TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption - Scientific Opinion of the Panel on Biological Hazards Question number: EFSA-Q-2007-202
Adopted date: 05/06/2008 Summary (0.1Mb)
Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different ages in young lambs and kids and of the weights of lymphoid tissue entering the food chain.
Publication date: 15/07/2008
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008 SUMMARY Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: • A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). • There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. • In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. Summary of opinion The EFSA Journal (2008) 719, 2-2 • The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. • Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. • In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption 1 Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008
1. General conclusions: • Lambs and kids from TSE affected flocks in the form of classical scrapie have a clearly higher probability of infection than those from the general population. In the general EU sheep population TSE prevalence at animal level is estimated to be about 0.1 %. In classical scrapie affected sheep flocks the reported prevalence vary from 3% to 41%. • In susceptible lambs (VRQ/VRQ), infectivity will replicate in lymphoid tissues from birth and involve most secondary lymphoid formations before 4 months old. • In worst cases, infectivity in lymphoid organs reaches its maximal level before 6 months old. This maximal level infectivity in lymphoid organs (per mass unit) can be estimated to be about 1/50 of the infectivity found in obex from a terminally affected ewe. • According to currently available data, carcasses of animals of less than two months of age, providing that the head and the thoracic and abdominal viscera are removed, do not contain detectable PrPres but this does not exclude the possibility of infectivity.
APPENDIX II. FURTHER DATA RELEVANT TO THE TIMING AND SPREAD OF INFECTION IN VRQ/VRQ LAMBS
a. Colostrum/Milk as a potential source of infectivity. Qualitative TSE risk assessments of the safety of milk from sheep and goats have been made in the past, but little published data have been available. Konold and colleagues have recently published a study of the transmission of scrapie from scrapie-affected dams to lambs by feeding from birth milk (and colostrum) taken during the later stages of scrapie-infection in the dams (Konold et al., 2008). Evidence of infection was detected as early as 44-46 days in the distal ileum of two lambs by immunohistochemistry for abnormal PrP (PrPres) and widespread infection inferred by RAMALT6 testing by 190-210 days of age. Both donor ewes and lambs were of the susceptible VRQ/VRQ genotype and the donor ewes were sourced from a flock with a ~ 10% prevalence of natural infection. This is directly relevant to the consideration of “a worst case scenario” and confirms previous work indicating lambs can become infected very soon after birth and that, within 6-7 months, the infection can be widely disseminated, at least in lymphoid tissue, in the susceptible animal.
b. The role of blood in spreading the agent within the body. One of the critical scientific uncertainties (for any naturally occurring TSE in any species) is that related to the possibility of infectivity in blood. Information on the incubation stage(s) wherein this happens is meagre and it is not yet known if this is an inconsistent chance event or an important way in which the pathogen spreads within the body. The data published by Houston et al. (2000) and Hunter et al. (2002) showed that a high volume blood transfusion from sheep to sheep can transmit BSE as well as scrapie within the same species. With both diseases, infectivity could also be transmitted using blood taken during the asymptomatic incubation period of the disease in the donor sheep. In the specific context of this mandate, Andreoletti and co-workers have reported infectivity in blood of pre-clinical VRQ/VRQ lambs at 3 months of age (Andreoletti et al., Neuroprion Edinburgh 2007).
c. Intestine: the anatomical location where infectivity is first detected. PrPres in the digestive tract has been described in sheep exposed to natural scrapie (van Keulen et al., 1999; Andreoletti et al., 2000). Most of the data available were obtained in natural scrapie and the prion protein genotype of the sheep is a critical factor in the uptake and dissemination of the agents of BSE and scrapie in the gut of the sheep. In VRQ/VRQ sheep exposed to natural scrapie infection, PrPres can be detected in ileal Peyer’s patches (PP) from 21 days post-partum and in other PP’s of the alimentary canal and in the tonsil of the lamb by 60 days of age. In similar conditions, PrPres is detectable in the enteric nervous system (ENS) at 7 months old, almost three months prior to its first detection in the obex (Andreoletti et al., 2000). Hence, during surveillance, screening the obex using rapid testing for PrPres is a poor indicator for the absence of TSE infection in the digestive tract of the lamb. 6 RAMALT stands for recto-anal mucosal associated lymphoid tissue.
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OPINION ON SAFE SOURCING OF SMALL RUMINANT MATERIALS (SAFE SOURCING OF SMALL RUMINANT MATERIALS SHOULD BSE IN SMALL RUMINANTS BECOME PROBABLE: GENOTYPE, BREEDING, RAPID TSE TESTING, FLOCKS CERTIFICATION AND SPECIFIED RISK MATERIALS) ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 4-5 APRIL 2002
III.1.2. As for BSE in sheep, research data are available for only a few tens of animals: - Results to date indicate that the relation between sheep genotype and susceptibility to a TSE is similar for scrapie and BSE: the ARR genotypes are apparently resistant to development of clinical disease on challenge with BSE and animals carrying the glutamine (Q) allele at codon 171 are potentially susceptible to BSE and to scrapie. The influence of the genotype at codon 136 and 154 is not yet known for BSE but is being tested by direct challenge studies at IAH, UK. - New research data summarised in EC (2002) are consistent with the previously expressed view that BSE in sheep after oral exposure is pathogenetically closely similar to scrapie, particularly with respect to the tissue distribution of infectivity and/or PrPSc.
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ISSUE All Member States are required to produce a contingency plan in the event BSE were found in sheep.
The UK is currently finalising its detailed plan, for submission to the Commission this summer. The European Commission has recently produced guidelines for Member States on the points which should be considered in drawing up their contingency plans. (Annex 1). The guidelines suggest that Member States should consider a worst case scenario where sheep meat is excluded from the food chain. This is based on an opinion, adopted by the Scientific Steering Committee (SSC) in April 2002, entitled “Safe sourcing of small ruminant materials” (Annex 2). The SSC Opinion states that if BSE were found in sheep, then only the following animals should be allowed into the food chain: • ARR homozygous sheep under the age of 18 months • ARR heterozygous sheep under the age of 6 months. • Sheep (and goat) milk, colostrum and milk products from suspect BSE cases should be excluded from the food chain. The EC guidelines (SANCO/19/2003 Rev.2) state a worst case scenario where: • small ruminant meat is excluded from the food chain unless derived from: - homozygous ARR sheep under the age of 18 months - heterozygous sheep under the age of 6 months • sheep and goat milk is excluded from the food and feed chain: - completely, or - unless derived from sheep carrying at least one ARR allele, or - unless derived from holdings certified TSE resistant or TSE free on the basis of solid criteria. They should also make an inventory of their capacity in terms of genotyping, individual identification and registration of animals, TSE testing and in terms of flock certification on the basis of history, monitoring etc.
CONFIDENTIAL PAPER No: SEAC 78/9 Amendment 2 2 In March 2002, a SEAC Sub-Group considered the risks associated with certain genotypes entering the food chain if BSE were ever isolated from sheep. In contrast to the SSC opinion, SEAC concluded that: • In line with previous SEAC advice, only animals carrying the ARR allele should enter the food chain • On a precautionary basis, the 12 month cut off previously advised by SEAC remained appropriate for ARR heterozygotes. However, in view of existing SRM regulations there was no justification for any age cut off in ARR homozygotes • In line with SEAC advice in 2001, only milk from ARR homozygous sheep could be considered as highly unlikely to contain the infectious agent. Further experimental work was required before potential risks from small ruminant milk from goats and semi-resistant or susceptible sheep could be excluded. There is therefore a disparity of opinion between the SSC and SEAC on this issue. Whilst recognising the uncertainties relating to the science in this area, it is important that contingency planning is based on the most up to date scientific developments and assessments of risk that are available. SEAC will be presented with an update on the ongoing BSE in sheep studies, funded by Defra (Annex 31). This covering paper also provides a history of previous SEAC advice on this issue. BACKGROUND...snip...end
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
A The Present Position with respect to Scrapie The Problem
Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it is fatal. It is enzootic in the United Kingdom but not in all countries.
The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.
It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE
This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........
Like lambs to the slaughter
31 March 2001 Debora MacKenzie Magazine issue 2284
What if you can catch old-fashioned CJD by eating meat from a sheep infectedwith scrapie?FOUR years ago, Terry Singeltary watched his mother die horribly from adegenerative brain disease. Doctors told him it was Alzheimer's, butSingeltary was suspicious. The diagnosis didn't fit her violent symptoms,and he demanded an autopsy. It showed she had died of sporadicCreutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming bychance into a killer. But Singeltary thinks otherwise. He is one of a numberof campaigners who say that some sCJD, like the variant CJD related to BSE,is caused by eating meat from infected animals. Their suspicions havefocused on sheep carrying scrapie, a BSE-like disease that is widespread inflocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weightto the campaigners' fears. To their complete surprise, the researchers foundthat one strain of scrapie causes the same brain damage in ...
The complete article is 889 words long.
Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob disease: Implications for human health
Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*,Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, JamesIronside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys** Commissariat à l'Energie Atomique, Service de Neurovirologie, Directiondes Sciences du Vivant/Département de Recherche Medicale, Centre deRecherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc,BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique PierreWertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire deNeuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital,75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, WesternGeneral Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; andInstitute for Animal Health, Neuropathogenesis Unit, West Mains Road,Edinburgh EH9 3JF, United Kingdom
Edited by D. Carleton Gajdusek, Centre National de la RechercheScientifique, Gif-sur-Yvette, France, and approved December 7, 2000(received for review October 16, 2000)
There is substantial scientific evidence to support the notion that bovinespongiform encephalopathy (BSE) has contaminated human beings, causingvariant Creutzfeldt-Jakob disease (vCJD). This disease has raised concernsabout the possibility of an iatrogenic secondary transmission to humans,because the biological properties of the primate-adapted BSE agent areunknown. We show that (i) BSE can be transmitted from primate to primate byintravenous route in 25 months, and (ii) an iatrogenic transmission of vCJDto humans could be readily recognized pathologically, whether it occurs bythe central or peripheral route. Strain typing in mice demonstrates that theBSE agent adapts to macaques in the same way as it does to humans andconfirms that the BSE agent is responsible for vCJD not only in the UnitedKingdom but also in France. The agent responsible for French iatrogenicgrowth hormone-linked CJD taken as a control is very different from vCJD butis similar to that found in one case of sporadic CJD and one sheep scrapieisolate. These data will be key in identifying the origin of human cases ofprion disease, including accidental vCJD transmission, and could providebases for vCJD risk assessment.
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Saturday, December 08, 2007 SCRAPIE HB Parry Seriously’ (YB88/6.8/4.1)
HB Parry Seriously’ (YB88/6.8/4.1)
IF the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease.
1: Neuroepidemiology. 1985;4(4):240-9.
Sheep consumption: a possible source of spongiform encephalopathy in humans.
Davanipour Z, Alter M, Sobel E, Callahan M.
A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania.
Scrapie has been transmitted in our laboratory to five species of monkeys (Tables 9 and 10) (23, 31, 32), and such transmission has occurred using infected brain from naturally infected sheep and from experimentally infected goats and mice (Figures 22a, b, c). The disease produced is clinically and pathologically indistinguishable from experimental CJD in these species. .........
22b. Primary transmission of goat-adapted scrapie (Compton, England strain) to the squirrel monkey and to mice and the transmission of mouse-adapted scrapie to two species of Old World and three species of New World monkeys. Numbers in parentheses are the number of months elapsed since inoculation, during which the animal remained asymptomatic.
22c. Transmission of mouse-adapted sheep scrapie (U. S. strain 434-3-897) to a squirrel monkey 38 months following intracerebral inoculation with a suspension of scrapie-infected mouse brain containing 10a7.3 infectious units of virus per ml. This animal showed signs of ataxia, tremors and incoordination, and the disease was confirmed histologically. See (b) for an explanation of symbols.
Figure 23. Transmissible mink encephalopathy (TME), a rare disease of American ranch mink, is possibly a form of scrapie. The clinical picture and histopathological lesions attendant in the brain, resemble that of scrapie, and scrapie sheep carcasses were fed to mink on ranches on which TME appeared. The disease is transmissible to sheep, goats, certain rodents and New and Old World monkeys. Illustrative data on the primary transmissions of transmissible mink encephalopathy to one species of New World monkey and two species of Old World monkeys, and serial passage of the virus in squirrel, rhesus and stumptailed monkeys are presented in this Figure. Incubation periods are shown in months that elapsed between inoculation and onset of clinical disease. (Figure includes information from our laboratory and from R. F. Marsh, R. J. Eckroade, and R. P. Hanson.)
UNCONVENTIONAL VIRUSES AND THE ORIGIN
AND DISAPPEARANCE OF KURU
Nobel Lecture, December 13, 1976
by D. CARLETON GAJDUSEK
National Institutes of Health, Bethesda, Maryland, U.S.A.
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Monday, December 24, 2007 Pathogenesis of bovine spongiform encephalopathy in sheep
Friday, February 15, 2008 SCRAPIE and TSE to human UPDATE 2008 (ambiguous terms of transition and reality set in)
2. In relation to conclusion 2 in page 7 the Authority is invited to specify the scientific evidences which do not allow to exclude transmissibility to humans of “other TSE agents” other than BSE. Conclusion 2 in page 7 of the EFSA 2007 opinion states that: “The BSE agent is the only TSE agent identified as zoonotic. However, in view of their diversity it is currently not possible to exclude transmissibility to humans of other animal TSE agents.”
In the EFSA 2007 opinion under 3.2.3. the Panel states that:
• “There are significant uncertainties associated with the question whether TSE agents in their whole spectrum may cross the human transmission barrier under natural conditions”.
This statement is supported both by scientific evidence and considerations, referenced in the EFSA 2007 opinion:
• Scientific evidence from transmission studies to primates: - Transmission of Classical Scrapie from a TSE agent adapted in hamster was demonstrated by oral challenge in squirrel monkey (Saimiri sciureus) (Gibbs et al., 1980);
- Transmission of Classical Scrapie from two distinct sheep sources by intracerebral challenge in cynomologus monkey (Macaca fascicularis) and marmoset monkey (Callithrix jacchus) (Gibbs and Gajdusek, 1972; Baker et al., 1988).
• Scientific considerations on TSE epidemiology: - “The assumed lack of association between TSEs in humans and those in small ruminants […] may be biased by a number of factors: (i) The lack of a data on the historical real prevalence and distribution of small ruminant TSEs, at a time where only passive surveillance was performed; (ii) the lack of understanding of the true biodiversity of TSEs in small ruminants in terms of both Classical and Atypical agents; (iii) the lack of understanding of the diversity of TSEs in humans due to the limited molecular and bioassay characterisation of human TSEs also in relation to the number and spectrum of neurodegenerative diseases of humans; (iv) the predicted phenotype of disease that might arise should an animal derived TSE transmit to humans.” The EFSA Journal (2008) 626, 5-11
Further evidence is provided by:
• In vitro conversion assays: Raymond et al. (1997) studied whether there is a correlation between in vitro conversion efficiencies and known transmissibility of BSE, sheep Scrapie and CJD, and found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both Scrapie (PrPSc) and BSE (PrPBSE). They concluded that “the inherent ability of these infectious agents of BSE and Scrapie to affect humans following equivalent exposure may be finite but similarly low”. Nevertheless, uncertainty arises from the fact that this is a simple in vitro model of a complex in vivo situation.
• Laboratory transmission studies with animal models: Since the publication of the Opinion new data have become available with regards to L type of BSE, which has now been identified in various EU members states (Biacabe et al., 2004; Casalone et al., 2004; Baron et al., 2007). This TSE agent, differing from that causing Classical BSE by its biochemical signature and transmission features in mouse models, has been transmitted to a Tg mouse model expressing Human M129 PRP gene (Beringue et al. 2007)2. Here again, uncertainty arises from the limitations of these animal models for the estimation of the human species barrier. These ‘proof of principle’ experiments provide data supporting the ability of TSE agents other than those causing Classical BSE to cross the human species barrier.
Even so, it is important to remember that as mentioned in the EFSA 2007 opinion, transmission to primates:
• “… does not allow to take into account the human gene PRNP polymorphisms (in particular the M/V 129), that have been identified to play a major role on relative susceptibility towards prion disease. In addition, genes other than the PrP gene may also be influential in determining overall susceptibility to TSEs.” Despite the interests in the area, studies of the transmissibility of currently known TSE agents using animal models will remain incomplete for several years.
In conclusion, the reply to the ToR number 2 is:
• Experimental transmissions to primate and to transgenic (Tg) mouse models expressing the human PrP gene, are currently used as to evaluate the potential capacity of a TSE agent to cross the human species barrier.
• TSE agents other than the Classical BSE agent from three field TSE cases (two Classical Scrapie cases and one L type BSE case) have been demonstrated to cross the modelled human species barrier.
• Some limitations to these models have to be considered, which include:
(i) The uncertainty of how well they represent the human species barrier. (ii) The uncertainty of how well the experimental inoculation route employed represents exposure under natural conditions. 2 Transmission of this TSE agent by intracerebral challenge to primates (Macaques) has been reported by Comoy et al. at the 2006 Prion Congress held in Torino. A scientific paper reporting this finding has been submitted for peer review publication. The EFSA Journal (2008) 626, 6-11
EFSA 2005. Opinion of the Scientific Panel on Biological Hazards on the request from the European Commission on classification of Atypical Transmissible Spongiform Encephalopathy (TSE) cases in small ruminants. The EFSA Journal 276: 1-30.
The EFSA Journal (2008) 626, 11-11
EFSA 2007. Opinion of the Scientific Panel on Biological Hazards on a request from the European Commission on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal 466: 1-10.
Date: September 26, 2007 at 4:06 pm PST
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway
Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. *** The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
Saturday, April 12, 2008 Evidence of scrapie transmission via milk
Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)
Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
In FY 2007, 331 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), including 59* Regulatory Scrapie Slaughter Surveillance (RSSS) cases (Figure 5 and Slide 16). In FY 2007, two field cases, one validation case, and two RSSS cases were consistent with Nor-98 scrapie. The Nor98-like cases originated from flocks in California, Minnesota, Colorado, Wyoming and Indiana respectively. Nineteen cases of scrapie in goats have been reported since 1990 (Figure 6). The last goat case was reported in September 2007.
see full report here ;
now, confusious is confused again. why do some countries have their TSE reported on the OIE weekly listing of disease on the OIE website, but others like the USA, do not $$$
case in point ;
Information received on 16/07/2008 from Mr Carlos Agrela Pinheiro, Chief Veterinary Officer, Director General, Direcçao-Geral de Veterinária, Ministério da Agricultura, LISBONNE, Portugal
Wednesday, June 11, 2008
OIE Recognition of the BSE Status of Members RESOLUTION No. XXI (Adopted by the International Committee of the OIE on 27 May 2008)
1. Adoption of subsequent Resolutions* since the 67th General Session of the OIE International Committee has established a procedure for annually updating a list of Members, categorised by their BSE risk according to the provisions of theTerrestrial Code,
2. During the 70th General Session, the International Committee adopted Resolution No. XVIII asking Members applying for a BSE risk evaluation to meet part of the costs sustained by the OIE Central Bureau in the evaluation process,
3. During the 72nd General Session, the OIE adopted Resolution No. XXI requesting the Director General to inform Delegates of Members whose country or zones are recognised with regard to their BSE risk status should annually confirm during the month of November whether their risk status and the criteria by which their status was recognised have remained unchanged,
4. Information published by the OIE is derived from declarations made by the official Veterinary Services of Members. The OIE is not responsible for inaccurate publication of a Member disease status based on inaccurate information, changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau, subsequent to the time of declaration of the BSE risk status.
1. The Director General publish the following list of Members recognised as having a negligible BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:
Australia, Argentina, Finland, Iceland, New Zealand, Norway, Paraguay, Singapore, Sweden and Uruguay.
2. The Director General publish the following list of Members recognised as having a controlled BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:
Austria Belgium Brazil Canada Chile Chinese Taipei Cyprus Czech Republic Denmark Estonia France Germany Greece Hungary Ireland Italy Latvia Lichtenstein Lithuania Luxembourg Malta Mexico Netherlands Poland Portugal Slovak Republic Slovenia Spain Switzerland United Kingdom United States of America
3. The Delegates of these Members will immediately notify the Central Bureau if BSE occurs in their countries or their territories.
(Adopted by the International Committee of the OIE on 27 May 2008)
* 67th General Session (GS) Resolution No (Res) XVI and Res XI; 69th GS Res XV, and 71st GS Res XXII, 72nd GS Res XXIV and Res XXI..
IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,
snip...SEE FULL TEXT with facts and sources @ ;
BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA
Attachment to Singeltary comment
January 28, 2007
I would kindly like to submit the following to ;
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01
[Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST
bottom line, you don't look, you dont find, you don't report, you dont have, thus, you have this imaginary classification called the BSE MRR 'CONTROLLED RISK' ;-)
THE REALITY IS ;
EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA)
Summary of the Scientific Report
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90's when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.
Wednesday, July 16, 2008
Implementation of 2008 Feed Ban Enhancements Questions and Answers July 15, 2008
Thursday, July 10, 2008
A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
SEAC Draft minutes of the 100th meeting held on 25th April 2008
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
Wednesday, July 16, 2008 Prevalence of the prion protein gene E211K variant in U.S. cattle Research Project:
Haplotype Structure of the Bovine Prion Gene Complex and Association with Bovine Spongiform Encephalopathy (Bse) Location: Animal Health Systems Research
Title: Prevalence of the prion gene E211K variant in U.S. cattle
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518