Transmissible Spongiform Encephalopathy

Monday, January 27, 2014

Evidence of in utero transmission of classical scrapie in sheep

John Spiropoulos⇑, Stephen A.C. Hawkins, Marion M. Simmons and Susan J. Bellworthy

+ Author Affiliations Animal Health and Veterinary Laboratories Agency (AHVLA) Weybridge, Addlestone, Surrey KT15 3NB, UK

ABSTRACT

Classical scrapie is one of the Transmissible Spongiform Encephalopathies (TSE), a group of fatal infectious diseases that affect the central nervous system (CNS). Classical scrapie can transmit laterally from ewe to lamb perinatally, or between adult animals. Here we report detection of infectivity in tissues of an unborn foetus, providing evidence that in utero transmission of classical scrapie is also possible.

FOOTNOTES Corresponding Author: John Spiropoulos: Department of Pathology, Animal Health and Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, Email: john.spiropoulos@ahvla.gsi.gov.uk, Tel: +44 (0) 1932 357795, Fax: +44 (0) 1932 357805 Copyright © 2014, American Society for Microbiology. All Rights Reserved.

http://jvi.asm.org/content/early/2014/01/16/JVI.03264-13.abstract?etoc

Tuesday, September 17, 2013

Mother to Offspring Transmission of Transmissible Spongiform Encephalopathy TSE prion disease snip... Maternal CWD infection also appears to result in lower percentage of live birth offspring. In addition, evolving evidence from protein misfolding cyclic amplification (PMCA) assays on fetal tissues suggest that covert prion infection occurs in utero. Overall, our findings demonstrate that transmission of prions from mother to offspring can occur, and may be underestimated for all prion diseases.

snip...

Here, in an experimental model of CWD, we have demonstrated the transmission of infectious prions from clinical and subclinical mothers to full-term viable, nonviable and in utero harvested offspring, revealing that the transmission of TSEs from mother to offspring can occur and may be underestimated for all prion diseases. snip... please see full text ; Tuesday, September 17, 2013

*** Mother to Offspring Transmission of Transmissible Spongiform Encephalopathy TSE prion disease ***

http://transmissiblespongiformencephalopathy.blogspot.com/2013/09/mother-to-offspring-transmission-of.html

Friday, May 10, 2013

Evidence of effective scrapie transmission via colostrum and milk in sheep

http://scrapie-usa.blogspot.com/2013/05/evidence-of-effective-scrapie.html

Tuesday, April 30, 2013

Transmission of classical scrapie via goat milk

Veterinary Record2013;172:455 doi:10.1136/vr.f2613

http://scrapie-usa.blogspot.com/2013/04/transmission-of-classical-scrapie-via.html

Envt.18: Mother to Offspring Transmission of Chronic Wasting Disease

Candace K. Mathiason,† Amy Nalls, Kelly Anderson, Jeanette Hayes-Klug, Jenny G. Powers, Nicholas J. Haley and Edward A. Hoover

Colorado State University; Fort Collins, CO USA†Presenting author; Email: ckm@lamar.colostate.edu

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 four months post infection. Ten fawns were born to these CWD-infected doe— four of the fawns were viable, five were non-viable and one was a first trimester fetus harvested from a CWD-infected doe euthanized at end-stage disease. 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 by IHC as early as 40 days of age. Moreover, sPMCA performed on rectal lymphoid tissue has yielded positive results on another fawn at ten days of age. In addition, sPMCA assays have demonstrated amplifiable prions in fetal placental or spleen tissue of three non-viable fawns and mammary tissue of the dams.

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.

===========================

PPo3tss-18: A Possible Case of Maternal Transmission of the BSE Agent within Captive Cheetah Affected with Feline Spongiform Encephalopathy

Anna Bencsik, Sabine Debeer, Thierry Petit and Thierry Baron

Afssa; Unité ATNC; Lyon, France; Zoo de la Palmyre; Les Mathes, France

Key words: BSE, FSE, vertical transmission

Introduction. Feline spongiform encephalopathy (FSE) is considered to be related to bovine spongiform encephalopathy (BSE). It has been reported in domestic cats as well as in captive wild cats including cheetahs, first in the United Kingdom (UK) and then in other European countries. In France, several cases were described in cheetahs either imported from UK or born in France. Here we report details of two other FSE cases in captive cheetah. These cases are of particular interest since the 2nd case of FSE in a cheetah born in France, appears most likely due to maternal transmission.1

Results. Complete PrPd study showed the close likeness between the two cheetah cases. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah FSE revealed similar vacuolar lesion profiles, PrPd brain mapping with occurrence of typical florid plaques.

Materials and Methods. Using immunohistochemistry (IHC), pathological form of PrP(PrPd) was analyzed in the brains and peripheral organs of these two cheetahs. Transmission studies to the TgOvPrP4 mouse line were also performed, for comparison with the transmission of cattle BSE. Lesion profiles of the infected transgenic mice were analyzed as well as type and brain distribution of PrPd.

Conclusion. Collectively, these data indicate that both FSE cases harbor the same strain of agent as the cattle BSE agent. Because this is most probably a case of maternal transmission of the disease, this new observation may have some impact on our knowledge of vertical transmission of BSE agent-linked TSEs such as in human variant Creutzfeldt Jakob disease.

References

1. Bencsik et al. PLoS One 2009; 4:6929.

=========================

PPo3tss-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.

PRION 2011

landesbioscience.com

International Prion Congress: From agent to diseaseSeptember 8–11, 2010Salzburg, Austria

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Friday, December 23, 2011

Detection of PrPres in Genetically Susceptible Fetuses from Sheep with Natural Scrapie

http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/detection-of-prpres-in-genetically.html

Monday, November 22, 2010

SHEEP WITH MASTITIS TRANSMIT INFECTIOUS PRIONS THROUGH THE MILK

http://scrapie-usa.blogspot.com/2010/11/sheep-with-mastitis-transmit-infectious.html

Saturday, April 12, 2008

Evidence of scrapie transmission via milk

http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html

[6] Date: Fri 4 Feb 2005

From: Terry S. Singeltary Sr. flounder@wt.net

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

http://www.seac.gov.uk/statements/cjdtransmissionfinal.pdf

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. flounder@wt.net ******

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

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

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

[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:

Background:

Breast milk banks:

Conclusions

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

******[6]Date: Fri 4 Feb 2005

From: Terry S. Singeltary Sr.

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

<http://www.seac.gov.uk/statements/cjdtransmissionfinal.pdf>

snip...

******[6]Date: Fri 4 Feb 2005

From: Terry S. Singeltary Sr.

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

<http://www.seac.gov.uk/statements/cjdtransmissionfinal.pdf>

SNIP...

SEE FULL TEXT ;

p.s. ProMed archives are pay-per-view now. ...tss

http://apex.oracle.com/pls/otn/f?p=2400:1001:1720436792652856::::F2400_P1001_BACK_PAGE,F2400_P1001_ARCHIVE_NUMBER,F2400_P1001_USE_ARCHIVE:1001,20050211.0467,Y

SNIP...SEE FULL TEXT ;

http://transmissiblespongiformencephalopathy.blogspot.com/2013/09/mother-to-offspring-transmission-of.html

http://scrapie-usa.blogspot.com/2010_11_01_archive.html

cjd mother to child transmission ???

Mother passes on CJD to unborn baby Sun, 17 Sep 2000 Telegraph By Rajeev Syal, Jenny Booth and Chris Hastings

http://www.mad-cow.org/00/mar00_mid_news.html#mmm

http://www.mad-cow.org/00/sep00_late_news.html#bbb

Dr Will offers me a tour of the laboratories. As we are getting up to go, I broach something that has been bothering me. Does he think the victims will get any younger?

'Well, we now have a 12-year-old.'

A 12-year-old?

'That's what I said.' He looks almost ashamed.

Girl or boy?

'I can't say.'

But if the incubation period is at least 10 years, then the child was barely eating solid food when it contracted the infection. 'I'm not saying anything,' the neurologist says wearily. 'You've got small children of your own, Allison. You do the maths.'

http://www.mad-cow.org/00/sep00_late_news.html#ddd

The child has been ill since she was born but tests to pinpoint the cause of the problem have so far proved inconclusive INCONCLUSIVE. What does not put an end to a thing. Inconclusive presumptions are those which may be overcome by opposing proof; for example, the law presumes that he who possesses personal property is the owner of it, but evidence is allowed to contradict this presumption, and show who is . At birth the baby, who cannot be named for legal reasons, could not swallow and was unable to gain weight.

http://www.thefreelibrary.com/Tests+for+baby+after+mother+killed+by+CJD.-a062486993

Wednesday, December 30, 2009

Is there evidence of vertical transmission of variant CJD ?

J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2009.172148

Is there evidence of vertical transmission of variant CJD?

Katy Murray (kmurray12@doctors.org.uk) + Author Affiliations

NationalCJD Surveillance Unit, United Kingdom James Peters (jimmypeters1980@yahoo.co.uk) + Author Affiliations

NationalCJD Surveillance Unit, United Kingdom Lesley Stellitano (lesley.stellitano@addenbrookes.nhs.uk) + Author Affiliations

Addenbrooke's Hospital, United Kingdom Annemarie Winstone (annemarie.winstone@addenbrookes.nhs.uk) + Author Affiliations

Addenbrooke's Hospital, United Kingdom Christopher Verity (christopher.verity@addenbrookes.nhs.uk) + Author Affiliations

Addenbrooke's Hospital, United Kingdom Robert Will (r.g.will@ed.ac.uk) + Author Affiliations

NationalCJD Surveillance Unit, United Kingdom Published Online First 27 April 2009 Abstract Objectives: The possibility of vertical transmission of variant CJD (vCJD) has been raised, because of the widespread distribution of infectivity in vCJD and the demonstration that this condition can be transmitted through blood transfusion. The aim is to search for evidence of this type of transmission of vCJD.

Methods: A national surveillance system for CJD has been established in the UK since 1990. Through this register details were extracted of all children born to vCJD cases up to March 2009. This list was checked against the CJD register and cases identified through the UK study of progressive intellectual and neurological deterioration in children (PIND) to determine whether any of the children of vCJD cases had themselves developed a progressive neurological disorder or vCJD.

Results: 125 children have been born to parents with a diagnosis of vCJD. Nine of these children were born to females with vCJD who were symptomatic at conception, birth or within a year of clinical onset. Only one woman was known to have breast fed her child. None of the children of vCJD cases have been referred to the NCJDSU as suspected vCJD and none have been classified as suffering from a progressive neurodegenerative disorder through the PIND study. One of the children has been investigated by the National Prion Unit (see accompanying case report).

Interpretation: To date there is no evidence of vertical transmission of vCJD. However, the incubation period through this mechanism might be prolonged and it will be many years before observational data can exclude this possibility.

http://jnnp.bmj.com/content/early/2009/04/27/jnnp.2009.172148.abstract

snip...see more here ;

Wednesday, December 30, 2009

Is there evidence of vertical transmission of variant CJD ?

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/is-there-evidence-of-vertical.html

Thursday, January 23, 2014

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]

http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/medical-devices-containing-materials.html

2013 Tuesday, September 17, 2013

*** Mother to Offspring Transmission of Transmissible Spongiform Encephalopathy TSE prion disease ***

To date, 125 children have been born to women who later developed CJD [11]. This is concerning because PrPCJD has been detected in the fetal and pregnancy related tissues of a woman infected with CJD [12]. Although decades may pass before the onset of clinical effects associated with such transmission due to a long subclinical carrier state, the probability that these individuals harbor infectious prions remains high.

http://transmissiblespongiformencephalopathy.blogspot.com/2013/09/mother-to-offspring-transmission-of.html

Sunday, August 25, 2013

Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission

snip...

Oral.08: Mother to offspring transmission of chronic wasting disease in Reeve's Muntjac deer Amy Nalls,1 Erin McNulty,1 Jenny Powers,2 Davis Seelig,1 Clare Hoover,1 Nicholas Haley,1 Jeanette Hayes-Klug,1 Kelly Anderson,1 Paula Stewart,3 Wilfred Goldmann,3 Edward A. Hoover1 and Candace K. Mathiason1 1Colorado State University; Fort Collins, CO USA; 2National Park Service; Fort Collins, CO USA; 3The Roslin Institute and Royal School of Veterinary Studies; Edinburgh, UK To investigate the role mother to offspring transmission plays in chronic wasting disease (CWD), we have developed a cervid model employing the Reeve's muntjac deer (Muntiacus reevesi). Eight muntjac doe were orally inoculated with CWD and tested PrPCWD lymphoid positive by 4 mo post infection. Fourteen fawns were born to these eight CWD-infected doe-3 were born viable, 6 were born non-viable and 5 were harvested as fetuses from early or end-stage CWD-infected doe. All three viable fawns have demonstrated CWD IHC lymphoid biopsy positivity between 43 d post birth and 11 mo post birth. Two of these three CWD positive viable offspring have developed clinical signs consistent with TSE disease (28-33 mo post birth). Moreover, CWD prions have been detected by sPMCA in 11 of 16 tissues harvested from 6 full-term non-viable fawns and in 7 of 11 fetal tissues harvested in utero from the second and third trimester fetuses. Additional tissues and pregnancy related fluids from doe and offspring are being analyzed for CWD prions. In summary, using the muntjac deer model we have demonstrated CWD clinical disease in offspring born to CWD-infected doe, and in utero transmission of CWD from mother to offspring. These studies provide basis to further investigate the mechanisms of maternal transfer of prions.

snip...

Sunday, August 25, 2013

Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission

http://chronic-wasting-disease.blogspot.com/2013/08/prion2013-chronic-wasting-disease-cwd.html

>>> Here, in an experimental model of CWD, we have demonstrated the transmission of infectious prions from clinical and subclinical mothers to full-term viable, nonviable and in utero harvested offspring, revealing that the transmission of TSEs from mother to offspring can occur and may be underestimated for all prion diseases. <<<

2014

Sunday, January 19, 2014

National Prion Disease Pathology Surveillance Center Cases Examined1 as of January 8, 2014

http://prionunitusaupdate.blogspot.com/2014/01/national-prion-disease-pathology.html

Thursday, January 23, 2014

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]

http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/medical-devices-containing-materials.html

Terry S. Singeltary Sr.

Thursday, January 23, 2014

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]

Terry S. Singeltary Sr. Submission [Docket No. FDA–2013–D–1574]

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices)

Draft Guidance for Industry and Food and Drug Administration Staff

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.

Document issued on January 23, 2014.

You should submit comments and suggestions regarding this draft guidance document within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov . Identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register.

For questions regarding this document contact Dr. Charles Durfor at 301-796-6970 (charles.durfor@fda.hhs.gov) or Dr. Scott McNamee at 301-796-5523 or 301-796-5500 (scott.mcnamee@fda.hhs.gov).

This document, when final, will supersede “Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices)” issued November 6, 1998.

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Devices and Radiological Health

Transmissible Spongiform Encephalopathy Working Group

Office of Compliance

Office of Device Evaluation

Contains Nonbinding Recommendations

Preface

Additional Copies

Additional copies are available from the Internet. You may also send an e-mail request to dsmica@fda.hhs.gov to receive an electronic copy of the guidance or send a fax request to 301-847-8149 to receive a hard copy. Please use the document number 2206 to identify the guidance you are requesting.

Contains Nonbinding Recommendations

Table of Contents

I. Introduction......................................................................................................................................................... 1

II. Background........................................................................................................................................................ 1

III. Scope ................................................................................................................................................................ 2

IV. Policy Issues..................................................................................................................................................... 2

A. Control of Animal Tissue Collection............................................................................................................. 2

B. Manufacturing Controls for Animal Tissue Components.............................................................................. 3

C. Sterilization.................................................................................................................................................... 3

D. Transmissible Spongiform Encephalopathy-Specific Issues......................................................................... 4

V. References ........................................................................................................................................................ 7

Contains Nonbinding Recommendations

Draft – Not for Implementation

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices)

Draft Guidance for Industry and Food and Drug Administration Staff

This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.

I. Introduction

The Food and Drug Administration (FDA) is issuing this draft guidance to update the policy regarding the use of animal-derived material in medical device manufacturing. The role of animal derived-material in medical devices is well established. However, these materials may carry a risk of transmitting infectious disease when improperly collected, stored or manufactured. The guidance describes the information you should document at the manufacturing facility and include in any premarket submissions. This guidance, when finalized, will supersede “Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices)” issued November 6, 1998 (the 1998 guidance).

FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

II. Background

This draft guidance updates the 1998 guidance by addressing aspects of potential risk from the use of animal tissues (e.g., viruses and bacteria) and now includes recommendations

Contains Nonbinding Recommendations

Draft – Not for Implementation

related to all transmissible spongiform encephalopathies (TSEs). The 1998 guidance addressed ways to reduce the potential for exposure to bovine spongiform encephalopathy (BSE). This document continues to focus on the control of transmissible disease, and contains recommendations for documenting the source of animal tissue and conducting viral inactivation validation studies. Commercial production of animals as the source of animal tissues used in medical devices can introduce several kinds of risks. The 1998 document primarily addressed geographical factors in the sourcing of the animal tissue. In addition to geographical factors, this document includes recommendations that recognize the role of careful animal husbandry to ensure safe tissue sources.

This guidance is intended to help you identify the possible risks related to tissues from animal sources when these tissues are used in medical devices.1

III. Scope

The information in this guidance is applicable to all medical devices that contain or are exposed to animal-derived materials (e.g., bovine, ovine, porcine, avian materials) with the exception of in vitro diagnostic devices. Consideration of these issues should aid in reducing the risk of infectious disease transmission by medical devices.

IV. Considerations When Using Animal-Derived Materials

A. Control of Animal Tissue Collection

FDA recommends you collect and document the following information for animal tissue-derived materials that are used as either device components (e.g., pericardium, viscera, bone, hyaluronic acid, collagen) or manufacturing reagents (e.g., tissue culture media, enzymes). You may document this information by reference to other regulatory submissions (e.g., Master File, PMA, 510(k)) that contain this information. Information that is helpful during the review of animal-derived device materials includes Certificates of Analysis and Materials Safety Data Sheets, when available. Regulatory submissions and facility records (see 21 CFR 820.180) should describe the following:

• animal species;

• age of animal;

• specific tissue(s) used;

• animal country of origin and residence (more specific geographic location when appropriate);

Contains Nonbinding Recommendations

Draft – Not for Implementation

• methods for monitoring the health of herd and the health of specific animals from which tissues are collected (e.g., vaccinations with live modified viruses that can co-purify in the desired tissue, active surveillance for human pathogens);

• the United States Department of Agriculture (USDA) status of the abattoir;

• methods and conditions for transporting animal tissue (e.g., tissue refrigeration and quarantine); and

• procedures for maintaining records on the above cited issues should be presented in regulatory submissions.

In addition, you should maintain records of the test results for any tests described above for each lot of material at the manufacturing facility and submitted in regulatory documents when appropriate.

B. Manufacturing Controls for Animal Tissue Components

FDA recommends you collect and document the information listed below for all animal-derived materials (and facilities) used in device manufacture. As stated previously, you may document this information by reference to other regulatory submissions (e.g., Master File, PMA, 510(k)) and Certificates of Analysis and Materials Safety Data Sheets, when available. Regulatory submissions and facility records (Device Master Record, see 21 CFR 820.181) should describe:

• test methods and release criteria permitting animal tissues to be further processed and/or combined with other animal tissue(s) or device components for manufacture;

• quarantine procedures for tissues until they have met/failed release criteria;

• test methods and acceptance criteria for assessing in-process and final product bioburden or sterility;

• methods for facility decontamination/sterilization so that cross-contamination is avoided; and

• procedures for maintaining records of the above cited issues should be provided in regulatory submissions.

You should maintain records of any test results for the tests described above for each lot of material at the manufacturing facility (see Device History Record (21 CFR 820.184)). When appropriate, you should also describe these results in regulatory submissions. In addition, you should demonstrate and validate manufacturing equipment cleaning, decontamination, and sterilization relative to the specific pathogen exposure, and document the results.

C. Sterilization

Because the issues for validating the sterilization of devices containing animal or human tissue are sufficiently complex to require a case by case assessment, we recommend you review the

Contains Nonbinding Recommendations

Draft – Not for Implementation

FDA-recognized consensus standards listed in the References to this guidance.2-8 Please note the extent of recognition of the current version of standards referenced in this document on the FDA web site in the database on

Recognized Consensus Standards (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm ). Enter the number of the Standard you wish to check into "Reference Number" field. In addition, we recommend you contact the FDA staff responsible for reviewing the specific device type to discuss your sterilization procedures.

When the risk to the public health is a virus that may be part of the animal tissue, we recommend that you consider the extent to which processing and sterilization inactivate or remove the virus. FDA recommendations for validating viral inactivation methods are described as follows:

Virus Validation Studies

You should assess the processing methods and sterilization techniques used in product manufacture for their ability to inactivate and remove viruses.Viral inactivation data are often obtained by determining the amount of virus in the unprocessed source material before and after exposure to production and sterilization processes.You may determine the extent to which viruses are inactivated using scaled down versions of the specific production and sterilization methods (e.g., acid extraction of collagen or dry heat sterilization) using appropriate model viruses. If you use a model virus during your viral inactivation study of your manufacturing and sterilization processes, you should document the relevance of the model virus you use to the actual virus present in the animal tissue (e.g., DNA-based or RNA-based, enveloped or non-enveloped).

The results of your viral inactivation studies should demonstrate that the sum of the log clearance of virus from the selected processing steps and sterilization processes are at least six logs greater than the concentration of virus anticipated in the unprocessed source material. While the design of viral clearance studies should take the specific product and manufacturing methods into consideration, insight into the general design of such studies is possible via review of the referenced guidance documents.9,10 Viral inactivation studies do not address reduction of possible prion contamination.

D. Transmissible Spongiform Encephalopathy-Specific Issues

The Food and Drug Administration may issue rules specifically on Bovine Spongiform Encephalopathy (BSE) and the regulation of medical devices. Any final rule on BSE would take precedence over the recommendations of this guidance document. Current issues regarding BSE may be addressed at the following FDA website: http://www.fda.gov/animalveterinary/guidancecomplianceenforcement/complianceenforcement/bovinespongiformencephalopathy/default.htm

BSE is a degenerative disease that affects the central nervous system of cattle and is similar to other transmissible spongiform encephalopathies (TSEs) found in sheep (scrapie), deer

Contains Nonbinding Recommendations

Draft – Not for Implementation

(chronic wasting disease),11 and humans (Creutzfeldt-Jakob Disease or CJD). Current data suggest that the incubation period of 2 to 8 years after exposure is required before BSE symptoms are detectable. Currently, there are no treatments for TSE diseases and no screening tests for the detection of disease in a live animal or man. Diagnosis is achieved by post-mortem microscopic examination of brain tissue, as well as assays using ELISA and Western Blot techniques.

The BSE infectious agent is widely theorized to be a prion, (i.e., an abnormally folded form of a normal cellular protein) that facilitates the conversion of additional normal cellular proteins to the infectious prion structure (PrP(res)). Infectious PrP(res) has been detected in bovine brain, spinal cord, eye, ileum, lymph nodes, proximal colon, spleen, tonsil, dura mater, pineal gland, placenta, cerebrospinal fluid, pituitary, adrenal, distal colon, nasal mucosa, peripheral nerves, bone marrow, liver, lung, pancreas, thymus.12 The detection of TSE-infection in other tissues may occur in the future when data are available from more sensitive assays or larger animal studies. Transmission has been experimentally demonstrated in animal studies. 13 The TSE agent is also known to be extremely resistant to traditional forms of disinfection and sterilization.

Epidemiologic data suggest that the BSE epidemic in Great Britain began in 1986 by feeding cattle contaminated meat and bone meal as their protein source. According to the World Organization for Animal Health (OIE), as of 2011, 184619 BSE cases have been identified in Britain and twenty-two cases have been detected in North American cattle. As of 2011, there were also 221 definite or probable cases of new variant CJD (vCJD) worldwide, which is the human form of BSE that appears to be transmitted by consumption of BSE-tainted beef.14 Since December 2003, four cases of Creutzfeldt-Jakob disease (vCJD) presumed to be transfusion-related vCJD have been reported.15 Epidemiological data is updated periodically and is available at http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/CreutzfeldtJakobDisease/EpidemiologicalData/.

Given the long incubation time for disease onset, the absence of a screening test for live animals, and vCJD’s fatal outcome, we recommend that you collect and document the following information for any material derived from an animal (e.g. cattle, sheep, goats, cervids such as deer and elk, etc.) with the potential to carry TSE infection:

• animal species;

• specific tissue used (if multiple tissues are used, identify all tissues used);

• animal’s country of origin and country of residence (or a more specific geographic information when appropriate);

• methods for actively monitoring the health of herd and the health of specific animals from which tissues are collected;

• information concerning the long term health of the herd (e.g., documented breeding history, animal traceability, absence of TSE disease, and standard vaccinations such as live modified viruses which could co-purify in the desired tissue);

Contains Nonbinding Recommendations

Draft – Not for Implementation

• the frequency and type of veterinarian inspections;

• animal feed composition (e.g., animal feed history records, including recordation of co-mingling of feeds, and, labeling of animal feed composition at distribution locations) (In 2008, FDA issued a rule prohibiting certain material from being fed to ruminants. The rule may be found at http://www.gpo.gov/fdsys/pkg/FR-2008-04-25/html/08-1180.htm);

• USDA status of the abattoir;

• animal age at sacrifice;

• animal sacrifice methods that reduce the risk of cross contaminating non-TSE tissues with material from tissues that could contain TSE;

• specifics of the pre and/or post mortem inspections (e.g., gross visual inspection, specific organs and anomalies exams, lab tests such as PrP testing);

• tests performed (and release criteria) for permitting tissue to be further processed and/or combined with other tissues and device components (e.g., a Certificate of Analysis); and

• methods for maintaining the records associated with the above cited issues should be provided in regulatory submissions.

You should maintain records of the test results for tests listed above for each lot of material at the manufacturing facility (see Device History Record (21 CFR 820.184)). When appropriate, you should also describe these results in regulatory submissions.

In addition, the residence time of TSE-infectious material on surfaces is unknown and methods to completely assure removal of TSE-infectious material from surfaces have yet to be fully understood. Products developed for use in abattoirs and non-manufacturing sites where surface contamination by materials from potentially TSE-infected animals (cattle, sheep, cervids such as deer and elk, etc.) may occur may not have been studied or validated for use on more critical sites or equipment such as those intended for the manufacture of devices from animal tissue. Therefore, in facilities involved in device manufacture using tissue from potentially TSE-infected animals (cattle, sheep, cervids such as deer and elk, etc.) your documentation should identify when/whether any potentially TSE-infected material may have been previously processed in your facility and what steps you have taken to address any potential contamination. This information could include the information previously discussed under “Manufacturing Controls for Animal Tissue Components” in section IV. B. of this guidance and the dates of previous tissue processing (see also 21 CFR 820.50).

Because screening assays that can ensure TSE-free bovine tissues have not been FDA-approved or introduced into general practice, the methods discussed above (e.g., monitoring animal feed, controlling animal husbandry and tissue handling) reflect the best available approaches for preparing safe medical devices from bovine tissue. However, when a TSE-screening assay is validated to accurately identify TSE-contaminated tissues, FDA will consider revising this guidance as appropriate and recommending that such a test be introduced into the standard operating procedures for bovine tissue collection and processing.

Contains Nonbinding Recommendations

Draft – Not for Implementation

V. References

1. January 3, 2003 letter from David W. Feigal, MD to Manufacturers of FDA-Regulated Medical Devices Containing Animal Tissue Products or Components available at http://www.fda.gov/ohrms/dockets/ac/04/briefing/4019B2_12.pdf

2. AAMI ANSI ISO 11135:2007 - Sterilization of health care products - Ethylene oxide - Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices

3. AAMI ANSI ISO 17665-1:2006 - Sterilization of health care products -- Moist heat -- Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices

4. AAMI ANSI ISO 11137-1:2006/(R) 2010 - Sterilization of health care products - Radiation - Part 1: Requirements for development, validation, and routine control of a sterilization process for medical devices

5. AAMI ANSI ISO 11737-1:2006 (R)2011 - Sterilization of medical devices - Microbiological methods Part 1: Determination of the population of microorganisms on product

6. AAMI ANSI ISO 11737-2:2009 - Sterilization of medical devices -- Microbiological methods -- Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process

7. AAMI ANSI ISO 14160:2011 - Sterilization of health care products - Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives - Requirements for characterization, development, validation and routine control of a sterilization process for medical devices

8. AAMI ANSI ISO 14937:2009 - Sterilization of health care products - General requirements for characterization of a sterilizing agent and the development, validation, and routine control of a sterilization process for medical devices

9. “ICH Viral Safety Document: QSA Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin (63 FR 51074, September 24, 1998)” http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129101.pdf

10. “Viral Safety Evaluation of Biotechnology Products derived from Cell Lines of Human or Animal Origin” 35 USP <1050>

11. The web site for the USDA’s Animal and Plant Health and Inspection Services concerning CWD (Chronic Wasting Disease) is

Contains Nonbinding Recommendations

Draft – Not for Implementation

http://usdasearch.usda.gov/search?utf8=%E2%9C%93&affiliate=usda&query=CWD&commit=Search

12. WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies, http://www.who.int/bloodproducts/tablestissueinfectivity.pdf

13. “Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle comparison to bovine spongiform encephalopathy in cattle” Cutlip, et.al., Journal of Veterinary Diagnostic Investigation May 2011 vol. 23 no. 3 407-420

14. "Transmissible Spongiform Encephalopathies Advisory Committee Meeting Presentation: vCJD World Situation and Updates” by RG Will (August 1, 2011)

15. Incidence of variant Creutzfeldt-Jakob disease diagnoses and deaths in the UK compiled by N J Andrews at the Statistics Unit, Centre for Infections, Health Protection Agency. (updated 18th May 2011, http://www.cjd.ed.ac.uk/)

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM381491.pdf

Draft Guidance for Industry and Staff; Availability: Medical Devices Containing Materials Derived From Animal Sources (Except for In Vitro Diagnostic Devices), 3826–3827 [2014–01232]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA–2013–D–1574]

Medical Devices Containing Materials Derived From Animal Sources (Except for In Vitro Diagnostic Devices); Draft Guidance for Industry and Food and Drug Administration Staff; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

http://www.gpo.gov/fdsys/pkg/FR-2014-01-23/pdf/2014-01232.pdf

http://www.gpo.gov/fdsys/pkg/FR-2014-01-23/html/2014-01232.htm

*** BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001 ***

Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001

Date: Tue, 9 Jan 2001 16:49:00 –0800

From: "Terry S. Singeltary Sr." flounder@wt.net

Reply-To: Bovine Spongiform Encephalopathy BSE-L@uni-karlsruhe.de

To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

I was lucky enough to sit in on this BSE conference call today and even managed to ask a question. that is when the trouble started.

I submitted a version of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so.

"They tell me it is a closed meeting and they will release whatever information they deem fit. Rather infuriating."

and i would have been doing just fine, until i asked my question. i was surprised my time to ask a question so quick.

(understand, these are taken from my notes for now. the spelling of names and such could be off.)

[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.

[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]

[host Richard] could you repeat the question?

[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[not sure whom ask this] what group are you with?

[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.

[not sure who is speaking] could you please disconnect Mr. Singeltary

[TSS] you are not going to answer my question?

[not sure whom speaking] NO

from this point, i was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;

[unknown woman] what group are you with?

[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?

at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference.

IF i were another Country, I would take heed to my notes, BUT PLEASE do not depend on them. ask for transcript from;

RBARNS@ORA.FDA.GOV 301-827-6906

he would be glad to give you one ;-)

Rockville Maryland, Richard Barns Host

BSE issues in the U.S., How they were labelling ruminant feed? Revising issues.

The conference opened up with the explaining of the U.K. BSE epidemic winding down with about 30 cases a week.

although new cases in other countries were now appearing.

Look at Germany whom said NO BSE and now have BSE.

BSE increasing across Europe.

Because of Temporary Ban on certain rendered product, heightened interest in U.S.

A recent statement in Washington Post, said the New Administration (old GW) has a list of issues. BSE is one of the issues.

BSE Risk is still low, minimal in U.S. with a greater interest in MBM not to enter U.S.

HOWEVER, if BSE were to enter the U.S. it would be economically disastrous to the render, feed, cattle, industries, and for human health.

(human health-they just threw that in cause i was listening. I will now jot down some figures in which they told you, 'no need to write them down'. just hope i have them correct. hmmm, maybe i hope i don't ???)

80% inspection of rendering

*Problem-Complete coverage of rendering HAS NOT occurred.

sizeable number of 1st time FAILED INITIAL INSPECTION, have not been reinspected (70% to 80%).

Compliance critical, Compliance poor in U.K. and other European Firms.

Gloria Dunason Major Assignment 1998 goal TOTAL compliance. This _did not_ occur. Mixed level of compliance, depending on firm.

Rendering FDA license and NON FDA license

system in place for home rendering & feed 76% in compliance 79% cross contamination 21% DID NOT have system 92% record keeping less than 60% total compliance

279 inspectors 185 handling prohibited materials

Renderer at top of pyramid, significant part of compliance. 84% compliance

failed to have caution statement render 72% compliance & cross contamination caution statement on feed, 'DO NOT FEED TO CATTLE'

56 FIRMS NEVER INSPECTED

1240 FDA license feed mills 846 inspected

"close to 400 feed mills have not been inspected"

80% compliance for feed.

10% don't have system.

NON-FDA licensed mills There is NO inventory on non licensed mills. approximately 6000 to 8000 Firms ??? 4,344 ever inspected. "FDA does not have a lot of experience with"

40% do NOT have caution statement 'DO NOT FEED'.

74% Commingling compliance

"This industry needs a lot of work and only half gotten to"

"700 Firms that were falitive, and need to be re-inspected, in addition to the 8,000 Firms."

Quote to do BSE inspection in 19 states by end of January or 30 days, and other states 60 days. to change feed status??? Contract check and ask questions and pass info.

At this time, we will take questions.

[I was about the third or fourth to ask question. then all B.S.eee broke loose, and i lost my train of thought for a few minutes. picked back up here]

someone asking about nutritional supplements and sourcing, did not get name. something about inspectors not knowing of BSE risk??? the conference person assuring that Steve Follum? and the TSE advisory Committee were handling that.

Some other Dr. Vet, whom were asking questions that did not know what to do???

[Dennis Wilson] California Food Agr. Imports, are they looking at imports?

[Conference person] they are looking at imports, FDA issued imports Bulletin.

[Linda Singeltary ??? this was a another phone in question, not related i don't think] Why do we have non-licensed facilities?

(conference person) other feed mills do not handle as potent drugs???

Dennis Blank, Ken Jackson licensed 400 non FDA 4400 inspected of a total of 6000 to 8000,

(they really don't know how many non licensed Firms in U.S. they guess 6000 to 8000??? TSS)

Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not'

Warren-Maryland Dept. Agr. Prudent to re-inspect after 3 years. concerned of Firms that have changed owners.

THE END

TSS

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

FROM New York TIMES

Subject: Re: BSE 50 STATE CONFERENCE CALL thread from BSE List and FDA Posting of cut version...

Date: Thu, 11 Jan 2001 22:02:47 -0700 From: "Sandy Blakeslee" sblakeslee@mindspring.com

To: "Terry S. Singeltary Sr." References: 1

Hi terry -- thanks for all your help. I know it made a difference with the FDA getting out that release.

----- Original Message -----

From: "Terry S. Singeltary Sr." flounder@wt.net

To: sblakeslee@mindspring.com

Sent: Thursday, January 11, 2001 2:06 PM

Subject: BSE 50 STATE CONFERENCE CALL thread from BSE List and FDA Posting of cut version...

> > hi sandy,

>From the New York Times NYTimes.com, January 11, 2001

Many Makers of Feed Fail to Heed Rules on Mad Cow Disease By SANDRA BLAKESLEE

Large numbers of companies involved in manufacturing animal feed are not complying with regulations meant to prevent the emergence and spread of mad cow disease in the United States, the Food and Drug Administration said yesterday.

The widespread failure of companies to follow the regulations, adopted in August 1997, does not mean that the American food supply is unsafe, Dr. Stephen Sundlof, director of the Center for Veterinary Medicine at the F.D.A., said in an interview.

But much more needs to be done to ensure that mad cow disease does not arise in this country, Dr. Sundlof said.

The regulations state that feed manufacturers and companies that render slaughtered animals into useful products generally may not feed mammals to cud-chewing animals, or ruminants, which can carry mad cow disease.

All products that contain rendered cattle or sheep must have a label that says, "Do not feed to ruminants," Dr. Sundlof said. Manufacturers must also have a system to prevent ruminant products from being commingled with other rendered material like that from chicken, fish or pork. Finally, all companies must keep records of where their products originated and where they were sold.

Under the regulations, F.D.A. district offices and state veterinary offices were required to inspect all rendering plants and feed mills to make sure companies complied. But results issued yesterday demonstrate that more than three years later, different segments of the feed industry show varying levels of compliance.

Among 180 large companies that render cattle and another ruminant, sheep, nearly a quarter were not properly labeling their products and did not have a system to prevent commingling, the F.D.A. said. And among 347 F.D.A.-licensed feed mills that handle ruminant materials - these tend to be large operators that mix drugs into their products - 20 percent were not using labels with the required caution statement, and 25 percent did not have a system to prevent commingling.

Then there are some 6,000 to 8,000 feed mills so small they do not require F.D.A. licenses. They are nonetheless subject to the regulations, and of 1,593 small feed producers that handle ruminant material and have been inspected, 40 percent were not using approved labels and 25 percent had no system in place to prevent commingling.

On the other hand, fewer than 10 percent of companies, big and small, were failing to comply with the record-keeping regulations.

The American Feed Industry Association in Arlington, Va., did not return phone calls seeking comment.

http://www.nytimes.com/2001/01/11/science/11COW.html

Subject: USDA/APHIS response to BSE-L--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001

Date: Wed, 10 Jan 2001 14:04:21 –0500

From: "Gomez, Thomas M." tmg1@CDC.GOV

Reply-To: Bovine Spongiform Encephalopathy BSE-L@uni-karlsruhe.de

To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

USDA/APHIS would like to provide clarification on the following point from Mr. Singeltary's 9 Jan posting regarding the 50 state conference call.

[Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not']

Dr. Detwiler was responding to an announcement made during the call to use the FDA emergency number if anyone wanted to report a cow with signs suspect for BSE. Mr. Singeltary is correct that Dr. Detwiler asked participants to use the FDA emergency number as a last resort to report cattle suspect for BSE. What Mr. Singeltary failed to do was provide the List with Dr. Detwiler's entire statement. Surveillance for BSE in the United States is a cooperative effort between states, producers, private veterinarians, veterinary hospitals and the USDA. The system has been in place for over 10 years. Each state has a system in place wherein cases are reported to either the State Veterinarian, the federal Veterinarian in Charge or through the veterinary diagnostic laboratory system. The states also have provisions with emergency numbers. Dr. Detwiler asked participants to use the systems currently in place to avoid the possibility of a BSE-suspect report falling through the cracks. Use of the FDA emergency number has not been established as a means to report diseased cattle of any nature.

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

Subject: Re: USDA/APHIS response to BSE-L--U.S. 50 STATE CONFERENCE CALL Jan.9, 2001

Date: Wed, 10 Jan 2001 13:44:49 -0800 From: "Terry S. Singeltary Sr." flounder@wt.net

Reply-To: Bovine Spongiform Encephalopathy BSE-L@uni-karlsruhe.de

To: BSE-L@uni-karlsruhe.de References: 1

######### Bovine Spongiform Encephalopathy #########

Hello Mr. Thomas,

> What Mr. Singeltary failed to do was provide > the List with Dr. Detwiler's entire statement.

would you and the USDA/APHIS be so kind as to supply this list with a full text version of the conference call and or post on your web-site? if so when, and thank you. if not, why not?

> The system has been in place for over 10 years.

that seems to be a very long time for a system to be in place, and only test 10,700 cattle from some 1.5 BILLION head (including calf crop). Especially since French are testing some 20,000 weekly and the E.U. as a whole, are testing many many more than the U.S., with less cattle, same risk of BSE/TSEs.

Why does the U.S. insist on not doing massive testing with the tests which the E.U. are using? Why is this, please explain?

Please tell me why my question was not answered?

> U.S. cattle, what kind of guarantee can you > give for serum or tissue donor herds?

It was a very simple question, a very important question, one that pertained to the topic of BSE/feed, and asked in a very diplomatic way. why was it not answered?

If all these years, we have been hearing that pharmaceutical grade bovines were raised for pharmaceuticals vaccines etc. But yet the USA cannot comply with feed regulations of the ruminant feed ban, PLUS cannot even comply with the proper labelling of the feed, cross contamination etc. Then how in the world can you Guarantee the feed fed to pharmaceutical grade bovine, were actually non ruminant feed?

Before i was ask to be 'disconnected', i did hear someone in the background say 'we can't'-- have him ask the question again.

could you please be so kind, as to answer these questions?

thank you, Terry S. Singeltary Sr. Bacliff, Texas USA

P.S. if you will also notice, i did not post that emergency phone number and do not intend on passing it on to anyone. I was joking when i said i should call and report the whole damn U.S. Herd. So please pass that on to Dr. Detwiler, so she can rest easily.

BUT, they should be reported, some are infected with TSE. The U.S. is just acting as stupid as Germany and other Countries that insist they are free of BSE.

TSS

Subject: Report on the assessment of the Georgraphical BSE-risk of the USA July 2000 (not good)

Date: Wed, 17 Jan 2001 21:23:51 -0800 From: "Terry S. Singeltary Sr." flounder@wt.net

Reply-To: Bovine Spongiform Encephalopathy BSE-L@uni-karlsruhe.de

To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

Greetings List Members and ALL EU Countries,

Because of this report, and the recent findings of the 50-state BSE Conference call, I respectfully seriously suggest that these Countries and the SSC re-evaluate the U.S.A. G.B.R. to a risk factor of #3.

I attempted to post this to list in full text, but would not accept...

thank you, kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA

Report on the assessment of the Geographical BSE-risk of the USA July 2000

PART II

REPORT ON THE ASSESSMENT OF THE GEOGRAPHICAL BSE RISK OF THE UNITED STATES OF AMERICA

- 29 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

EXECUTIVE SUMMARY

OVERALL ASSESSMENT

The current geographical BSE-risk (GBR) level is II, i.e. it is unlikely but cannot be excluded that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent.

Stability: Before 1990 the system was extremely unstable because feeding of MBM to cattle happened, rendering was inappropriate with regard to deactivation of the BSE-agent and SRM and fallen stock were rendered for feed. From 1990 to 1997 it improved to very unstable, thanks to efforts undertaken to trace imported animals and exclude them from the feed chain and intensive surveillance. In 1998 the system became neutrally stable after the RMBM-ban of 1997.

External challenges: A moderate external challenge occurred in the period before 1990 because of importation of live animals from BSE-affected countries, in particular from the UK and Ireland. It cannot be excluded that some BSE-infected animals have been imported by this route and did enter the US rendering and feed production system. The efforts undertaken since 1990 to trace back UK-imported cattle and to exclude them from the feed chain reduced the impact of the external challenge significantly.

Interaction of external challenges and stability: While extremely unstable, the US system was exposed to a moderate external challenge, mainly resulting from cattle imports from the UK. It can not be excluded that BSE-infectivity entered the country by this route and has been recycled to domestic cattle. The resulting domestic cases would have been processed while the system was still very unstable or unstable and would hence have initiated a number of second or third generation cases. However, the level of the possible domestic prevalence must be below the low detection level of the surveillance in place.

As long as there are no changes in stability or challenge the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent will remain at the current level.

JUSTIFICATION

1. DATA

The available information was suitable to carry out the GBR risk assessment.

- 30 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

2. STABILITY

2.1 Overall appreciation of the ability to identify BSE-cases and to eliminate animals at risk of being infected before they are processed

· Before 1989, the ability of the system to identify (and eliminate) BSE cases was limited. · Since 1990 this ability is significantly improved, thanks to a good BSE-surveillance and culling system (contingency plan). · Today the surveillance should be able to detect clinical BSE-cases within the limits set by an essential passive surveillance system, i.e. some cases might remain undetected.

2.2 Overall appreciation of the ability to avoid recycling BSE-infectivity, should it enter processing

· Before 1997 the US rendering and feed producing system would not have been able to avoid recycling of the BSE agent to any measurable extent. If the BSE-agent was introduced the feed chain, it could probably have reached cattle. · After the introduction of the RMBM-to-ruminants-ban in August 1997 the ability of the system to avoid recycling of BSE-infectivity was somewhat increased. It is still rather low due to the rendering system of ruminant material (including SRM and fallen stock) and the persisting potential for cross-contamination of cattle feed with other feeds and hence RMBM.

2.3 Overall assessment of the Stability

· Until 1990 the US BSE/cattle system was extremely unstable as RMBM was commonly fed to cattle, the rendering system was not able to reduce BSE-infectivity and SRM were rendered. This means that incoming BSE infectivity would have been most probably recycled to cattle and amplified and the disease propagated. · Between 1990 and 1995 improvements in the BSE surveillance and the efforts to trace back and remove imported cattle gradually improved the stability but the system remained very unstable. In 1998 the system became unstable because of an RMBM-ban introduced in 1997. After 1998 the ban was fully implemented and the system is regarded to be neutrally stable since 1998. The US system is therefore seen to neither be able to amplify nor to reduce circulating or incoming BSE-infectivity.

3. CHALLENGES

A moderate external challenge occurred in the period 1980-1989 because of importation of live animals from the UK. imports from other countries are regarded to have been negligible challenges. · As a consequence of this external challenge, infectivity could have entered the feed cycle and domestic animals could have been exposed to the agent. These domestic BSE-incubating animals might have again entered processing, leading to an internal challenge since 1991. · This internal challenge could have produced domestic cases of BSE, yet prevalence levels could have been below the detection limits of the surveillance system until now. (According to US calculations, the current surveillance

-31 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

system could detect clinical incidence of 1-3 cases per year per million adult cattle, i.e. in absolute numbers 43-129 cases per year). Between 1990 und 1995, with the exclusion of the imported animals from Europe from the feed chain, the effect of the external challenges decreased.

4. CONCLUSION ON THE RESULTING RISKS

4.1 Interaction of stability and challenqe

· In the late 80s, early 90s a moderate external challenges met an extremely unstable system. This would have amplified the incoming BSE-infectivity and propagated the disease. · With the exclusion of the imported animals from Europe from the feed chain between 1990 and 1995 the effect of the external challenge decreased. · Before 1998 an internal challenge, if it developed, would have met a still unstable system (inappropriate rendering, no SRM ban, RMBM ban only after 1997) and the BSE-infectivity could have been recycled and amplified. · After 1998 the neutrally stable system could still recycle the BSE-agent but due to the RMBM-ban of 1997 the BSE-infectivity circulating in the system would probably not be amplified.

4.2 Risk that BSE-infectivity enters processing

· A very low processing risk developed in the late 80s when the UK-imports were slaughtered or died. It increased until 1990 because of the higher risk to be infected with BSE of cattle imported from the UK in 1988/89, as these animals could have been processed prior to the back-tracing of the UK-imports in 1990. · From 1990 to 1995 a combination of surviving non-traced UK imports and some domestic (pre-)clinical cases could have arrived at processing resulting in an assumed constant low but non-negligible processing risk. · After 1995 any processing risk relates to assumed domestic cases arriving at processing. · The fact that no domestic cases have been shown-up in the BSE-surveillance is reassuring - it indicates that BSE is in fact not present in the country at levels above the detection limits of the country's surveillance system. This detection level has been calculated according to US-experts to be between 1 & 3 clinical cases per million adult cattle per year.

Note: The high turnover in parts of the dairy cattle population with a young age at slaughter makes it unlikely that fully developed clinical cases would occur (and could be detected) or enter processing. However, the theoretical infective load of the pre-clinical BSE-cases that under this scenario could be processed, can be assumed to remain relatively low.

4.3 Risk that BSE-infectivity is recycled and propagated

· During the period covered by this assessment (1980-1999) the US-system was not able to prevent propagation of BSE should it have entered, even if this ability was significantly improved with the MBM-ban of 1997. · However, since the likelihood that BSE-infectivity entered the system is regarded to be small but non-negligible, the risk that propagation of the disease took place is also small but not negligible.

- 32 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

5. CONCLUSION ON THE GEOGRAPHICAL BSE-RISK

5.1 The current GBR

The current geographical BSE-risk (GBR) level is II, i.e. it is unlikely but cannot be excluded that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent.

5.2 The expected development of the GBR

As long as there are no changes in stability or challenge the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent remains at the current level.

5.3 Recommendations for influencin.q the future GBR

· As long as the stability of the US system is not significantly enbanced above neutral levels it remains critically important to avoid any new external challenges. · All measures that would improve the stability of the system, in particular with regard to its ability to avoid recycling of the BSE-agent should it be present in the cattle population, would reduce, over time, the probability that cattle could be infected with the BSE-agent. Possible actions include: removal of SRMs and/or fallen stock from rendering, better rendering processes, improved compliance with the MBM-ban including control and reduction of cross-contamination. · Results from an improved intensive surveillance programme, targeting at risk sub-populations such as adult cattle in fallen stock or in emergency slaughter, could verify the current assessment.

snip...

end...tss

U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001

http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html

http://madcowusda.blogspot.com/2012/02/eight-former-secretaries-of-agriculture.html

FDA Singeltary submission 2001

Greetings again Dr. Freas and Committee Members, I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version). I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:

snip...see full text ;

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf

-----Original Message-----

From: Terry S. Singeltary Sr. [mailto:flounder@wt.net]

Sent: Tuesday, February 18, 2003 12:45 PM

To: Freas, William Cc: Langford, Sheila

Subject: Re: re-vCJD/blood and meeting of Feb. 20, 2003 Greetings FDA, Variant Creutzfeldt-Jakob Disease Guidance Topic of Feb. 20 TSE Cmte. [Committee Meeting on February 20, 2003] FDA’s Transmissible Spongiform Encephalopathies Advisory Committee will meet Feb. 20 to hear updates on the implementation of the agency’s variant Creutzfeldt-Jakob Disease guidance and its effect on blood supply.

FULL SUBMISSION ;

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.pdf

Docket Management Docket: 02D-0073 - Guidance: Validation of Procedures for Processing of Human Tissues Intended for Transplantation Comment Number: EC -4 Accepted - Volume 1

2003-01-16 16:33:04 http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfc.html

Docket: 02D-0073 - Guidance: Validation of Procedures for Processing of Human Tissues Intended for Transplantation Greetings, please be advised; with the new findings from Collinge et al; that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc, the commonest sporadic CJD, i only ponder how many of the sporadic CJDs in the USA are tied to this alternate phenotype? these new findings are very serious, and should have a major impact on the way sporadic CJDs are now treated as opposed to the vCJD that was thought to be the only TSE tied to ingesting beef, in the medical/surgical arena. these new findings should have a major impact on the way sporadic CJD is ignored, and should now be moved to the forefront of research as with vCJD/nvCJD.

SNIP...FULL TEXT ;

http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfc.html

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

Singeltary submission ;

http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf

FSIS, USDA, REPLY TO SINGELTARY

http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf

Animal and Plant Health Inspection Service (APHIS) Proposed Rule: Bovine Spongiform Encephalopathy; Minimal-Risk Regions; Importation of Live Bovines and Products Derived From Bovines

http://www.regulations.gov/#!documentDetail;D=APHIS-2006-0041-0006;oldLink=false

2014

Wednesday, January 01, 2014

Molecular Barriers to Zoonotic Transmission of Prions

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

http://wwwnc.cdc.gov/eid/article/20/1/13-0858_article.htm

http://chronic-wasting-disease.blogspot.com/2014/01/molecular-barriers-to-zoonotic.html

Subtype 1: (sCJDMM1 and sCJDMV1)

This subtype is observed in patients who are MM homozygous or MV heterozygous at codon 129 of the PrP gene (PRNP) and carry PrPSc Type 1. Clinical duration is short, 3‑4 months.32 The most common presentation in sCJDMM1 patients is cognitive impairment leading to frank dementia, gait or limb ataxia, myoclonic jerks and visual signs leading to cortical blindness (Heidenhain’s syndrome)...

https://www.landesbioscience.com/pdf/06Ahmad_Liberski.pdf

Animals injected with iatrogenic Creutzfeldt–Jakob disease MM1 and genetic Creutzfeldt–Jakob disease MM1 linked to the E200K mutation showed the same phenotypic features as those infected with sporadic Creutzfeldt–Jakob disease MM1 prions...

http://brain.oxfordjournals.org/content/early/2010/09/07/brain.awq234.full.pdf

*** our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals, e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions. ***

http://www.jbc.org/cgi/content/abstract/M704597200v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Cross-sequence+transmission+of+sporadic+Creutzfeldt-Jakob+disease+creates+a+new+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

snip...see full text ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.html

Wednesday, June 16, 2010

Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

The epidemiological findings in sCJD demonstrate that approximately 80% of patients are diagnosed with “classic CJD” types MM1 and MV1, which might intriguingly suggest an infectious rather than genetic origin for the majority of sCJD cases.

snip...

Therefore if sCJD(MV2) and sCJD(VV2) were to become iatrogenic sources of human infection, the host response may be indistinguishable from sCJD(MM1) and more transmissible with respect to further infection.

END...TSS

http://creutzfeldt-jakob-disease.blogspot.com/2010/06/defining-sporadic-creutzfeldt-jakob.html

Monday, December 02, 2013

*** A parliamentary inquiry has been launched today into the safety of blood, tissue and organ screening following fears that vCJD – the human form of ‘mad cow’ disease – may be being spread by medical procedures

http://creutzfeldt-jakob-disease.blogspot.com/2013/12/a-parliamentary-inquiry-has-been.html

Wednesday, December 11, 2013

Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease

http://creutzfeldt-jakob-disease.blogspot.com/2013/12/detection-of-infectivity-in-blood-of.html

http://www.plosone.org/annotation/listThread.action;jsessionid=43759816BCF4952B7D9504B8FD9D5CA7?root=363

Friday, November 22, 2013

Chronic Wasting disease CWD is threat to the entire UK deer population Singeltary submission to the Scottish Parliament

http://chronic-wasting-disease.blogspot.com/2013/11/wasting-disease-is-threat-to-entire-uk.html

Thursday, January 2, 2014

CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ???

http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/cwd-tse-prion-in-cervids-to-htgmice.html

Tuesday, March 5, 2013

*** Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)

FDA believes current regulation protects the public from BSE but reopens comment period due to new studies

http://transmissiblespongiformencephalopathy.blogspot.com/2013/03/use-of-materials-derived-from-cattle-in_6452.html

Friday, January 17, 2014

Annual report of the Scientific Network on BSE-TSE EFSA, Question No EFSA-Q-2013-01004, approved on 11 December 2013

TECHNICAL REPORT

http://efsaopinionbseanimalprotein.blogspot.com/2014/01/annual-report-of-scientific-network-on.html

Sunday, December 15, 2013

*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2013 UPDATE

http://madcowusda.blogspot.com/2013/12/fda-part-589-substances-prohibited-from.html

Saturday, December 21, 2013

**** Complementary studies detecting classical bovine spongiform encephalopathy infectivity in jejunum, ileum and ileocaecal junction in incubating cattle ****

http://madcowusda.blogspot.com/2013/12/complementary-studies-detecting.html

Saturday, November 16, 2013

Management of neurosurgical instruments and patients exposed to creutzfeldt-jakob disease 2013 December

Infect Control Hosp Epidemiol.

http://creutzfeldt-jakob-disease.blogspot.com/2013/11/management-of-neurosurgical-instruments.html

Thursday, November 14, 2013

Prion diseases in humans: Oral and dental implications

http://transmissiblespongiformencephalopathy.blogspot.com/2013/11/prion-diseases-in-humans-oral-and.html

Saturday, November 2, 2013

Recommendation of the Swiss Expert Committee for Biosafety on the classification of activities using prion genes and prion protein January 2013

http://transmissiblespongiformencephalopathy.blogspot.com/2013/11/recommendation-of-swiss-expert.html

Friday, August 16, 2013

*** Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and Contaminated blood products induce a highly atypical prion disease devoid of PrPres in primates

http://creutzfeldt-jakob-disease.blogspot.com/2013/08/creutzfeldt-jakob-disease-cjd-biannual.html

WHAT about the sporadic CJD TSE proteins ?

WE now know that some cases of sporadic CJD are linked to atypical BSE and atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all it’s sub-types $$$

Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013

*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010 ***

http://creutzfeldt-jakob-disease.blogspot.com/2013/08/creutzfeldt-jakob-disease-cjd-cases.html

Sunday, October 13, 2013

*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012

http://creutzfeldt-jakob-disease.blogspot.com/2013/10/cjd-tse-prion-disease-cases-in-texas-by.html

Thursday, January 2, 2014

*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/cwd-tse-prion-in-cervids-to-htgmice.html

Friday, January 10, 2014

*** vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ??? http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html

Monday, January 13, 2014

*** Prions in Variably Protease-Sensitive Prionopathy: An Update Pathogens 2013

Pathogens 2013, 2, 457-471; doi:10.3390/pathogens2030457http://prionopathy.blogspot.com/2014/01/prions-in-variably-protease-sensitive.html

Wednesday, January 15, 2014

*** INFECTION PREVENTION AND CONTROL OF CJD, VCJD AND OTHER HUMAN PRION DISEASES IN HEALTHCARE AND COMMUNITY SETTINGS Variably Protease-Sensitive Prionopathy (VPSPr) January 15, 2014http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/infection-prevention-and-control-of-cjd.html

Sunday, January 19, 2014

*** National Prion Disease Pathology Surveillance Center Cases Examined1 as of January 8, 2014 ***

http://prionunitusaupdate.blogspot.com/2014/01/national-prion-disease-pathology.html

Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518

flounder9@verizon.net

Sunday, January 19, 2014

USA TSE CJD VPSPr sFFI PRION DISEASE UPDATE 2014

Sunday, January 19, 2014

National Prion Disease Pathology Surveillance Center Cases Examined1 as of January 8, 2014

http://prionunitusaupdate.blogspot.com/2014/01/national-prion-disease-pathology.html

please note, the many different faces of the TSE prion disease, and their names that change during that time, have changed again.

now sFFI is being referenced as sFI, a TSE prion disease, but you would have never known it by it's name.

I believe it was Gambetti et al that coined this term sporadic FFI, from some conspicuous sub-type of sporadic CJD possibly?

seems they could not tie it to a true FFI by diagnostic standards to date, so it was then termed a sFFI, confusing matters even worse ;

A subtype of sporadic prion disease mimicking fatal familial insomnia

http://www.neurology.org/cgi/content/abstract/52/9/1757?ck=nck

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2009 Apr;23(2):124-6.
[Analysis for clinical and genetic characteristics of a sporadic FFI case].
[Article in Chinese]

Xia SL, Xu YM, Xu Q, Xie ZQ, Shen XJ, Zhou W, Du R, Zhang J, Han J, Xu BL, Dong XP.

http://www.ncbi.nlm.nih.gov/pubmed/20104755

http://prionopathy.blogspot.com/

http://prionpathy.blogspot.com/

http://sporadicffi.blogspot.com/

http://transmissiblespongiformencephalopathy.blogspot.com/

Transmissible Spongiform Encephalopathy

Followers

Blog Archive

About Me

Monday, January 27, 2014

Evidence of in utero transmission of classical scrapie in sheep

Thursday, January 23, 2014

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]

Sunday, January 19, 2014

USA TSE CJD VPSPr sFFI PRION DISEASE UPDATE 2014