, sCJD--which is considered by some researchers to begin by
spontaneous misfolding of the prion protein--usually takes more than 50
years to appear. Thus, in animals with a shorter life-span, such as sheep,
deer, and cattle, an analogous disease mechanism might not have time to
develop.
What can we conclude so far about BSE in North America? Is the BSE detected
in two North American cows sporadic or spontaneous or both? "Sporadic"
pertains to the rarity of disease occurrence. "Spontaneous" pertains to a
possible mechanism of origin of the disease. These are not equivalent terms.
The rarity of BSE in North America qualifies it as a sporadic disease, but
this low incidence does not provide information about cause. For the two
reported North American BSE cases, exposure to contaminated MBM remains the
most likely culprit. However, other mechanisms are still possible, including
cross-infection by sheep with scrapie or cervids with CWD, horizontal
transmission from cattle with endemic BSE, and spontaneous disease in
individual cattle. Based on our understanding of other TSEs, the spontaneous
mechanism is probably the least likely. Thus, "idiopathic" BSE--that is, BSE
of unknown etiology--might be a better term to describe the origin of this
malady.
What does all this imply about testing cattle for BSE in North America?
Current testing in the United States indicates that BSE is rare (one
positive result in 40,000 cattle tested). However, additional testing of
200,000 head of slaughtered cattle over the next 1 to 2 years, as recently
proposed by the U.S. Department of Agriculture (USDA), should tell us the
incidence more precisely. Nevertheless, if any rare cases are detected, we
may still not know their origin. If evidence arises of a focal occurrence of
BSE, we might gain important insight into unexpected sources of
contamination. However, because current tests do not seem to be able to
detect BSE in infected animals less than 30 months of age, even more
extensive testing will not completely guarantee the negative status of
younger animals in the food chain. Therefore, the alternative option of
testing all slaughtered cattle, as implemented in some countries such as
Japan, would appear to provide little additional benefit. This fact has been
acknowledged as the basis for a new agreement between the United States and
Japan aimed at reestablishing the beef trade between the two countries.
One problem with the current U.S. testing program was the announcement a few
months ago of unconfirmed positive BSE tests in two additional North
American animals that were subsequently found to be negative when tested
with the more accurate method of Western blotting. The public release of
information about unconfirmed positive tests detected by the rapid test used
for mass screening may be a good idea in the interest of openness, but it ha
s the potential to create unwarranted anxiety. If unconfirmed positives are
a frequent occurrence, it would seem reasonable to follow a more cautious
approach and wait until confirmatory testing is complete before publicly
announcing the details.
Based on the experience of many European countries, the mainstays of
controlling BSE in cattle and avoiding spread to humans are threefold:
first, eliminate feeding of ruminant tissues to ruminants; second, remove
high-risk cattle tissues from human food; and third, continue to test for
BSE in cattle in order to monitor progress with the elimination of the
disease on a local and national basis. In the next 12 months, after
extensive USDA test results are available, the extent of any possible BSE
spread in the United States will be better documented. But, in fact, the
United States and Canada have already instituted the most important steps to
prevent the spread of cattle BSE in advance of the results--that is, a ban
on feeding ruminant MBM to other ruminants and removal of high-risk tissues
from meat for human consumption. It is hoped that the new data will not
deviate enough from previous predictions to require further measures for
management of this problem. The most important line of defense against any
possible spread of BSE will be to maintain strict vigilance in the
implementation of the current regulations.
References
S. B. Prusiner, Proc. Natl. Acad. Sci. U.S.A 95, 13363 (1998) [Medline].
P. G. Smith, R. Bradley, Br. Med. Bull. 66, 185 (2003) [Medline].
C. Weissmann, A. Aguzzi, Curr. Opin. Neurobiol. 7, 695 (1997) [Medline].
A. F. Hill et al., J. Gen. Virol. 80, 11 (1999) [Medline].
R. Chiesa et al., J. Virol. 77, 7611 (2003) [Medline].
G. Legname et al., Science 305, 673 (2004).
D. Westaway et al., Cell 76, 117 (1994) [Medline].
B. Chesebro, Science 279, 42 (1998).
A. G. Biacabe et al., EMBO Rep. 5, 110 (2004) [Medline].
Y. Yamakawa et al., Jpn. J. Infect. Dis. 56, 221 (2003) [Medline].
C. Casalone et al., Proc. Natl. Acad. Sci. U.S.A. 101, 3065 (2004)
[Medline].
E. F. Houston et al., J. Gen. Virol. 83, 1247 (2002) [Medline].
http://www.sciencemag.org/cgi/content/full/305/5692/1918
However, Phillips did not have an explanation of how the first cow got BSE and other
explanations continue to be put forward. One journalist commented on the idea favoured
by the Phillips Committee that BSE started with a spontaneous mutation:
However, apart from there being little evidence for the idea, a random mutation
could not explain why Britain alone has suffered the problem. America, for
instance, has 10 times the number of cattle, and so must in theory run ten times
the risk of a similar random event leading to BSE and so being passed on in
recycled meat and bone meal.13
http://www.parliament.uk/commons/lib/research/rp2001/rp01-089.pdf
Evaluation of the Potential for Bovine Spongiform
Encephalopathy in the United States
Joshua T. Cohen
Keith Duggar
George M. Gray
Silvia Kreindel
Harvard Center for Risk Analysis
Harvard School of Public Health
Hatim Abdelrahman
Tsegaye HabteMariam
David Oryang
Berhanu Tameru
Center for Computational Epidemiology
College of Veterinary Medicine
Tuskegee University
November 26, 2001
snip...
2.3.1 Spontaneous BSE
A potential way in which BSE could be introduced into the United States is the
development of a spontaneous case of a BSE in a native animal. A “spontaneous case” is one that
occurs in an animal with no known risk factors for development of BSE. The presumed
mechanism by which a BSE could occur spontaneously is by the mutation of the PrP gene to a
Section 2
- 20 -
form that codes for PrPsc, and subsequent recruitment of PrPc until disease is manifest (Prusiner,
1989); (for review see: (Chesebro, 1999). There is no direct evidence of this mechanism,
although some argue that all mammals might have a low spontaneous rate of TSE (Hueston,
1997). In addition, a transgenic animal over-expressing the PrP gene has apparently replicated
the human TSE GSS (Hsiao et al., 1991). Recent results, in which mice expressing the same
point mutation but at normal levels failed to develop disease (Manson et al., 1999), suggest the
mutations may increase susceptibility rather than directly cause the disease. Although at this time
there is no scientific evidence suggesting that spontaneous BSE exists, the BSE Inquiry suggested
that TSEs could possibly develop sporadically in other species, as they do in humans (BSE
Inquiry, 2000). In contrast, the Review of the origin of BSE (Horn et al., 2001) concluded that
although the spontaneous case hypothesis cannot be excluded, there is no evidence supporting the
presence of sporadic form prion disease in cattle or sheep.
snip...
http://www.aphis.usda.gov/lpa/issues/bse/risk_assessment/mainreporttext.pdf
http://www.aphis.usda.gov/lpa/issues/bse/madcow.pdf
REPORT ON : THE RISK BORN BY RECYCLING ANIMAL BY-PRODUCTS AS FEED WITH
REGARD TO PROPAGATING TSE'S IN NON-RUMINANT FARMED ANIMALS. PREPARED BY A
WORKING GROUP FOR THE SCIENTIFIC STEERING COMMITTEE AS AN INPUT IN THE
ELABORATION OF THE OPINION ON THE SAME SUBJECT ADOPTED ON 16-17 SEPTEMBER
1999.
September 1999
The European Commission
snip...
The final outcome should contribute to the assessment of the possibility
of transmission of TSE to fish, the evaluation of the potential risk
connected to fish derived foods for human and animal, the establishment of
analytical protocols for PrP detection in fresh fish food and the
comparison of the molecular properties of normal and abnormal isoforms of
PrP. d. Ruminants A large number of experiments, abundantly reported on
in the scientific literature, has shown that cattle and sheep are
susceptible to TSE's originating from their own species and that ruminants
in general fed with infectious material originating from the same species
can be infected with TSE's. Also, experimental evidence (EC, 1998) shows
that BSE can be transmitted to sheep (and goats) via the oral route7. If
a spontaneous TSE occurred in cattle, one might reasonable have expected
this to have occurred in detectable levels of a BSE-like disease in a much
larger number of countries than presently is the case, and where the
rendering systems used are very much alike those used in the EU prior to
1992, that implies not in accordance with the EU rendering directive
90/667. The potential occurrence of spontaneous TSE in cattle has till yet
not lead to detectable levels of cattle TSE in most countries, and in
countries where TSE in cattle occurs, this has so far not been attributed
to spontaneous cases. In fact, most of the BSE incidence in countries
where native BSE occurs, is accounted for by feeding of infected or
contaminated feedstufs. It must nevertheless be mentioned that, following
epidemiological investigations after the occurrence of a case, not all BSE
cases can always be brought back to proven feeding practices.
(E.Vanopdenbosch, 1998, personal communication) If scrapie would also
spontaneously occur in sheep, it would more likely occur in those sheep
with the most susceptible PrP genotypes. However, it is now known that a
significant proportion of Australian and New Zealand sheep have such
genotypes, but have not developed scrapie (Hunter et al, 1997). e. Pigs,
poultry and fish as possible silent carriers Marsh et al (1969) reported
the recovery of transmissible mink encephalopathy (TME) infectivity from
the spleen of one chicken and from the spleen, caecum, tonsil and bursa of
Fabricius of a second chicken of two chickens challenged experimentally by
i/v inoculation of fourth passage mink brain with TME. They noted that
infectivity administered either intra-cranial, intra-venous,
intra-muscular or subcutaneously, persisted for extended periods (30 and
50 days in the case of chickens) in lymphoid tissues of rhesus monkeys,
chickens, mice, cats, ferrets, goats and calves that were studied. No
experimental data are available about oral infectivity tests. Race and
Chesebro (1998), reported the results of i/c challenge of mice with
hamster scrapie strain 263K that produces no clinical disease in mice,
followed by sub-passage from brain and spleen into further mice and into
scrapie susceptible hamsters. Infectivity was detected in the spleen and
brain tissues by the hamsters, but not by the mice. The authors' view was
that the mice had not replicated the agent. They noted that they had not
tested to see if the same results were obtained after oral challenge.
However, they suggested that food animal species resistant to BSE, such as
poultry, exposed to BSE infectivity via feed but might show persistent
infectivity in their tissues without replication. Over 80% of pig meat
and 80% of poultry meat produced in the EU originates from pigs less than
8 months of age and broilers less than 2 months of age respectively.
However, the life expectancy of both pigs and chickens raised for
slaughter may be too short to show any signs of SE-s whenever they are
infected. Taking account of all our knowledge on prion diseases in
animals, it is unlikely that clinical evidence of disease would occur at
such a young age. Only adult breeding pigs would be expected to be old
enough to exhibit clinical signs if ever a TSE of pigs was found. However,
it can be hypothesized that infectivity of extra-neural tissues,
particularly lymphoreticular tissues, could theoretically arise in these
species exposed to TSE infection via feed whether or not replication and
neuroinvasion subsequently occurred. The results of the studies using the
BSE agent mentioned above do not support the hypothesis that infectivity
can be sequestered in the manner described and particularly this is a
unlikely event in pigs exposed to the BSE agent by the oral route two
years earlier. It is noted however, that these studies used mice to detect
any infectivity, cattle would be more susceptible. Furthermore the results
of bioassays done at the termination of the porcine studies are still
awaited as are those from poultry (see also sections 7.a and 7.b).
However, special attention should be drawn to the eventuality that in pigs
under natural conditions the intestinal barrier is would be very
efficacious in respect to the development of clinical TSE, but that by
feeding infected ruminant MBM and/or intraspecies recycling of pigs with
low levels of infectivity, an increasing level of infectivity could be
built up in the intestine. Such low levels could only be detected by the
most sensitive methods i.e. intracerebral inoculation of calves with
intestinal tissue of orally exposed pigs. This would be in accordance with
the results of the experiments of Race and Cesebro to detect infectivity
in resistant species. f. Risks related to the content of the gut and to
manure (faeces) The content of the gut and manure represent an increased
risk, if the animals were fed with (possibly TSE-contaminated) ruminant
material even if it was previously treated at "133!C/20'/3 bars", because
this standard is considered not to eliminate all possible TSE infectivity
if the initial titer was high. If the presence of a BSE risk is not
excluded, these materials should therefore be considered as "condemned
materials" as described in the SSC's opinion on "Fallen stock" of 24-25
June 1999. Provided they are appropriately processed and if any TSE risk
is excluded, they could be recycled into industrial products or
fertilizers. However, if a TSE risk exists, they should be disposed of.
5. Conclusions from the Working Group Concerning the susceptibility of
pigs, poultry and fish to become infected with TSE's, there is evidence
that pigs can become infected with BSE through intra-cerebral inoculation
with infectious BSE material. Infectivity could be recovered from poultry
inoculated via the i/v route with TME. No evidence was found of TSE's in
fish. Till date no experiments have shown that pigs, poultry and fish
could be infected with TSE through the oral route. The hypothesis
proposed that orally TSE-inoculated non-ruminants without any signs of
disease could carry over the TSE-infection through there tissues has till
date not been proven. Concerning ruminants, a large number of
experiments, abundantly reported on in the scientific literature, has
shown that cattle and sheep are susceptible to TSE's originating from
their own species and that ruminants in general fed8 with infectious
material originating from the same species can be infected with TSE's.
Should a country be free of any animal TSE, epidemiological evidence
suggests that the onset of an endemic of a certain TSE based on a
spontaneous native case of TSE is very unlikely.9 6. General remark on the
safety of derived products. Recycling of animal by-products processed
into basic biochemical substances as fat and protein is recognised as an
effective way of re-use of valuable materials. When an animal is
decomposed through processing into protein, fat and other basic
biochemical materials, consumption of this material is not anymore
recognised as being intra-species recycling. Besides the feed-value of
these slaughter by-products, effective disposal and processing is of
importance to protect human and animal health and to preserve the
environment. An effective system that prevents the uncontrolled dispersion
of slaughter by-products in the environment is important to preserve human
and animal health. Longitudinal integrated safety assurance (LISA) should
be implemented based on the HACCP concept to assure the safety of the
processed products and to make them available for the market. From
environmental point of view protection strategies should be directed
towards: firstly a reduction of waste and secondly towards a full re-use
of waste. The use of energy and the production of waste water and odour
should be implemented in the strategies to comply with these policies.
Intra-species recycling can be acceptable when the material of origin is
from epidemiological point of view safely sourced with regard to TSE's and
treated accordingly to prevent any spread of conventional diseases. 7.
Non-exhaustive list of the consulted literature and documents Agrimi U.,
Ru G., Cardone, F., Pocchiari, M, Caramelli, M., 1999. Epidemic of
transmissible spongiform encephalopathy in sheep and goats in Italy. The
Lancet 353, 560-561 Animal Health, 1996. Report of the Chief Veterinary
Officer. HMSO, London, pp22-45. Animal Health, 1997. Report of the Chief
Veterinary Officer. HMSO, London, pp22-45. Capucchio MT, Guarda F, Isaia
MC, Caracappa S, Di Marco, V., 1998. Natural occurrence of scrapie in
goats in Italy. The Veterinary Record, 143, 452-453 Dawson, M., Wells,
G.A.H., Parker, B.N.J., Francis, M.E., Scott, A.,C., 1991. Transmission
studies of BSE in cattle, hamsters, pigs and domestic fowl. In: Current
topics in Vet. Med. and Anim. Sci., Sub-acute spongiform encephalopathies,
Bradley R., Savey M., Marchant B., eds. 55, 25-32. Kluwer Academic
Publishers, Dordrecht. Dawson, M., Wells, G.A.H., Parker, B.N.J.,
Francis, M.E., Scott, A.,C., Hawkins, S.A.C., Martin, T.C., Simmons, M.,
Austin, A.R., 1994. Transmission studies of BSE in cattle, pigs and
domestic fowl. In: Proceedings of a Consultation on BSE with the
Scientific Veterinary Committee of the EC, Brussels, 14-15 Sep 1993.
Bradley R., Savey M., Marchant B., eds. pp 161-167. EC, Brussels. Dawson,
M., Wells, G.A.H., Parker, B.N.J., Scott, A.,C., 1990. Primary,
parenteral transmission of BSE to a pig. Vet. Rec. 127, 338.
Environmental Agency, 1998. Processes Subject to Integrated Pollution
Control. IPC Guidance Note S2 1.05. Amplification Note N! 1.Combustion of
Meat-and-bone meal (MBM). 23 pp. FIN (Fishmeal Information Network),
1998. Information package on fishmeal provided to the Secretariat of the
Scientific Steering Committee. FIN (Fishmeal Information Network), 1999.
Letter and annexes of 1 March 1999 of C.Trotman to the SSC secretariat
providing information on (1) the processing of fish, including trimmins,
for use in animal feed, (2) the heat sensitivity of fish pathogens and (3)
the possible occurrence of TSEs in fish. Fransen, N.G., Urlings, H.A.P.,
Bijker, P.G.H., van Logtestijn, J.G., 1996. The use of slaughterhouse
sludge. Fleischwirtschaft, 76, 1179-1184. Gibbs, C.J., Gajdusek, C.J.,
Amyx, 1979. Strain variation in the viruses of Creutzfeldt-Jakob disease
and kuru. In :Slow Transmissible Diseases of the Nervous System. (S.B.
Prusiner and W.J. Hadlow, Eds), Vol.2, pp 87-110, Academic Press, New
York. Gordon, W.S., 1946. Advances in veterinary research: louping ill,
tick-borne fever and scrapie. Vet Rec 58, 516-525. Greig, J.R., 1950.
Scrapie in sheep. J Comp Path, 60, 263-266. Hansen, M., Halloran, J.,
1997. Letter of 24 March 1997 of Hansen and Halloran (Consumer Policy
Institute, Consumer Union, US) to Dr. S.F.Sundlof (Centre for veterinary
Medicine, USFood and Drug Administration, Rockville, US). Hawkins,
S.A.C., Ryder, S.J., Wells, G.A.H., Austin, A.R., Dawson, M., 1998.
Studies of the experimental transmissibility of BSE and scrapie to pigs.
In: Proceedings of the 15th IVPS Congress, Birmingham, England, 5-9 July
1998. P. 186. Hunter, N., Cairns, D., Foster, J., Smith, G., Goldmann, W.
and Donnelly, K. 1997. Is scrapie a genetic disease? Evidence from
scrapie-free countries. Nature, 386, 137. Marsh, R.F., Burger, D.,
Eckroade, R., ZuRhein, G.M., Hanson, R.P., 1969. A preliminary report on
the experimental host range of transmissible mink encephalopathy agent. J.
Inf. Dis. 120 713-719. Race, R., Chesebro, B., 1998. Scrapie infectivity
found in resistant species. Nature, 392, 770. Robinson, M.M., Hallow,
W.J., Huff, T.P., Wells, G.A., Dawson,M., Marsh,R.F., Gorham,J.R.; 1994:
Experimental infection of mink with BSE. Journal of General Virology,
(75), 1994, pp. 2151-2155 Schoon, H.-A., Brunckhorst, D., Pohlenz J.,
1991a. Spongiforme Enzephalopathie beim Rothalsstraus (Struthio camelus)
Ein kasuistischer Beitrag. Tier
rztl. Praxis, 19, 263-265.
Schoon, H.-A., Brunckhorst, D. & Pohlenz, J., 1991b. Beitrag zur
Neuropathologie beim Rothalsstrauss (Struthio camelus) - Spongiforme
Enzephalopathie. Verh. ber. Erkrg. Zootiere, 33, 309-313.
SSC (Scientific Steering Committee of the European Commission):
Scientific opinions :
* Safety of Gelatine, last update,19/2/99
* Safety of Meat and Bone Meal (MBM) from mammalian animals, naturally
or experimentally susceptible to Transmissible
Spongiform Encephalopathies. 27/3/98
* Safety of Tallow, 27/3/98
* Safety of Dicalcium Phosphate precipitated from ruminant bones and
used as an animal feed, 26/6/98
* Safety of Hydrolysed Proteins produced from bovine hides,
23/10/98
* Safety of Organic Fertilizers derived from mammalian animals, 25/9/98
* Risk of Infection of Sheep and Goats with the Bovine Spongiform
Encephalopathy agent, 25/9/98
* "Fallen Stock": The risks of non conventional transmissible agents,
conventional infectious agents or other hazards such as toxic substances
entering the human food or animal feed chains via raw material from fallen
stock and dead animals (including also: ruminants, pigs, poultry, fish,
wild/exotic/zoo animals, fur animals, cats, laboratory animals and fish)
or via condemned materials, 23/7/99
Reports of Working Groups
* Report on the safety of meat and bone meal derived from mammalian
animals fed to non-ruminant food-producing farm animals, 25/9/98
* Report on the possible vertical transmission of Bovine Spongiform
Encephalopathy (BSE),19/3/99.
Opinions of the SSC and related Reports of Working Group are published on
the Internet under
http://europa.eu.int/comm/dg24/health/sc/ssc/outcome_en.html as soon as
possible after the adoption of the opinions by the SSC. Van Sonsbeek,
J.Th.M., van Beek, P., Urlings, H.A.P., Bijker, P.G.H., Hagelaar, J.F.L.,
1997. Mixed integer programming for strategic decision support in
slaughter by-product chain. OR Spektrum, 19, 159-168.
Wells, G.A.H., Hawkins,S.A.C. and Dawson, M. 1998. Transmissible
Spongiforme Encephalopathy in Pigs: Did natural exposure to BSE
lead to infection. In: Proceedings of the 15th IPVS Congress,
Birmingham, England, 5-9 July 1998
8. Acknowledgements
The present report was prepared by a Working Group chaired by Dr. H.A.P.
Urlings. Other members of the working group were:
Prof.Dr. R.Bhm, Prof.Dr.Mac Johnston, Prof.Dr. Milhaud, Prof.D.V.M. Esko
Nurmi, Prof. Dr. A.-L. Parodi, Prof.Dr.G.Piva, Dr. M.Riedinger, Prof.Soren
Alexandersen, Dr. J.Schlatter, Prof.Dr.D.W.Taylor, Dr.D.M.Taylor,
Prof.Dr.M.Vanbelle, Prof.Dr. M.Wierup, Prof.Dr. P.Willeberg.
Contributions were also received from Dr.R.Bradley, Dr.L.Detwiler and
Dr.N.Hunter.
----------------------------------------
1 Intra-species recycling of fur animals is discussed in the SSC opinion
on "Fallen stock", adopted on 24-25.06.99 2 See the "Fallen stock"
opinion.
3 Healthy animals are defined as animals which have undergone an ante
mortem inspection by an official veterinarian where it was determined that
the animals were not suffering from a disease which is communicable to man
and animals and that they do not show symptoms or are in a general
condition such as to indicate that such disease may occur and they show no
symptoms of disease or of a disorder of their general conditions which is
likely to make their meat unfit for human consumption. (Definition as
given in Directive 64/433/EEC, laying down the rules for ante mortem
inspection)
4 Based also on the following USA documents: (1) Dr.W.J.Hadlow's Report of
10.04.97 on the microscopic examination of pig brain N! 2709, (2)
Dr.J.Miller's comments of 31.03.97 on the incident and (3) H.W.Moon's
review of 31 March of the pathology reports of the pigs.
5 According to Alderman (1996) there are a few recognised diseases of
viral and protozoal aetiology which affect nervous tissues of farmed and
wild fish which result in pathologies and which, whilst they may be
described as encephalopathies, can not in any way be confused with
spongiform encephalopathy group of diseases, which include BSE, CJD and
scrapie either in their gross, behavioural or pathological
characteristics. Such viruses and protozoans are regarded as being
extremely host specific and adapted for cold blooded animals.
6 It is easier to section the entire head, thus including the brain, than
to concentrate only on gill.
7 See also Section 2 Scope, on other ways of transmission.
8 See also Section 2 Scope, on other routes of transmission. 9 On the
latter sentence, there was no consensus, as some found it misleading: if
epidemic BSE originated from recycling of sporadic BSE, this could have
happened everywhere with the right conditions.
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http://www.oac.uoguelph.ca/riskcomm
archived at:
http://www.ansc.purdue.edu/courses/ansc481/animal_net.html
http://209.85.165.104/search?q=cache:OYo6dIyFZuYJ:www.foodcontamination.ca/animalnet/1999/9-1999/an-09-26-99-01.txt+spontaneous+TSE+bse+inquiry+little+evidence&hl=en&ct=clnk&cd=29&gl=us
The ongoing BSE surveillance program will sample approximately 40,000 animals each year. Under the program, USDA will continue to collect samples from a variety of sites and from the cattle populations where the disease is most likely to be detected, similar to the enhanced surveillance program procedures.
The new program will not only comply with the science-based international guidelines set forth by the World Animal Health organization (OIE), it will provide testing at a level ten times higher than the OIE recommended level.
http://www.usda.gov/wps/portal/usdahome?contentidonly=true&contentid=2006/07/0255.xml
WHY would several strains of TSE in feed not be a plausible theory rather than a theory never proven, the spontaneous theory $$$
WHY is it not plausible to think that BASE might have come from feed too ???
WHY WOULD ONE STRAIN AMPLIFY AND TRANSMIT, AND THE OTHER NOT ???
WHY would one strain of TSE in cattle transmit orally via feed i.e. BSE, and the other i.e. BASE not transmit orally ???
answer =
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed
compounders.
To minimise the potential damage to compound feed markets through adverse publicity.
To maximise freedom of action for feed compounders, notably by
maintaining the availability of meat and bone meal as a raw
material in animal feeds, and ensuring time is available to make any
changes which may be required.
snip...
THE FUTURE
4..........
MAFF remains under pressure in Brussels and is not skilled at
handling potentially explosive issues.
5. Tests _may_ show that ruminant feeds have been sold which
contain illegal traces of ruminant protein. More likely, a few positive
test results will turn up but proof that a particular feed mill knowingly
supplied it to a particular farm will be difficult if not impossible.
6. The threat remains real and it will be some years before feed
compounders are free of it. The longer we can avoid any direct
linkage between feed milling _practices_ and actual BSE cases,
the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
3. Prof. A. Robertson gave a brief account of BSE. The US approach
was to accord it a _very low profile indeed_. Dr. A Thiermann showed
the picture in the ''Independent'' with cattle being incinerated and
thought this was a fanatical incident to be _avoided_ in the US _at all
costs_...
snip...
http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the
prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A
MUTATION FOUND IN CASES OF SPORADIC CJD.
snip...
http://www.seac.gov.uk/minutes/95.pdf
3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse
Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve
University
Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain
discovered recently in Italy, and similar or different atypical BSE cases
were also reported in other countries. The infectivity and phenotypes of
these atypical BSE strains in humans are unknown. In collaboration with
Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have
inoculated transgenic mice expressing human prion protein with brain
homogenates from BASE or BSE infected cattle. Our data shows that about half
of the BASE-inoculated mice became infected with an average incubation time
of about 19 months; in contrast, none of the BSE-inoculated mice appear to
be infected after more than 2 years.
***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than
classical BSE in humans.***
6:30 Close of Day One
http://www.healthtech.com/2007/tse/day1.asp
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance
collection.
He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
TSS
Date: February 13, 2007 at 2:46 pm PST
Agenda
96th meeting on Tuesday 20 February 2007
http://www.seac.gov.uk/minutes/95.pdf
CONFERENCE ON PRION DISEASES OF NEUROPRION, NETWORK OF EXCELLENCE, TURIN, ITALY, 3-6 OCTOBER 2006
BASE
OUR OBSERVATIONS UNDERLINE THE HIGH SUSCEPTIBILITY OF A PRIMATE SPECIES TO THE BASE PRION STRAIN AND PROVIDE A BIOCHEMICAL BASIS FOR THE IDENTIFICATION OF A POTENTIAL OCCURRENCE IN MAN. ...page 9...tss
http://www.seac.gov.uk/papers/96-2.pdf
UPDATE ATYPICAL SCRAPIE IN A TSE RESEARCH FLOCK
http://www.seac.gov.uk/papers/96-4.pdf
> Some unofficial information from a source on the inside looking out -
>
> Confidential!!!!
>
> As early as 1992-3 there had been long studies conducted on small
> pastures containing scrapie infected sheep at the sheep research station
> associated with the Neuropathogenesis Unit in Edinburgh, Scotland.
> Whether these are documented...I don't know. But personal recounts both
> heard and recorded in a daily journal indicate that leaving the pastures
> free and replacing the topsoil completely at least 2 feet of thickness
> each year for SEVEN years....and then when very clean (proven scrapie
> free) sheep were placed on these small pastures.... the new sheep also
> broke out with scrapie and passed it to offspring. I am not sure that TSE
> contaminated ground could ever be free of the agent!!
> A very frightening revelation!!!
>
http://www.microbes.info/forums/index.php?showtopic=306
Science 24 September 2004:
Vol. 305. no. 5692, pp. 1918 - 1921
DOI: 10.1126/science.1103581
Perspectives
BIOMEDICINE:
A Fresh Look at BSE
Bruce Chesebro*
Mad cow disease, or bovine spongiform encephalopathy (BSE), is the cattle
form of a family of progressive brain diseases. These diseases include
scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and chronic
wasting disease (CWD) in deer and elk. They are also known as either "prion
diseases" because of the association of a misfolded cellular prion protein
in pathogenesis or "transmissible spongiform encephalopathies" (TSEs)
because of the spongelike nature of the damaged brain tissue (1).
The recent discovery of two BSE-infected cows, one in Canada and one in the
United States, has dramatically increased concern in North America among
meat producers and consumers alike over the extent to which BSE poses a
threat to humans as well as to domestic and wild animals. The European BSE
epidemic of the late-1980s seems to have been initiated a decade earlier in
the United Kingdom by changes in the production of meat and bone meal (MBM)
from rendered livestock, which led to contamination of MBM with the BSE
infectious agent. Furthermore, the fact that UK farmers fed this rendered
MBM to younger animals and that this MBM was distributed to many countries
may have contributed to the ensuing BSE epidemic in the United Kingdom and
internationally (2).
Despite extensive knowledge about the spread of BSE through contaminated
MBM, the source of BSE in Europe remains an unsolved mystery (2). It has
been proposed that BSE could be derived from a cross-species infection,
perhaps through contamination of MBM by scrapie-infected sheep tissues (see
the figure). Alternatively, BSE may have been an endemic disease in cattle
that went unnoticed because of its low level of horizontal transmission.
Lastly, BSE might have originated by "spontaneous" misfolding of the normal
cellular prion protein into the disease-associated abnormal isoform (3),
which is postulated to be the infectious agent or "prion."
Five possible sources of BSE in North American cattle. Sheep, deer, and elk
could spread prion diseases (TSEs) to cattle through direct animal contact
or contamination of pastures. Endemic BSE has not been proven to exist
anywhere in the world, but it is difficult to exclude this possibility
because of the inefficient spread of BSE infectivity between individual
animals (2). BSE caused by spontaneous misfolding of the prion protein has
not been proven.
CREDIT: KATHARINE SUTLIFF/SCIENCE
Spontaneous protein misfolding is not a new phenomenon as proteins are known
to sometimes misfold after synthesis. Cells in turn have devised ingenious
ways to deal with this problem. These include molecular chaperone proteins
that bind to misfolded proteins and help them to unfold, and organelles
called proteosomes that degrade misfolded or unwanted proteins. However,
although misfolded prion proteins have been generated in test tubes as well
as in cultured cells, it has been difficult to demonstrate that such
misfolded abnormal prion proteins are infectious (4, 5). Even the most
recent data do not prove conclusively that infectivity has been generated in
vitro because misfolded synthetic prion proteins were not able to transfer
disease directly to wild-type mice (6). To obtain infectivity and subsequent
prion disease, the misfolded proteins had to be inoculated and incubated for
1 to 2 years in transgenic mice that overexpressed a mutant version of the
prion protein. Previous data from this group showed that transgenic mice
expressing high amounts of prion protein developed neurological disease
without inoculation of misfolded prion protein (7). Thus, at the biochemical
level, the critical attributes of the misfolded prion protein required for
infectivity are not known, and misfolding of prion protein alone may not be
sufficient to generate an infectious agent (.
Nevertheless, the idea that BSE might originate due to the spontaneous
misfolding of prion proteins has received renewed interest in the wake of
reports suggesting the occurrence of atypical BSE (9-11). These results
imply that new strains of cattle BSE might have originated separately from
the main UK outbreak. Where and how might such strains have originated?
Although such rare events cannot be studied directly, any number of sources
of the original BSE strain could also explain the discovery of additional
BSE strains in cattle (see the figure). However, it would be worrisome if
spontaneous BSE were really a valid etiology because such a mechanism would
be impossible to prevent--unlike other possible scenarios that could be
controlled by large-scale eradication of TSE-positive animals.
Another way to look at this problem is to examine evidence for possible
spontaneous TSE disease in other animals besides cattle. Spontaneous BSE
would be extremely difficult to detect in cattle, where horizontal spread is
minimal. However, in the case of the sheep TSE disease, scrapie, which
spreads from ewes to lambs at birth as well as between adults, spontaneous
disease should be detectable as new foci of clinical infection. In the early
1950s scrapie was eradicated in both Australia and New Zealand, and the
mainland of both these countries has remained scrapie-free ever since. This
scrapie-free status is not the result of selection of sheep resistant to
scrapie because sheep from New Zealand are as susceptible as their UK
counterparts to experimental scrapie infection (12). These experiments of
man and nature appear to indicate that spontaneous clinical scrapie does not
occur in sheep. Similarly, because CWD is known to spread horizontally, the
lack of CWD in the deer or elk of eastern North America but its presence in
western regions would also argue against a spontaneous disease mechanism.
This is particularly noteworthy in New Zealand, where there are large
numbers of deer and elk farms and yet no evidence of spontaneous CWD. If
spontaneous scrapie does not occur in sheep or deer, this would suggest that
spontaneous forms of BSE and sporadic Creutzfeldt-Jakob disease (sCJD) are
unlikely to be found in cattle or humans. The main caveat to this notion is
that spontaneous disease may arise in some animal species but not others. In
humans, sCJD--which is considered by some researchers to begin by
spontaneous misfolding of the prion protein--usually takes more than 50
years to appear. Thus, in animals with a shorter life-span, such as sheep,
deer, and cattle, an analogous disease mechanism might not have time to
develop.
What can we conclude so far about BSE in North America? Is the BSE detected
in two North American cows sporadic or spontaneous or both? "Sporadic"
pertains to the rarity of disease occurrence. "Spontaneous" pertains to a
possible mechanism of origin of the disease. These are not equivalent terms.
The rarity of BSE in North America qualifies it as a sporadic disease, but
this low incidence does not provide information about cause. For the two
reported North American BSE cases, exposure to contaminated MBM remains the
most likely culprit. However, other mechanisms are still possible, including
cross-infection by sheep with scrapie or cervids with CWD, horizontal
transmission from cattle with endemic BSE, and spontaneous disease in
individual cattle. Based on our understanding of other TSEs, the spontaneous
mechanism is probably the least likely. Thus, "idiopathic" BSE--that is, BSE
of unknown etiology--might be a better term to describe the origin of this
malady.
What does all this imply about testing cattle for BSE in North America?
Current testing in the United States indicates that BSE is rare (one
positive result in 40,000 cattle tested). However, additional testing of
200,000 head of slaughtered cattle over the next 1 to 2 years, as recently
proposed by the U.S. Department of Agriculture (USDA), should tell us the
incidence more precisely. Nevertheless, if any rare cases are detected, we
may still not know their origin. If evidence arises of a focal occurrence of
BSE, we might gain important insight into unexpected sources of
contamination. However, because current tests do not seem to be able to
detect BSE in infected animals less than 30 months of age, even more
extensive testing will not completely guarantee the negative status of
younger animals in the food chain. Therefore, the alternative option of
testing all slaughtered cattle, as implemented in some countries such as
Japan, would appear to provide little additional benefit. This fact has been
acknowledged as the basis for a new agreement between the United States and
Japan aimed at reestablishing the beef trade between the two countries.
One problem with the current U.S. testing program was the announcement a few
months ago of unconfirmed positive BSE tests in two additional North
American animals that were subsequently found to be negative when tested
with the more accurate method of Western blotting. The public release of
information about unconfirmed positive tests detected by the rapid test used
for mass screening may be a good idea in the interest of openness, but it ha
s the potential to create unwarranted anxiety. If unconfirmed positives are
a frequent occurrence, it would seem reasonable to follow a more cautious
approach and wait until confirmatory testing is complete before publicly
announcing the details.
Based on the experience of many European countries, the mainstays of
controlling BSE in cattle and avoiding spread to humans are threefold:
first, eliminate feeding of ruminant tissues to ruminants; second, remove
high-risk cattle tissues from human food; and third, continue to test for
BSE in cattle in order to monitor progress with the elimination of the
disease on a local and national basis. In the next 12 months, after
extensive USDA test results are available, the extent of any possible BSE
spread in the United States will be better documented. But, in fact, the
United States and Canada have already instituted the most important steps to
prevent the spread of cattle BSE in advance of the results--that is, a ban
on feeding ruminant MBM to other ruminants and removal of high-risk tissues
from meat for human consumption. It is hoped that the new data will not
deviate enough from previous predictions to require further measures for
management of this problem. The most important line of defense against any
possible spread of BSE will be to maintain strict vigilance in the
implementation of the current regulations.
References
S. B. Prusiner, Proc. Natl. Acad. Sci. U.S.A 95, 13363 (1998) [Medline].
P. G. Smith, R. Bradley, Br. Med. Bull. 66, 185 (2003) [Medline].
C. Weissmann, A. Aguzzi, Curr. Opin. Neurobiol. 7, 695 (1997) [Medline].
A. F. Hill et al., J. Gen. Virol. 80, 11 (1999) [Medline].
R. Chiesa et al., J. Virol. 77, 7611 (2003) [Medline].
G. Legname et al., Science 305, 673 (2004).
D. Westaway et al., Cell 76, 117 (1994) [Medline].
B. Chesebro, Science 279, 42 (1998).
A. G. Biacabe et al., EMBO Rep. 5, 110 (2004) [Medline].
Y. Yamakawa et al., Jpn. J. Infect. Dis. 56, 221 (2003) [Medline].
C. Casalone et al., Proc. Natl. Acad. Sci. U.S.A. 101, 3065 (2004)
[Medline].
E. F. Houston et al., J. Gen. Virol. 83, 1247 (2002) [Medline].
http://www.sciencemag.org/cgi/content/full/305/5692/1918
However, Phillips did not have an explanation of how the first cow got BSE and other
explanations continue to be put forward. One journalist commented on the idea favoured
by the Phillips Committee that BSE started with a spontaneous mutation:
However, apart from there being little evidence for the idea, a random mutation
could not explain why Britain alone has suffered the problem. America, for
instance, has 10 times the number of cattle, and so must in theory run ten times
the risk of a similar random event leading to BSE and so being passed on in
recycled meat and bone meal.13
http://www.parliament.uk/commons/lib/research/rp2001/rp01-089.pdf
Evaluation of the Potential for Bovine Spongiform
Encephalopathy in the United States
Joshua T. Cohen
Keith Duggar
George M. Gray
Silvia Kreindel
Harvard Center for Risk Analysis
Harvard School of Public Health
Hatim Abdelrahman
Tsegaye HabteMariam
David Oryang
Berhanu Tameru
Center for Computational Epidemiology
College of Veterinary Medicine
Tuskegee University
November 26, 2001
snip...
2.3.1 Spontaneous BSE
A potential way in which BSE could be introduced into the United States is the
development of a spontaneous case of a BSE in a native animal. A “spontaneous case” is one that
occurs in an animal with no known risk factors for development of BSE. The presumed
mechanism by which a BSE could occur spontaneously is by the mutation of the PrP gene to a
Section 2
- 20 -
form that codes for PrPsc, and subsequent recruitment of PrPc until disease is manifest (Prusiner,
1989); (for review see: (Chesebro, 1999). There is no direct evidence of this mechanism,
although some argue that all mammals might have a low spontaneous rate of TSE (Hueston,
1997). In addition, a transgenic animal over-expressing the PrP gene has apparently replicated
the human TSE GSS (Hsiao et al., 1991). Recent results, in which mice expressing the same
point mutation but at normal levels failed to develop disease (Manson et al., 1999), suggest the
mutations may increase susceptibility rather than directly cause the disease. Although at this time
there is no scientific evidence suggesting that spontaneous BSE exists, the BSE Inquiry suggested
that TSEs could possibly develop sporadically in other species, as they do in humans (BSE
Inquiry, 2000). In contrast, the Review of the origin of BSE (Horn et al., 2001) concluded that
although the spontaneous case hypothesis cannot be excluded, there is no evidence supporting the
presence of sporadic form prion disease in cattle or sheep.
snip...
http://www.aphis.usda.gov/lpa/issues/bse/risk_assessment/mainreporttext.pdf
http://www.aphis.usda.gov/lpa/issues/bse/madcow.pdf
REPORT ON : THE RISK BORN BY RECYCLING ANIMAL BY-PRODUCTS AS FEED WITH
REGARD TO PROPAGATING TSE'S IN NON-RUMINANT FARMED ANIMALS. PREPARED BY A
WORKING GROUP FOR THE SCIENTIFIC STEERING COMMITTEE AS AN INPUT IN THE
ELABORATION OF THE OPINION ON THE SAME SUBJECT ADOPTED ON 16-17 SEPTEMBER
1999.
September 1999
The European Commission
snip...
The final outcome should contribute to the assessment of the possibility
of transmission of TSE to fish, the evaluation of the potential risk
connected to fish derived foods for human and animal, the establishment of
analytical protocols for PrP detection in fresh fish food and the
comparison of the molecular properties of normal and abnormal isoforms of
PrP. d. Ruminants A large number of experiments, abundantly reported on
in the scientific literature, has shown that cattle and sheep are
susceptible to TSE's originating from their own species and that ruminants
in general fed with infectious material originating from the same species
can be infected with TSE's. Also, experimental evidence (EC, 1998) shows
that BSE can be transmitted to sheep (and goats) via the oral route7. If
a spontaneous TSE occurred in cattle, one might reasonable have expected
this to have occurred in detectable levels of a BSE-like disease in a much
larger number of countries than presently is the case, and where the
rendering systems used are very much alike those used in the EU prior to
1992, that implies not in accordance with the EU rendering directive
90/667. The potential occurrence of spontaneous TSE in cattle has till yet
not lead to detectable levels of cattle TSE in most countries, and in
countries where TSE in cattle occurs, this has so far not been attributed
to spontaneous cases. In fact, most of the BSE incidence in countries
where native BSE occurs, is accounted for by feeding of infected or
contaminated feedstufs. It must nevertheless be mentioned that, following
epidemiological investigations after the occurrence of a case, not all BSE
cases can always be brought back to proven feeding practices.
(E.Vanopdenbosch, 1998, personal communication) If scrapie would also
spontaneously occur in sheep, it would more likely occur in those sheep
with the most susceptible PrP genotypes. However, it is now known that a
significant proportion of Australian and New Zealand sheep have such
genotypes, but have not developed scrapie (Hunter et al, 1997). e. Pigs,
poultry and fish as possible silent carriers Marsh et al (1969) reported
the recovery of transmissible mink encephalopathy (TME) infectivity from
the spleen of one chicken and from the spleen, caecum, tonsil and bursa of
Fabricius of a second chicken of two chickens challenged experimentally by
i/v inoculation of fourth passage mink brain with TME. They noted that
infectivity administered either intra-cranial, intra-venous,
intra-muscular or subcutaneously, persisted for extended periods (30 and
50 days in the case of chickens) in lymphoid tissues of rhesus monkeys,
chickens, mice, cats, ferrets, goats and calves that were studied. No
experimental data are available about oral infectivity tests. Race and
Chesebro (1998), reported the results of i/c challenge of mice with
hamster scrapie strain 263K that produces no clinical disease in mice,
followed by sub-passage from brain and spleen into further mice and into
scrapie susceptible hamsters. Infectivity was detected in the spleen and
brain tissues by the hamsters, but not by the mice. The authors' view was
that the mice had not replicated the agent. They noted that they had not
tested to see if the same results were obtained after oral challenge.
However, they suggested that food animal species resistant to BSE, such as
poultry, exposed to BSE infectivity via feed but might show persistent
infectivity in their tissues without replication. Over 80% of pig meat
and 80% of poultry meat produced in the EU originates from pigs less than
8 months of age and broilers less than 2 months of age respectively.
However, the life expectancy of both pigs and chickens raised for
slaughter may be too short to show any signs of SE-s whenever they are
infected. Taking account of all our knowledge on prion diseases in
animals, it is unlikely that clinical evidence of disease would occur at
such a young age. Only adult breeding pigs would be expected to be old
enough to exhibit clinical signs if ever a TSE of pigs was found. However,
it can be hypothesized that infectivity of extra-neural tissues,
particularly lymphoreticular tissues, could theoretically arise in these
species exposed to TSE infection via feed whether or not replication and
neuroinvasion subsequently occurred. The results of the studies using the
BSE agent mentioned above do not support the hypothesis that infectivity
can be sequestered in the manner described and particularly this is a
unlikely event in pigs exposed to the BSE agent by the oral route two
years earlier. It is noted however, that these studies used mice to detect
any infectivity, cattle would be more susceptible. Furthermore the results
of bioassays done at the termination of the porcine studies are still
awaited as are those from poultry (see also sections 7.a and 7.b).
However, special attention should be drawn to the eventuality that in pigs
under natural conditions the intestinal barrier is would be very
efficacious in respect to the development of clinical TSE, but that by
feeding infected ruminant MBM and/or intraspecies recycling of pigs with
low levels of infectivity, an increasing level of infectivity could be
built up in the intestine. Such low levels could only be detected by the
most sensitive methods i.e. intracerebral inoculation of calves with
intestinal tissue of orally exposed pigs. This would be in accordance with
the results of the experiments of Race and Cesebro to detect infectivity
in resistant species. f. Risks related to the content of the gut and to
manure (faeces) The content of the gut and manure represent an increased
risk, if the animals were fed with (possibly TSE-contaminated) ruminant
material even if it was previously treated at "133!C/20'/3 bars", because
this standard is considered not to eliminate all possible TSE infectivity
if the initial titer was high. If the presence of a BSE risk is not
excluded, these materials should therefore be considered as "condemned
materials" as described in the SSC's opinion on "Fallen stock" of 24-25
June 1999. Provided they are appropriately processed and if any TSE risk
is excluded, they could be recycled into industrial products or
fertilizers. However, if a TSE risk exists, they should be disposed of.
5. Conclusions from the Working Group Concerning the susceptibility of
pigs, poultry and fish to become infected with TSE's, there is evidence
that pigs can become infected with BSE through intra-cerebral inoculation
with infectious BSE material. Infectivity could be recovered from poultry
inoculated via the i/v route with TME. No evidence was found of TSE's in
fish. Till date no experiments have shown that pigs, poultry and fish
could be infected with TSE through the oral route. The hypothesis
proposed that orally TSE-inoculated non-ruminants without any signs of
disease could carry over the TSE-infection through there tissues has till
date not been proven. Concerning ruminants, a large number of
experiments, abundantly reported on in the scientific literature, has
shown that cattle and sheep are susceptible to TSE's originating from
their own species and that ruminants in general fed8 with infectious
material originating from the same species can be infected with TSE's.
Should a country be free of any animal TSE, epidemiological evidence
suggests that the onset of an endemic of a certain TSE based on a
spontaneous native case of TSE is very unlikely.9 6. General remark on the
safety of derived products. Recycling of animal by-products processed
into basic biochemical substances as fat and protein is recognised as an
effective way of re-use of valuable materials. When an animal is
decomposed through processing into protein, fat and other basic
biochemical materials, consumption of this material is not anymore
recognised as being intra-species recycling. Besides the feed-value of
these slaughter by-products, effective disposal and processing is of
importance to protect human and animal health and to preserve the
environment. An effective system that prevents the uncontrolled dispersion
of slaughter by-products in the environment is important to preserve human
and animal health. Longitudinal integrated safety assurance (LISA) should
be implemented based on the HACCP concept to assure the safety of the
processed products and to make them available for the market. From
environmental point of view protection strategies should be directed
towards: firstly a reduction of waste and secondly towards a full re-use
of waste. The use of energy and the production of waste water and odour
should be implemented in the strategies to comply with these policies.
Intra-species recycling can be acceptable when the material of origin is
from epidemiological point of view safely sourced with regard to TSE's and
treated accordingly to prevent any spread of conventional diseases. 7.
Non-exhaustive list of the consulted literature and documents Agrimi U.,
Ru G., Cardone, F., Pocchiari, M, Caramelli, M., 1999. Epidemic of
transmissible spongiform encephalopathy in sheep and goats in Italy. The
Lancet 353, 560-561 Animal Health, 1996. Report of the Chief Veterinary
Officer. HMSO, London, pp22-45. Animal Health, 1997. Report of the Chief
Veterinary Officer. HMSO, London, pp22-45. Capucchio MT, Guarda F, Isaia
MC, Caracappa S, Di Marco, V., 1998. Natural occurrence of scrapie in
goats in Italy. The Veterinary Record, 143, 452-453 Dawson, M., Wells,
G.A.H., Parker, B.N.J., Francis, M.E., Scott, A.,C., 1991. Transmission
studies of BSE in cattle, hamsters, pigs and domestic fowl. In: Current
topics in Vet. Med. and Anim. Sci., Sub-acute spongiform encephalopathies,
Bradley R., Savey M., Marchant B., eds. 55, 25-32. Kluwer Academic
Publishers, Dordrecht. Dawson, M., Wells, G.A.H., Parker, B.N.J.,
Francis, M.E., Scott, A.,C., Hawkins, S.A.C., Martin, T.C., Simmons, M.,
Austin, A.R., 1994. Transmission studies of BSE in cattle, pigs and
domestic fowl. In: Proceedings of a Consultation on BSE with the
Scientific Veterinary Committee of the EC, Brussels, 14-15 Sep 1993.
Bradley R., Savey M., Marchant B., eds. pp 161-167. EC, Brussels. Dawson,
M., Wells, G.A.H., Parker, B.N.J., Scott, A.,C., 1990. Primary,
parenteral transmission of BSE to a pig. Vet. Rec. 127, 338.
Environmental Agency, 1998. Processes Subject to Integrated Pollution
Control. IPC Guidance Note S2 1.05. Amplification Note N! 1.Combustion of
Meat-and-bone meal (MBM). 23 pp. FIN (Fishmeal Information Network),
1998. Information package on fishmeal provided to the Secretariat of the
Scientific Steering Committee. FIN (Fishmeal Information Network), 1999.
Letter and annexes of 1 March 1999 of C.Trotman to the SSC secretariat
providing information on (1) the processing of fish, including trimmins,
for use in animal feed, (2) the heat sensitivity of fish pathogens and (3)
the possible occurrence of TSEs in fish. Fransen, N.G., Urlings, H.A.P.,
Bijker, P.G.H., van Logtestijn, J.G., 1996. The use of slaughterhouse
sludge. Fleischwirtschaft, 76, 1179-1184. Gibbs, C.J., Gajdusek, C.J.,
Amyx, 1979. Strain variation in the viruses of Creutzfeldt-Jakob disease
and kuru. In :Slow Transmissible Diseases of the Nervous System. (S.B.
Prusiner and W.J. Hadlow, Eds), Vol.2, pp 87-110, Academic Press, New
York. Gordon, W.S., 1946. Advances in veterinary research: louping ill,
tick-borne fever and scrapie. Vet Rec 58, 516-525. Greig, J.R., 1950.
Scrapie in sheep. J Comp Path, 60, 263-266. Hansen, M., Halloran, J.,
1997. Letter of 24 March 1997 of Hansen and Halloran (Consumer Policy
Institute, Consumer Union, US) to Dr. S.F.Sundlof (Centre for veterinary
Medicine, USFood and Drug Administration, Rockville, US). Hawkins,
S.A.C., Ryder, S.J., Wells, G.A.H., Austin, A.R., Dawson, M., 1998.
Studies of the experimental transmissibility of BSE and scrapie to pigs.
In: Proceedings of the 15th IVPS Congress, Birmingham, England, 5-9 July
1998. P. 186. Hunter, N., Cairns, D., Foster, J., Smith, G., Goldmann, W.
and Donnelly, K. 1997. Is scrapie a genetic disease? Evidence from
scrapie-free countries. Nature, 386, 137. Marsh, R.F., Burger, D.,
Eckroade, R., ZuRhein, G.M., Hanson, R.P., 1969. A preliminary report on
the experimental host range of transmissible mink encephalopathy agent. J.
Inf. Dis. 120 713-719. Race, R., Chesebro, B., 1998. Scrapie infectivity
found in resistant species. Nature, 392, 770. Robinson, M.M., Hallow,
W.J., Huff, T.P., Wells, G.A., Dawson,M., Marsh,R.F., Gorham,J.R.; 1994:
Experimental infection of mink with BSE. Journal of General Virology,
(75), 1994, pp. 2151-2155 Schoon, H.-A., Brunckhorst, D., Pohlenz J.,
1991a. Spongiforme Enzephalopathie beim Rothalsstraus (Struthio camelus)
Ein kasuistischer Beitrag. Tier
rztl. Praxis, 19, 263-265.
Schoon, H.-A., Brunckhorst, D. & Pohlenz, J., 1991b. Beitrag zur
Neuropathologie beim Rothalsstrauss (Struthio camelus) - Spongiforme
Enzephalopathie. Verh. ber. Erkrg. Zootiere, 33, 309-313.
SSC (Scientific Steering Committee of the European Commission):
Scientific opinions :
* Safety of Gelatine, last update,19/2/99
* Safety of Meat and Bone Meal (MBM) from mammalian animals, naturally
or experimentally susceptible to Transmissible
Spongiform Encephalopathies. 27/3/98
* Safety of Tallow, 27/3/98
* Safety of Dicalcium Phosphate precipitated from ruminant bones and
used as an animal feed, 26/6/98
* Safety of Hydrolysed Proteins produced from bovine hides,
23/10/98
* Safety of Organic Fertilizers derived from mammalian animals, 25/9/98
* Risk of Infection of Sheep and Goats with the Bovine Spongiform
Encephalopathy agent, 25/9/98
* "Fallen Stock": The risks of non conventional transmissible agents,
conventional infectious agents or other hazards such as toxic substances
entering the human food or animal feed chains via raw material from fallen
stock and dead animals (including also: ruminants, pigs, poultry, fish,
wild/exotic/zoo animals, fur animals, cats, laboratory animals and fish)
or via condemned materials, 23/7/99
Reports of Working Groups
* Report on the safety of meat and bone meal derived from mammalian
animals fed to non-ruminant food-producing farm animals, 25/9/98
* Report on the possible vertical transmission of Bovine Spongiform
Encephalopathy (BSE),19/3/99.
Opinions of the SSC and related Reports of Working Group are published on
the Internet under
http://europa.eu.int/comm/dg24/health/sc/ssc/outcome_en.html as soon as
possible after the adoption of the opinions by the SSC. Van Sonsbeek,
J.Th.M., van Beek, P., Urlings, H.A.P., Bijker, P.G.H., Hagelaar, J.F.L.,
1997. Mixed integer programming for strategic decision support in
slaughter by-product chain. OR Spektrum, 19, 159-168.
Wells, G.A.H., Hawkins,S.A.C. and Dawson, M. 1998. Transmissible
Spongiforme Encephalopathy in Pigs: Did natural exposure to BSE
lead to infection. In: Proceedings of the 15th IPVS Congress,
Birmingham, England, 5-9 July 1998
8. Acknowledgements
The present report was prepared by a Working Group chaired by Dr. H.A.P.
Urlings. Other members of the working group were:
Prof.Dr. R.Bhm, Prof.Dr.Mac Johnston, Prof.Dr. Milhaud, Prof.D.V.M. Esko
Nurmi, Prof. Dr. A.-L. Parodi, Prof.Dr.G.Piva, Dr. M.Riedinger, Prof.Soren
Alexandersen, Dr. J.Schlatter, Prof.Dr.D.W.Taylor, Dr.D.M.Taylor,
Prof.Dr.M.Vanbelle, Prof.Dr. M.Wierup, Prof.Dr. P.Willeberg.
Contributions were also received from Dr.R.Bradley, Dr.L.Detwiler and
Dr.N.Hunter.
----------------------------------------
1 Intra-species recycling of fur animals is discussed in the SSC opinion
on "Fallen stock", adopted on 24-25.06.99 2 See the "Fallen stock"
opinion.
3 Healthy animals are defined as animals which have undergone an ante
mortem inspection by an official veterinarian where it was determined that
the animals were not suffering from a disease which is communicable to man
and animals and that they do not show symptoms or are in a general
condition such as to indicate that such disease may occur and they show no
symptoms of disease or of a disorder of their general conditions which is
likely to make their meat unfit for human consumption. (Definition as
given in Directive 64/433/EEC, laying down the rules for ante mortem
inspection)
4 Based also on the following USA documents: (1) Dr.W.J.Hadlow's Report of
10.04.97 on the microscopic examination of pig brain N! 2709, (2)
Dr.J.Miller's comments of 31.03.97 on the incident and (3) H.W.Moon's
review of 31 March of the pathology reports of the pigs.
5 According to Alderman (1996) there are a few recognised diseases of
viral and protozoal aetiology which affect nervous tissues of farmed and
wild fish which result in pathologies and which, whilst they may be
described as encephalopathies, can not in any way be confused with
spongiform encephalopathy group of diseases, which include BSE, CJD and
scrapie either in their gross, behavioural or pathological
characteristics. Such viruses and protozoans are regarded as being
extremely host specific and adapted for cold blooded animals.
6 It is easier to section the entire head, thus including the brain, than
to concentrate only on gill.
7 See also Section 2 Scope, on other ways of transmission.
8 See also Section 2 Scope, on other routes of transmission. 9 On the
latter sentence, there was no consensus, as some found it misleading: if
epidemic BSE originated from recycling of sporadic BSE, this could have
happened everywhere with the right conditions.
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archived at:
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http://209.85.165.104/search?q=cache:OYo6dIyFZuYJ:www.foodcontamination.ca/animalnet/1999/9-1999/an-09-26-99-01.txt+spontaneous+TSE+bse+inquiry+little+evidence&hl=en&ct=clnk&cd=29&gl=us
The ongoing BSE surveillance program will sample approximately 40,000 animals each year. Under the program, USDA will continue to collect samples from a variety of sites and from the cattle populations where the disease is most likely to be detected, similar to the enhanced surveillance program procedures.
The new program will not only comply with the science-based international guidelines set forth by the World Animal Health organization (OIE), it will provide testing at a level ten times higher than the OIE recommended level.
http://www.usda.gov/wps/portal/usdahome?contentidonly=true&contentid=2006/07/0255.xml
WHY would several strains of TSE in feed not be a plausible theory rather than a theory never proven, the spontaneous theory $$$
WHY is it not plausible to think that BASE might have come from feed too ???
WHY WOULD ONE STRAIN AMPLIFY AND TRANSMIT, AND THE OTHER NOT ???
WHY would one strain of TSE in cattle transmit orally via feed i.e. BSE, and the other i.e. BASE not transmit orally ???
answer =
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed
compounders.
To minimise the potential damage to compound feed markets through adverse publicity.
To maximise freedom of action for feed compounders, notably by
maintaining the availability of meat and bone meal as a raw
material in animal feeds, and ensuring time is available to make any
changes which may be required.
snip...
THE FUTURE
4..........
MAFF remains under pressure in Brussels and is not skilled at
handling potentially explosive issues.
5. Tests _may_ show that ruminant feeds have been sold which
contain illegal traces of ruminant protein. More likely, a few positive
test results will turn up but proof that a particular feed mill knowingly
supplied it to a particular farm will be difficult if not impossible.
6. The threat remains real and it will be some years before feed
compounders are free of it. The longer we can avoid any direct
linkage between feed milling _practices_ and actual BSE cases,
the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
3. Prof. A. Robertson gave a brief account of BSE. The US approach
was to accord it a _very low profile indeed_. Dr. A Thiermann showed
the picture in the ''Independent'' with cattle being incinerated and
thought this was a fanatical incident to be _avoided_ in the US _at all
costs_...
snip...
http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the
prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A
MUTATION FOUND IN CASES OF SPORADIC CJD.
snip...
http://www.seac.gov.uk/minutes/95.pdf
3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse
Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve
University
Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain
discovered recently in Italy, and similar or different atypical BSE cases
were also reported in other countries. The infectivity and phenotypes of
these atypical BSE strains in humans are unknown. In collaboration with
Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have
inoculated transgenic mice expressing human prion protein with brain
homogenates from BASE or BSE infected cattle. Our data shows that about half
of the BASE-inoculated mice became infected with an average incubation time
of about 19 months; in contrast, none of the BSE-inoculated mice appear to
be infected after more than 2 years.
***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than
classical BSE in humans.***
6:30 Close of Day One
http://www.healthtech.com/2007/tse/day1.asp
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance
collection.
He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
TSS