SHEEP WITH MASTITIS TRANSMIT INFECTIOUS PRIONS THROUGH THE MILK

J. Virol. doi:10.1128/JVI.02022-10 Copyright (c) 2010, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

SHEEP WITH MASTITIS TRANSMIT INFECTIOUS PRIONS THROUGH THE MILK

Ciriaco Ligios*, Maria Giovanna Cancedda, Antonello Carta, Cinzia Santucciu, Caterina Maestrale, Francesca Demontis, Mariangela Saba, Cristiana Patta, James C. DeMartini, Adriano Aguzzi*, and Christina J. Sigurdson* Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy; Research Unit: Genetics and Biotechnology, DIRPA, AGRIS Sardinia, Olmedo, Italy; Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA; Institute of Neuropathology, UniversitätsSpital Zürich, Zürich, Switzerland; Department of Pathology, School of Medicine, University of California, San Diego, CA, USA; Department of Pathology, Microbiology, and Immunology, University of California, Davis, CA USA

* To whom correspondence should be addressed. Email: ciriaco.ligios@izs-sardegna.it . adriano.aguzzi@usz.ch . csigurdson@ucsd.edu .

Abstract Prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. Prion shedding routes have been shown to be modified by inflammation in excretory organs such as kidney. Here we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of suckling naive lambs. Thus lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generations. This study also indicates a risk of prion spread to sheep and potentially to other animals through dietary exposure to pooled sheep milk or milk products.


snip...


Previous studies have found that the cellular fraction of milk harbours the most infectivity (4), and the higher leukocyte count in milk that occurs with mastitis could conceivably have increased the infectious prion titres in milk. Although our studies in ARQ/ARQ sheep suggest that mammary gland inflammation is necessary for prion transmission through milk, it remains possible that large milk volumes from sheep without mastitis would transmit prions to nursing lambs. Milk from VRQ/VRQ sheep without clinical mastitis was previously shown to transmit prion infection to the lambs as evidenced by PrPSc deposits in lymphoid tissue biopsies (3).


Taken together, these findings demonstrate that ingestion of as little as 1 – 2 L of milk from sheep with scrapie and lymphofollicular mastitis can cause prion infection in ARQ/ARQ lambs with an attack rate of 86%. These data show that a common lentivirus can induce an inflammatory setting highly conducive for prion propagation and release into the environment, although a role for the virus in transporting prions into the milk or stimulating PrPSc release from infected cells (6) cannot be excluded. Considering that MVV and other lentiviruses are endemic in sheep and goat populations worldwide, the possibility that lentiviruses have enabled prion transmission through milk and ultimately propagation of scrapie through some flocks should be considered. Together with two other recent reports on infectious prions in sheep milk (3, 4), these studies indicate a risk of prion spread to sheep and potentially other animals through dietary exposure to sheep milk or milk products. World milk production contributes to 13% of the protein supply for humans, thus studies to determine the extent of infectious prions entering our global food supply would be worthwhile and important for accurate risk assessment.

Acknowledgements

snip...end

http://jvi.asm.org/cgi/content/abstract/JVI.02022-10v1?etoc



Fourth threat

Prion infectivity has now been detected in blood, urine and milk and this has potential consequences on risk assessments for the environment and food as well as for contamination of surfaces including medical instruments. Furthermore the procedures recommended for decontamination of MBM (Meat and Bone Meal), which are based on older methodologies not designed for this purpose, have turned out to be of very limited efficacy and compromise current policies concerning the reuse of these high value protein supplements (cross-contamination of feed circuits are difficult to control). It should be noted that the destruction or very limited use of MBM is estimated to still cost 1 billion euros per year to the European economy,

whereas other countries, including the US,

Brazil, and Argentine do not have these constraints.



http://www.neuroprion.org/en/np-neuroprion.html


Thursday, August 12, 2010

Seven main threats for the future linked to prions

http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html


http://prionpathy.blogspot.com/


PPo3-40: Mother to Offspring Transmission of Chronic Wasting Disease

Candace K. Mathiason, Amy V. Nalls, Kelly Anderson, Jeanette Hayes-Klug, Nicholas Haley and Edward A. Hoover

Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO USA

Key words: Chronic wasting disease, vertical transmission, muntjac deer

We have developed a new cervid model in small Asian muntjac deer (Muntiacus reevesi) to study potential modes of vertical transmission of chronic wasting disease (CWD) from mother to offspring. Eight of eight (8/8) muntjac doe orally infected with CWD tested PrPCWD lymphoid positive by 4 months post infection. Six fawns were born to these CWD-infected doe. Six fawns were born to 6 CWD-infected doe; 4 of the fawns were non-viable. The viable fawns have been monitored for CWD infection by immunohistochemistry and sPMCA performed on serial tonsil and rectal lymphoid tissue biopsies. PrPCWD has been detected in one fawn as early as 40 days of age. Moreover, sPMCA performed on rectal lymphoid tissue has yield positive results on another fawn at 10 days of age. In addition, sPMCA assays have also demonstrated amplifiable prions in maternal placental (caruncule) and mammary tissue of the dam.

Additional pregnancy related fluids and tissues from the doe as well as tissue from the nonviable fawns are currently being probed for the presence of CWD. In summary, we have employed the muntjac deer model, to demonstrate for the first time the transmission of CWD from mother to offspring. These studies provide the foundation to investigate the mechanisms and pathways of maternal prion transfer.

PRION 2010 Meeting Report International Prion Congress: From agent to disease; September 8–11, 2010; Salzburg, Austria Volume 4, Issue 3 July/August/September 2010

http://www.landesbioscience.com/journals/prion/article/12764/


P.4.31

Prion infectivity in milk from ARQ/ARQ sheep experimentally infected with Scrapie and MAEDI-VISNA virus

Ciriaco Ligios1, Maria Giovanna Cancedda1, Antonello Carta2, Cinzia Santucciu1 Caterina Maestrale1, Francesca Demontis1, Sonia Attene1, Maria Giovanna Tilocca1, Cristiana Patta1, Massimo Basagni5, Paola Melis1, James C. De- Martini3, Christina Sigurdson4 1Istituto Zooprofilattico Sperimentale della Sardegna, Italy; 2Research Unit: Genetics and Biotechnology, DIRPA, AGRIS Sardinia, Italy; 3Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA; 4Department of Pathology, School of Medicine, University of California San Diego, USA; 5Prion Diagnostica Rho, Italy

Background:

Scrapie in sheep is characterized by the deposition of misfolded and aggregated prion protein (PrPSc) in the central nervous system (CNS) and within the lymphoreticular system (LRS). PrPSc was shown to accumulate in organs beyond the CNS and the LRS when lymphofollicular or granulomatous inflammation was also present.

Objectives:

Our aim was to determine whether ectopic PrPSc accumulation in the inflamed mammary gland of sheep with scrapie results in infectious prion secretion into the milk.

Methods:

We fed approximately 1.1 - 2.1 L of milk from sheep with lymphofollicular mastitis and clinical scrapie to each of 8 ARQ/ARQ lambs derived from scrapie-free flocks. The milk donor sheep had been previously inoculated with Maedi-Visna virus (MVV) intratracheally and intravenously and scrapie brain homogenate orally. In addition, 3 ARQ/ARQ lambs were fed approximately 1.4 – 1.7 L of milk from ARQ/ARQ sheep that had been experimentally infected with only scrapie. Additional control ARQ/ARQ lambs were inoculated with scrapie brain homogenate only, or with milk from uninfected sheep.

Results:

Two lambs which had received milk from sheep with mastitis and scrapie developed clinical signs of scrapie at 677 and 745 days post-inoculation. One additional clinically healthy lamb from this group, which was sacrificed for a cause unrelated to scrapie, was found to have PrPSc in brain and tonsil. The control lambs and those which received milk from sheep affected only with scrapie are, to date, clinically healthy.

Discussion:

This is the first evidence of clinical scrapie in sheep fed milk from scrapie sick sheep. The experiment is ongoing, however these preliminary results indicate that milk and/or colostrum from ARQ/ARQ sheep with clinical scrapie and lymphofollicular mastitis could contribute to scrapie transmission.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf


Monday, August 03, 2009

Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed Sheep

Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16 0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.

http://jvi.asm.org/cgi/content/abstract/83/16/8293


http://scrapie-usa.blogspot.com/2009/08/prions-are-secreted-in-milk-from.html


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

http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_TRANSMISSION_SCRAPIE_MILK_2009.pdf


Prions in Milk from Ewes Incubating Natural Scrapie

http://www.plospathogens.org/article/info:doi%2F10.1371%2Fjournal.ppat.1000238


ProMED-mail

Archive Number 20050211.0467 Published

Date 11-FEB-2005 Subject PRO/AH/EDR> CJD (new var.) update 2005 (02)

snip...

******

[3] Date: Thu 20 Jan 2005 From: Terry S. Singeltary Sr.

Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

----------------------------------------------------------------------

[The following is the summary of a paper by Mathias Heikenwalder and 8 others, published in Science online, 10.1126/science.1106460, Thu 20 Jan 2005 .

This paper describes work that illustrates that chronic inflammatory conditions may affect and expand the natural and iatrogenic transmission of prions - Mod.CP]

Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with 5 inflammatory diseases of kidney, pancreas or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin upregulation and ectopic induction of PrPC-expressing FDC-M1+ cells, whereas inflamed organs of mice lacking lymphotoxin-alpha or its receptor accumulate neither PrPSc nor infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

****** [4] Date: Thu 20 Jan 2005 From: Terry S. Singeltary Sr. Source: Reuters News Agency, Thu 20 Jan 2005 [edited]



Study Finds that Illness May Promote Spread of Mad Cow Prion

------------------------------------------------------------

The agent that transmits mad cow disease and related diseases may spread further in the body of an animal suffering from certain illnesses, scientists said on Thu 20 Jan 2005. Their finding raises the question of whether measures aimed at curbing the spread of mad cow disease, or bovine spongiform encephalopathy (BSE), are adequate, the researchers said.

Tests on mice showed that prions, the protein-like fragments that transmit BSE and related diseases [e.g. variant Creutzfeldt-Jakob disease in humans], can show up in organs they are not supposed to if the mouse has an inflammatory condition. Scientists have believed that BSE-causing prions are limited to the brain, spleen, spinal cord and lymph tissue, although some tests have suggested blood and muscle tissue may also harbor the prions. The latest study, published in the journal Science, suggests prions may also sometimes be found in the kidney, pancreas and liver. "We administered prions to mice with 5 inflammatory diseases of kidney, pancreas or liver," wrote the researchers, led by top prion expert Dr. Adriano Aguzzi of the University Hospital of Zurich in Switzerland.

Aguzzi and colleagues in Britain and the United States inoculated specially bred mice with prions and checked to see if the prions spread in their bodies when the mice had an inflammatory condition. This is because other studies had suggested that prions might be attracted to immune system inflammatory cells. "In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs," the researchers wrote.

BSE peaked in British cattle herds in the mid-1990s, and a few cases have been reported in other countries. Canada reported its 3rd case this month. People who eat BSE-infected beef products can develop a related human brain disease called variant Creutzfeldt-Jakob disease or vCJD. There is no treatment or cure. [As of 4 Feb 2005, so far in the UK for the year 2005 there have 8 referrals of suspected CJD; and there have been 8 deaths from sporadic CJC, one from GSS and none from familial, iatrogenic or variant CJD. - Mod.CP]. It has killed 148 Britons, and 5 [now 6] Britons are alive with the disease, according to the British Department of Health's monthly report on the disease. The World Health Organization says it has reports of 6 cases in France, one in Ireland, one in Italy, one in Canada and one in the United States [and one in Japan: see; ProMED-mail post "CJD (new var.) - Japan: death 20050204.0381" - Mod.CP]

Experts believed BSE first appeared when cattle were fed improperly rendered remains of sheep infected with scrapie, a related disease. In 1997, the United States and Canada imposed animal feed bans, and have mandated the removal of materials believed to carry infectious prions. These include the skull, brain, nerves attached to the brain, eyes, tonsils, spinal cord and attached nerves, plus a portion of the small intestine. The study suggests that even symptom-free animals may also have prions in their liver, kidney, and pancreas.

-- Terry S. Singeltary Sr.

****** [5] Date: Fri 21 Jan 2005 From: ProMED-mail Souce: New York Times, Fri 21 Jan 2005 [edited]



Study Finds Broader Reach for Mad Cow Proteins

----------------------------------------------

Mad cow disease has long been thought to occur in just the brains and nervous systems of infected animals. But scientists are reporting today that the proteins thought to cause the disease can travel to other organs as well. The research is based on experiments with mice, but if it is borne out in other species, it may suggest that no part of an infected animal is safe to eat. The disease leads to a fatal brain disease in humans [variant Creutzfeldt-Jakob disease].

In the mouse experiments, reported in the journal Science [see [3] above], researchers in Switzerland found that prions, proteins that are the infectious agent in mad cow disease, follow immune cells, called lymphocytes, in the body. When mice were given chronic infectious diseases of the liver, kidney and pancreas and then inoculated with prions, the prions made their way to the infected organs. Dr. Adriano Aguzzi, a neuropathologist at the University Hospital in Zurich, who led the experiments, said this meant that cows and sheep infected with prions could harbor the disease in any inflamed organ.

But Dr. David R. Smith, a veterinarian at the University of Nebraska, said the research did not raise alarms about American beef. For one thing, he said, livestock with obvious signs of systemic infection, like a fever, are not allowed into the food supply. And most American cattle are slaughtered while they are young and at reduced risk of infection.

Many countries, including the United States, require the removal of skulls, brains, eyes, spinal cords and other nervous tissues from slaughtered animals because prions are known to accumulate in those tissues. Even in countries with mad cow disease, mainly in Europe, meat is considered safe if those tissues are removed, Dr. Aguzzi said. But the disease could spread more readily if infections are not obvious or if inspections are sloppily done, he said.

[Byline: Sandra Blakeslee]

-- ProMED-mail

****** [6] Date: Fri 4 Feb 2005 From: Terry S. Singeltary Sr.

Source: Spongiform Encephalopathy Advisory Committee (SEAC), Position Paper, January 2005 [edited]



Position Statement: Maternal Transmission of variant Creutzfeldt-Jakob disease

-----------------------------------------------

Issue:

1. The Chief Medical Officer for England asked SEAC to consider current evidence and comment on the potential transmission of variant Creutzfeldt-Jakob disease (vCJD) from mother to child via human breast milk. In utero transmission was also considered. The committee also commented on the scientific basis of a risk reduction measure for possible transmission of vCJD via banked breast milk.

Background:

2. No diagnostic test is currently available for the detection of abnormal PrP in milk. Research is under way to develop tests to screen for the possible presence of abnormal prion protein (PrP) in milk samples from cattle experimentally infected with BSE [A joint FSA/SEAC milk working group is monitoring and providing advice on this research carried out at the Veterinary Laboratories Agency.] These modified tests may also be applicable to human milk. However, it is not yet clear when/if a reliable test will be available.

3. A small number of breast milk banks in the UK supply highly vulnerable premature babies for whom no milk may be available from the mother. A model developed by the Department of Health to assess the effect of pooling breast milk from multiple donors on the possible risks of transmission of vCJD via breast milk banks was considered.

4. There is some, albeit limited, published epidemiological and experimental research on maternal transmission of prion diseases. There are also unpublished surveillance data of children born to vCJD cases from the National CJD Surveillance Unit and UK surveillance of neurological illness in children which might inform on potential risks of maternal transmission.

Breast milk banks:

5. There is no evidence that vCJD infectivity has ever been transmitted through breast milk. However, a theoretical risk exists. Modelling studies clearly show that the practice of pooling breast milk increases the number of donors to which a recipient is exposed and thereby increases the potential risk of an infant receiving milk contaminated with vCJD infectivity. The theoretical risk of infection can be minimised by not pooling the milk, by the use of individual hand operated breast milk pumps for single donors, and by the use of single-use sterilised bottles for collection. In addition, available evidence suggests that infection/inflammation of the breast results in increased lymphocytes in milk and therefore increased risk of infectivity. This risk would be minimised if milk from donors showing signs of infection were not used.

6. The committee suggested that, if practicable, milk could be stored for an appropriate period of time to allow the health status of donors to be monitored, before it is released. However, information was not available to the committee on whether long-term storage of human milk is detrimental to its nutritional quality. Maternal transmission

7. There is evidence from animal studies for low-level maternal transmission of prions in cattle and sheep. This transmission may occur in utero, via milk and/or perinatally. However, the possibility that this putative maternal transmission might have been due to another mode of transmission, for example through a contaminated environment or feed, cannot be ruled out.

8. In contrast, in humans there is no evidence for maternal transmission in cases of familial prion disease, other than the transfer of a mutant form of the PrP gene, and there is no evidence of maternal transmission of Kuru [a chronic, progressive, uniformly fatal nervous system disorder caused by prions, associated with cannibalism among the Fore tribe and neighboring peoples in New Guinea. - CopyEd.PG]. However, compared with other human prion diseases vCJD may pose a greater risk because of the greater involvement of the lymphoreticular system in vCJD pathogenesis. Although, breast tissue (and placenta) from a single vCJD case tested negative for PrPvCJD, transfer of infectivity to breast milk may depend on the physiological status of the mammary gland. Similar tests or infectivity bioassays have not been conducted on breast tissue from lactating patients with vCJD.

9. A published study suggesting transmission of sCJD in colostrum (ref. 1) was considered unreliable because tissues not normally associated with high levels of infectivity (blood and placenta) showed equivalent infectivity to that of the brain in this study.

10. Analysis of prospective surveillance data of UK children born to mothers with, or that had subsequently developed clinical vCJD, provide no evidence for maternal transmission of vCJD. However, the number of cases is very small and the incubation period of vCJD, if transmitted from mother to child, is unknown and so the children may yet be too young to have developed symptoms.

11. The phenotype of BSE infection in humans expressing PrP genotypes other than M/M at codon 129 is not known. Given recently published studies in mice expressing the human PrP gene (ref. 2), which suggest that the human PrP genotype may affect disease phenotype, the committee considered it very important that undiagnosed neurological diseases be carefully monitored. In this respect, amongst others, it is recommended that the careful monitoring of neurological illnesses through the PIND surveillance of children (ref. 3) continue.

Conclusions

12. In summary, there is currently no epidemiological evidence for maternal transmission of vCJD, including transmission via breast milk. However, there is a hypothetical risk. Although available evidence is limited and mostly indirect rather than direct, this risk, if any, appears to be low. As a risk cannot be excluded, a watching brief should be maintained.

References:

(1) Tamai Y et al. Demonstration of the transmissible agent in tissue from a pregnant woman with CJD. New Eng J Med 1992 327, 649.

(2) Wadsworth et al. Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science. 2004 306, 1793-1796.

(3) Devereux G et al. Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND). Arch DisChild. 2004 89, 8-12.

-- Terry S. Singeltary Sr.

******

snip...

ProMED-mail promed@promedmail.org


http://www.promedmail.org/pls/apex/f?p=2400:1202:10581428266066::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_MAIL_ID:X,28068



Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html



TSS

Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed Sheep

Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16 0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed Sheep

B. C. Maddison,1 C. A. Baker,1 H. C. Rees,2 L. A. Terry,3 L. Thorne,3 S. J. Bellworthy,3 G. C. Whitelam,2 and K. C. Gough4* ADAS UK, Department of Biology, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom,1 Department of Biology, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom,2 Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom,3 School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire LE12 5RD, United Kingdom4

Received 9 January 2009/ Accepted 27 May 2009

The potential spread of prion infectivity in secreta is a crucial concern for prion disease transmission. Here, serial protein misfolding cyclic amplification (sPMCA) allowed the detection of prions in milk from clinically affected animals as well as scrapie-exposed sheep at least 20 months before clinical onset of disease, irrespective of the immunohistochemical detection of protease-resistant PrPSc within lymphoreticular and central nervous system tissues. These data indicate the secretion of prions within milk during the early stages of disease progression and a role for milk in prion transmission. Furthermore, the application of sPMCA to milk samples offers a noninvasive methodology to detect scrapie during preclinical/subclinical disease.

--------------------------------------------------------------------------------

* Corresponding author. Mailing address: School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire LE12 5RD, United Kingdom. Phone: 44-115-9516272. Fax: 44-115-9516440. E-mail: kevin.gough@nottingham.ac.uk

Published ahead of print on 3 June 2009.

--------------------------------------------------------------------------------

Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16 0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.





http://jvi.asm.org/cgi/content/abstract/83/16/8293





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





http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_TRANSMISSION_SCRAPIE_MILK_2009.pdf





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





Sheep consumption: a possible source of spongiform encephalopathy in humans.

Davanipour Z, Alter M, ***el 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.





http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract





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





Full Scientific Reports

Experimental oral transmission of United States origin scrapie to neonatal sheep

Amir N. Hamir1, Robert A. Kunkle, Justin J. Greenlee and Juergen A. Richt Correspondence: 1Corresponding Author: Amir N. Hamir, National Animal Disease Center, ARS, USDA, 2300 Dayton Avenue, PO Box 70, Ames, IA 50010. amir.hamir@ars.usda.gov

Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. The current study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (PrPSc) by immunohistochemistry and Western blot in tissues of genetically susceptible and resistant neonatal lambs inoculated with pooled brain homogenates from 13 U.S. origin scrapie-affected ewes. Nine Suffolk lambs with genotypes AA/RR/QQ (n = 5) and AA/RR/QR (n = 4) at codons 136, 154, and 171, respectively) were orally inoculated, within 12 hr of birth, with 1 ml of a 10% (w/v) brain homogenate prepared from scrapie-affected sheep brains. Inoculated animals were euthanized when advanced clinical signs of scrapie were observed. All QQ sheep developed clinical signs of scrapie, with a mean survival time of 24 months. Spongiform lesions in the brains and PrPSc deposits in the central nervous system and lymphoid tissues were present in these sheep. None of the QR sheep succumbed to the disease. A previous study that used a larger volume (30 ml of 10% brain suspension) of the same inoculum in 4-month-old Suffolk lambs of susceptible genotype documented longer survival periods (average 32 months), and only 5 of 9 inoculated sheep developed scrapie. Findings of this study suggest that orally exposed neonatal lambs of a susceptible (QQ) genotype exhibit a higher attack rate and shorter incubation period than older (4-month-old) lambs exposed to a larger dose (30x) of the same inoculum.

Key Words: Immunohistochemistry . neonatal sheep . scrapie . spongiform encephalopathy . Western blot





http://jvdi.org/cgi/content/abstract/21/1/64?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=21&issue=1&resourcetype=HWCIT





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. ........





http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf





Title: Characterization of a U.S. Sheep Scrapie Isolate with Short Incubation Time

Authors

Hamir, Amirali Richt, Juergen Kunkle, Robert Greenlee, Justin Bulgin, M - UNIVERSITY OF IDAHO Gregori, L - VA MEDICAL CENTER, MD Rohwer, R - VA MEDICAL CENTER, MD

Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: April 16, 2009 Publication Date: N/A

Interpretive Summary: Scrapie is a naturally occurring fatal disease of sheep and goats. In a previous study it was shown that sheep inoculated with US scrapie inoculum (No. 13-7) induced terminal disease within an average of 19 months. We have since produced an inoculum, No. X124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents laboratory findings in tissues of sheep inoculated with No. X124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post inoculation (MPI). Sheep that were genetically susceptible developed the disease faster (within 6 months). Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was supposed to be highly resistant to scrapie. This indicates that inoculum No. X124 appears to be more virulent than inoculum No. 13-7. Importantly this strain of scrapie represents a significant development in that it provides a natural model that requires less than 25 percent of the time for the disease to develop, thus enabling a faster pace for research investigating prion disease pathogenesis and inactivation. Technical Abstract: Scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. Susceptibility to the disease is partly dependent upon the genetic makeup of the host. In a previous study it was shown that sheep intracerebrally inoculated with US scrapie inoculum (No. 13-7) developed terminal disease within an average of 19 months. We have since produced an inoculum, No. x124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents clinicopathological findings and the distribution of abnormal prion proteins (PrP**Sc) by immunohistochemical (IHC) and Western blot (WB) techniques, in tissues of sheep inoculated with No. x124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post-inoculation (MPI). Sheep that had VV or AV at codon 136 of prion protein (PRNP) gene developed the disease faster and were euthanized at an average of 4.3 and 5.6 MPI, respectively. Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was relatively resistant (QR at codon 171) to scrapie. This indicates that inoculum No. x124 appears to induce scrapie in shorter time than inoculum No. 13-7, especially in sheep homozygous or heterozygous for valine at codon 136.





http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=230885





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

A1 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/





Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...





http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html







http://nor-98.blogspot.com/





http://scrapie-usa.blogspot.com/





Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009





http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html





SEE THIS DAMNING VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;





http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html





Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed Sheep

Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16 0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed Sheep

B. C. Maddison,1 C. A. Baker,1 H. C. Rees,2 L. A. Terry,3 L. Thorne,3 S. J. Bellworthy,3 G. C. Whitelam,2 and K. C. Gough4* ADAS UK, Department of Biology, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom,1 Department of Biology, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom,2 Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom,3 School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire LE12 5RD, United Kingdom4

Received 9 January 2009/ Accepted 27 May 2009

The potential spread of prion infectivity in secreta is a crucial concern for prion disease transmission. Here, serial protein misfolding cyclic amplification (sPMCA) allowed the detection of prions in milk from clinically affected animals as well as scrapie-exposed sheep at least 20 months before clinical onset of disease, irrespective of the immunohistochemical detection of protease-resistant PrPSc within lymphoreticular and central nervous system tissues. These data indicate the secretion of prions within milk during the early stages of disease progression and a role for milk in prion transmission. Furthermore, the application of sPMCA to milk samples offers a noninvasive methodology to detect scrapie during preclinical/subclinical disease.

-------------------------------------------------------------------------------- *

Corresponding author. Mailing address: School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire LE12 5RD, United Kingdom. Phone: 44-115-9516272. Fax: 44-115-9516440. E-mail:
kevin.gough@nottingham.ac.uk

Published ahead of print on 3 June 2009.

--------------------------------------------------------------------------------

Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16 0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.





http://jvi.asm.org/cgi/content/abstract/83/16/8293?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=PRION&searchid=1&FIRSTINDEX=0&volume=83&issue=16&resourcetype=HWCIT





Wednesday, March 18, 2009 Detection of CWD Prions in Urine and Saliva of Deer by Transgenic Mouse Bioassay





http://chronic-wasting-disease.blogspot.com/2009/03/detection-of-cwd-prions-in-urine-and.html





Friday, December 12, 2008 Prions in Milk from Ewes Incubating Natural Scrapie

Prions in Milk from Ewes Incubating Natural Scrapie





http://scrapie-usa.blogspot.com/2008/12/prions-in-milk-from-ewes-incubating.html





****** [5] Italy: Prions suspected in sheep milk Date: Tue 8 Nov 2005 From: ProMED-mail <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000473/!x-usc:mailto:promed@promedmail.org> Source: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000473/!x-usc:mailto:News@nature.com, 3 Nov 2005 [edited]




<http://www.nature.com/news/2005/051031/full/051031-7.html>





http://www.promedmail.org/pls/otn/f?p=2400:1202:5548991170320905::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_MAIL_ID:X,30998






TSS

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.

TAFS

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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

TAFS

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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

Introduction.........

SNIP...

full text ;



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

Prions in Milk from Ewes Incubating Natural Scrapie

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: o.andreoletti@envt.fr

Introduction.........


SNIP...


full text ;


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

-------------------- BSE-L@LISTS.AEGEE.ORG --------------------

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: 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

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

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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.

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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