TAFS1 STATEMENT ON TRANSMISSION OF SCRAPIE VIA MILK (January, 2009)
TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
(January, 2009)
TAFS1 STATEMENT ON TRANSMISSION OF SCRAPIE VIA MILK
Introduction In April 2008, TAFS published a statement on the transmission of scrapie via milk, prompted by the publication of results that provided strong evidence of transmission of scrapie to lambs by the feeding of milk from scrapie-infected ewes(4). More recently, another publication has further clarified the mechanisms of transmission(5), and together the results have enabled a review of the implications by the European Food Safety Authority(3), and prompted initial regulatory action by the European Commission. This statement represents a revision of the TAFS statement to take into account the recent data and interpretation.
TAFS welcomes publication of these findings. They contribute to the understanding of the mechanisms of transmission of scrapie as a prion disease of sheep and goats that has been known for over 200 years. Scrapie is not a highly contagious disease. It does not spread easily, but it is difficult to eradicate. It is known to spread between sheep, both from ewe to lamb and to other unrelated sheep and goats. The exact route of transmission has not been determined so far. There are several possible routes, which include contact with placenta of infected ewes, or possibly before birth while the lamb is still in the womb. Transmission via milk and/or uterine fluids after birth are additional possibilities. Ewe to lamb transmission(4) This study attempted to assess the scope for transmission, under a worst-case scenario, by collecting milk from sheep of highly susceptible genetic makeup (high risk group), at a time when they were either about to die of scrapie, or when the first clinical signs were seen. Their milk was collected and fed to lambs that were born to uninfected mothers and kept in isolation while they received the milk. These lambs were also of the most susceptible genotype (VRQ/VRQ).
The lambs have been shown to be infected by the testing of tissue samples collected either while still alive, by biopsy, or from some that had died of other diseases. None have yet reached the point of clinical disease themselves, and infectivity itself has not been demonstrated. Tests have revealed the
1 TAFS is an international platform created by a group of scientists, food industry experts, animal health regulators, epidemiologists, diagnosticians, food producers, and consumers. Its purpose is to establish and maintain lines of communication for the dissemination of reliable information to the public that can maintain confidence in the safety of food with regard to Transmissible Animal Diseases.
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presence of abnormal prion protein (PrPSc) that is normally recognised as a marker for the presence of infectivity. The success of the study was dependent on having scrapie-free lambs to receive the milk. Despite having fully susceptible ewes and susceptible lambs, the ease with which the lambs were infected is a surprise. The experimental design anticipated transmission to smaller numbers of lambs. For this reason lambs received both milk and colostrum (the milk produced within the first 24-48 hours after lambing) from the same ewe in order to maximise the likelihood of transmission. As a result, the authors could not conclude whether transmission occurred via colostrum, milk or both. The study will therefore now be repeated, feeding lambs with either colostrum or milk. This is important for several reasons.
* Firstly, colostrum would not be used for human consumption.
* Secondly, colostrum is rich in protein and antibodies that help to protect the lamb in the early days of life before its own immune system is fully developed. For that reason farmers sometimes collect and freeze colostrum to feed to other lambs, sometimes pooling it to feed to several lambs. This practice could increase the potential for infection of lambs at their most vulnerable time of life.
Although the study described below confirms the presence of infectivity in colostrum, it is necessary to establish the status of colostrum from sheep that are unaffected by other pathogens. In other words, the result should be dependent solely on the presence of scrapie in an otherwise healthy sheep. Ewe to mouse transmission(5) This study also made use of a naturally infected experimental flock of sheep in France, but differed from the previous study in that the flock was infected with both scrapie and Maedi-Visna (MV). MV is a viral disease, that has previously been shown to potentially predispose to the transmission of scrapie via milk(6). It causes a form of mastitis (lympho-proliferative chronic mastitis) that particularly involves the formation of discrete ectopic lymphoid follicles in the mammary tissue. These have previously been shown to stain heavily for abnormal prion protein(9) in scrapie infected sheep(6). In the French study, the researchers compensated for some of the difficulties normally presented by mouse inoculation studies, of not being able to inoculate sufficient material into a mouse to guarantee transmission, by concentrating their starting material (colostrum and milk). In addition, they used highly sensitive mice (Tg338)(7), that were genetically modified to produce sheep prion protein of the VRQ genotype(10). The study was supported by post-mortem examination of many sheep for the presence of abnormal PrP in the udder, and for the presence or absence of mastitis. Although the biological assay study has not been completed, it has reached a point where it is possible to conclude conclusively that particular fractions of milk are infectious. Preliminary findings include:
* Abnormal PrP was only detected in ewes that harboured ectopic lymphoid follicles, and correlated with the detection of abnormal PrP in other peripheral lymph nodes. This therefore limited the positivity to sheep with the most susceptible genotypes that are predisposed to peripheral infection (VRQ/VRQ; VRQ/ARQ; ARQ/ARQ).
* In addition, abnormal PrP was detected in lacteal ducts and mammary acini suggesting a high probability that it would be excreted in milk/colostrum.
* Nevertheless, infectivity studies detected scrapie infectivity in both colostrum (collected within 12 hours of lambing) and milk (collected 20 days after lambing). The infectivity was associated with cellular, cream and casein-whey fractions.
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* Most critically, infectivity was even detected in fractions derived from sheep in which there was no visible clinical or pathological evidence of mastitic lesions.
* In all samples, preliminary estimations suggest that infectivity levels are very low, but potentially higher in mastitic milk or colostrum than from healthy udders.
EFSA BioHazards Panel Opinion(3) The findings summarised above were supported by EFSA, but the BioHazards panel stressed that in both studies conditions had been maximised to facilitate detection of infectivity. In other words, they were worst-case scenarios, and may not be fully representative of natural infection in farm animals. Nevertheless, the conclusion, that both animals and humans were clearly at risk of exposure to scrapie infectivity via milk could not be ignored. Scrapie prevalence varies between countries, but is so low as to represent only a small risk to consumers from national populations of small ruminants. The risk relating to flocks/herds in which scrapie has been diagnosed was, however, greater and possibly warranted specific action to limit exposure risks. This is important as past assumptions that risk management measures could be limited to the exclusion of mastitic milk from the human food chain have been demonstrated to be untenable, given the findings in the French study of infectivity in milk from sheep with apparently healthy udders. EFSA stressed that it’s assessment of human health risk had not changed from its previous positions in 2007 and 2008(1,2). As suggested by the French researchers, a combination of low infectivity levels in milk, and low prevalence of scrapie, coupled with the historical absence of a definite link between scrapie and human disease, suggested that milk from the general population of small ruminants could be considered low risk. The BioHazards Panel could not offer specific advice with respect to risk from milk of sheep infected with BSE or atypical scrapie(8,10), but anticipated that the recognised peripheral distribution of infectivity in some small ruminants infected with BSE could lead to the presence of infectivity in milk. Atypical scrapie has not yet been identified in peripheral tissues of infected animals. Risk Management Options Further to the EFSA and AFSSA Opinions, the EU agreed to new controls on 26 November 2008 (SANCO/3660/2008), but will be applied when legislative changes are in force. These recognise the potential role of milk in spreading classical scrapie (or BSE) between small ruminants, and are primarily intended to protect animal health. Consequently:-
* While investigations into a case of suspect TSE in a sheep or goat continue, the use of milk and milk products derived from the animals in the flock/herd in question will be restricted to that holding until confirmatory results are available.
* After confirmation that the diagnosis is of classical scrapie, milk and milk products from the flock cannot be sold for feeding to ruminant species. Sale for feeding to non-ruminants will be confined to use within the borders of the Member State concerned. These measures apply until all susceptible animals have been culled.
* A derogation allowing the deferring of culling for up to 5 years in specific circumstances has been reduced to 18 months in dairy herds/flocks. ? Imports of milk and milk products into Member States, intended for feeding to ruminants, will need to be subject to additional certification relating to the scrapie status of the flock/herd of origin. These represent only a part of the raft of regulatory actions that apply to classical scrapie affected flocks or herds in Europe. The culling of genetically susceptible sheep or all sheep or goats in the flock/herd, and voluntary programmes of breeding for resistance in sheep are also involved. If BSE cannot be excluded, the flock or the herd must be culled and any milk or milk products on the holding destroyed. The new measures do highlight however that the focus of attention is on the
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protection of animal health, by reducing opportunities for the spread of infection. Realistically, it is probable that the effect of the measures will vary significantly from country to county, depending on the prevalence of scrapie, the number of small ruminant dairy herds/flocks and the extent to which milk from sheep and goats is sold for animal feed. In many countries small ruminant milk production is only a minor component of industry objectives. TAF Position Scrapie is not recognised as a risk to humans, although this cannot be ruled out with certainty .The risk to humans from scrapie, and the scientific uncertainties that underpin any statement on risk, have been discussed at length in the EFSA Opinions cited below. Since there is no established evidence to date that scrapie poses a risk to human health, the finding that infectivity is present in milk of scrapie-infected animals does not give any reason to change our view that ovine and caprine milk are safe for human consumption. These results do not at the moment have any direct implications with respect to the risk from BSE in milk from cattle. Although an equivalent study has not been conducted in cattle, other studies attempting to find infectivity in bovine milk have not succeeded. Proving the total absence of infectivity is extremely difficult. The evidence for the absence of natural spread of BSE between cattle, from cow to calf or between unrelated cattle does however suggest that even in natural equivalent of this experiment, the feeding of calves on cows’ milk, transmission has not occurred, or does so only rarely. Consequently, cows’ milk is unlikely to carry BSE infectivity that might put consumers at risk. Furthermore, the control measures that have been put in place to eradicate BSE, and protect consumers in the interim, are succeeding in reducing numbers of infected cattle year by year. In conclusion, the studies, and their interpretation by EFSA, help to better understand the epidemiology of scrapie and exposure risks faced. Despite the precautionary impetus for additional measures to further strengthen animal health protection in regard to small ruminant TSEs, the question of the safety of products derived from bovine milk destined for human consumption remains unchanged.
References.
1. EFSA (2007). Opinion of the Scientific Panel on Biological Hazards on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. 8 March 2007. The EFSA Journal. 466:1-10. Available at:-
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620775196.htm
2. EFSA (2008). Scientific and technical clarification in the interpretation and consideration of some facets of the conclusions of its Opinion of 8 March 2007 on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal. 626:1-11. Available at:
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178685986247.htm
3. EFSA (2008). Scientific opinion of the Scientific Panel on Biological Hazards on the human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants. The EFSA Journal. 849:2-38.Available at:-
http://www.efsa.europa.eu/cs/BlobServer/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_en,0.pdf?ssbinary=true
4. Konold et al.: Evidence of scrapie transmission via milk, BMC Veterinary Research 2008, 4:14;
http://www.biomedcentral.com/1746-6148/4/14
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5. Lacroux, C., Simon, S., Benestad, S.L., Maillet, S., Mathey, J., Lugan, S., Corbiere, F., Cassard, H., Costes, P., Bergonier, D., WEisbecker, J-L., Moldal, T., Simmons, H., Lantier, F., Feraudet-Tarisse, C., Morel, N., Schelcher, F., Grassi, J. & Andreoletti, O. (2008) Prions in milk from ewes incubating natural scrapie. PLoS Pathogens. 4:12.
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238
6. Ligios, C., Sigurdson, C.J., Santucciu, C., Carcassola, G., Manco, G., Basagni, M., Maestrale, C., Cancedda, M.G., Madau, L. & Aguzzi, A. (2005). PrPSc in mammary glands of sheep affected by scrapie and mastitis. Nat. Med. 11:1137-1138.
7. Vilotte, J.L., Soulier, S., Essalmani, R., Stinnakre, M.G., Vaiman, D., Lepourry, L., Da Silva, J.C., Besnard, N., Dawson, M., Buschmann, A., Groschup, M., Petit, S., Madelaine, M.F., Rakatobe, S., Le Dur, A., Vilette, D. & Laude, H. (2001). Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine prp. J. Virol. 75:5977-84.
8. TAFS (2007) – Position paper on Atypical scrapie and Atypical BSE.
(http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_ATYPICAL_SCRAPIE_AND_%20ATYPICAL_BSE_070516.pdf)
9. TAFS (2007) – Position paper on the safety of bovine milk and bovine milk products
(http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_MILK_05-04-07.pdf)
10. TAFS (May 2007/2009) – Position paper on BSE in small ruminants.
(http://www.tafsforum.org/position_papers/TAFS%20POSITION%20STATEMENT%20ON%20BSE%20IN%20SMALL%20RUMINANTS_2009.pdf)
http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_TRANSMISSION_SCRAPIE_MILK_2009.pdf
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Prions in Milk from Ewes Incubating Natural Scrapie
Caroline Lacroux1, Stéphanie Simon2, Sylvie L. Benestad3, Séverine Maillet2, Jacinthe Mathey1, Séverine Lugan1, Fabien Corbière1, Hervé Cassard1, Pierrette Costes1, Dominique Bergonier1, Jean-Louis Weisbecker4, Torffin Moldal3, Hugh Simmons5, Frederic Lantier6, Cécile Feraudet-Tarisse1,2, Nathalie Morel2, François Schelcher1, Jacques Grassi2, Olivier Andréoletti1*
1 UMR INRA ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France, 2 CEA, Service de Pharmacologie et d'Immunoanalyse, IBiTec-S, DSV, CEA/Saclay, Gif sur Yvette, France, 3 National Veterinary Institute, Sentrum, Oslo, Norway, 4 INRA Domaine de Langlade, Pompertuzat, France, 5 VLA Weybridge, New Haw, Addlestone, Surrey, United Kingdom, 6 INRA IASP, Centre INRA de Tours, Nouzilly, France
Abstract Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species.
Author Summary A decade ago, a new variant form of Creutzfeldt-Jakob disease was identified. The emergence of this prion disease in humans was the consequence of the zoonotic transmission of bovine spongiform encephalopathy through dietary exposure. Since then, the control of human exposure to prions has become a priority, and a policy based on the exclusion of known infectious materials from the food chain has been implemented. Because all investigations carried out failed to reveal evidence of infectivity in milk from affected ruminants, this product has continuously been considered as safe. In this study, we demonstrate the presence of prions in colostrum and milk from sheep incubating natural scrapie and displaying apparently healthy mammary glands. This finding indicates that milk from small ruminants could contribute to the transmission of prion disease between animals. It also raises some concern with regard to the risk to humans associated with milk products from ovine and other dairy species.
Citation: Lacroux C, Simon S, Benestad SL, Maillet S, Mathey J, et al. (2008) Prions in Milk from Ewes Incubating Natural Scrapie. PLoS Pathog 4(12): e1000238. doi:10.1371/journal.ppat.1000238
Editor: Umberto Agrimi, Istituto Superiore di Sanità, Italy
Received: July 1, 2008; Accepted: November 12, 2008; Published: December 12, 2008
Copyright: © 2008 Lacroux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was financially supported by GIS infections à prion (French Research Ministry), EU FAIR (QLK-CT 2001-390), and DEFRA (SE2004, contract: CSA 6914).
Competing interests: The authors have declared that no competing interests exist.
* E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000172/!x-usc:mailto:o.andreoletti@envt.fr
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http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238
TSS Human and animal exposure risk related to TSEs from milk Sun Nov 9, 2008 08:46 71.248.131.35
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Opinions
Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants Scientific opinion of the Panel on Biological Hazards Question number: EFSA-Q-2008-310
Adopted date: 22 October 2008 Summary (0.1Mb)
Opinion (0.2Mb)
Summary
Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.
In a recent scientific article from Konold et al., published on 8 April 2008 in BMC Veterinary Research, on "Evidence of scrapie transmission via milk" it is concluded that: ".there is a risk of the transmission of scrapie from ewe to lamb via milk or colostrum. Infection of lambs via milk may result in shedding of the infectious agent into the environment.".
The BIOHAZ Panel was invited to provide an opinion on the conclusions from the article of Konold et al. (2008), and if considered necessary, based on any additional available scientific data, to update the current risk assessments on the human and animal exposure related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.
When approaching the mandate the BIOHAZ Panel did not consider the zoonotic potential of small ruminant TSE agents. This aspect is considered in detail in previous EFSA documents[1],[2]. The TSE agents considered in the assessment were Classical scrapie, Atypical scrapie and BSE. Moreover, the assessment was performed employing mainly data from TSE in sheep, which were considered valid also for TSE in goats due to the lack of more specific data in that species.
The Panel considered valid the conclusion of the article of Konold et al. (2008). Expanding the article of Konold et al. (2008), another study from Lacroux et al. (2008) independently demonstrated that Classical scrapie can be transmitted from susceptible ewe to transgenic mice via colostrum and milk. It was emphasized that both studies were designed to achieve the highest possibility of transmission success and that this could differ from the field situation. The Panel noted that in both studies, milk from asymptomatic donor ewes transmitted disease, indicating that clinically healthy, Classical scrapie-incubating sheep may shed the causal agents of these TSEs in milk. Moreover, the level of prion infectivity in small ruminant milk could become higher during the course of mastitis but the somatic cell count was considered as an unreliable indicator for presence or absence of TSE infectivity in small ruminant milk.
The Panel concluded that the use of milk and milk products from a flock with Classical scrapie may carry a TSE exposure risk for humans and animals. Furthermore, the use of milk and milk products from the general small ruminant population may carry a TSE exposure risk for humans and animals due to the presence of undetected affected flocks in that population. However, because of the difference in scrapie prevalence between affected flocks and the general small ruminant population, the risk of exposure for humans and animals associated with milk and milk products from the general small ruminant population will be lower than the risk from detected scrapie affected flocks.
The Panel also concluded that the exposure to a Classical scrapie agent via milk of an infected animal can be estimated to be 4 to 5 logs10 lower than the infectivity found in the same weight of brainstem from a terminally affected animal, and 2 to 3 logs10 lower the than infectivity found in the same weight of lymphoid tissues from an animal incubating scrapie or from a clinically affected animal.
The BIOHAZ Panel further noted that no information is available concerning the presence of infectivity or PrPSc in colostrum or milk from small ruminants affected by Atypical scrapie or BSE. However, the Panel emphasized that due to the early and progressive peripheral tissue dissemination of the BSE agent in experimentally infected susceptible sheep, the occurrence of infectivity in colostrum and milk of BSE infected susceptible small ruminants would be likely. On the other hand, the apparent restricted dissemination of the agent of Atypical scrapie in affected individuals could limit its transmissibility through milk.
As there is large variation between MS in prevalence of scrapie and production of small ruminant milk, the human and animal exposure associated with small ruminant dairy products varies greatly between MS.
The Panel further concluded that breeding of sheep for relative resistance to Classical scrapie according to the previous EFSA opinion[3] can be expected to reduce human and animal exposure associated with small ruminant dairy products.
The Panel recommended to perform research in order to characterise the exposure risk via milk especially in Atypical scrapie and BSE in small ruminants, to investigate on the stability of prion infectivity in milk during further processing, and to obtain more data to confirm and expand the preliminary information available on the quantitation of infectivity levels in small ruminant milk fractions. ___________________________________ [1]Opinion of the Scientific Panel on Biological Hazards on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2007) 466, 1-10 [2] Scientific and technical clarification in the interpretation and consideration of some facets of the conclusions of its Opinion of 8 March 2007 on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2008) 626, 1-11 [3] Opinion of the Scientific Panel on Biological Hazards on "the breeding programme for TSE resistance in sheep", The EFSA Journal (2006), 382, 1-46
Publication date: 6 November 2008
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_summary_en,0.pdf?ssbinary=true
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_en,0.pdf?ssbinary=true
Prion Protein in Milk Nicola Franscini1, Ahmed El Gedaily1, Ulrich Matthey1, Susanne Franitza1, Man-Sun Sy2, Alexander Bürkle3, Martin Groschup4, Ueli Braun5, Ralph Zahn1*
1 Alicon AG, Schlieren, Switzerland, 2 Institute of Pathology, Biomedical Research Building, Case Western University School of Medicine, Cleveland, Ohio, United States of America, 3 Lehrstuhl Molekulare Toxikologie, University of Konstanz, Konstanz, Germany, 4 Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit, Greifswald, Gemany, 5 Departement für Nutztiere, University of Zurich, Zurich, Switzerland
Abstract Background Prions are known to cause transmissible spongiform encephalopathies (TSE) after accumulation in the central nervous system. There is increasing evidence that prions are also present in body fluids and that prion infection by blood transmission is possible. The low concentration of the proteinaceous agent in body fluids and its long incubation time complicate epidemiologic analysis and estimation of spreading and thus the risk of human infection. This situation is particularly unsatisfactory for food and pharmaceutical industries, given the lack of sensitive tools for monitoring the infectious agent.
Methodology/Principal Findings We have developed an adsorption matrix, Alicon PrioTrap®, which binds with high affinity and specificity to prion proteins. Thus we were able to identify prion protein (PrPC)-the precursor of prions (PrPSc)-in milk from humans, cows, sheep, and goats. The absolute amount of PrPC differs between the species (from µg/l range in sheep to ng/l range in human milk). PrPC is also found in homogenised and pasteurised off-the-shelf milk, and even ultrahigh temperature treatment only partially diminishes endogenous PrPC concentration.
Conclusions/Significance In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrPC in milk implies the possibility that milk of TSE-infected animals serves as source for PrPSc.
Citation: Franscini N, Gedaily AE, Matthey U, Franitza S, Sy M-S, et al. (2006) Prion Protein in Milk. PLoS ONE 1(1): e71. doi:10.1371/journal.pone.0000071
Academic Editor: Matthew Baylis, University of Liverpool, United Kingdom
Received: October 19, 2006; Accepted: November 6, 2006; Published: December 20, 2006
Copyright: © 2006 Franscini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
* To whom correspondence should be addressed. E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000172/!x-usc:mailto:info@alicon.ch
http://www.plosone.org/article/fetchObjectAttachment.action;jsessionid=4BBFF07E478CCD52A627126F9BCC995A?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0000071&representation=PDF
Saturday, April 12, 2008 Evidence of scrapie transmission via milk
Saturday, April 12, 2008 Evidence of scrapie transmission via milk
http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html
HAVE ANOTHER GLASS OF CWD PRIONS COURTESY Dane County Wisconsin Mike DiMaggio, solid waste manager
http://chronic-wasting-disease.blogspot.com/2008/08/have-another-glass-of-cwd-prions.html
Friday, October 24, 2008
CBER 2007 Annual Report Assessing the Potential Risk of variant Creutzfeldt-Jakob Disease from Blood Products
http://creutzfeldt-jakob-disease.blogspot.com/2008/10/cber-2007-annual-report-assessing.html
Friday, November 07, 2008 Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants
Opinions
http://scrapie-usa.blogspot.com/2008/11/human-and-animal-exposure-risk-related.html
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.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] 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 ia 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 emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise 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 acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Epidemiology of Scrapie in the United States 1977
http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
http://scrapie-usa.blogspot.com/
CHAPTER 3 Animal Disease Eradication Programs and Control and Certification Programs
snip...
In FY 2007, two field cases, one validation study case, and two RSSS cases were consistent with a variant of the disease known as Nor98 scrapie.1 These five cases originated from flocks in California, Minnesota, Colorado, Wyoming, and Indiana, respectively.
snip...
http://www.aphis.usda.gov/publications/animal_health/content/printable_version/AHR_Web_PDF_07/D_Chapter_3.pdf
NOR-98 Scrapie FY 2008 to date 1
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007
http://nor-98.blogspot.com/
TSS
Friday, December 12, 2008 Prions in Milk from Ewes Incubating Natural Scrapie
http://scrapie-usa.blogspot.com/2008/12/prions-in-milk-from-ewes-incubating.html
Attending Dr.: Date / Time Admitted : 12/14/97 1228
UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report
FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html
TSS
(January, 2009)
TAFS1 STATEMENT ON TRANSMISSION OF SCRAPIE VIA MILK
Introduction In April 2008, TAFS published a statement on the transmission of scrapie via milk, prompted by the publication of results that provided strong evidence of transmission of scrapie to lambs by the feeding of milk from scrapie-infected ewes(4). More recently, another publication has further clarified the mechanisms of transmission(5), and together the results have enabled a review of the implications by the European Food Safety Authority(3), and prompted initial regulatory action by the European Commission. This statement represents a revision of the TAFS statement to take into account the recent data and interpretation.
TAFS welcomes publication of these findings. They contribute to the understanding of the mechanisms of transmission of scrapie as a prion disease of sheep and goats that has been known for over 200 years. Scrapie is not a highly contagious disease. It does not spread easily, but it is difficult to eradicate. It is known to spread between sheep, both from ewe to lamb and to other unrelated sheep and goats. The exact route of transmission has not been determined so far. There are several possible routes, which include contact with placenta of infected ewes, or possibly before birth while the lamb is still in the womb. Transmission via milk and/or uterine fluids after birth are additional possibilities. Ewe to lamb transmission(4) This study attempted to assess the scope for transmission, under a worst-case scenario, by collecting milk from sheep of highly susceptible genetic makeup (high risk group), at a time when they were either about to die of scrapie, or when the first clinical signs were seen. Their milk was collected and fed to lambs that were born to uninfected mothers and kept in isolation while they received the milk. These lambs were also of the most susceptible genotype (VRQ/VRQ).
The lambs have been shown to be infected by the testing of tissue samples collected either while still alive, by biopsy, or from some that had died of other diseases. None have yet reached the point of clinical disease themselves, and infectivity itself has not been demonstrated. Tests have revealed the
1 TAFS is an international platform created by a group of scientists, food industry experts, animal health regulators, epidemiologists, diagnosticians, food producers, and consumers. Its purpose is to establish and maintain lines of communication for the dissemination of reliable information to the public that can maintain confidence in the safety of food with regard to Transmissible Animal Diseases.
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presence of abnormal prion protein (PrPSc) that is normally recognised as a marker for the presence of infectivity. The success of the study was dependent on having scrapie-free lambs to receive the milk. Despite having fully susceptible ewes and susceptible lambs, the ease with which the lambs were infected is a surprise. The experimental design anticipated transmission to smaller numbers of lambs. For this reason lambs received both milk and colostrum (the milk produced within the first 24-48 hours after lambing) from the same ewe in order to maximise the likelihood of transmission. As a result, the authors could not conclude whether transmission occurred via colostrum, milk or both. The study will therefore now be repeated, feeding lambs with either colostrum or milk. This is important for several reasons.
* Firstly, colostrum would not be used for human consumption.
* Secondly, colostrum is rich in protein and antibodies that help to protect the lamb in the early days of life before its own immune system is fully developed. For that reason farmers sometimes collect and freeze colostrum to feed to other lambs, sometimes pooling it to feed to several lambs. This practice could increase the potential for infection of lambs at their most vulnerable time of life.
Although the study described below confirms the presence of infectivity in colostrum, it is necessary to establish the status of colostrum from sheep that are unaffected by other pathogens. In other words, the result should be dependent solely on the presence of scrapie in an otherwise healthy sheep. Ewe to mouse transmission(5) This study also made use of a naturally infected experimental flock of sheep in France, but differed from the previous study in that the flock was infected with both scrapie and Maedi-Visna (MV). MV is a viral disease, that has previously been shown to potentially predispose to the transmission of scrapie via milk(6). It causes a form of mastitis (lympho-proliferative chronic mastitis) that particularly involves the formation of discrete ectopic lymphoid follicles in the mammary tissue. These have previously been shown to stain heavily for abnormal prion protein(9) in scrapie infected sheep(6). In the French study, the researchers compensated for some of the difficulties normally presented by mouse inoculation studies, of not being able to inoculate sufficient material into a mouse to guarantee transmission, by concentrating their starting material (colostrum and milk). In addition, they used highly sensitive mice (Tg338)(7), that were genetically modified to produce sheep prion protein of the VRQ genotype(10). The study was supported by post-mortem examination of many sheep for the presence of abnormal PrP in the udder, and for the presence or absence of mastitis. Although the biological assay study has not been completed, it has reached a point where it is possible to conclude conclusively that particular fractions of milk are infectious. Preliminary findings include:
* Abnormal PrP was only detected in ewes that harboured ectopic lymphoid follicles, and correlated with the detection of abnormal PrP in other peripheral lymph nodes. This therefore limited the positivity to sheep with the most susceptible genotypes that are predisposed to peripheral infection (VRQ/VRQ; VRQ/ARQ; ARQ/ARQ).
* In addition, abnormal PrP was detected in lacteal ducts and mammary acini suggesting a high probability that it would be excreted in milk/colostrum.
* Nevertheless, infectivity studies detected scrapie infectivity in both colostrum (collected within 12 hours of lambing) and milk (collected 20 days after lambing). The infectivity was associated with cellular, cream and casein-whey fractions.
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* Most critically, infectivity was even detected in fractions derived from sheep in which there was no visible clinical or pathological evidence of mastitic lesions.
* In all samples, preliminary estimations suggest that infectivity levels are very low, but potentially higher in mastitic milk or colostrum than from healthy udders.
EFSA BioHazards Panel Opinion(3) The findings summarised above were supported by EFSA, but the BioHazards panel stressed that in both studies conditions had been maximised to facilitate detection of infectivity. In other words, they were worst-case scenarios, and may not be fully representative of natural infection in farm animals. Nevertheless, the conclusion, that both animals and humans were clearly at risk of exposure to scrapie infectivity via milk could not be ignored. Scrapie prevalence varies between countries, but is so low as to represent only a small risk to consumers from national populations of small ruminants. The risk relating to flocks/herds in which scrapie has been diagnosed was, however, greater and possibly warranted specific action to limit exposure risks. This is important as past assumptions that risk management measures could be limited to the exclusion of mastitic milk from the human food chain have been demonstrated to be untenable, given the findings in the French study of infectivity in milk from sheep with apparently healthy udders. EFSA stressed that it’s assessment of human health risk had not changed from its previous positions in 2007 and 2008(1,2). As suggested by the French researchers, a combination of low infectivity levels in milk, and low prevalence of scrapie, coupled with the historical absence of a definite link between scrapie and human disease, suggested that milk from the general population of small ruminants could be considered low risk. The BioHazards Panel could not offer specific advice with respect to risk from milk of sheep infected with BSE or atypical scrapie(8,10), but anticipated that the recognised peripheral distribution of infectivity in some small ruminants infected with BSE could lead to the presence of infectivity in milk. Atypical scrapie has not yet been identified in peripheral tissues of infected animals. Risk Management Options Further to the EFSA and AFSSA Opinions, the EU agreed to new controls on 26 November 2008 (SANCO/3660/2008), but will be applied when legislative changes are in force. These recognise the potential role of milk in spreading classical scrapie (or BSE) between small ruminants, and are primarily intended to protect animal health. Consequently:-
* While investigations into a case of suspect TSE in a sheep or goat continue, the use of milk and milk products derived from the animals in the flock/herd in question will be restricted to that holding until confirmatory results are available.
* After confirmation that the diagnosis is of classical scrapie, milk and milk products from the flock cannot be sold for feeding to ruminant species. Sale for feeding to non-ruminants will be confined to use within the borders of the Member State concerned. These measures apply until all susceptible animals have been culled.
* A derogation allowing the deferring of culling for up to 5 years in specific circumstances has been reduced to 18 months in dairy herds/flocks. ? Imports of milk and milk products into Member States, intended for feeding to ruminants, will need to be subject to additional certification relating to the scrapie status of the flock/herd of origin. These represent only a part of the raft of regulatory actions that apply to classical scrapie affected flocks or herds in Europe. The culling of genetically susceptible sheep or all sheep or goats in the flock/herd, and voluntary programmes of breeding for resistance in sheep are also involved. If BSE cannot be excluded, the flock or the herd must be culled and any milk or milk products on the holding destroyed. The new measures do highlight however that the focus of attention is on the
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protection of animal health, by reducing opportunities for the spread of infection. Realistically, it is probable that the effect of the measures will vary significantly from country to county, depending on the prevalence of scrapie, the number of small ruminant dairy herds/flocks and the extent to which milk from sheep and goats is sold for animal feed. In many countries small ruminant milk production is only a minor component of industry objectives. TAF Position Scrapie is not recognised as a risk to humans, although this cannot be ruled out with certainty .The risk to humans from scrapie, and the scientific uncertainties that underpin any statement on risk, have been discussed at length in the EFSA Opinions cited below. Since there is no established evidence to date that scrapie poses a risk to human health, the finding that infectivity is present in milk of scrapie-infected animals does not give any reason to change our view that ovine and caprine milk are safe for human consumption. These results do not at the moment have any direct implications with respect to the risk from BSE in milk from cattle. Although an equivalent study has not been conducted in cattle, other studies attempting to find infectivity in bovine milk have not succeeded. Proving the total absence of infectivity is extremely difficult. The evidence for the absence of natural spread of BSE between cattle, from cow to calf or between unrelated cattle does however suggest that even in natural equivalent of this experiment, the feeding of calves on cows’ milk, transmission has not occurred, or does so only rarely. Consequently, cows’ milk is unlikely to carry BSE infectivity that might put consumers at risk. Furthermore, the control measures that have been put in place to eradicate BSE, and protect consumers in the interim, are succeeding in reducing numbers of infected cattle year by year. In conclusion, the studies, and their interpretation by EFSA, help to better understand the epidemiology of scrapie and exposure risks faced. Despite the precautionary impetus for additional measures to further strengthen animal health protection in regard to small ruminant TSEs, the question of the safety of products derived from bovine milk destined for human consumption remains unchanged.
References.
1. EFSA (2007). Opinion of the Scientific Panel on Biological Hazards on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. 8 March 2007. The EFSA Journal. 466:1-10. Available at:-
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620775196.htm
2. EFSA (2008). Scientific and technical clarification in the interpretation and consideration of some facets of the conclusions of its Opinion of 8 March 2007 on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal. 626:1-11. Available at:
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178685986247.htm
3. EFSA (2008). Scientific opinion of the Scientific Panel on Biological Hazards on the human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants. The EFSA Journal. 849:2-38.Available at:-
http://www.efsa.europa.eu/cs/BlobServer/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_en,0.pdf?ssbinary=true
4. Konold et al.: Evidence of scrapie transmission via milk, BMC Veterinary Research 2008, 4:14;
http://www.biomedcentral.com/1746-6148/4/14
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5. Lacroux, C., Simon, S., Benestad, S.L., Maillet, S., Mathey, J., Lugan, S., Corbiere, F., Cassard, H., Costes, P., Bergonier, D., WEisbecker, J-L., Moldal, T., Simmons, H., Lantier, F., Feraudet-Tarisse, C., Morel, N., Schelcher, F., Grassi, J. & Andreoletti, O. (2008) Prions in milk from ewes incubating natural scrapie. PLoS Pathogens. 4:12.
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238
6. Ligios, C., Sigurdson, C.J., Santucciu, C., Carcassola, G., Manco, G., Basagni, M., Maestrale, C., Cancedda, M.G., Madau, L. & Aguzzi, A. (2005). PrPSc in mammary glands of sheep affected by scrapie and mastitis. Nat. Med. 11:1137-1138.
7. Vilotte, J.L., Soulier, S., Essalmani, R., Stinnakre, M.G., Vaiman, D., Lepourry, L., Da Silva, J.C., Besnard, N., Dawson, M., Buschmann, A., Groschup, M., Petit, S., Madelaine, M.F., Rakatobe, S., Le Dur, A., Vilette, D. & Laude, H. (2001). Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine prp. J. Virol. 75:5977-84.
8. TAFS (2007) – Position paper on Atypical scrapie and Atypical BSE.
(http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_ATYPICAL_SCRAPIE_AND_%20ATYPICAL_BSE_070516.pdf)
9. TAFS (2007) – Position paper on the safety of bovine milk and bovine milk products
(http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_MILK_05-04-07.pdf)
10. TAFS (May 2007/2009) – Position paper on BSE in small ruminants.
(http://www.tafsforum.org/position_papers/TAFS%20POSITION%20STATEMENT%20ON%20BSE%20IN%20SMALL%20RUMINANTS_2009.pdf)
http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_TRANSMISSION_SCRAPIE_MILK_2009.pdf
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Prions in Milk from Ewes Incubating Natural Scrapie
Caroline Lacroux1, Stéphanie Simon2, Sylvie L. Benestad3, Séverine Maillet2, Jacinthe Mathey1, Séverine Lugan1, Fabien Corbière1, Hervé Cassard1, Pierrette Costes1, Dominique Bergonier1, Jean-Louis Weisbecker4, Torffin Moldal3, Hugh Simmons5, Frederic Lantier6, Cécile Feraudet-Tarisse1,2, Nathalie Morel2, François Schelcher1, Jacques Grassi2, Olivier Andréoletti1*
1 UMR INRA ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France, 2 CEA, Service de Pharmacologie et d'Immunoanalyse, IBiTec-S, DSV, CEA/Saclay, Gif sur Yvette, France, 3 National Veterinary Institute, Sentrum, Oslo, Norway, 4 INRA Domaine de Langlade, Pompertuzat, France, 5 VLA Weybridge, New Haw, Addlestone, Surrey, United Kingdom, 6 INRA IASP, Centre INRA de Tours, Nouzilly, France
Abstract Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species.
Author Summary A decade ago, a new variant form of Creutzfeldt-Jakob disease was identified. The emergence of this prion disease in humans was the consequence of the zoonotic transmission of bovine spongiform encephalopathy through dietary exposure. Since then, the control of human exposure to prions has become a priority, and a policy based on the exclusion of known infectious materials from the food chain has been implemented. Because all investigations carried out failed to reveal evidence of infectivity in milk from affected ruminants, this product has continuously been considered as safe. In this study, we demonstrate the presence of prions in colostrum and milk from sheep incubating natural scrapie and displaying apparently healthy mammary glands. This finding indicates that milk from small ruminants could contribute to the transmission of prion disease between animals. It also raises some concern with regard to the risk to humans associated with milk products from ovine and other dairy species.
Citation: Lacroux C, Simon S, Benestad SL, Maillet S, Mathey J, et al. (2008) Prions in Milk from Ewes Incubating Natural Scrapie. PLoS Pathog 4(12): e1000238. doi:10.1371/journal.ppat.1000238
Editor: Umberto Agrimi, Istituto Superiore di Sanità, Italy
Received: July 1, 2008; Accepted: November 12, 2008; Published: December 12, 2008
Copyright: © 2008 Lacroux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was financially supported by GIS infections à prion (French Research Ministry), EU FAIR (QLK-CT 2001-390), and DEFRA (SE2004, contract: CSA 6914).
Competing interests: The authors have declared that no competing interests exist.
* E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000172/!x-usc:mailto:o.andreoletti@envt.fr
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http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238
TSS Human and animal exposure risk related to TSEs from milk Sun Nov 9, 2008 08:46 71.248.131.35
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Opinions
Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants Scientific opinion of the Panel on Biological Hazards Question number: EFSA-Q-2008-310
Adopted date: 22 October 2008 Summary (0.1Mb)
Opinion (0.2Mb)
Summary
Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.
In a recent scientific article from Konold et al., published on 8 April 2008 in BMC Veterinary Research, on "Evidence of scrapie transmission via milk" it is concluded that: ".there is a risk of the transmission of scrapie from ewe to lamb via milk or colostrum. Infection of lambs via milk may result in shedding of the infectious agent into the environment.".
The BIOHAZ Panel was invited to provide an opinion on the conclusions from the article of Konold et al. (2008), and if considered necessary, based on any additional available scientific data, to update the current risk assessments on the human and animal exposure related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.
When approaching the mandate the BIOHAZ Panel did not consider the zoonotic potential of small ruminant TSE agents. This aspect is considered in detail in previous EFSA documents[1],[2]. The TSE agents considered in the assessment were Classical scrapie, Atypical scrapie and BSE. Moreover, the assessment was performed employing mainly data from TSE in sheep, which were considered valid also for TSE in goats due to the lack of more specific data in that species.
The Panel considered valid the conclusion of the article of Konold et al. (2008). Expanding the article of Konold et al. (2008), another study from Lacroux et al. (2008) independently demonstrated that Classical scrapie can be transmitted from susceptible ewe to transgenic mice via colostrum and milk. It was emphasized that both studies were designed to achieve the highest possibility of transmission success and that this could differ from the field situation. The Panel noted that in both studies, milk from asymptomatic donor ewes transmitted disease, indicating that clinically healthy, Classical scrapie-incubating sheep may shed the causal agents of these TSEs in milk. Moreover, the level of prion infectivity in small ruminant milk could become higher during the course of mastitis but the somatic cell count was considered as an unreliable indicator for presence or absence of TSE infectivity in small ruminant milk.
The Panel concluded that the use of milk and milk products from a flock with Classical scrapie may carry a TSE exposure risk for humans and animals. Furthermore, the use of milk and milk products from the general small ruminant population may carry a TSE exposure risk for humans and animals due to the presence of undetected affected flocks in that population. However, because of the difference in scrapie prevalence between affected flocks and the general small ruminant population, the risk of exposure for humans and animals associated with milk and milk products from the general small ruminant population will be lower than the risk from detected scrapie affected flocks.
The Panel also concluded that the exposure to a Classical scrapie agent via milk of an infected animal can be estimated to be 4 to 5 logs10 lower than the infectivity found in the same weight of brainstem from a terminally affected animal, and 2 to 3 logs10 lower the than infectivity found in the same weight of lymphoid tissues from an animal incubating scrapie or from a clinically affected animal.
The BIOHAZ Panel further noted that no information is available concerning the presence of infectivity or PrPSc in colostrum or milk from small ruminants affected by Atypical scrapie or BSE. However, the Panel emphasized that due to the early and progressive peripheral tissue dissemination of the BSE agent in experimentally infected susceptible sheep, the occurrence of infectivity in colostrum and milk of BSE infected susceptible small ruminants would be likely. On the other hand, the apparent restricted dissemination of the agent of Atypical scrapie in affected individuals could limit its transmissibility through milk.
As there is large variation between MS in prevalence of scrapie and production of small ruminant milk, the human and animal exposure associated with small ruminant dairy products varies greatly between MS.
The Panel further concluded that breeding of sheep for relative resistance to Classical scrapie according to the previous EFSA opinion[3] can be expected to reduce human and animal exposure associated with small ruminant dairy products.
The Panel recommended to perform research in order to characterise the exposure risk via milk especially in Atypical scrapie and BSE in small ruminants, to investigate on the stability of prion infectivity in milk during further processing, and to obtain more data to confirm and expand the preliminary information available on the quantitation of infectivity levels in small ruminant milk fractions. ___________________________________ [1]Opinion of the Scientific Panel on Biological Hazards on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2007) 466, 1-10 [2] Scientific and technical clarification in the interpretation and consideration of some facets of the conclusions of its Opinion of 8 March 2007 on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2008) 626, 1-11 [3] Opinion of the Scientific Panel on Biological Hazards on "the breeding programme for TSE resistance in sheep", The EFSA Journal (2006), 382, 1-46
Publication date: 6 November 2008
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_summary_en,0.pdf?ssbinary=true
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_en,0.pdf?ssbinary=true
Prion Protein in Milk Nicola Franscini1, Ahmed El Gedaily1, Ulrich Matthey1, Susanne Franitza1, Man-Sun Sy2, Alexander Bürkle3, Martin Groschup4, Ueli Braun5, Ralph Zahn1*
1 Alicon AG, Schlieren, Switzerland, 2 Institute of Pathology, Biomedical Research Building, Case Western University School of Medicine, Cleveland, Ohio, United States of America, 3 Lehrstuhl Molekulare Toxikologie, University of Konstanz, Konstanz, Germany, 4 Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit, Greifswald, Gemany, 5 Departement für Nutztiere, University of Zurich, Zurich, Switzerland
Abstract Background Prions are known to cause transmissible spongiform encephalopathies (TSE) after accumulation in the central nervous system. There is increasing evidence that prions are also present in body fluids and that prion infection by blood transmission is possible. The low concentration of the proteinaceous agent in body fluids and its long incubation time complicate epidemiologic analysis and estimation of spreading and thus the risk of human infection. This situation is particularly unsatisfactory for food and pharmaceutical industries, given the lack of sensitive tools for monitoring the infectious agent.
Methodology/Principal Findings We have developed an adsorption matrix, Alicon PrioTrap®, which binds with high affinity and specificity to prion proteins. Thus we were able to identify prion protein (PrPC)-the precursor of prions (PrPSc)-in milk from humans, cows, sheep, and goats. The absolute amount of PrPC differs between the species (from µg/l range in sheep to ng/l range in human milk). PrPC is also found in homogenised and pasteurised off-the-shelf milk, and even ultrahigh temperature treatment only partially diminishes endogenous PrPC concentration.
Conclusions/Significance In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrPC in milk implies the possibility that milk of TSE-infected animals serves as source for PrPSc.
Citation: Franscini N, Gedaily AE, Matthey U, Franitza S, Sy M-S, et al. (2006) Prion Protein in Milk. PLoS ONE 1(1): e71. doi:10.1371/journal.pone.0000071
Academic Editor: Matthew Baylis, University of Liverpool, United Kingdom
Received: October 19, 2006; Accepted: November 6, 2006; Published: December 20, 2006
Copyright: © 2006 Franscini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
* To whom correspondence should be addressed. E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000172/!x-usc:mailto:info@alicon.ch
http://www.plosone.org/article/fetchObjectAttachment.action;jsessionid=4BBFF07E478CCD52A627126F9BCC995A?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0000071&representation=PDF
Saturday, April 12, 2008 Evidence of scrapie transmission via milk
Saturday, April 12, 2008 Evidence of scrapie transmission via milk
http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html
HAVE ANOTHER GLASS OF CWD PRIONS COURTESY Dane County Wisconsin Mike DiMaggio, solid waste manager
http://chronic-wasting-disease.blogspot.com/2008/08/have-another-glass-of-cwd-prions.html
Friday, October 24, 2008
CBER 2007 Annual Report Assessing the Potential Risk of variant Creutzfeldt-Jakob Disease from Blood Products
http://creutzfeldt-jakob-disease.blogspot.com/2008/10/cber-2007-annual-report-assessing.html
Friday, November 07, 2008 Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants
Opinions
http://scrapie-usa.blogspot.com/2008/11/human-and-animal-exposure-risk-related.html
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.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] 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 ia 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 emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise 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 acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Epidemiology of Scrapie in the United States 1977
http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
http://scrapie-usa.blogspot.com/
CHAPTER 3 Animal Disease Eradication Programs and Control and Certification Programs
snip...
In FY 2007, two field cases, one validation study case, and two RSSS cases were consistent with a variant of the disease known as Nor98 scrapie.1 These five cases originated from flocks in California, Minnesota, Colorado, Wyoming, and Indiana, respectively.
snip...
http://www.aphis.usda.gov/publications/animal_health/content/printable_version/AHR_Web_PDF_07/D_Chapter_3.pdf
NOR-98 Scrapie FY 2008 to date 1
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007
http://nor-98.blogspot.com/
TSS
Friday, December 12, 2008 Prions in Milk from Ewes Incubating Natural Scrapie
http://scrapie-usa.blogspot.com/2008/12/prions-in-milk-from-ewes-incubating.html
Attending Dr.: Date / Time Admitted : 12/14/97 1228
UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report
FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html
TSS
posted by Terry S. Singeltary Sr. | 9:58 AM
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