flounder said:
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Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice
Brent Race1#, Kimberly Meade-White1#, Michael B. A. Oldstone2, Richard Race1, Bruce Chesebro1*
1 Laboratory of Persistent Virus Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America, 2 Department of Immunology and Microbial Science, The Scripps Research Institute, LaJolla, California, United States of America
Abstract Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection.
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Friday, December 05, 2008
Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice
http://scrapie-usa.blogspot.com/2008/12/detection-of-prion-infectivity-in-fat.html
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This is topic PRIONS IN SKELETAL MUSCLES OF DEER WITH CWD (full text) in forum Chronic Wasting Disease FAQ's at NGPC FAQ's.
To visit this topic, use this URL: http://www.ngpc.state.ne.us/cgi-bin/ultimatebb.cgi?ubb=get_topic;f=12;t=000461
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Posted by TSS (Member # 1734) on January 26, 2006 02:51 PM:
Subject: Prions in Skeletal Muscles of Deer with Chronic Wasting Disease [SCIENCE FULL TEXT] Date: January 26, 2006 at 12:23 pm PST
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers,1* Shawn R. Browning,1*† Tanya S. Seward,2 Christina J. Sigurdson,4‡ Michael W. Miller,5 Edward A. Hoover,4 Glenn C. Telling1,2,3§
1Department of Microbiology, Immunology and Molecular Genetics, 2Sanders Brown Center on Aging, 3Department of Neurology, University of Kentucky, Lexington, KY 40536, USA. 4Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. 5Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526, USA.
*These authors contributed equally to this work.
†Present address: Department of Infectology, Scripps Research Institute, 5353 Parkside Drive, RF-2, Jupiter, Florida, 33458, USA.
‡Present address: Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
§To whom correspondence should be addressed: E-mail:
[email protected]
Prions are transmissible proteinaceous agents of mammals that cause fatal neurodegenerative diseases of the central nervous system (CNS). The presence of infectivity in skeletal muscle of experimentally infected mice raised the possibility that dietary exposure to prions might occur through meat consumption (1). Chronic wasting disease (CWD), an enigmatic and contagious prion disease of North American cervids, is of particular concern. The emergence of CWD in an increasingly wide geographic area and the interspecies transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt Jakob disease (vCJD) have raised concerns about zoonotic transmission of CWD.
To test whether skeletal muscle of diseased cervids contained prion infectivity, Tg(CerPrP)1536 mice (2) expressing cervid prion protein (CerPrP), were inoculated intracerebrally with extracts prepared from the semitendinosus/semimembranosus muscle group of CWD-affected mule deer or from CWD-negative deer. The availability of CNS materials also afforded direct comparisons of prion infectivity in skeletal muscle and brain. All skeletal muscle extracts from CWD-affected deer induced progressive neurological dysfunction in Tg(CerPrP)1536 mice with mean incubation times ranging between 360 and ~490 d, whereas the incubation times of prions from the CNS ranged from ~230 to 280 d (Table 1). For each inoculation group, the diagnosis of prion disease was confirmed by the presence of PrPSc in the brains of multiple infected Tg(CerPrP)1536 mice (see supporting online material for examples). In contrast, skeletal muscle and brain material from CWD-negative deer failed to induce disease in Tg(CerPrP)1536 mice (Table 1) and PrPSc was not detected in the brains of sacrificed asymptomatic mice as late as 523 d after inoculation (supporting online material).
Our results show that skeletal muscle as well as CNS tissue of deer with CWD contains infectious prions. Similar analyses of skeletal muscle BSE-affected cattle did not reveal high levels of prion infectivity (3). It will be important to assess the cellular location of PrPSc in muscle. Notably, while PrPSc has been detected in muscles of scrapie-affected sheep (4), previous studies failed to detect PrPSc by immunohistochemical analysis of skeletal muscle from deer with natural or experimental CWD (5, 6). Since the time of disease onset is inversely proportional to prion dose (7), the longer incubation times of prions from skeletal muscle extracts compared to matched brain samples indicated that prion titers were lower in muscle than in CNS where infectivity titers are known to reach high levels. Although possible effects of CWD strains or strain mixtures on these incubation times cannot be excluded, the variable 360 to ~490 d incubation times suggested a range of prion titers in skeletal muscles of CWD-affected deer. Muscle prion titers at the high end of the range produced the fastest incubation times that were ~30% longer than the incubation times of prions from the CNS of the same animal. Since all mice in each inoculation group developed disease, prion titers in muscle samples producing the longest incubation times were higher than the end point of the bioassay, defined as the infectious dose at which half the inoculated mice develop disease. Studies are in progress to accurately assess prion titers.
While the risk of exposure to CWD infectivity following consumption of prions in muscle is mitigated by relatively inefficient prion transmission via the oral route (8), these
results show that semitendinosus/semimembranosus muscle, which is likely to be consumed by humans, is a significant source of prion infectivity. Humans consuming or handling meat from CWD-infected deer are therefore at risk to prion exposure.
References and Notes
1. P. J. Bosque et al., Proc. Natl. Acad. Sci. U.S.A. 99, 3812 (2002).
2. S. R. Browning et al., J. Virol. 78, 13345 (2004).
3. A. Buschmann, M. H. Groschup, J. Infect. Dis. 192, 934 (2005).
4. O. Andreoletti et al., Nat. Med. 10, 591 (2004).
5. T. R. Spraker et al., Vet. Pathol. 39, 110 (2002).
6. A. N. Hamir, J. M. Miller, R. C. Cutlip, Vet. Pathol. 41, 78 (2004).
7. S. B. Prusiner et al., Biochemistry 21, 4883 (1980).
8. M. Prinz et al., Am. J. Pathol. 162, 1103 (2003).
9. This work was supported by grants from the U.S. Public Health Service 2RO1 NS040334-04 from the National Institute of Neurological Disorders and Stroke and N01-AI-25491 from the National Institute of Allergy and Infectious Diseases.
Supporting Online Material
www.sciencemag.org/
Materials and Methods
Fig. S1
21 November 2005; accepted 13 January 2006 Published online 26 January 2006; 10.1126/science.1122864 Include this information when citing this paper.
Table 1. Incubation times following inoculation of Tg(CerPrP)1536 mice with prions from skeletal muscle and brain samples of CWD-affected deer.
Inocula Incubation time, mean d ± SEM (n/n0)*
Skeletal muscle Brain
CWD-affected deer
H92 360 ± 2 d (6/6) 283 ± 7 d (6/6)
33968 367 ± 9 d (8/8) 278 ± 11 d (6/6)
5941 427 ± 18 d (7/7)
D10 483 ± 8 d (8/8) 231 ± 17 d (7/7)
D08 492 ± 4 d (7/7)
Averages 426 d 264 d
Non-diseased deer
FPS 6.98 >523 d (0/6)
FPS 9.98 >454 d (0/7) >454 d (0/6)
None >490 d (0/6)
PBS >589 d (0/5)
*The number of mice developing prion disease divided by the original number of inoculated mice is shown in parentheses. Mice dying of intercurrent illnesses were excluded.
http://www.sciencemag.org/
www.sciencemag.org/
Supporting Online Material for
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers, Shawn R. Browning, Tanya S. Seward, Christina J. Sigurdson,
Michael W. Miller, Edward A. Hoover, Glenn C. Telling§
§To whom correspondence should be addressed: E-mail:
[email protected]
Published 26 January 2006 on Science Express
DOI: 10.1126/science.1122864
This PDF file includes:
Materials and Methods
Fig. S1
Supporting Online Materials
Materials and Methods
Homogenates of semitendinosus/semimembranosus muscle (10% w/v in phosphate
buffered saline) were prepared from five emaciated and somnolent mule deer, naturally
infected with CWD at the Colorado Division of Wildlife, Wildlife Research Center.
These deer were identified as D10, D08, 33968, H92, and 5941. CWD infection was
confirmed in all cases by the presence of histologic lesions in the brain including
spongiform degeneration of the perikaryon, the immunohistochemical detection of
disease-associated PrP in brain and tonsil, or by immunoblotting of protease-resistant,
disease associated PrP (CerPrPSc). Semitendinosus/semimembranosus muscle was also
obtained from two asymptomatic, mock inoculated deer, referred to as FPS 6.68 and 9.98,
that originated from a CWD non-endemic area and which were held indoors at Colorado
State University from ten days of age. These control deer were confirmed negative for
CWD by histopathological and immunohistochemical analysis of brain tissue at autopsy.
The utmost care was taken to avoid inclusion of obvious nervous tissue when muscle
biopsies were prepared and to ensure that contamination of skeletal muscle samples with
CNS tissue did not occur. Fresh, single-use instruments were used to collect each sample
biopsy and a central piece from each sample was prepared with fresh, disposable
instruments to further isolate muscle tissue for inoculum preparation. Brain samples for
transmission were prepared separately from muscle as additional insurance against cross
contamination.
1
Groups of anesthetized Tg(CerPrP)1536 mice were inoculated intracerebrally with 30 µl
of 1 % skeletal muscle or brain extracts prepared in phosphate buffered saline (PBS).
Inoculated Tg(CerPrP) mice were diagnosed with prion disease following the progressive
development of at least three neurologic symptoms including truncal ataxia, ‘plastic’ tail,
loss of extensor reflex, difficultly righting, and slowed movement. The time from
inoculation to the onset of clinical signs is referred to as the incubation time.
For PrP analysis in brain extracts of Tg(CerPrP)1536 mice, 10 % homogenates prepared
in PBS were either untreated (-) or treated (+) with 40 µg/ml proteinase K (PK) for one
hour at 37oC in the presence of 2% sarkosyl. Proteins were separated by sodium dodecyl
sulfate polyacrylamide gel electrophoresis, analyzed by immunoblotting using anti PrP
monoclonal antibody 6H4 (Prionics AG, Switzerland), incubated with appropriate
secondary antibody, developed using ECL-plus detection (Amersham), and analyzed
using a FLA-5000 scanner (Fuji).
2
Fig. S1
PrP in brain extracts from representative Tg(CerPrP)1536 mice receiving muscle or CNS
tissue inocula from CWD-affected or CWD-negative deer. Extracts were either treated
(+) or untreated (-) with proteinase K (PK) as indicated. The positions of protein
molecular weight markers at 21.3, 28.7, 33.5 kDa (from bottom to top) are shown to the
left of the immunoblot.
3
http://www.sciencemag.org/
Thursday, August 28, 2008
cwd, feeding, and baiting piles
http://chronic-wasting-disease.blogspot.com/2008/08/cwd-feeding-and-baiting-piles.html
Thursday, August 28, 2008
CWD TISSUE INFECTIVITY brain, lymph node, blood, urine, feces, antler velvet and muscle
http://chronic-wasting-disease.blogspot.com/2008/08/cwd-tissue-infectivity-brain-lymph-node.html
Tuesday, August 26, 2008 CWD Stakeholder Advisory Group Wednesday, August 22, 2007 11:31 AM
http://chronic-wasting-disease.blogspot.com/2008/08/cwd-stakeholder-advisory-group.html
PrPSc distribution of a natural case of bovine spongiform encephalopathy
Yoshifumi Iwamaru, Yuka Okubo, Tamako Ikeda, Hiroko Hayashi, Mori- kazu Imamura, Takashi Yokoyama and Morikazu Shinagawa Priori Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba 305-0856 Japan
[email protected]
Abstract
Bovine spongiform encephalopathy (BSE) is a disease of cattle that causes progressive neurodegeneration of the central nervous system. Infectivity of BSE agent is accompanied with an abnormal isoform of prion protein (PrPSc). The specified risk materials (SRM) are tissues potentially carrying BSE infectivity. The following tissues are designated as SRM in Japan: the skull including the brain and eyes but excluding the glossa and the masse- ter muscle, the vertebral column excluding the vertebrae of the tail, spinal cord, distal illeum. For a risk management step, the use of SRM in both animal feed or human food has been prohibited. However, detailed PrPSc distribution remains obscure in BSE cattle and it has caused controversies about definitions of SRM. Therefore we have examined PrPSc distribution in a BSE cattle by Western blotting to reassess definitions of SRM. The 11th BSE case in Japan was detected in fallen stock surveillance. The carcass was stocked in the refrigerator. For the detection of PrPSc, 200 mg of tissue samples were homogenized. Following collagenase treatment, samples were digested with proteinase K. After digestion, PrPSc was precipitated by sodium phosphotungstate (PTA). The pellets were subjected to Western blotting using the standard procedure. Anti-prion protein monoclonal antibody (mAb) T2 conjugated horseradish peroxidase was used for the detection of PrPSc. PrPSc was detected in brain, spinal cord, dorsal root ganglia, trigeminal ganglia, sublingual ganglion, retina. In addition, PrPSc was also detected in the peripheral nerves (sciatic nerve, tibial nerve, vagus nerve). Our results suggest that the currently accepted definitions of SRM in 9/13/2005
179 Page 10 of 17
BSE cattle may need to be reexamined.
T. Kitamoto (Ed.) PRIONS Food and Drug Safety
================
ALSO from the International Symposium of Prion Diseases held in Sendai, October 31, to November 2, 2004; Bovine spongiform encephalopathy (BSE) in Japan
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"Furthermore, current studies into transmission of cases of BSE that are atypical or that develop in young cattle are expected to amplify the BSE prion" NO. Date conf. Farm Birth place and Date Age at diagnosis 8. 2003.10.6. Fukushima Tochigi 2001.10.13. 23 9. 2003.11.4. Hiroshima Hyogo 2002.1.13. 21 Test results # 8b, 9c cows Elisa Positive, WB Positive, IHC negative, histopathology negative b = atypical BSE case c = case of BSE in a young animal b,c, No PrPSc on IHC, and no spongiform change on histology International Symposium of Prion Diseases held in Sendai, October 31, to November 2, 2004. Tetsuyuki Kitamoto Professor and Chairman Department of Prion Research Tohoku University School of Medicine 2-1 SeiryoAoba-ku, Sendai 980-8575, JAPAN TEL +81-22-717-8147 FAX +81-22-717-8148 e-mail;
[email protected] Symposium Secretariat Kyomi Sasaki TEL +81-22-717-8233 FAX +81-22-717-7656 e-mail:
[email protected] ================================= 9/13/2005
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Page 11 of 17 From: TSS () Subject: Atypical Proteinase K-Resistant Prion Protein (PrPres) observed in an Apparently Healthy 23-Month-Old Holstein Steer Date: August 26, 2005 at 10:24 am PST Atypical Proteinase K-Resistant Prion Protein (PrPres) observed in an Apparently Healthy 23-Month-Old Holstein Steer Jpn. J. Infect. Dis., 56, 221-222, 2003 Laboratory and Epidemiology Communications Atypical Proteinase K-Resistant Prion Protein (PrPres) Observed in an Apparently Healthy 23-Month-Old Holstein Steer Yoshio Yamakawa*, KenÕichi Hagiwara, Kyoko Nohtomi, Yuko Nakamura, Masahiro Nishizima ,Yoshimi Higuchi1, Yuko Sato1, Tetsutaro Sata1 and the Expert Committee for BSE Diagnosis, Ministry of Health, Labour and Welfare of Japan2 Department of Biochemistry & Cell Biology and 1Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640 and 2Miistry of Health, Labour and Welfare, Tokyo 100-8916 Communicated by Tetsutaro Sata (Accepted December 2, 2003) *Corresponding author: Mailing address: Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 1628640, Japan. Tel: +81-3-5285-1111, Fax: +81-3-5285-1157, E-mail:
[email protected]
Since October 18, 2001, 'bovine spongiform encephalopathy (BSE) examination for all cattle slaughtered at abattoirs in the country' has been mandated in Japan by the Ministry of Health, Labour and Welfare (MHLW). 'Plateria' ELISA-kit (Bio-Rad Laboratories, Hercules, Calif., USA) is routinely used at abattoirs for detecting proteinase K (PK)-resistant prion protein (PrPSc) in the obex region. Samples positive according to the ELISA screening are further subjected to Western blot (WB) and histologic and immunohistochemical examination (IHC) at the National Institute of Infectious Diseases (NIID) or Obihiro University. If PrPSc is detected either by WB or by IHC, the cattle are diagnosed as BSE. The diagnosis is approved by the Expert Committee for BSE Diagnosis, MHLW. From October 18, 2001 to September 30, 2003, approximately 2.5 million cattle were screened at abattoirs. A hundred and ten specimens positive according to ELISA were subjected to WB/IHC. Seven showed positive by both WB and IHC, all exhibiting the typical electrophoretic profile of a high content of the di-glycosylated molecular form of PrPSc (1-3) and the distinctive granular deposition of PrPSc in neuronal cells and neuropil of the dorsal nucleus of vagus. An ELISA-positive specimen from a 23 month-old Holstein steer slaughtered on September 29, 2003, in Ibaraki Prefecture (Ibaraki case) was sent to the NIID for confirmation. The animal was reportedly healthy before slaughter. The OD titer in ELISA was slightly higher than the 'cut-off' level given by the manufacturer. The histology showed no spongiform changes and IHC revealed no signal of PrPSc accumulation typical for BSE. However, WB analysis of the homogenate that was prepared from the obex region and used for ELISA revealed a small amount of PrPSc with an electrophoretic profile different from that of typical BSE-associated PrPSc (1-3). The characteristics were (i) low content of the di-glycosylated molecular form of PrPSc, (ii) a faster migration of the non-glycosylated form of PrPSc on SDS-PAGE, and (iii) less resistance against PK digestion as compared with an authentic PrPSc specimen derived from an 83-month-old Holstein (Wakayama case) (Fig. 1). Table 1 summarizes the relative amounts of three distinctive glycoforms (di-, mono, non-glycosylated) of PrPSc calculated by densitometric analysis of the blot shown in Fig. 1. As 2.5 mg wet weight obex-equivalent homogenate of the Ibaraki case (Fig. 1, lane 4) gave slightly stronger band intensities of PrPSc than an 8 mg wet weight obex-equivqlent homogenate of a typical BSE-affected Wakayama case (Fig. 1, lane 2), the amount of PrPSc accumulated in the Ibaraki case was calculated to be 1/500 - 1/1000 of the Wakayama case. In the Ibaraki case, the PrPSc bands were not detectable in the homogenates of the proximal surrounding region of the obex. These findings were consistent with the low OD value in ELISA, i.e., 0.2 -0.3 for the Ibaraki case versus over 3.0 for the Wakayama case. The DNA sequence of the PrP coding region of the Ibaraki case was the same as that appearing in the database (GenBank accession number: AJ298878). More recently, we encountered another case that resembled the Ibaraki case. It was a 21-monthold Holstein steer from Hiroshima Prefecture. WB showed typical BSE-specific PrPSc deposition though IHC did not detect positive signals of PrPSc (data not shown). Though the clinical onset of BSE is usually at around 5 years of age or later, a 20-month-old case showing the clinical signs has been reported (4). Variant forms of BSE similar to our cases, i.e., with atypical histopathological and/or biochemical phenotype, have been recently reported in Italy (5) and in France (6). Such variant BSE was not associated with mutations in the prion protein (PrP) coding region as in our case (5,6). The Ministry of Agriculture, Forestry and Fisheries of Japan (MAFF) announced a ban of feeding ruminants with meat bone meal (MBM) on September 18, 2001, and a complete ban was made on October 15 of the same year. According to the recent MAFF report, the previous seven cases of BSE in Japan were cattle born in 1995 - 1996 and possibly fed with cross-contaminated feed. However, the two cattle in this report were born after the complete ban. Whether contaminated MBM was implicated in the present cases remains to be investigated.
REFERENCES Collinge, J., Sidle, K. C. L., Meads, J., Ironside, J. and Hill, A. F. (1996): Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature, 383, 685690. Bruce, M. E., Will, R. G., Ironside, J. W., McConnell, I., Drummond, D., Suttie, A., McCardle, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. J. (1997): Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature, 389, 498-501. Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C. L., Gowland, I. and Collinge, J. (1997): The same prion strain causes vCJD and BSE. Nature, 389, 448-450. Matravers, W., Bridgeman, J. and Smith, M.-F. (ed.)(2000): The BSE Inquiry. p. 37. vol. 16. The Stationery Office Ltd., Norwich, UK. Casalone, C., Zanusso, G., Acutis, P. L., Crescio, M. I., Corona, C., Ferrari, S., Capobianco, R., Tagliavini, F., Monaco, S. and Caramelli, M. (2003): Identification of a novel molecular and neuropathological BSE phenotype in Italy. International Conference on Prion Disease: from basic research to intervention concepts. Gasreig, Munhen, October 8-10. Bicaba, A. G., Laplanche, J. L., Ryder, S. and Baron, T. (2003): A molecular variant of bovine spongiform encephalopatie. International Conference on Prion Disease: from basic research to intervention concepts. Gasreig, Munhen, October 8-10. Asante, E. A., Linehan, J. M., Desbruslais, M., Joiner, S., Gowland, I., Wood, A. L., Welch, J., Hill, A. F., Lloyd, S. E., Wadsworth, J. D. F. and Collinge, J. (2002). BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J., 21, 6358-6366. 9/13/2005 Page 12 of 17 SEE SLIDES IN PDF FILE; http://www.nih.go.jp/JJID/56/221.pdf
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
December 20, 2005 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: As scientists and recognized experts who have worked in the field of TSEs for decades, we are deeply concerned by the recent discoveries of indigenous BSE infected cattle in North America and appreciate the opportunity to submit comments to this very important proposed rule We strongly supported the measures that USDA and FDA implemented to protect public health after the discovery of the case of bovine spongiform encephalopathy (BSE) found in Washington State in 2003. We know of no event or discovery since then that could justify relaxing the existing specified risk material (SRM) and non-ambulatory bans and surveillance that were implemented at that time. Further, we strongly supported the codification of those changes, as well as additional measures to strengthen the entire feed and food system. The discovery of additional cases of indigenous BSE in North America since that time has validated our position and strengthened our convictions. We caution against using the 18 month enhanced surveillance as a justification to relax or impede further actions. While this surveillance has not uncovered an epidemic, it does not clear the US cattle herd from infection. While it is highly likely that US and Canadian cattle were exposed to BSE prior to the 1997 feed ban, we do not know how many cattle were infected or how widely the infection was dispersed. BSE cases are most likely clustered in time and location, so while enhanced surveillance provides an 18 month snapshot, it does not negate the fact that US and Canadian cattle were exposed to BSE. We also do not know in any quantitative or controlled way how effective the feed ban has been, especially at the farm level. At this point we cannot even make a thorough assessment of the USDA surveillance as details such as age, risk category and regional distribution have not been released.
A number of countries initially attempted to take partial steps in regard to feed controls only to face repeated disappointments in predicted downturns of the epidemic course. We in North America could do this experiment all over again, waiting for each new warning before adding more stringency to our control measures, or we can benefit from the experience of others and take decisive measures now to arrest any further development of underlying cases that is implicit in those already discovered to date. The discovery of 5 indigenous North American cases, including one born after the implementation of the current feed ban, should provide the necessary incentive to implement, monitor and enforce a comprehensive and protective feed ban that is more congruent with the measures that have been proven to be effective throughout the world. In particular, we urge the FDA to act without further delay to strengthen the animal feed regulations by implementing the program proposed by the Canadian Food Inspection Agency (CFIA) in the December 11, 2004 Gazette. This includes removing all specified risk materials (SRMs) and deadstock from all animal feed. We also urge that the FDA discontinues the legal exemptions which allow ruminant protein to be fed back to ruminants (with the exception of milk). Many of these exemptions do not exist in other countries. Bovine products and byproducts are used for both food and pharmaceuticals. These human uses require the highest level of safety. Because of the hardy nature of the BSE agent and its high potential for cross contamination, the most effective way to protect bovine products and bovine derived materials from contamination by BSE is to ensure that infected animals or carcasses never enter processing plants. The goal would be to discover and remove infected animals from production as early as possible in the infection and long before they would be sent to slaughter. Until we have diagnostic tools powerful enough to allow us to discover the disease early in its prolonged pre-clinical incubation, we have to rely on the next best strategy which is to prevent any exposure through feed. The exemptions in the current ban as well as in the newly proposed rule make this difficult if not impossible, as they still provide legal avenues for ruminants to consume potentially contaminated ruminant protein. It is our opinion that the proposed rule falls woefully short in effective measures to minimize the potential for further transmissions of the disease. By the FDA’s own analysis, exempted tissues (such as distal ileum, DRGs, etc) contain approximately 10% of the infectivity in affected animals. Thus the proposed rule still allows the possibility for cattle to be exposed to BSE through: 1. Feeding of materials currently subject to legal exemptions from the ban (e.g., poultry litter, plate waste) 2. Cross feeding (the feeding of non-ruminant rations to ruminants) on farms; and 3. Cross contamination of ruminant and non-ruminant feed We are most concerned that the FDA has chosen to include a provision that would allow tissues from deadstock into the feed chain. We do not believe that down or dead stock
should be allowed into the food or feed chain whatever the age of the animal and whether or not the CNS tissues are removed. We do not support the provision to allow removal of brain and spinal cord from deadstock over 30 months for a number of reasons. This category of animals contains the highest level of infectivity and that infectivity is in other tissues besides just brain and spinal cord. Recent improvements in the BSE bioassay, have now made it possible to detect BSE infectivity 1000 time more efficiently than before. This assay has revealed the presence of BSE infectivity in some but not all peripheral nerves and in one muscle. (Buschmann and Groschup, 2005) This published and peer reviewed work is consistent with other publicly reported studies in Japan where, by western blot testing, prions were found in the peripheral nerves of a naturally infected 94-month-old cow. We feel that the studies as reported above have merit. The current studies not only re-enforce the risk of down and deadstock but also appear to provide additional information that these animals may be a potential source of greater levels of infectivity into the feed system. We also doubt that brain and spinal cord can be completely removed especially during warmer weather. Given the biological composition of these tissues, they are predisposed to rapid autolysis. As world wide surveillance for BSE increases, several atypical cases of bovine TSE have been discovered. These cases either show no clinical signs, or present as ‘downers’, and have an atypical neuropathology with respect to lesion morphology and distribution, causing problems in both clinical and post-mortem diagnosis. The origin of the cases are unclear but they suggest that even should typical BSE be eliminated, there may be other TSE diseases of cattle that could result by “mutation” and selection. Refeeding of contaminated protein could potentially perpetuate transmission much like typical BSE. An effective feed ban could prevent the expansion of such strains. We also note that there are other species which are susceptible to BSE and the current regulations allow for SRMs to be included in feed for these animals. For BSE to be perpetuated, the animal production system must have a source of agent and a means by which cattle or other susceptible species are exposed to this agent. We feel that in North America, the source and routes of exposure still exist, hence allowing for the continued recycling of BSE. We have detailed the scientific justifications for our position below. Source of the agent: SRMs (Specified Risk Materials) SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed, they may introduce BSE infectivity and continue to provide a source of animal feed contamination. For example, the skull and vertebral column which encase the brain and spinal cord, respectively, can be assumed to have gross contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is significant as research in the United Kingdom has shown that a calf may be infected with BSE by the ingestion of as little as .001 gram of untreated brain.
The tissue distribution of infectivity in BSE infected cattle has primarily been determined by 3 studies conducted in the United Kingdom all of which had limitations. In two of the studies, bioassays were done in mice which are at least 1000 fold less sensitive to BSE infection than cattle themselves. Only higher titers of infectivity can be detected by this method. These investigations found infectivity in the brain, spinal cord, retina, trigeminal ganglia, dorsal root ganglia, distal ileum and bone marrow (the bone marrow finding was from one animal). Infectivity was found in distal ileum of experimentally infected calves beginning six months after challenge and continuing at other intervals throughout life. (Wells et. al., 1994; 1998). The bioassay study in calves has produced similar results and in addition infectivity has been found in tonsil. The study is still in progress. Another project has found infectivity in the lymphoid tissue of third eyelid from naturally infected animals. (Dr. Danny Matthews, UK DEFRA, personal communication). While bioassay in cattle is far preferable to mice in terms of sensitivity, cattle nevertheless present their own limitations in terms of the long incubation time and the limited number of animals that can be used for assay compared to rodents. As a consequence the significance of the negative finding for many tissues is questionable. In fact, by the end of 2004 there was increasing evidence in species other than cattle that peripheral nerves and muscle have infectivity. (Bosque et al., 2002; Glatzel et al., 2003;Bartz et al., 2002; Androletti et al., 2004; Mulcahy et al., 2004; Thomzig et al., 2003; Thomzig et al., 2004) In some of these species, studies indicate that the agent migrates to the brain and spinal cord, replicates to high levels in the CNS and then spreads centrifugally from the spinal cord back down through the spinal neurons to the junction of the nerves and muscle into the muscle cells themselves. A recent German study (Buschmann and Groschup, 2005) examined nerves and muscle from a cow naturally infected with BSE and found that infectivity was present in several peripheral nerves and one muscle. The method of detection was bioassay in bovinized transgenic mice that show the same or greater sensitivity to transmission of BSE as cattle. This research concurs with findings by Japanese scientists that BSE infectivity is present in peripheral nerves at least in the clinical stage of disease. It is our opinion that there is increasing evidence that the pathogenesis of BSE might not be entirely different from TSEs in other species at the point of clinical disease in that there is peripheral involvement. We feel that the studies as reported above have merit. The current studies not only re-enforce the risk of down and deadstock but also appear to provide additional information that these animals may be a potential source of greater levels of infectivity into the feed system. In the event that FDA may confer with USDA about the risks associated with peripheral nerves we want to point out one issue. In the recent publication of the final rule on the importation of whole cuts of boneless beef from Japan, 9 CFR Part 94 [Docket No. 05- 004-2] RIN 0579-AB93, we disagree with the interpretation provided by USDA, APHIS. APHIS seems to discount the studies conducted by Groschup et al. 2005. on the basis that the transgenic mouse bioassay that they used may be too sensitive. In taking this position they have failed to realize that the point of an assay is to reveal in which tissues the infectivity resides and its relative concentration to brain or spinal cord. For this purpose, no assay can be too sensitive. Of course, the probability of an actual infection will be affected by the efficiency of infection which will be a function of dose, route of exposure and any host barrier effects that are present. We would also like to point out a factual error in the conclusion. APHIS states, “Given these factors, APHIS has determined that the finding of BSE infectivity in facial and sciatic nerves of the transgenic mice is not directly applicable to cattle naturally infected with BSE. Therefore, we do not consider it necessary to make any adjustments to the risk analysis for this rulemaking or to extend the comment period to solicit additional public comment on this issue.” It is incorrect that the infectivity was found in the peripheral nerves of transgenic mice. The peripheral nerves were harvested from a cow naturally infected with BSE. Transgenic mice were used as a bioassay model. From [Docket No. 05-004-2] RIN 0579-AB93: “Peripheral Nerves Issue: Two commenters stated that the underlying assumption of the proposed rule, that whole cuts of boneless beef from Japan will not contain tissues that may carry the BSE agent, is no longer valid because researchers have found peripheral nervous system tissues, including facial and sciatic nerves, that contain BSE infectivity.\2\ One of these commenters requested APHIS to explain whether and what additional mitigation measures are needed to reduce the risks that these tissues may be present in Japanese beef. This commenter further requested an additional comment period to obtain public comments to treat this new scientific finding.
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\2\ Bushmann, A., and Groschup, M.; Highly Bovine Spongiform Encephalopathy-Sensitive Transgenic Mice Confirm the Essential Restriction of Infectivity to the Nervous System in Clinically Diseased Cattle. The Journal of Infectious Diseases, 192: 934-42, September 1, 2005.
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Response: APHIS is familiar with the results of the study mentioned by the commenters in which mice, genetically engineered to be highly susceptible to BSE and to overexpress the bovine prion protein, were inoculated with tissues from a BSE-infected cow. This study demonstrated low levels of infectivity in the mouse assay in the facial and sciatic nerves of the peripheral nervous system. APHIS has evaluated these findings in the context of the potential occurrence of infectivity in the peripheral nerves of cattle and the corresponding risks of the presence of infectivity in such tissues resulting in cattle or human exposure to the BSE agent. The results from these experiments in genetically engineered mice should be interpreted with caution, as the findings may be influenced by the overexpression of prion proteins and may not accurately predict the natural distribution of BSE infectivity in cattle. Further, the overexpression of prion proteins in transgenic mice may not accurately mimic the natural disease process because the transgenic overexpressing mice have been shown to develop spontaneous lethal neurological disease involving spongiform changes in the brain and muscle degeneration.\3\ In addition, the route of administration to the mice was both intraperitoneal and intracerebral, which are two very efficient routes of infection as compared to oral consumption. Given these factors, APHIS has determined that the finding of BSE infectivity in facial and sciatic nerves of the transgenic mice is not directly applicable to cattle naturally infected with BSE. Therefore, we do not consider it necessary to make any adjustments to the risk analysis for this rulemaking or to extend the comment period to solicit additional public comment on this issue.”
Source of the agent: Deadstock
snip...
The May 2003 Canadian BSE case illustrates the difficulty of on farm enforcement and its serious ramifications. The BSE positive cow was rendered and the MBM distributed to various locations. Two of these locations were poultry farms which mixed their own feed. The farms also had cattle. The subsequent investigation could not eliminate the possibility that the cattle had been fed the same feed as the poultry. The cattle on these farms were completely depopulated. Human error is extremely difficult to prevent, and managing the risk through enforcement is problematical when confronted with the extreme logistical challenges of on farm monitoring. By eliminating the highest risk materials (SRMs and deadstock) which could introduce infectivity into the feed stream, the MBM resulting from processing becomes inherently safer. If mistakes are then made on farm, they no longer contribute to the recycling of BSE. Exposure: Susceptibility of other Species Felines A transmissible spongiform encephalopathy has been diagnosed in eight species of captive wild ruminants as well as exotic felines (cheetahs, pumas, a tiger and an ocelot) and domestic cats (Wyatt 1991). There have been over 80 domestic cat cases of Feline Spongiform Encephalopathy (FSE) in Great Britain, and cats in Norway, Northern Ireland, Lichtenstein and Switzerland. The agent isolated from several of these cases is indistinguishable from BSE in cattle using strain typing in mice, suggesting that FSE is actually BSE in exotic and domestic cats. Epidemiological evidence suggests BSE contaminated feed to be the probable source of infection in these species. (MAFF Progress Report, June 1997), thus providing additional supporting evidence for the dangers of BSE contaminated feed and reinforcing the necessity of removing all sources of potential contamination from the feed stream. Other species Studies conducted at the National Institutes of Health Rocky Mountain Laboratory caution against assuming that animals which do not become clinically ill are not infected. It is unknown if certain animals may become carriers, i.e., become infected, shed agent but do not progress to clinical disease. Infection of certain rodent species with different TSE strains suggests the possibility of a carrier state (Race and Chesebro, 1998; Race et. al, 2001, Race et al., 2002). In the more recent studies, mice were inoculated with 263K hamster scrapie. There was a prolonged period (approximately one year) where there was no evidence of replication of infectivity. Furthermore, there was no evidence of PrPres during this phase of inactive persistence, which was followed by a period of active replication of infectivity and agent adaptation. In most cases, PrPres was not detected in the active phase as well. It is important to determine if this persistence and adaptation occurs in other species exposed to TSEs as it may have significance in feeding programs which continually expose other species to BSE infectivity. For example, if BSE infected brain and spinal cord are continually fed to certain species, it may be possible for the agent to persist and adapt in these new species. Over time, the ‘resistant’ species may become a source of agent. The results of Race and colleagues, warns that an inactive persistent phase might not produce detectable PrPres, yet there would be infectivity (Race et. al., 2001). Pigs displayed evidence of TSE infection after exposure to BSE by 3 distinct parenteral routes. Evidence of infectivity was found in the CNS, stomach, intestine and pancreas (Dawson et. al., 1990). Oral transmission has also been attempted in swine, but after an observation period of 84 months there was neither clinical nor pathological evidence of infection (Dawson et. al., 1990). Parenteral and oral transmission has also been attempted in chickens with no evidence of disease. Tissues from the BSE-challenged pigs and chickens were inoculated into susceptible mice to look for residual infectivity, but to date none has been found. In both instances the detection sensitivity was limited by the use of mice for bioassay instead of same species transmissions into cattle (or pigs and chickens). If any of these scenarios played out and inapparent infections became established in commercial species, those species could become reservoirs for reinfection of cattle and perpetuation or reintroduction of the epidemic. We also do not know if atypical cases of BSE are more pathogenic for other species and if chronic inflammation may influence the susceptibility of other species. We offer these possibilities to reinforce the need to eliminate all possible sources of infectivity from the feed stream. In January 2005, the European Union announced that BSE had been confirmed in a goat in France illustrating that the disease can be naturally transmitted to one of the small ruminants. The potential ramifications of this and the logistical challenges associated contamination and cross feeding aspects stated for cattle are applicable. The need to remove high risk material from all animal feed is also supported by other bodies with expertise in the field of TSEs: Recommendations of the World Health Organization (WHO) The World Health Organization (WHO) has issued the following recommendations for countries with BSE or those where a known exposure exists: • No part or product of any animal which has shown signs of a TSE should enter any food chain (human or animal). In particular: o All countries must ensure the killing and safe disposal of all parts or products of such animals so that TSE infectivity cannot enter any food chain. o Countries should not permit tissues that are likely to contain the BSE agent to enter any food chain (human or animal). From the report of a WHO Consultation on Public Health Issues related to Human and Animal Transmissible Spongiform Encephalopathies WHO/EMC/DIS 96.147, Geneva, 2-3 April 1996. Office of International Epizooties (OIE) The OIE is recommending that a list of SRMs which include brain, spinal cord, eyes, skull and vertebral column be removed from preparations used for food, feed, fertilizer, etc. If these tissues should not be traded we feel that they should not be used in domestic products either. BSE Code Article 2.3.13.18 “From cattle, originating from a country or zone with a minimal BSE risk, that were at the time of slaughter over 30 months of age, the following commodities, and any commodity contaminated by them, should not be traded for the preparation of food, feed, fertilizers, cosmetics, pharmaceuticals including biologicals, or medical devices: brains, eyes and spinal cord, skull, vertebral column and derived protein products. Food, feed, fertilizers, cosmetics, pharmaceuticals or medical devices prepared using these commodities should also not be traded.” Conclusion In conclusion we urge the FDA to implement, monitor and enforce a comprehensive and protective feed ban that is more congruent with the measures that have been proven to be effective in other countries that have experienced BSE. We do not feel that we can overstate the dangers from the insidious threat from these diseases and the need to control and arrest them to prevent any possibility of spread. We also wish to emphasize that as scientists who have dedicated substantive portions of our careers to defining the risks from TSEs as well as developing strategies for managing those risks, we are confident that technical solutions will be found for many of the challenges posed by these diseases. Thus, we urge the FDA to frame its regulations in terms that allow for the future use of any banned material if it can be proven safe for a given application.
FDA Proposed Rule December 20, 2005
snip...
Signatories:
Paul W. Brown, M.D. Medical Director, USPHS, and Senior Investigator, NIH (retired) Consultant, TSE Risk Management 7815 Exeter Rd. Bethesda, MD 20814 Fax 301-652-4312 Email:
[email protected]
Neil R. Cashman MD Professor, Department of Medicine (Neurology) Diener Chair of Neurodegenerative Diseases Centre for Research in Neurodegenerative Diseases 6 Queen's Park Crescent West Toronto Ontario M5S3H2 Ph: 416-978-1875 Fax: 416-978-1878 e-mail:
[email protected]
Linda A. Detwiler, DVM Consultant, TSE Risk Management 225 Hwy 35 Red Bank, NJ 07701 Ph 732-741-2290 Fax 732-741-7751 Email:
[email protected]
Laura Manuelidis, MD Professor and Head of Neuropathology, Department of Surgery and Faculty of Neurosciences Yale Medical School 333 Cedar St. New Haven, CT 06510 email:
[email protected] Tel: 203-785-4442
Jason C. Bartz, Ph.D. Assistant Professor Department of Medical Microbiology and Immunology Creighton University 2500 California Plaza Omaha, NE 68178 (402) 280-1811 voice (402) 280-1875 fax
[email protected]
Robert B. Petersen, Ph.D. Associate Professor of Pathology and Neuroscience Case Western Reserve University 5-123 Wolstein Building 2103 Cornell Road Cleveland, OH 44106-2622 Phone 216-368-6709 FAX 360-838-9226 Email
[email protected]
Robert G. Rohwer, Ph.D. Director, Molecular Neurovirology Laboratory Veterans Affairs Medical Center Medical Research Service 151 Assoc. Professor of Neurology School of Medicine University of Maryland at Baltimore 10 N. Greene St. Baltimore, MD 21201 ph. 410-605-7000 x6462 Fax 410-605-7959 email:
[email protected]
see full text ;
http://www.fda.gov/OHRMS/DOCKETS/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
November 25, 2008
November 2008 Update On Feed Enforcement Activities To Limit The Spread Of BSE
To help prevent the establishment and amplification of Bovine Spongiform Encephalophathy (BSE) through feed in the United States, the Food and Drug Administration (FDA) implemented a final rule that prohibits the use of most mammalian protein in feeds for ruminant animals. This rule, Title 21 Part 589.2000 of the Code of Federal Regulations, here called the Ruminant Feed Ban, became effective on August 4, 1997.
The following is an update on FDA enforcement activities regarding the ruminant feed ban. FDA's Center for Veterinary Medicine (CVM) has assembled data from the inspections that have been conducted AND whose final inspection report has been recorded in the FDA's inspection database as of November 15, 2008. As of November 15, 2008, FDA had received over 66,000 inspection reports. The majority of these inspections (approximately 71%) were conducted by State feed control officials, with the remainder conducted by FDA officials.
Inspections conducted by FDA or State investigators are classified to reflect the compliance status at the time of the inspection based upon the objectionable conditions documented. These inspection conclusions are reported as Official Action Indicated (OAI), Voluntary Action Indicated (VAI), or No Action Indicated (NAI).
An OAI inspection classification occurs when significant objectionable conditions or practices were found and regulatory sanctions are warranted in order to address the establishment's lack of compliance with the regulation. An example of an OAI inspection classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspections classified with OAI violations will be promptly re-inspected following the regulatory sanctions to determine whether adequate corrective actions have been implemented.
A VAI inspection classification occurs when objectionable conditions or practices were found that do not meet the threshold of regulatory significance, but do warrant advisory actions to inform the establishment of findings that should be voluntarily corrected. Inspections classified with VAI violations are more technical violations of the Ruminant Feed Ban. These include provisions such as minor recordkeeping lapses and conditions involving non-ruminant feeds.
An NAI inspection classification occurs when no objectionable conditions or practices were found during the inspection or the significance of the documented objectionable conditions found does not justify further actions.
The results to date are reported here both by "segment of industry" and "in total". NOTE - A single firm can operate as more than one firm type. As a result, the categories of the different industry segments are not mutually exclusive.
RENDERERS
These firms are the first to handle and process (i.e., render) animal proteins and to send these processed materials to feed mills and/or protein blenders for use as a feed ingredient.
Number of active firms whose initial inspection has been reported to FDA - 267
Number of active firms handling materials prohibited from use in ruminant feed - 155 (58% of those active firms inspected)
Of the 155 active firms handling prohibited materials, their most recent inspection revealed that:
0 firms (0%) were classified as OAI
3 firms (2.0%) were classified as VAI
LICENSED FEED MILLS
FDA licenses these feed mills to produce medicated feed products. The license is required to manufacture and distribute feed using certain potent drug products, usually those requiring some pre-slaughter withdrawal time. This licensing has nothing to do with handling prohibited materials under the feed ban regulation. A medicated feed license from FDA is not required to handle materials prohibited under the Ruminant Feed Ban.
Number of active firms whose initial inspection has been reported to FDA - 1.075
Number of active firms handling materials prohibited from use in ruminant feed - 494 (46% of those active firms inspected)
Of the 494 active firms handling prohibited materials, their most recent inspection revealed that:
0 firms (0%) were classified as OAI
4 firms (0.8 %) were classified as VAI
FEED MILLS NOT LICENSED BY FDA
These feed mills are not licensed by the FDA to produce medicated feeds.
Number of active firms whose initial inspection has been reported to FDA - 5,290
Number of active firms handling materials prohibited from use in ruminant feed - 2,685 (51% of those active firms inspected)
Of the 2,685 active firms handling prohibited materials, their most recent inspection revealed that:
0 firms (0%) were classified as OAI
29 firms (1.1%) were classified as VAI
PROTEIN BLENDERS
These firms blend rendered animal protein for the purpose of producing quality feed ingredients that will be used by feed mills.
Number of active firms whose initial inspection has been reported to FDA - 387
Number of active firms handling materials prohibited from use in ruminant feed - 196 (51% of those active firms inspected)
Of the 196 active firms handling prohibited materials, their most recent inspection revealed that:
0 firms (0%) was classified as OAI
0 firms (0%) were classified as VAI
RENDERERS, FEED MILLS, AND PROTEIN BLENDERS MANUFACTURING WITH PROHIBITED MATERIAL
This category includes only those firms that actually use prohibited material to manufacture, process, or blend animal feed or feed ingredients.
Total number of active renderers, feed mills, and protein blenders whose initial inspection has been reported to FDA - 6,712
Number of active renderers, feed mills, and protein blenders processing with prohibited materials - 506 (7.5%)
Of the 506 active renderers, feed mills, and protein blenders processing with prohibited materials, their most recent inspection revealed that:
0 firms (0%) were classified as OAI
11 firms (2.2%) were classified as VAI
OTHER FIRMS INSPECTED
Examples of such firms include ruminant feeders, on-farm mixers, pet food manufacturers, animal feed salvagers, distributors, retailers, and animal feed transporters.
Number of active firms whose initial inspection has been reported to FDA - 21,865
Number of active firms handling materials prohibited from use in ruminant feed - 7,295 (33% of those active firms inspected)
Of the 7,295 active firms handling prohibited materials, their most recent inspection revealed that:
0 firm (0%) were classified as OAI
113 firms (1.5%) were classified as VAI
TOTAL FIRMS
Note that a single firm can be reported under more than one firm category; therefore, the summation of the individual OAI/VAI firm categories will be more than the actual total number of OAI/VAI firms, as presented below.
Number of active firms whose initial inspection has been reported to FDA - 24,065
Number of active firms handling materials prohibited from use in ruminant feed - 7,876 (33% of those active firms inspected)
Of the 7,876 active firms handling prohibited materials, their most recent inspection revealed that:
0 firms (0%) were classified as OAI
121 firms (1.5%) were classified as VAI
http://www.fda.gov/cvm/CVM_Updates/BseInspNov08.htm
unacceptable! in 2008, almost 2009, this many firms still in violation of mad cow feed ban rules. the infamous august 4, 1997 partial and voluntary mad cow feed ban was nothing more than ink on paper. ...TSS
Plasma & Serum Proteins Receive Continued FDA Approval
4/25/2008 APC, Inc. is pleased to advise our customers and industry partners that as anticipated, the Food and Drug Administration (FDA) will continue to allow the use of bovine blood, plasma and serum proteins in ruminant feeds.
In April 2008 FDA announced the publication of its Final Rule for 21 CFR Part 589.2001 - Substances Prohibited From Use in Animal Food or Feed. FDA specifically stated in their opinion that, "FDA is not prohibiting the use of blood and blood products in animal feed because we believe such a prohibition would do very little to reduce the risk of BSE transmission."
Known as a leader in developing nutritional products for the swine industry, where 95% of pig starter diets in the United States contain functional proteins, APC has more recently developed their line of colostrum replacers, supplements, feed additives and milk replacer ingredients for calves. Products include plasma, serum and immunoglobulin concentrate based Acquire®, Lifeline®, Gammulin® and Nutrapro® used to optimize the health and performance of calves.
To view the full report for Final Rule 21 CFR Part 589.2001 visit:
http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2002-N-0031-nfr.pdf
To view the complete Feed Rule 21 CFR Part 589 visit:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=589&showFR=1
Friday, November 21, 2008 Plasma & Serum Proteins Receive Continued FDA Approval
http://madcowfeed.blogspot.com/2008/11/plasma-serum-proteins-receive-continued.html
http://madcowfeed.blogspot.com/
TRANSFUSION MEDICINE
Prion diseases are efficiently transmitted by blood transfusion in sheep
Fiona Houston1, Sandra McCutcheon1, Wilfred Goldmann2, Angela Chong2, James Foster2, Silvia Sisó3, Lorenzo González3, Martin Jeffrey3, and Nora Hunter2 1 Neuropathogenesis Division, Roslin Institute, Compton, United Kingdom; 2 Neuropathogenesis Division, Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom; and 3 Lasswade Laboratory, Veterinary Laboratories Agency, Penicuik, United Kingdom
The emergence of variant Creutzfeld-Jakob disease, following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly high transmission rates by transfusion of 36% for BSE and 43% for scrapie. A proportion of BSE-infected tranfusion recipients (3 of 8) survived for up to 7 years without showing clinical signs of disease. The majority of transmissions resulted from blood collected from donors at more than 50% of the estimated incubation period. The high transmission rates and relatively short and consistent incubation periods in clinically positive recipients suggest that infectivity titers in blood were substantial and/or that blood transfusion is an efficient method of transmission. This experiment has established the value of using sheep as a model for studying transmission of variant Creutzfeld-Jakob disease by blood products in humans.
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/12/4739?ct
PLEASE BE ADVISED, also, such 'significant objectionable conditions or practices' such as this, allow millions and millions of pounds of banned ruminant feed into commerce, such as the one in 2007. I suppose this is why they DO NOT release such data anymore i.e. in tonnage or pounds, much too embarrassing considering .005 grams is lethal for a cow. ...TSS
In 2007, in one weekly enforcement report, the fda recalled 10,000,000+ pounds of BANNED MAD COW FEED, 'in commerce', and i can tell you that most of it was fed out ;
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. MBM IN COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
REASON
Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI
REASON
Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
http://www.fda.gov/bbs/topics/enforce/2007/ENF00996.html
Subject: MAD COW FEED RECALL USA SEPT 6, 2006 1961.72 TONS IN COMMERCE AL, TN, AND WV Date: September 6, 2006 at 7:58 am PST
snip... see listings and references of enormous amounts of banned mad cow protein 'in commerce' in 2006 and 2005 ;
see full text ;
Friday, April 25, 2008
Substances Prohibited From Use in Animal Food or Feed [Docket No. 2002N-0273] (Formerly Docket No. 02N-0273) RIN 0910-AF46
http://madcowfeed.blogspot.com/2008/04/substances-prohibited-from-use-in.html
SPECIFIED RISK MATERIALS
http://madcowspontaneousnot.blogspot.com/2008/02/specified-risk-materials-srm.html
0C3.01
Transmission of atypical BSE to Microcebus murinus, a non-human primate: Development of clinical symptoms and tissue distribution of PrPres
Background: Atypical BSE cases have been observed in Europe, Japan and North America. They differ in their PrPres profiles from those found in classical BSE. These atypical cases fall into 2 types, depending on the molecular mass of the unglycosylated PrPres band observed by Western blot: the L -type (lower molecular mass than the typical BSE cases) and H-type (higher molecular mass than the typical BSE cases).
Objectives and Methods: In order to see if the atypical BSE cases were transmissible to primates, either animals (were intracerebrally inoculated with 50 ul of a 10% brain homogenates of two atypical French BSE case, a H-type (2 males and 2 females) and a L-type (2 males and 2 females).
Results: Only one of the four lemurs challenged with H-type BSE died without clinical signs after 19 months post inoculation (mpi), whereas all the 4 animals inoculated with L -type BSE died at 19 mpi (2 males) and 22 mpi (2 females). Three months before their sacrifice, they developed blindness, tremor, abnormal posture, incoordinated movements, balance loss. Symptoms got worse according to the disease progression, until severe ataxia. The brain tissue were biochemically and immunocytochemically investigated for PrPres. For the H-type, spongiform changes without PrPres accumulation were observed in the brainstem. However Western blot analysis did not allow to detect PrPres into the brain. For the L-type, severe spongiosis was evidenced into the thalamus, the striatum, the mesencephalon, and the brainstem. whereas into the cortex the spongiosis was evidenced, but the Vacuolisation was weaker. Strong deposits of PrPres were detected by western blot, PET-blot and immunocytochemistry in the CNS: dense accumulation was observed into the thalamus, the striatum, and the hippocampus whereas in the cerebral cortex, PrPres was prominently accumulated in plaques. Western blot analysis also readily confirmed the presence of protease-resistant prion protein.
Conclusions: L-type infected lemurs showed survival times considerably shorter than for classical BSE strain, indicating that the disease is caused by a very virulent distinct prion strain in a model of non human primate.
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf
P7.09
Biochemical screening for identification of atypical bse in belgium, 1999-present
Authors
Alexandre DobIy: Caroline Rodeghiero, Riet Geeroms; Stephanie Durand, Jessica De Sloovere, Emanuel Yanopdenbosch, Stefan Roels,
Content
Background: Recently atypical forms of BSE have been described. Western blot analyses showed that, in comparison to the classic BSE (C-type), they are demonstrable by a higher or lower molecular weight of the unglycosylated PrPres. They Viere thus named H-type and L-type BSE (L-type is also called BASE). In