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

Accepted - Volume 1

Comment Record
Commentor Mr. Terry Singeltary Date/Time 2003-01-16 16:33:04
Organization CJD WATCH
Category Individual

Comments for FDA General
Questions
1. General Comments 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. the USA has many TSEs, the USA lacks sufficient testing for TSEs in cattle, and the USA still refuses to rapid TSE test USA cattle in sufficient numbers to find, when the late Dr. Richard Marsh had proven that mink had gone down with a TSE (TME), from being fed on 95%+ downer cattle. the GAO has also warned the industry and the FDA that the ruminant-to-ruminant feed ban has to significantly improved if they expect to keep BSE/TSEs out of USA cattle. Scrapie has increased significantly, and CWD is spreading. all this should warrant CJD/TSEs in humans in the USA to be made reportable on a National bases, immediately... Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD Date: Thu, 28 Nov 2002 10:23:43 -0000 From: Asante, Emmanuel A To: 'flounder@wt.net' Dear Terry, I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention. Thank you for your interest in the paper. In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc. I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes. Emmanuel Asante <> ____________________________________ Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 PLEASE SEE FULL TEXT OF THIS ARTICLE; http://www.vegsource.com/talk/madcow/messages/9912118.html ROUND TABLE ON BSE -- WASHINGTON -- 27-28 JUNE 1989 snip... The summary does tend to give a particular slant to the epidemiology of BSE which is not totally sound. It is a possibility that the agent of BSE may be in the cattle population in a number of countries already apart from the USA and that clinical cases are occurring on rare occasions. It is also important to off the possibility of the relationship between BSE and certain low-temperature rendering systems. For that reason a number of other countries apart from the USA and France are at risk and, in particular, the Netherlands, Denmark, Germany and Belgium. For these reasons it would be wise to move to an international ban on the feeding of ruminant protein to ruminants. Clearly the summary also needs to refer to the incidence of BSE in the UK and not solely to Great Britain. No doubt this has been tidied up in your comments on the summary conclusions. It is a pity that more of the comments put forward by Dr. Kimberlin have not been included in the summary since his views on page 13 are succinct and valuable... snip... http://www.bseinquiry.gov.uk/files/yb/1989/08/29003001.pdf Is there a Scrapie-like disease in cattle ? IN CONFIDENCE R.F. MARSH snip... re-mink rancher 'Wisconsin' dead stock feeder using >95% downer or dead dairy and a few horses... http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf Part of the Proceedings of an International Roundtable on Bovine Spongiform Encephalopathy, Bethesda, Maryland, USA, June 27-28, 1989. The possibility of infection with BSE in the United States, as defined by studies on the disease in Great Britain, is judged to be low on the basis of the following: (1) meat and bonemeals imported into the United States from Great Britain between 1980 and 1988 were used mainly in poultry, not ruminant feed; (2) the Scrapie Eradication Program had reduced the prevalence of scrapie in the United States compared with that in Great Britain; and (3) little, if any, rendered animal products are used for protein supplements in cattle feed in the United States. However, there is some evidence that there may already be a scrapie-like disease in cattle in the United States. This evidence comes from epidemiologic studies on an incident of transmissible mink encephalopathy (TME) in Stetsonville, Wis, in 1985. This mink farmer used no commercially available animal by-product mixtures in his feed, but instead slaughtered all animals going into the mink diet, which included mostly (>95%) downer dairy cows, a few horses, but never sheep. To examine the possibility that cattle may have been the source of this incident of TME, two 6-week-old Holstein bull calves were inoculated intracerebrally with mink brain from the affected farm. The bulls developed neurologic disease 18 and 19 months after inoculation. Both brains had spongiform degeneration at necropsy and both were transmissible back to mink by either intracerebral (incubation period of 4 months) or oral (incubation period of 7 months) inoculation Whereas TME has been thought to be caused by feeding scrapie-infected sheep to mink, this theory has no conclusive evidence. Experimental oral inoculation of mink with several different sources of sheep scrapie has never been successful, and an incubation period of less than 12 months has never (sic) produced by intracerebral inoculation. Transmissible mink encephalopathy can develop naturally by infection with incubation periods of less than 12 months. There is reason to believe that scrapie has not been transmitted in the United States from sheep to cattle by rendered protein concentrates as it was in Great Britain. However, some circumstantial evidence exists that cattle may be a source of some TME infections. It is recommended that we increase our surveillance for a BSE-like disease in American cattle by encouraging state diagnostic laboratories to formalin-fix specimens of midbrain and brain stem from bovine brains submitted for rabies testing. If results of these tests are negative, these fixed tissues can then be examined for evidence of spongiform degeneration of the gray matter. -Comments on bovine spongiform encephalopathy J Am Vet Med Assoc 197 (4): (1990) Letter to the Editor, Journal of the American Veterinary Medical Association, August 15, 1990 In my article, Bovine spongiform encephalopathy in the United States (JAVMA, May 15, 1990, p 1677), I stated that little, if any, rendered animal products are used for protein supplements in cattle feed in the United States. I have since learned that this is incorrect, because of the recent trend of using less assimilated by-pass proteins in cattle feed. A large amount of meat-and-bone meal is being fed to American cattle, and this change in feeding practice has greatly increased the risk of bovine spongiform encephalopathy (BSE) developing in the United States. Epidemiologic studies on BSE in Great Britain have indicated that the disease originated in cattle by exposure to the heat-resistant transmissible agent in compounded feed containing rendered animal protein. The most likely source of infection was assumed to be meat-and-bone meal prepared from scrapie-infected sheep, but it is also possible that a heretofore unrecognized scrapie-like infection of cattle could have been spread in the same manner. Because of concern for the possible development of BSE in the United States, the American rendering industry discontinued the processing of fallen and sick sheep last December. In my opinion, this was a prudent policy, but one that will not prevent the possible transmission of BSE from cattle to cattle. As emphasized in my article, there is some evidence that BSE-like infection may already exist in American cattle. The current practice of feeding meat-and-bone meal to cattle solidifies the most important means to perpetuate and amplify the disease cycle. In Great Britain, BSE has produced a great economic and emotional burden. We must take all reasonable measures to prevent BSE from developing in the United States. Therefore, the practice of using animal protein in cattle feed should be discontinued as soon as possible. Waiting until the first case of BSE is diagnosed in the United States will certainly be closing the barn door after the horse is gone. With a disease having a 3- to 6-year incubation period, thousands of animals would be exposed before we recognize the problem and, if that happens, we would be in for a decade of turmoil. R. F. Marsh, DVM, PhD Madison, Wis ============= PAGE 25 Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculam (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in _all_ of these species with the shortest incubation period in the ferret. http://www.vegsource.com/talk/lyman/messages/7536.html http://www.vegsource.com/talk/lyman/messages/7535.html FULL TEXT OF GOA REPORT BELOW (takes a while to load) 2. Mad Cow Disease: Improvements in the Animal Feed Ban and Other Regulatory Areas Would Strengthen U.S. Prevention Efforts. GAO-02-183, January 25. http://www.gao.gov/cgi-bin/getrpt?GAO-02-183 ============================================= Subject: SCRAPIE 'USA' ANNUAL REPORT (105 newly infected flocks 2002) & CWD IN USA Date: Tue, 10 Dec 2002 08:17:17 -0600 From: Terry S. Singeltary Sr. To: flounder@wt.net Date: Mon, 9 Dec 2002 21:21:10 -0600 Reply-To: Bovine Spongiform Encephalopathy Sender: Bovine Spongiform Encephalopathy From: Terry S. Singeltary Sr. Subject: SCRAPIE 'USA' ANNUAL REPORT (105 newly infected flocks 2002) & CWD IN USA As of September 30, 2002, there were 45 scrapie infected and source flocks (figure 3). There were 105 newly infected flocks, reported in FY2002 (figure 4). In addition, 379 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2002 (figure 5) and (figure 6). Five cases of scrapie in goats were reported in FY 2002 (figure 7), the last of which was confirmed in August 2002. New infected and source flocks numbers and the number of these flocks released in FY 2002 are depicted in chart 4. One hundred (100) flocks which is 67 percent of the scrapie infected and source flocks present in FY 2002 were released or put on clean-up plans in FY2002. Slaughter Surveillance Slaughter Surveillance is currently in Phase II which is intended to determine the prevalence of scrapie in the US culled sheep population. Through September 2002 samples from 3,269 sheep were submitted to NVSL for testing. Samples from a total of 6,795 sheep have been submitted since the beginning of Phase II on April 1, 2002. Surveillance regions are depicted in (figure 8). Scrapie Testing During FY 2002 11,751 animals have been tested for scrapie which includes: 2,711 regular necropsy cases, 1,343 third eyelid biopsies for the test validation project, 546 third eyelid biopsies for the regulatory program, and approximately 7,151 animals for Phase I & II of SOSS (chart 5). Laboratory testing has been taking 10 - 11 days on average with a range of 3 - 34 days. Ear Tag Orders During FY 2002 9.9 million plastic and 6.0 million metal tags were distributed by APHIS (chart 6). http://www.aphis.usda.gov/vs/nahps/scrapie/annual_report/annual-report.html NEW SCRAPIE INFECTED AND SOURCE FLOCKS http://www.aphis.usda.gov/vs/nahps/scrapie/annual_report/figure04.gif DISTRIBUTION OF CHRONIC WASTING DISEASE THROUGHOUT THE STATES (as of Oct. 2002) http://www.aphis.usda.gov/vs/nahps/cwd/cwd-distribution.html CWD USA surveillance http://www.aphis.usda.gov/vs/nahps/cwd/cwd-state.html CJD WATCH http://www.fortunecity.com/healthclub/cpr/349/part1cjd.htm CJD Watch message board http://disc.server.com/Indices/167318.html TSS MADCOW http://www.vegsource.com/talk/madcow/index.html Moms death from hvCJD http://www.vegsource.com/talk/lyman/messages/7252.html 'MOMS AUTOPSY REPORT' http://www.vegsource.com/talk/lyman/messages/7548.html TSS




EC -4