27 Mar 2013 News
U-turn considered on European PAP animal feed ban
Nutritionlegislation Nutrition food safety Feed safety consumer issues
Processed animal protein Australia China Europe Thailand US
370
The European Union is considering lifting a ban on processed animal
proteins (PAPs) to ease the cost of protein used to make animal feed.
The change would come at a time of heightened consumer concern about food
safety in Europe following the horsemeat scandal, Reuters reports. Stricter
safety rules on PAPs, that include intestine, bones, blood and feather, would be
imposed when the ban was lifted to prevent, for example, the "cannibalism" of
pig feed being given to pigs.
But the cost to industry of implementing the new rules as well as consumer
wariness means it is not clear how much the protein would be used. "We are
currently discussing with member states the potential re-authorisation of
processed animal proteins in feed for poultry and pigs from 2014," said a
spokesman for Tonio Borg, the EU's Health and Consumer Policy
Commissioner.
The by-products from pig and poultry slaughter were banned in 2000 as a
precaution after the BSE outbreak and the number of cases in the EU fell from
2,167 cases in 2001 to 45 cases in 2009 according to the World Health
Organisation.
In Europe, PAPs can currently be used in pet food. As of June this year
they will also be allowed in EU fish feed.The next planned step would be to
allow them in poultry and pig feed. This would bring Europe back in line with
many other countries, including the United States, China, Thailand, Australia
where there were no major reported outbreaks of BSE.
Animal by-products are a good alternative and would reduce reliance on
expensive imports, producers say.
"It is a very good source of protein in terms of nutritional composition
and digestibility and thus feed efficiency," said Leo den Hartog, director of
Research and Development and Quality Affairs at the Dutch animal nutrition
company Nutreco.
Whether the feed sector will use PAPs once the ban is lifted will depend on
price and availability and the extent of consumer concerns, an industry source
who declined to be named said.
"All chicken protein currently produced is being used by pet food sector
now. If the ban for compound feed is lifted, there will be even more demand and
prices will go up. It will become too expensive," the source said.
by World Poultry 27 Mar 2013
Wednesday, March 20, 2013
VETS have discovered 57 tonnes of banned British mutton in the freezers of
meat products firm Spanghero – and raised fears of a new BSE scare
Friday, March 8, 2013
Dogs may have been used to make Petfood and animal feed
Monday, August 8, 2011
Susceptibility of Domestic Cats to CWD Infection
Oral.29: Susceptibility of Domestic Cats to CWD Infection
Friday, April 20, 2012
Ultrastructural findings in pigs experimentally infected with bovine
spongiform encephalopathy agent
PORCINE SPONGIFORM ENCEPHALOPATHY PSE
Tuesday, March 5, 2013
FSA notified of BSE control breaches again and again 5 March 2013
(see 2012 BSE breaches as well...tss)
Monday, February 18, 2013 EU
Reauthorisation of non-ruminant processed animal proteins for fish feed and
welcomes the likely potential for more TSE prion disease
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
snip...
In the USA, under the Food and Drug Administration’s BSE Feed Regulation
(21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin)
from deer and elk is prohibited for use in feed for ruminant animals. With
regards to feed for non-ruminant animals, under FDA law, CWD positive deer may
not be used for any animal feed or feed ingredients. For elk and deer considered
at high risk for CWD, the FDA recommends that these animals do not enter the
animal feed system. However, this recommendation is guidance and not a
requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD
eradication zones and
2) deer and elk that at some time during the 60-month period prior to
slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive
animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from
the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin
processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible
risk___ that (nonruminant) animal feed and pet food containing deer and/or elk
protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data
on the amount of deer and/or elk protein possibly being imported in these
products.
snip...
36% in 2007 (Almberg et al., 2011). In such areas, population declines of
deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of
Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and
behavioural changes that can span weeks or months (Williams, 2005). In addition,
signs might include excessive salivation, behavioural alterations including a
fixed stare and changes in interaction with other animals in the herd, and an
altered stance (Williams, 2005). These signs are indistinguishable from cervids
experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB,
for example, infected deer populations would need to be tested to differentiate
if they were infected with CWD or BSE to minimise the risk of BSE entering the
human food-chain via affected venison.
snip...
The rate of transmission of CWD has been reported to be as high as 30% and
can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil
and surrounding environment is contaminated with CWD prions and in a
bioavailable form. In rural areas where CWD has not been reported and deer are
present, there is a greater than negligible risk the soil is contaminated with
CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving
between GB and North America, the probability of at least one person travelling
to/from a CWD affected area and, in doing so, contaminating their clothing,
footwear and/or equipment prior to arriving in GB is greater than negligible.
For deer hunters, specifically, the risk is likely to be greater given the
increased contact with deer and their environment. However, there is significant
uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher
probability of exposure to CWD transferred to the environment than wild deer
given the restricted habitat range and higher frequency of contact with tourists
and returning GB residents.
snip...
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
please note, I do not know how much of this 125 TONS of banned mad cow
protein was part of the ;
e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;
bbbut, this was about 10 years post mad cow feed ban from 1997. 10 years
later, and still feeding banned mad cow protein to cervids???
considering that .005 gram is lethal to several bovines, and we know that
the oral consumption of CWD tainted products is very efficient mode of
transmission of CWD.
Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125
TONS Products manufactured from 02/01/2005 until 06/06/2006
Date: August 6, 2006 at 6:16 pm PST
PRODUCT
a) CO-OP 32% Sinking Catfish, Recall # V-100-6;
b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall #
V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;
d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;
e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;
f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50
lb. bag, Recall # V-105-6;
g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%,
Recall # V-106-6;
h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to
20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall #
V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6;
j) CO-OP LAYING CRUMBLES, Recall # V-109-6;
k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall #
V-110-6;
l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;
m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6
CODE
Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER
Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email
and visit on June 9, 2006. FDA initiated recall is complete.
REASON
Animal and fish feeds which were possibly contaminated with ruminant based
protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE
125 tons
DISTRIBUTION
AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
Subject: bovine blood meal was cross-contaminated with prohibited bovine
meat and bone meal 1,366,128 lbs. WI, TX, NE, TN, CO, and MN FEBRUARY 7, 2007
PRODUCT
Bulk Darling's 85% Blood Meal, Flash Dried, distributed in totes and in
1-ton bags (for one customer only), Recall # V-012-2007
CODE
Blood meal distributed between 9/7/2006-2/3/2007.
RECALLING FIRM/MANUFACTURER
Darling National LLC, Omaha, NB, by telephone on January 12, 2007. Firm
initiated recall is ongoing.
REASON
Some of the exempt bovine blood meal was cross-contaminated with prohibited
bovine meat and bone meal that had been manufactured on common equipment and the
labeling did not bear the cautionary BSE statement that it should not be fed to
ruminants.
VOLUME OF PRODUCT IN COMMERCE
1,366,128 lbs.
DISTRIBUTION
WI, TX, NE, TN, CO, and MN
END OF ENFORCEMENT REPORT FOR FEBRUARY 7, 2007
###
PRODUCT
O-NO-MORE (Formerly ORPHAN-NO-MORE) Calf Claimer Powder, packaged in 11-oz.
bottles, For Animal Use Only. Recall # V-043-2007
CODE
A06
RECALLING FIRM/MANUFACTURER
Springer Magrath Co., Mc Cook, NE, by telephone on January 2, 2007, fax
dated January 9, 2007, by letters on February 22, 2007, March 12, March 14 and
March 21, 2007. Firm initiated recall is ongoing.
REASON
The finished product was manufactured with prohibited bovine blood meal and
did not bear the cautionary BSE statement that the product should not be fed to
ruminants.
VOLUME OF PRODUCT IN COMMERCE
Approximately 13,255 bottles
DISTRIBUTION
Nationwide
END OF ENFORCEMENT REPORT FOR JUNE 13, 2007 ###
2007
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
PRODUCT
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried,
Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross-
contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
___________________________________
PRODUCT
Custom dairy premix products:
MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX
Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL
PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST
PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN
Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J -
PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN,
BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT
Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with
commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm
initiated recall is complete.
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
Saturday, August 4, 2012
Final Feed Investigation Summary - California BSE Case - July 2012
Saturday, August 4, 2012
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
2012-2013
Wednesday, March 20, 2013
GAO-13-244, Mar 18, 2013 Dietary Supplements FDA May Have Opportunities to
Expand Its Use of Reported Health Problems to Oversee Product
From: Terry S. Singeltary Sr.
Sent: Tuesday, March 19, 2013 2:46 PM
To: gomezj@gao.gov
Cc: siggerudk@gao.gov ; youngc1@gao.gov ; oighotline@gao.gov
Wednesday, February 20, 2013
World Organization for Animal Health Recommends United States' BSE Risk
Status Be Upgraded
Statement from Agriculture Secretary Tom Vilsack:
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
Monday, March 25, 2013
Minnesota Firm Recalls Bone-In Ribeye That May Contain Specified Risk
Materials Recall Release CLASS II RECALL FSIS-RC-024-2013
look at the table and you'll see that as little as 1 mg (or 0.001 gm)
caused 7% (1 of 14) of the cows to come down with BSE;
Risk of oral infection with bovine spongiform encephalopathy agent in
primates
Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog,
Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie
Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe
Deslys Summary The uncertain extent of human exposure to bovine spongiform
encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease
(vCJD)--is compounded by incomplete knowledge about the efficiency of oral
infection and the magnitude of any bovine-to-human biological barrier to
transmission. We therefore investigated oral transmission of BSE to non-human
primates. We gave two macaques a 5 g oral dose of brain homogenate from a
BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months
after exposure, whereas the other remained free of disease at 76 months. On the
basis of these findings and data from other studies, we made a preliminary
estimate of the food exposure risk for man, which provides additional assurance
that existing public health measures can prevent transmission of BSE to man.
snip...
BSE bovine brain inoculum
100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg
Primate (oral route)* 1/2 (50%)
Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%)
1/15 (7%)
RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)
PrPres biochemical detection
The comparison is made on the basis of calibration of the bovine inoculum
used in our study with primates against a bovine brain inoculum with a similar
PrPres concentration that was inoculated into mice and cattle.8 *Data are number
of animals positive/number of animals surviving at the time of clinical onset of
disease in the first positive animal (%). The accuracy of bioassays is generally
judged to be about plus or minus 1 log. ic ip=intracerebral and
intraperitoneal.
Table 1: Comparison of transmission rates in primates and cattle infected
orally with similar BSE brain inocula
Published online January 27, 2005
Experimental BSE Infection of Non-human Primates: Efficacy of the Oral
Route
Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3;
Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6;
Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique,
France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious
Disease control, Sweden; 5Georg August University, Germany; 6German Primate
Center, Germany
Background: In 2001, a study was initiated in primates to assess the risk
for humans to contract BSE through contaminated food. For this purpose, BSE
brain was titrated in cynomolgus monkeys.
Aims: The primary objective is the determination of the minimal infectious
dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this,
to assess the risk for humans. Secondly, we aimed at examining the course of the
disease to identify possible biomarkers.
Methods: Groups with six monkeys each were orally dosed with lowering
amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration
study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005
mg).
Results: In an ongoing study, a considerable number of high-dosed macaques
already developed simian vCJD upon oral or intracerebral exposure or are at the
onset of the clinical phase. However, there are differences in the clinical
course between orally and intracerebrally infected animals that may influence
the detection of biomarkers.
Conclusions: Simian vCJD can be easily triggered in cynomolgus monkeys on
the oral route using less than 5 g BSE brain homogenate. The difference in the
incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus
4 years). However, there are rapid progressors among orally dosed monkeys that
develop simian vCJD as fast as intracerebrally inoculated animals.
The work referenced was performed in partial fulfilment of the study “BSE
in primates“ supported by the EU (QLK1-2002-01096).
Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route
using less than 5 g BSE brain homogenate.
It is clear that the designing scientists must also have shared Mr Bradleys
surprise at the results because all the dose levels right down to 1 gram
triggered infection.
it is clear that the designing scientists must have also shared Mr
Bradleyâs surprise at the results because all the dose levels right down to 1
gram triggered infection.
Prion 7:2, 99–108; March/April 2013; © 2013 Landes Bioscience
mini-Rev iew Mini-REVIEW
A closer look at prion strains
Characterization and important implications
Laura Solforosi,†,* Michela Milani,† Nicasio Mancini, Massimo Clementi and
Roberto Burioni
Laboratory of Microbiology and Virology; University Vita-Salute San
Raffaele; Milan, Italy
†These authors contributed equally to this work.
Keywords: cellular prion protein (PrPC), scrapie prion protein (PrPSc),
transmissible spongiform encephalopathies (TSEs), prion strains, strain
mutation, variant Creutzfeldt-Jakob disease, sporadic Creutzfeldt-Jakob
disease
Abbreviations: PrPC, cellular prion protein; PrPSc, scrapie prion protein;
TSEs, transmissible spongiform encephalopathies; TME, transmissible mink
encephalopathy; CJD, Creutzfeldt-Jakob disease; sCJD, sporadic CJD; vCJD,
variant CJD; FFI, fatal familial insomnia; BSE, bovine spongiform
encephalopathy; CWD, chronic wasting disease; PK, proteinase K; SAF,
scrapie-associated fibrils; CNS, central nervous system; WB, western blot; PE,
phosphatidylethanolamine; sPMCA, serial protein misfolding cyclic amplification;
CPA, cell panel assay
Prions are infectious proteins that are responsible for transmissible
spongiform encephalopathies (TSEs) and consist primarily of scrapie prion
protein (PrPSc), a pathogenic isoform of the host-encoded cellular prion protein
(PrPC). The absence of nucleic acids as essential components of the infectious
prions is the most striking feature associated to these diseases. Additionally,
different prion strains have been isolated from animal diseases despite the lack
of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific
features segregate with different PrPSc conformational and aggregation states.
Strains are of practical relevance in prion diseases as they can
drastically differ in many aspects, such as incubation period, PrPSc biochemical
profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of
brain lesions. Importantly, such different features are maintained after
inoculation of a prion strain into genetically identical hosts and are
relatively stable across serial passages.
This review focuses on the characterization of prion strains and on the
wide range of important implications that the study of prion strains involves.
Introduction
Transmissible spongiform encephalopathies (TSEs) or prion diseases, such as
Creutzfeldt-Jakob disease (CJD) in human, bovine spongiform encephalopathy (BSE)
in cattle, chronic wasting disease (CWD) in cervids and scrapie in sheep, are a
group of fatal neurodegenerative disorders. The major neuropathological
hallmarks of TSEs are extensive spongiosis, neuronal cell loss in the central
nervous system, gliosis,1 and deposition of amyloid plaques.2
*Correspondence to: Laura Solforosi; Email: solforosi.laura@hsr.it
Submitted: 08/13/12; Revised: 12/20/12; Accepted: 01/03/13 http://dx.doi.org/10.4161/pri.23490
Prions are infectious proteins that are responsible for transmissible
spongiform encephalopathies (TSEs) and consist primarily of scrapie prion
protein (PrPSc), a pathogenic isoform of the host-encoded cellular prion protein
(PrPC). The absence of nucleic acids as essential components of the infectious
prions is the most striking feature associated to these diseases. Additionally,
different prion strains have been isolated from animal diseases despite the lack
of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific
features segregate with different PrPSc conformational and aggregation states.
Strains are of practical relevance in prion diseases as they can
drastically differ in many aspects, such as incubation period, PrPSc biochemical
profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of
brain lesions. Importantly, such different features are maintained after
inoculation of a prion strain into genetically identical hosts and are
relatively stable across serial passages.
This review focuses on the characterization of prion strains and on the
wide range of important implications that the study of prion strains involves.
...
snip...
This classification arises from the hypothesis that if the polymorphism 129
can modulate the phenotype of the familial prion diseases (fCJD and FFI, as
explained earlier in this review), then probably it can modulate also that of
sporadic prion diseases, justifying their heterogeneity. According to this
hypothesis, the cases affected by sCJD were divided into six groups according to
the genotype of the polymorphism in position 129 and the type of PrPSc. Then,
the phenotypes of every group were analyzed to evaluate the homogeneity within
every group. The results have permitted a molecular sub-classification of the
sCJD.90,91 However, this classification seems not to be sufficient to explain
the complexity of the sporadic form of CJD. In fact, in some molecular subtypes,
additional variants have been reported, such as MM or VV patients with amyloid
plaques, which are absent in the majority of patients with these genotypes.44
Moreover, among patients belonging to the same subgroup, important phenotypic
differences can be found, such as, for instance, the extent of neuronal loss or
PrPSc deposition differences.92
Even at the biochemical level the complexity is higher: indeed, aside from
the migratory differences of the PrPSc of types 1 and 2, there are other
properties that could be important during the propagation of the strain, like
the presence of other fragments derived from differential cleavage at the C- and
N-terminus of the protein, which probably coincide with the presence of other
forms of PrPSc with different resistance to PK digestion.44 All these molecular
classifications are based upon the principle that in all CNS districts the type
of PrPSc is the same, but there are pieces of evidence pointing to the fact that
different types of PrPSc can be found in different brain areas.64,93 The first
evidence of the presence of more than one form of PrPSc in the brain of a sCJD
patient was reported by Puoti in 1999.94 These different types of PrPSc can be
found to coexist in the same brain region or they can infect distinct districts.
Such co-infection influences the vacuolization and the amyloid aggregates
formation.95 Even the ratio between the different glycoforms is determined in a
regionspecific manner according to the type of PrPSc (1 or 2) and the genotype
of codon 129.
The high degree of phenotypic heterogeneity characterizing sCJD90 can lead
to the conclusion that transmission studies will probably identify a broad panel
of different prions with a great divergence between strains. However, quite
surprisingly, many of the recent studies focusing on the characterization of
sCJD subtypes have shown that there is a strong tendency to converge to a
limited number of strains. This aspect can find an explanation considering the
selection conditions, already described in this review, mediated by the
environment in which the prion replicates and by the differences in the amino
acid sequence of the PrPC. In particular, studies with bank voles96 and mice97
lead to results that support the idea that there are two principal strains
responsible of the sCJD, M1 and V2, and two potential strains, M2 and V1, which
need further studies to be confirmed.
Different is the case of vCJD. vCJD has been observed in 12 different
countries, but in every registered case the same clinical and pathological
characteristics have been found.39 In particular, the PrPSc responsible of the
vCJD shows a peculiar WB profile, with the unglycosylated form of the
protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the
diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using
specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a
high percentage of diglycosilated form can be detected in association with PrPSc
2B.98 The 2B type is a useful marker for identifying the replication of BSE
prions also in other species, including non-human primates.99 In addition,
unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type)
has been found in all the analyzed brain areas.100 This strong biochemical and
pathological homogeneity is in agreement with the hypothesis of the existence of
a unique strain. However, unexpectedly, typization experiments of the strains in
different transgenic models have given divergent results. In one of these
studies, in a context of homotropic transmission, transgenic mice expressing
high levels of human PrPC-M129 were inoculated with vCJD isolates coming from
France and from the UK.101 All of the French isolates propagated as vCJD, with
abundant amyloid plaques and presence of PrPSc 2B.102 Instead, the isolates from
the UK led to the propagation of either vCJD or sCJD.103 In particular, the
incubation time was shorter and the lesion profile was different compared with
the one obtained with the propagation of the classical vCJD strain. Moreover,
early replication of the typical agent of the vCJD in lymphoid tissues was
detected, indicating that both strains were present in the inoculum.
This new strain with phenotypical features that were similar to sCJD was
found to be of type 1 and the transmission in transgenic mice expressing the
bovine PrPC failed, unlike the vCJD classical strain (Type 2B).26 The idea that
the infection of vCJD contains a minor component of sCJD prions is supported by
many pieces of evidence such as the presence of this prion strain at the first
passage or the persistence of both types of PrPSc through serial passages in
mice.98 In conclusion, although vCJD is one of the most standardized phenotypes
among the prion human diseases characterized by a typical form of PrPSc, the
transmission studies of vCJD have shown the great potential of divergence of
prions, contrary to the results obtained from the studies of sCJD. This data
challenge our ability to recognize the pathologies that can derive from the
divergence of the BSE strains when they infect humans, both at the pathological
and at the biochemical level.
Conclusion
The discovery of prions has led to new interpretations of the pathogenetic
mechanism of protein misfolding diseases. Indeed, the common thought was that a
protein misfolding disease could only be caused by a mutation in the primary
sequence of an endogenous protein, but the discovery of prions changed this
view. In fact, it was demonstrated that a seed of misfolded protein can arise
from an exogenous infectious protein, which is able to act as a template or as a
catalyst for the formation of new aberrant protein.5,6 Importantly, new evidence
shows how processes similar to those described for prions could be implicated in
the propagation of misfolded proteins of other neurodegenerative pathologies
like Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic
lateral sclerosis.104,105
Certainly, one of the most puzzling aspects in the prion field is the
existence of different strains of an infectious protein. Nevertheless, such
diversity can be accommodated within the protein-only hypothesis, as several
robust pieces of experimental evidence indicate that strain-specificity is
encoded at the level of the different conformations that the pathogenic protein
can adopt. The identification of factors and mechanisms influencing the
generation of new prion strains or the selection, from a conformationally
heterogeneous PrPSc population, of the most suitable prion conformation in a
specific environment, represents an important milestone toward the understanding
of the mechanisms of prion strain diversity, which can have fundamental clinical
and therapeutic implications. Although considerable advances have been made in
the understanding of the phenomenon of prion strains, many pieces of information
are still missing, foremost among them the definitive evidence for the
structural nature of the differences between prion strains.
Thursday, February 21, 2013
National Prion Disease Pathology Surveillance Center Cases Examined January
16, 2013
16 YEAR OLD SPORADIC FFI ?
Monday, January 14, 2013
Gambetti et al USA Prion Unit change another highly suspect USA mad cow
victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes
along with this BSe
Monday, December 31, 2012
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State,
2006–2011-2012
Tuesday, December 25, 2012
CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25,
2012
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
Wednesday, June 13, 2012
MEXICO IS UNDER or MIS DIAGNOSING CREUTZFELDT JAKOB DISEASE AND OTHER PRION
DISEASE SOME WITH POSSIBLE nvCJD
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission
until now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
*** atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011
San Antonio, Texas
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
TSS
