Vet Res. 2018; 49: 122.
Published online 2018 Dec 20. doi: 10.1186/s13567-018-0618-7
PMCID: PMC6302288
PMID: 30572960
Low levels of classical BSE infectivity in rendered fat tissue
Christine Fast, Markus Keller, Martin Kaatz, Ute Ziegler, and Martin H. Groschupcorresponding author
Author information Article notes Copyright and License information Disclaimer
Abstract
BSE infectivity in mesentery fat is most likely associated with embedded nervous tissue. To prove this mesentery containing celiac ganglion was taken from oral BSE infected cattle in different stages of the disease and from one control animal. Fat was rendered according to standard tallow production methods and the prion infectivity therein analysed in transgenic mouse bioassay. Rendered fat of the clinical animal revealed low infectivity levels, whereas preclinical and control animals remained negative. This study, although not representative, provides a proof of principle, indicating the potential contamination of melted mesenteric fat by embedded nervous structures during standard tallow production.
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Discussion The results presented here indicate that a certain amount of BSE infectivity must be present in the mesentery to contaminate the rendered fat in a detectable level during tallow production methods. As shown by [8] BSE infectivity increases in the CMGC of orally BSE infected cattle from early to late preclinical up to the highest levels at clinical stage. Hence, it comes without surprise that the infectious fat presented here originates from the CMGC of the clinical animal, which also showed a clear PrPSc accumulation pattern [8]. Additionally these results are in accordance with the infectivity data reported for fat tissue of CWD infected deer at later stages of the disease [12].
In our hands only low level of infectivity were found. However, the experimental adipose/CMGC tissue dilution factor needed for the fat rendering should also be considered, so the actual infectious load of the samples might be higher. However, the low infectivity load found here might explain why earlier studies failed to detect BSE infectivity in adipose tissue. For one reason this studies did not definitely regard nerves and ganglia which are involved in the pathogenesis of BSE and for another reason less susceptible conventional wild type mice were used [10, 15, 16]. Interestingly omental fat of deer infected with CWD at a clinical stage revealed a much higher infectivity level as compared to our results [12]. Therefore, it is tempting to speculate that these differences might be due to the qualitative and quantitative more widespread CWD distribution in bodily tissues [17] as compared to cattle BSE. However, it has to bear in mind that the two TSE strains are different, different mouse line were used and neither for CWD samples nor for our BSE sample a calibration curve for infectivity exist. Nevertheless, it would be of interest to what extent rendered fat could be contaminated by using mesentery from sheep and goats infected with classical scrapie or BSE, all entities showing in most cases a higher PrPSc accumulation in the autonomous nervous system than BSE infected cattle [18–21].
Our results, in particular the close relationship with the infectivity/PrPSc data of the CMGC samples, clearly support the widespread accepted assumption that infectivity in the mesentery is most probably associated with nerves and autonomous ganglia [9], whereas the direct involvement of fatty cells is uncertain [11]. Another source of infectivity could be in mesentery fat embedded lymph nodes. However, no infectivity has ever been detected in mesenterial lymph nodes of BSE infected cattle so far [13, 22] and all grossly evident lymphoreticular tissue was removed from our samples. Additionally a long term study showed that full blood transfusion from clinical BSE infected cattle to naïve calves did not transmit BSE [23]. Therefore, a blood contamination of the sample as possible source of infectivity is highly unlikely. Furthermore, as all tissue remnants in the rendered fat were removed by a centrifugation step before inoculation, all infectivity must be bound to the liquid fat solely.
These results might not be representative due to the small sample size and therefore provide only a proof of principle. In particular with regard to the negative early and late preclinical samples, there still remain some uncertainties, which can only be resolved by a more extended, that say statistical profound study. However, the inocula were generated according to standard tallow production methods [9], therefore our results clearly show that such a contamination is conceivable. Rendered fat can been used for food (i.e. premier jus, frying agent), pet food and feed application [24], therefore BSE/TSE infectivity could enter both the food and feed chain. At the time of writing the current SRM legislation prevented the usage of mesentery fat from animals whose origin is from countries with controlled or undetermined BSE risk. However, this regulation is still under discussion and might be changed in near future (EU Commission, personal communication).
P169 Low levels of classical BSE infectivity in rendered fat tissue
Dr. Christine Fast1, Dr. Markus Keller2, Dr. Ute Ziegler3, Prof. Dr. Martin Groschup4 1Friedrich-Loeffler-Institut, Greifswald, Germany, 2Friedrich-Loeffler-Institut, Greifswald, Germany, 3Friedrich-Loeffler-Institut, Greifswald, Germany, 4Friedrich-Loeffler-Institut, Greifswald, Germany
Aims: Specified Risk Materials (SRM) are the animal tissues potentially containing the highest levels of Bovine Spongiform Encephalopathy (BSE) prions; and their removal is the most important consumer protection measure against BSE. BSE infectivity in the mesentery fat is most likely associated with embedded nervous tissue. To date, it is unclear if contamination of the rendered fat could have occurred during tallow production at a slaughterhouse.
Methods: Samples were taken from five cattle originating from the German BSE pathogenesis study. Two animals were at preclinical, one at late preclinical and one animal at clinical stage of disease; one control animal was included. For all cattle, mouse bioassay results for the celiac and mesenteric ganglion complex (CMGC) were generated previously, showing either no, mild, moderate or substantial infectivity loads. Fat was rendered from CMGC samples embedded in mesentery fat by incubating for 20 minutes at 95°C, according to standard tallow production methods. Subsequently, the melted fat was 1:5 diluted in physiological saline and thoroughly vortexed. The liquid fat was cleaned by a short centrifugation at 10.000 rpm. Finally, 7-12 bovine prion protein overexpressing transgenic mice (Tgbov XV) were i.c. inoculated with 25-30 μl of the supernatant. Mice were sacrificed after 730 days or when showing clinical symptoms and mouse brains were subsequently examined by biochemical and immunohistochemical methods.
Results: Neither the control and the preclinical nor the late preclinical animals showed signs of infectivity in mouse bioassay of the fat samples after up to 730 days p.i. In contrast, low levels of infectivity were detected in the fat of the clinical animal as one mouse displayed a clear accumulation of pathological prion protein in the brain after an incubation period of 598 days p.i.
Conclusions: Our results clearly indicate the potential contamination of melted mesenteric fat by embedded nervous structures during standard tallow production. However, the BSE infectivity level was weak and detectable only in the fat rendered from one sample with documented high infectivity load in the ganglion itself (Kaatz et al. 2012). Albeit, this study is not representative as only one clinical animal was included, it provides a proof of principle. A broader examination would allow a better insight into temporal and spatial distribution pattern of BSE infectivity in rendered fat tissues of different origins.Such estimates have a critical role in qualitative and quantitative risk assessments and in providing advice on the designation and removal of certain SRM tissues.
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PRION 2018 CONFERENCE
P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge
Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2)
(1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
In 2006, a case of H-type bovine spongiform encephalopathy (BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K).
The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease.
Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route.
The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure.
Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with either H-type BSE from the 2004 US Htype BSE case (n=3) or from the 2006 US H-type case associated with the E211K polymorphism (n=4) using 10% w/v brain homogenates.
Cattle were observed daily throughout the course of the experiment for the development of clinical signs.
At approximately 50 months post-inoculation, one steer (EK211 inoculated with E211K associated H-BSE) developed clinical signs including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and was euthanized.
Enzyme immunoassay confirmed that abundant misfolded protein was present in the brainstem, and immunohistochemistry demonstrated PrPSc throughout the brain.
Western blot analysis of brain tissue from the clinically affected steer was consistent with the E211K H-type BSE inoculum.
With the experiment currently at 55 months post-inoculation, no other cattle in this study have developed clinical signs suggestive of prion disease.
This study demonstrates that the H-type BSE agent is transmissible by the oronasal route.
These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
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O10 Zoonotic potential of atypical BSE prions: a systematic evaluation
Marín-Moreno A (1), Espinosa JC (1), Douet JY (2), Aguilar-Calvo P (1), Píquer J (1), Lorenzo P (1), Lacroux C (2), Huor A (2), Lugan S (2), Tillier C (2), Andreoletti O (2) and Juan María Torres (1)
(1) Centro de Investigación en Sanidad Animal, CISA-INIA, Carretera Algete-El Casar s/n, Valdeolmos, 28130 Madrid, Spain.(2) UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, France.
Bovine Spongiform Encephalopathy (BSE) is the only zoonotic prion recognized to date. The transmission of BSE to humans caused the emergence of variant Creutzfeldt-Jakob disease (vCJD). In 2004 two new atypical prion agents were identified in cattle: H- and L- BSE prion strains.
The zoonotic potential of atypical BSE prions was assessed by inoculating three different isolates of cattle H- and L-BSE in transgenic mouse lines that overexpress the human PrP covering the three different genotypes of the aminoacid 129 (TgMet129, TgMet/Val129 and TgVal129). This polymorphism is known to be a key element involved in human resistance/susceptibility to BSE. In addition, TgMet129 and TgVal129 were challenged with one H- and L-BSE isolates adapted to sheep PrP expressing hosts to assess if intermediate passage in sheep could modify the capacity of these prions to cross the human species barrier.
Our results confirm that L-BSE transmits to TgMet129 even better than epidemic BSE. However, atypical L-BSE agent was unable to infect TgVal129 or TgMet/Val129 mice, even after passage in TgMet129. No transmission was observed with H-BSE in any mice model inoculated, irrespectively of the 129 polymorphism. After passage in sheep PrP expressing host, the properties of both H and LBSE including their capacity to cross the human species barrier were dramatically affected, emerging prion strains features that resemble those of sporadic Creutzfeldt-Jakob disease (sCJD).
To date, this is the more extensive and complete analysis of the zoonotic potential of atypical BSE prions. These results advise not to ignore the zoonotic potential of these agents.
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P77 In vitro approach to estimate the human transmission risk of prions
Iwamaru Y (1) Imamura M (2) Matsuura Y (1) Kohtaro Miyazawa (1) Takashi Yokoyama (3)
(1 ) National Institute of Animal Health, Prion Disease Unit, Ibaraki, Japan (2) University of Miyazaki, Division of Microbiology, Miyazaki, Japan (3) National Institute of Animal Health, Department of Planning and General Administration, Ibaraki, Japan.
Prion diseases are fatal neurodegenerative disorders in humans and animals. The key event in the pathogenesis of these disease is the conversion of host-encoded normal cellular prion protein (PrPC) into its pathogenic isoform (PrPSc) and its accumulation in the central nervous system. One of the characteristics of prion is the species barrier that limits the transmission between different species. Currently, bioassays using transgenic mice (Tg) overexpressing PrP of different species have become valuable tools for assessing cross species transmissibility of prions.
The recent reports describing the emergence of novel bovine spongiform encephalopathy (BSE) from H-BSE and the transmission of chronic wasting disease to swine have generated concerns of human infections of newly identified prions. Although Tg expressing human PrP have been used to model human susceptibility to animal prions, these experiments are costly and time-consuming. In addition, the results of bioassays are influenced by the lines of transgenic mice used and the lifespan of the challenged animals. These factors are needed to be taken into account when assessing the human risk of prions.
In attempt to develop the more time- and cost-saving method for assessment of the human transmission risk of prions, we performed experiments using protein misfolding cyclic amplification (PMCA) technique to investigate whether PMCA can be compatible with bioassay. Using brain homogenates of Tg expressing bovine PrP as the PrP substrate, we optimized the versatile PMCA condition that could amplify PrPSc from cattle affected with C-, H- or L-BSE. We measured the 50% PMCA seeding activity dose and the 50% lethal dose in 1 g equivalent of C-, H- or L-BSE cattle brain tissue by using PMCA or bioassay, respectively, and assessed the correlations between these doses.
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P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge
Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
reading up on this study from Prion 2018 Conference, very important findings ;
***> This study demonstrates that the H-type BSE agent is transmissible by the oronasal route.
***> These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
WEDNESDAY, AUGUST 15, 2018
The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge
***> P.108: Successful oral challenge of adult cattle with classical BSE
Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge; Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology Laboratory; Truro, Nova Scotia, Canada
Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and food-borne fatal neurological disease which can be orally transmitted to cattle and humans. Due to the presence of contaminated milk replacer, it is generally assumed that cattle become infected early in life as calves and then succumb to disease as adults. Here we challenged three 14 months old cattle per-orally with 100 grams of C-type BSE brain to investigate age-related susceptibility or resistance. During incubation, the animals were sampled monthly for blood and feces and subjected to standardized testing to identify changes related to neurological disease. At 53 months post exposure, progressive signs of central nervous system disease were observed in these 3 animals, and they were euthanized. Two of the C-BSE animals tested strongly positive using standard BSE rapid tests, however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.. Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE.
We are further examining explanations for the unusual disease presentation in the third challenged animal.
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
***P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food Inspection Agency; Lethbridge, AB Canada
Keywords: Atypical BSE, oral transmission, RT-QuIC
The detection of bovine spongiform encephalopathy (BSE) has had a significant negative impact on the cattle industry worldwide. In response, governments took actions to prevent transmission and additional threats to animal health and food safety. While these measures seem to be effective for controlling classical BSE, the more recently discovered atypical BSE has presented a new challenge. To generate data for risk assessment and control measures, we have challenged cattle orally with atypical BSE to determine transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon presentation of clinical symptoms, animals were euthanized and tested for characteristic histopathological changes as well as PrPSc deposition.
The H-type challenged animal displayed vacuolation exclusively in rostral brain areas but the L-type challenged animal showed no evidence thereof. To our surprise, neither of the animals euthanized, which were displaying clinical signs indicative of BSE, showed conclusive mis-folded prion accumulation in the brain or gut using standard molecular or immunohistochemical assays. To confirm presence or absence of prion infectivity, we employed an optimized real-time quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain Laboratory, Hamilton, USA.
Detection of PrPSc was unsuccessful for brain samples tests from the orally inoculated L type animal using the RT-QuIC. It is possible that these negative results were related to the tissue sampling locations or that type specific optimization is needed to detect PrPSc in this animal. We were however able to consistently detect the presence of mis-folded prions in the brain of the H-type inoculated animal. Considering the negative and inconclusive results with other PrPSc detection methods, positive results using the optimized RT-QuIC suggests the method is extremely sensitive for H-type BSE detection. This may be evidence of the first successful oral transmission of H type atypical BSE in cattle and additional investigation of samples from these animals are ongoing.
Detection of PrPBSE and prion infectivity in the ileal Peyer’s patch of young calves as early as 2 months after oral challenge with classical bovine spongiform encephalopathy
Ivett Ackermann1 , Anne Balkema‑Buschmann1 , Reiner Ulrich2 , Kerstin Tauscher2 , James C. Shawulu1 , Markus Keller1 , Olanrewaju I. Fatola1 , Paul Brown3 and Martin H. Groschup1*
Abstract
In classical bovine spongiform encephalopathy (C-BSE), an orally acquired prion disease of cattle, the ileal Peyer’s patch (IPP) represents the main entry port for the BSE agent. In earlier C-BSE pathogenesis studies, cattle at 4–6 months of age were orally challenged, while there are strong indications that the risk of infection is highest in young animals. In the present study, unweaned calves aged 4–6 weeks were orally challenged to determine the earli‑ est time point at which newly formed PrPBSE and BSE infectivity are detectable in the IPP. For this purpose, calves were culled 1 week as well as 2, 4, 6 and 8 months post-infection (mpi) and IPPs were examined for BSE infectivity using a bovine PrP transgenic mouse bioassay, and for PrPBSE by immunohistochemistry (IHC) and protein misfolding cyclic amplifcation (PMCA) assays. For the frst time, BSE prions were detected in the IPP as early as 2 mpi by transgenic mouse bioassay and PMCA and 4 mpi by IHC in the follicular dendritic cells (FDCs) of the IPP follicles. These data indi‑ cate that BSE prions propagate in the IPP of unweaned calves within 2 months of oral uptake of the agent.
In summary, our study demonstrates for the frst time PrPBSE (by PMCA) and prion infectivity (by mouse bioassay) in the ileal Peyer’s patch (IPP) of young calves as early as 2 months after infection. From 4 mpi nearly all calves showed PrPBSE positive IPP follicles (by IHC), even with PrPBSE accumulation detectable in FDCs in some animals. Finally, our results confrm the IPP as the early port of entry for the BSE agent and a site of initial propagation of PrPBSE and infectivity during the early pathogenesis of the disease. Terefore, our study supports the recommendation to remove the last four metres of the small intestine (distal ileum) at slaughter, as designated by current legal requirements for countries with a controlled BSE risk status, as an essential measure for consumer and public health protection.
A study comparing preclinical cattle infected naturally with BSE to clinically affected cattle either naturally or experimentally infected with BSE by the oral route found the most abundant PrPSc in the brainstem area (39), which is consistent with ascension to the brain from the gut by sympathetic and parasympathetic projections (40). In our experiment, abundant prions were observed in the brainstem of cattle with clinical signs of BSE, which is similar to the amount in their thalamus or midbrain regions. Interestingly, prions in the brainstem of cattle with clinical evidence of BSE seeded the RT-QuIC reactions faster than any other brain region despite the brainstem area having lower EIA OD values (Table 2) in comparison to other brain regions. This suggests that higher concentrations of prions do not necessarily seed the reaction faster. Perhaps prions of the brainstem exist in a preferred conformation for better conversion despite being present in lower concentrations.
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TUESDAY, NOVEMBER 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
Wednesday, July 15, 2015
Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts
S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***
Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.
*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these countries.. ***
see page 176 of 201 pages...tss
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang 1 , Sandor Dudas 2 , Catherine Graham 2 , Markus Czub 3 , Tim McAllister 1 , Stefanie Czub 1 1 Agriculture and Agri-Food Canada Research Centre, Canada; 2 National and OIE BSE Reference Laboratory, Canada; 3 University of Calgary, Canada
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle. Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.
Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal-specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. It also suggests a similar cause or source for atypical BSE in these countries.
see page 176 of 201 pages...tss
SEEMS THE POSTER ABSTRACTS HAVE BEEN REMOVED ALONG WITH ALL NEUROPRION URL LINKS. SEE;
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;
***> PRION CONFERENCE 2018 <***
O3 Experimental studies on prion transmission barrier and TSE pathogenesis in large animals
Rosa Bolea(1), Acín C(1)Marín B(1), Hedman C(1), Raksa H(1), Barrio T(1), Otero A(1), LópezPérez O(1), Monleón E(1),Martín-Burriel(1), Monzón M(1), Garza MC(1), Filali H(1),Pitarch JL(1), Garcés M(1), Betancor M(1), GuijarroIM(1), GarcíaM(1), Moreno B(1),Vargas A(1), Vidal E(2), Pumarola M(2), Castilla J(3), Andréoletti O(4), Espinosa JC(5), Torres JM(5), Badiola JJ(1).
1Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, VeterinaryFaculty, Universidad de Zaragoza; Zaragoza,Spain.2 RTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) 3 4 INRA, ÉcoleVétérinaire, Toulouse, France.5CIC bioGUNE, Prion researchlab, Derio, Spain CISA- INIA, Valdeolmos, Madrid 28130, Spain.
Experimental transmission of Transmissible Spongiform Encephalopathies (TSE) has been understood and related with several factors that could modify the natural development of these diseases. In fact, the behaviour of the natural disease does not match exactly in each animal, being modified by parameters such as the age at infection, the genotype, the breed or the causative strain. Moreover, different TSE strains can target different animal species or tissues, what complicate the prediction of its transmissibility when is tested in a different species of the origin source. The aim of the experimental studies in large animals is to homogenize all those factors, trying to minimize as much as possible variations between individuals. These effects can be flattened by experimental transmission in mice, in which a specific strain can be selected after several passages. With this objective, several experimental studies in large animals have been developed by the presenter research team.
Classical scrapie agent has been inoculated in cow, with the aim of demonstrate the resistance or susceptibility of this species to the first well known TSE; Atypical scrapie has been inoculated in sheep (using several routes of infection), cow and pig, with the objective of evaluating the potential pathogenicity of this strain; Classical Bovine Spongiform Encephalopathy (BSE) has been inoculated in goats aiming to demonstrate if the genetic background of this species could protect against this strain; goat BSE and sheep BSE have been inoculated in goats and pigs respectively to evaluate the effect of species barrier; and finally atypical BSE has been inoculated in cattle to assess the transmissibility properties of this newly introduced strain.
Once the experiments have been carried out on large animal species, a collection of samples from animals studied were inoculated in different types of tg mice overexpressing PrPcin order to study the infectivity of the tissues, and also were studied using PMCA.
In summary, the parameters that have been controlled are the species, the strain, the route of inoculation, the time at infection, the genotype, the age, and the environmental conditions.
To date,
***> eleven of the atypical scrapie intracerebrally inoculated sheep have succumbed to atypical scrapie disease;
***> six pigs to sheep BSE;
***> one cow to classical scrapie;
***> nine goats to goat BSE and
***> five goats to classical BSE.
***> PrPSC has been demonstrated in all cases by immunohistochemistry and western blot.
=====> PRION CONFERENCE 2018
***> 2018 PRION CONFERENCE REPORTS AND ARS USA RESEARCH REPORTS <***
Scrapie, CWD, tse prion, transmit to pigs by oral route
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" oral="">6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period.
This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.
Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
MONDAY, NOVEMBER 26, 2018
***>The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP
Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿
Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations
In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
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In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.
snip.....
The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip.....
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
snip.....
In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip.....
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip.....
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
SUNDAY, DECEMBER 02, 2018
CWD TSE PRION, REGULATORY LEGISLATION, PAY TO PLAY, and The SPREAD of Chronic Wasting Disease
Prion Conference 2018
O5 Prion Disease in Dromedary Camels
Babelhadj B (1), Di Bari MA (2), Pirisinu L (2), Chiappini B (2), Gaouar SB (3), Riccardi G (2), Marcon S (2), Agrimi U (2), Nonno R (2), Vaccari G (2) (1) École Normale Supérieure Ouargla. Laboratoire de protection des écosystèmes en zones arides et semi arides University Kasdi Merbah Ouargla, Ouargla, Algeria; (2) Istituto Superiore di Sanità, Department of Food Safety, Nutrition and Veterinary Public Health, Rome, Italy (3) University Abou Bekr Bélkaid, Tlemcen, Algeria.
Prions are responsible for fatal and transmissible neurodegenerative diseases including CreutzfeldtJakob disease in humans, scrapie in small ruminants and bovine spongiform encephalopathy (BSE). Following the BSE epidemic and the demonstration of its zoonotic potential, general concerns have been raised on animal prions.
Here we report the identification of a prion disease in dromedary camels (Camelus dromedarius) in Algeria and designate it as Camel Prion Disease (CPD). In the last years, neurological symptoms have been observed in adult male and female dromedaries presented for slaughter at the Ouargla abattoir. The symptoms include weight loss, behavioral abnormalities and neurological symptoms such as tremors, aggressiveness, hyper-reactivity, typical down and upwards movements of the head, hesitant and uncertain gait, ataxia of the hind limbs, occasional falls and difficult getting up. During 2015 and 2016, symptoms suggestive of prion disease were observed in 3.1% of 2259 dromedaries presented at ante-mortem examination. Laboratory diagnosis was obtained in three symptomatic dromedaries, sampled in 2016 and 2017, by the detection of typical neurodegeneration and disease-specific prion protein (PrPSc) in brain tissues.
Histopathological examination revealed spongiform change, gliosis and neuronal loss preferentially in grey matter of subcortical brain areas. Abundant PrPSc deposition was detected in the same brain areas by immunohistochemistry and PET-blot. Western blot analysis confirmed the presence of PK-resistant PrPSc, whose N-terminal cleaved PK-resistant core was characterized by a mono-glycosylated dominant form and by a distinctive N-terminal cleavage, different from that observed in BSE and scrapie.
PrPSc was also detected, by immunohistochemistry, in all sampled lymph nodes (cervical, prescapular and lumbar aortic) of the only animal from which they were collected.
The PRNP sequence of the two animals for which frozen material was available, showed 100% nucleotide identity with the PRNP sequence already reported for dromedary camel.
Overall, these data demonstrate the presence of a prion disease in dromedary camelswhose nature, origin and spread need further investigations. However, our preliminary observations on the rather high prevalence of symptomatic dromedaries and the involvement of lymphoid tissues, are consistent with CPD being an infectious disease. In conclusion, the emergence of a new prion disease in a livestock species of crucial importance for millions of people around the world, makes urgent to assess the risk for humans and to develop policies able to control the spread of the disease in animals and to minimize human exposure.
CDC
New Outbreak of TSE Prion in NEW LIVESTOCK SPECIES
Mad Camel Disease
Volume 24, Number 6—June 2018 Research
Prion Disease in Dromedary Camels, Algeria
Abstract
Prions cause fatal and transmissible neurodegenerative diseases, including Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE). After the BSE epidemic, and the associated human infections, began in 1996 in the United Kingdom, general concerns have been raised about animal prions. We detected a prion disease in dromedary camels (Camelus dromedarius) in Algeria. Symptoms suggesting prion disease occurred in 3.1% of dromedaries brought for slaughter to the Ouargla abattoir in 2015–2016. We confirmed diagnosis by detecting pathognomonic neurodegeneration and disease-specific prion protein (PrPSc) in brain tissues from 3 symptomatic animals. Prion detection in lymphoid tissues is suggestive of the infectious nature of the disease. PrPSc biochemical characterization showed differences with BSE and scrapie. Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.
SNIP...
The possibility that dromedaries acquired the disease from eating prion-contaminated waste needs to be considered.
Tracing the origin of prion diseases is challenging. In the case of CPD, the traditional extensive and nomadic herding practices of dromedaries represent a formidable factor for accelerating the spread of the disease at long distances, making the path of its diffusion difficult to determine. Finally, the major import flows of live animals to Algeria from Niger, Mali, and Mauritania (27) should be investigated to trace the possible origin of CPD from other countries.
Camels are a vital animal species for millions of persons globally. The world camel population has a yearly growth rate of 2.1% (28). In 2014, the population was estimated at ≈28 million animals, but this number is probably underestimated.. Approximately 88% of camels are found in Africa, especially eastern Africa, and 12% are found in Asia. Official data reported 350,000 dromedaries in Algeria in 2014 (28).
On the basis of phenotypic traits and sociogeographic criteria, several dromedary populations have been suggested to exist in Algeria (29). However, recent genetic studies in Algeria and Egypt point to a weak differentiation of the dromedary population as a consequence of historical use as a cross-continental beast of burden along trans-Saharan caravan routes, coupled with traditional extensive/nomadic herding practices (30).
Such genetic homogeneity also might be reflected in PRNP. Studies on PRNP variability in camels are therefore warranted to explore the existence of genotypes resistant to CPD, which could represent an important tool for CPD management as it was for breeding programs for scrapie eradication in sheep.
In the past 10 years, the camel farming system has changed rapidly, with increasing setup of periurban dairy farms and dairy plants and diversification of camel products and market penetration (13). This evolution requires improved health standards for infectious diseases and, in light of CPD, for prion diseases.
The emergence of another prion disease in an animal species of crucial importance for millions of persons worldwide makes it necessary to assess the risk for humans and develop evidence-based policies to control and limit the spread of the disease in animals and minimize human exposure. The implementation of a surveillance system for prion diseases would be a first step to enable disease control and minimize human and animal exposure. Finally, the diagnostic capacity of prion diseases needs to be improved in all countries in Africa where dromedaries are part of the domestic livestock.
***> IMPORTS AND EXPORTS <***
***SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BAN ***
USA MAD COW CASE 2018 FLORIDA
WEDNESDAY, SEPTEMBER 26, 2018
JAVMA In Short Update USDA announces detection of atypical BSE
WEDNESDAY, SEPTEMBER 26, 2018
JAVMA In Short Update USDA announces detection of atypical BSE
-----Original Message-----
From: Terry Singeltary
To: bse-l
Cc: vlc ; medialibrary ; DBanasiak ; rvalentine ; llien ; jhorvath ; kbrandt ; agonda ; DBanasiak ; AVMAinfo
Sent: Wed, Sep 26, 2018 11:10 am
Subject: JAVMA In Short Update USDA announces detection of atypical BSE
USDA announces detection of atypical BSE
On Aug. 29, the Department of Agriculture announced an atypical case of bovine spongiform encephalopathy in a 6-year-old mixed-breed beef cow in Florida. The animal was never brought to slaughter. The National Veterinary Services Laboratories of the USDA Animal and Plant Health Inspection Service confirmed that the cow tested positive for atypical H-type BSE. The animal was initially tested at the Colorado State University Veterinary Diagnostic Laboratory as part of routine surveillance of cattle that are deemed unsuitable for slaughter. Of the five previous U.S. cases of BSE, the first was a case of classical BSE in a cow imported from Canada. The primary source of infection for classical BSE is feed contaminated with the infectious prion agent. The rest of the cases were atypical BSE, which seems to arise rarely and spontaneously in all cattle populations.
''Atypical BSE is different, and it generally occurs in older cattle, usually 8 years of age or greater. It seems to arise rarely and spontaneously in all cattle populations.''
FALSE!
''The primary source of infection for classical BSE is feed contaminated with the infectious prion agent, such as meat-and-bone meal containing protein derived from rendered infected cattle. Regulations from the Food and Drug Administration (FDA) have prohibited the inclusion of mammalian protein in feed for cattle and other ruminants since 1997 and have also prohibited high risk tissue materials in all animal feed since 2009.''
FALSE!
oh what webs of deceit we weave, when all we do is practice to deceive $$$
LET'S REVIEW RECENT AND PAST SCIENCE THAT SHOWS THE ABOVE TWO STATEMENTS ARE FAR FROM TRUE;
PRION 2018 CONFERENCE
P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge
Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
reading up on this study from Prion 2018 Conference, very important findings ;
***> This study demonstrates that the H-type BSE agent is transmissible by the oronasal route.
***> These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
PRION 2018 CONFERENCE ABSTRACT
WEDNESDAY, OCTOBER 24, 2018
Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy
MONDAY, JANUARY 09, 2017
Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle
CDC Volume 23, Number 2—February 2017
*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
TUESDAY, AUGUST 28, 2018
USDA finds BSE infection in Florida cow 08/28/18 6:43 PM
http://animalhealthreportpriontse..blogspot.com/2018/08/usda-finds-bse-infection-in-florida-cow.html
WEDNESDAY, AUGUST 29, 2018
USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT
WEDNESDAY, AUGUST 29, 2018
Transmissible Spongiform Encephalopathy TSE Prion Atypical BSE Confirmed Florida Update USA August 28, 2018
WEDNESDAY, AUGUST 29, 2018
OIE Bovine spongiform encephalopathy, United States of America Information received on 29/08/2018 from Dr John Clifford, Official Delegate, Chief Trade Advisor, APHIS USDA
''The event is resolved. No more reports will be submitted.''
well, so much for those herd mates exposed to this atypical BSE cow, and all those trace in and trace outs.
The OIE, USDA, and the BSE MRR policy is a joke, a sad, very sad joke...
THURSDAY, AUGUST 30, 2018
Florida Department of Agriculture and Consumer Services announced it is working closely with U.S. Department of Agriculture regarding an atypical case of Bovine Spongiform Encephalopathy BSE
THURSDAY, AUGUST 30, 2018
TRACKING HERD MATES USDA MAD COW DISEASE, TRACE FORWARD, TRACE BACK RECORDS, WHO CARES, NOT THE OIE
USDA ONLY TESTING 20k HEAD OF CATTLE A YEAR FOR MAD COW DISEASE ...LOL!
WEDNESDAY, AUGUST 29, 2018
USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT
http://animalhealthreportpriontse..blogspot.com/2018/08/usda-finds-bse-infection-in-florida-cow.html
WEDNESDAY, AUGUST 29, 2018
***> USDA DROPS MAD COW TESTING FROM 40K A YEAR TO JUST 20K A YEAR, IMPOSSIBLE TO FIND BSE, BUT THEY DID, IN FLORIDA!
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016
Monday, June 20, 2016
Specified Risk Materials SRMs BSE TSE Prion Program
THURSDAY, NOVEMBER 01, 2018
***> National Scrapie Eradication Program September 2018 Monthly Report Fiscal Year 2018 October 15, 2018
Friday, December 14, 2018
FSIS Recalling 10,828 pounds raw intact bone-in beef quarters cattle Products may contain Specified Risk Materials (SRM) MOST HIGH RISK FOR BSE MAD COW DISEASE
THURSDAY, JANUARY 3, 2019
MAD COW USDA DISEASE BSE TSE Prion
FRIDAY, DECEMBER 28, 2018
Chronic Wasting Disease CWD TSE Prion 2019 Where The Rubber Meets The Road
Saturday, December 15, 2018
http://www.house.gov/reform/min/pdfs_108_2/pdfs_inves/pdf_food_usda_mad_cow_july_13_ig_rep.pdf
ADRD Summit RFI Singeltary COMMENT SUBMISSION BSE, SCRAPIE, CWD, AND HUMAN TSE PRION DISEASE December 14, 2018
ZOONOSIS OF SCRAPIE TSE PRION
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man.
***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough.
***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
***> Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility. <***
Transmission of scrapie prions to primate after an extended silent incubation period
Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.
SNIP...
Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.
The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.
We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.
The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
Singeltary on Scrapie and human transmission way back, see;
FRIDAY, NOVEMBER 30, 2018
The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSEs) in 2017
***> 2018 URGENT DATA <***
***2018***
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
Abstract
Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans.
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;
(3) Reliable essays can be established to detect CWD infection in humans; and
(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.
Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of humanized Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental human CWD samples will also be generated for Aim 3.
Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1.
Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental human CWD samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.
Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.
Public Health Relevance
There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.
Funding Agency
Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS088604-04
Application #
9517118
Study Section
Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)
Program Officer Wong, May
Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2018-08-01 Budget End 2019-07-31 Support Year 4 Fiscal Year 2018 Total Cost Indirect Cost Institution Name Case Western Reserve University Department Pathology Type Schools of Medicine DUNS # 077758407 City Cleveland State OH Country United States Zip Code 44106
Related projects
NIH 2018 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University
NIH 2017 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University
NIH 2016 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University
NIH 2015 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University $337,507
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
here is the latest;
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge). To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip...see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below...terry
just out CDC...see;
Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. Barria
Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell) M. A. Barria et al.
ABSTRACT
Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form.
We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
Molecular Barriers to Zoonotic Transmission of Prions
Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author
snip...
The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine.
***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.
snip...
However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring.
***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain.
Prion 2017 Conference Abstracts
CWD 2017 PRION CONFERENCE
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes.
Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product.
Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain).
Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments.
We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem.
Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes.
All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.
Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing.
Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years.
Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017
DECIPHERING NEURODEGENERATIVE DISORDERS
Subject: PRION 2017 CONFERENCE
DECIPHERING NEURODEGENERATIVE DISORDERS
VIDEO PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
*** PRION 2017 CONFERENCE VIDEO
ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION
10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question...
''In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II)
EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors
First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132
also, see;
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
snip...
The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure.
zoonosis zoonotic cervid tse prion cwd to humans, preparing for the storm
***An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE..116***
To date there is no direct evidence that CWD has been or can be transmitted from animals to humans.
However, initial findings from a laboratory research project funded by the Alberta Prion Research Institute (APRI) and Alberta Livestock Meat Agency (ALMA), and led by a Canadian Food Inspection Agency (CFIA) scientist indicate that CWD has been transmitted to cynomolgus macaques (the non-human primate species most closely related to humans that may be used in research), through both the intracranial and oral routes of exposure.
Both infected brain and muscle tissues were found to transmit disease.
Health Canada’s Health Products and Food Branch (HPFB) was asked to consider the impact of these findings on the Branch’s current position on CWD in health products and foods.
Summary and Recommendation:
snip...
Health Portfolio partners were recently made aware of initial findings from a research project led by a CFIA scientist that have demonstrated that cynomolgus macaques can be infected via intracranial exposure and oral gavage with CWD infected muscle.
These findings suggest that CWD, under specific experimental conditions, has the potential to cross the human species barrier, including by enteral feeding of CWD infected muscle.
*** WDA 2016 NEW YORK ***
We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions.
In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.
***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.
Student Presentations Session 2
The species barriers and public health threat of CWD and BSE prions
Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University
Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein.
These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species.
The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time.
We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations.
We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species.
***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
FRIDAY, DECEMBER 28, 2018
Chronic Wasting Disease CWD TSE Prion 2019 Where The Rubber Meets The Road
SUNDAY, DECEMBER 09, 2018
Creutzfeldt Jakob Disease CJD, BSE, Scrapie, CWD, TSE Prion Annual Report December 14, 2018
Sunday, December 9, 2018
Variable Protease-Sensitive Prionopathy Transmission to Bank Voles CDC Volume 25, Number 1—January 2019
Saturday, December 15, 2018
ADRD Summit RFI Singeltary COMMENT SUBMISSION BSE, SCRAPIE, CWD, AND HUMAN TSE PRION DISEASE December 14, 2018
TUESDAY, JANUARY 1, 2019
CHILDHOOD EXPOSURE TO CADAVERIC DURA
THIS April, 4, 2017
violation of the mad cow 21 CFR 589.2000 OAI is very serious for the great state of Michigan, some 20 years post FDA mad cow feed of August 1997. if would most likely take a FOIA request and a decade of wrangling to find out more.
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
I would kindly like to comment on this FDA BSE/Ruminant Feed Inspections Firms Inventory (excel format)4 format, for reporting these breaches of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters the fda use to put out for each violations. simply put, this excel format sucks, and the FDA et al intentionally made it this difficult to follow the usda fda mad cow follies. this is an intentional format to make it as difficult as possible to follow these breaches of the mad cow TSE prion safety feed protocols. to have absolutely no chronological or numerical order, and to format such violations in a way that they are almost impossible to find, says a lot about just how far the FDA and our fine federal friends will go through to hide these continued violations of the BSE TSE prion mad cow feed ban, and any breaches of protocols there from. once again, the wolf guarding the henhouse $$$
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions.
2016
ONE more thing, please remember, the label does not have to say ''deer ration'' for cervid to be pumped up with. you can get the same ''high protein'' from many sources of high protein feed for animals other than cattle, and feed them to cervid...
Saturday, August 29, 2009
FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009
Friday, September 4, 2009
FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009
WEDNESDAY, JULY 11, 2018
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000
TUESDAY, JULY 10, 2018 CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS ***
''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''
CONFIDENTIAL
SPONGIFORM ENCEPHALOPATHY OF PIGS
***>10 years post mad cow feed ban August 1997
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
PRODUCT
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing.
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
___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.
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
PLEASE NOTE, NO MORE ENFORCEMENT REPORTS HERE. ...TSS
however, it has not stopped there, lets jump to 2006 alone ;
Subject: MAD COW FDA FEED WARNING LETTER NO. 2007-NOL-01 October 26, 2006 H.J. Baker & Bro., Inc. Date: November 7, 2006 at 9:08 am PST Food and Drug Administration
New Orleans District
404 BNA Drive, Building 200, Suite 500
Nashville, TN 37217
Telephone: 615-366-7801
Facsimile: 615-366-7802
October 26, 2006
WARNING LETTER NO. 2007-NOL-01
FEDERAL EXPRESS
OVERNIGHT DELIVERY
Mr. Christopher V. B. Smith
Corporate President, CEO
H. J. Baker & Bro., Inc.
228 Saugatuck Avenue
Westport, Connecticut 06880
Dear Mr. Smith:
On June 6, 8, 12-15, and 23, 2006, a U.S . Food and Drug Administration (FDA) investigator inspected
your animal feed protein supplement manufacturing facility, located at 603 Railroad Avenue,
Albertville, Alabama. The inspection revealed significant deviations from the requirements set forth in
Title 21, Code ofFederal Regulations, Part 589.2000 (21 CFR 589.2000), Animal Proteins Prohibited in
Ruminant Feed. This regulation is intended to prevent the establishment and amplification of Bovine
Spongiform Encephalopathy (BSE). You failed to follow the requirements of this regulation, resulting
in products being manufactured and distributed by your facility because they are adulterated within the
meaning of Section 402(a)(4) [21 USC 342(a)(4)] of the Federal Food, Drug, and Cosmetic Act (the
Act) and misbranded within the meaning of Section 403(a)(1) [21 USC 343(a)(1)] of the Act.
Our investigation determined adulteration resulted from the failure of your firm to establish and
implement measures sufficient to prevent commingling or cross-contamination . The adulterated feed
was subsequently misbranded because it was not properly labeled. Specifically, we found :
" Your firm failed to establish and use cleanout procedures or other means to prevent carry-over of
products which contain or may contain protein derived from mammalian tissues into animal protein
or feeds which may be used for ruminants, as required by 21 CFR 589.2000(e)(1)(iii)(B) .
Specifically, you failed to establish and use such measures for a screw auger installed in February
2005 . This auger is used to convey both prohibited and non-prohibited material to bulk storage bins.
In addition, you failed to follow the cleanout procedure your firm had developed for the receiving
systems. Your feed is, therefore, adulterated under Section 402(a)(4) [21 USC 342(a)(4)] of the Act.
" You failed to label all products which contained or may have contained prohibited materials with the
BSE cautionary statement, "Do not feed to cattle or other ruminants," as required by 21 CFR
589.2000(e)(1)(i) . Such products are misbranded under Section 403(3) [21 USC 343(a)(1)] of the
Act. These misbranded products include the three Pro-Pak products mentioned below, as well as
Page 2 - H. J . Baker & Bro., Inc., Albertville, Alabama Warning Letter No. 2007-NOL-O 1
those bulk loads of individual feed ingredients processed through this common screw auger and
distributed between the time it was installed in February 2005, and June 9, 2006 .
This letter is not intended to serve as an all-inclusive list of violations at your facility. As a
manufacturer of materials intended for animal feed use, you are responsible for ensuring your overall
operation and the products you manufacture and distribute are in compliance with the law. You should take prompt action to correct these violations, and you should establish a system whereby violations do not recur. Failure to promptly correct these violations may result in regulatory action, such as seizure and/or injunction, without further notice.
We acknowledge your June 16, 2006, voluntary recall of three products you manufactured from
February 2005 to June 2006. The three products recalled were: Pro-Lak Protein Concentrate for
Lactating Dairy Animals; Pro-Amino II for PreFresh and Lactating Cows; and, Pro-Pak Marine & Animal Protein Concentrate for Use in Animal Feed. Recall effectiveness checks and other measures
will determine the merit of this recall . We recognize you now label all products with the required BSE
cautionary statement and we also acknowledge your intent, given verbally to New Orleans District
management of the FDA, to discontinue the production of supplements which do not contain prohibited
materials. In your written response to this letter, please confirm in writing you have taken these steps.
You should notify this office in writing within 15 working days of receiving this letter, outlining the specific steps you have taken to bring your firm into compliance with the law, including the steps we acknowledge above and any additional steps you have taken. Your response should include an
explanation of each step taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within 15 working days, state the reason for the delay and the date by which the corrections will be completed. Include copies of any available documentation demonstrating corrections have been made.
Your reply should be directed to Kari L. Batey, Compliance Officer, at the address above. If you have
questions regarding any issue in this letter, please contact Ms. Batey at (615) 366-7808.
Sincerely,
,
Carol S . Sanchez
Acting District Director
New Orleans District
Enclosure: Form FDA 483
cc: Craig R. Waterhouse
Plant Manager
H.J. Baker & Bros., Inc.
603 Railroad Avenue
Albertville, Alabama 35951-3419
http://www.fda.gov/foi/warning_letters/g6104d.pdf
USDA/FDA MAD COW PROTEIN IN COMMERCE 2006
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
PRODUCT
a) EVSRC Custom dairy feed, Recall # V-130-6;
b) Performance Chick Starter, Recall # V-131-6;
c) Performance Quail Grower, Recall # V-132-6;
d) Performance Pheasant Finisher, Recall # V-133-6.
CODE
None
RECALLING FIRM/MANUFACTURER
Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman, AL, by telephone
on June 23, 2006 and by letter dated July 19, 2006. Firm initiated recall is
complete.
REASON
Dairy and poultry feeds were possibly contaminated with ruminant based
protein.
VOLUME OF PRODUCT IN COMMERCE
477.72 tons
DISTRIBUTION
AL
______________________________
PRODUCT
a) Dairy feed, custom, Recall # V-134-6;
b) Custom Dairy Feed with Monensin, Recall # V-135-6.
CODE
None. Bulk product
RECALLING FIRM/MANUFACTURER
Recalling Firm: Burkmann Feed, Greeneville, TN, by Telephone beginning on
June 28, 2006.
Manufacturer: H. J. Baker & Bro., Inc., Albertville, AL. Firm initiated
recall is complete.
REASON
Possible contamination of dairy feeds with ruminant derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE
1,484 tons
DISTRIBUTION
TN and WV
Subject: MAD COW FEED RECALLS ENFORCEMENT REPORT FOR AUGUST 9, 2006 KY, LA,
MS, AL, GA, AND TN 11,000+ TONS
Date: August 16, 2006 at 9:19 am PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE - CLASS II
______________________________
PRODUCT
Bulk custom made dairy feed, Recall # V-115-6
CODE
None
RECALLING FIRM/MANUFACTURER
Hiseville Feed & Seed Co., Hiseville, KY, by telephone and letter on or
about July 14, 2006. FDA initiated recall is ongoing.
REASON
Custom made feeds contain ingredient called Pro-Lak which may contain
ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE
Approximately 2,223 tons
DISTRIBUTION
KY
______________________________
PRODUCT
Bulk custom made dairy feed, Recall # V-116-6
CODE
None
RECALLING FIRM/MANUFACTURER
Rips Farm Center, Tollesboro, KY, by telephone and letter on July 14, 2006.
FDA initiated recall is ongoing.
REASON
Custom made feeds contain ingredient called Pro-Lak which may contain
ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE
1,220 tons
DISTRIBUTION
KY
______________________________
PRODUCT
Bulk custom made dairy feed, Recall # V-117-6
CODE
None
RECALLING FIRM/MANUFACTURER
Kentwood Co-op, Kentwood, LA, by telephone on June 27, 2006. FDA initiated
recall is completed.
REASON
Possible contamination of animal feed ingredients, including ingredients
that are used in feed for dairy animals, with ruminant derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE
40 tons
DISTRIBUTION
LA and MS
______________________________
PRODUCT
Bulk Dairy Feed, Recall V-118-6
CODE
None
RECALLING FIRM/MANUFACTURER
Cal Maine Foods, Inc., Edwards, MS, by telephone on June 26, 2006. FDA
initiated recall is complete.
REASON
Possible contamination of animal feed ingredients, including ingredients
that are used in feed for dairy animals, with ruminant derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE
7,150 tons
DISTRIBUTION
MS
______________________________
PRODUCT
Bulk custom dairy pre-mixes, Recall # V-119-6
CODE
None
RECALLING FIRM/MANUFACTURER
Walthall County Co-op, Tylertown, MS, by telephone on June 26, 2006. Firm
initiated recall is complete.
REASON
Possible contamination of dairy animal feeds with ruminant derived meat and
bone meal.
VOLUME OF PRODUCT IN COMMERCE
87 tons
DISTRIBUTION
MS
______________________________
PRODUCT
Bulk custom dairy pre-mixes, Recall # V-120-6
CODE
None
RECALLING FIRM/MANUFACTURER
Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm
initiated recall is complete.
REASON
Possible contamination of dairy animal feeds with ruminant derived meat and
bone meal.
VOLUME OF PRODUCT IN COMMERCE
350 tons
DISTRIBUTION
AL and MS
______________________________
PRODUCT
a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet,
50 lb. bags, Recall # V-121-6;
b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet,
50 lb. bags, Recall # V-122-6;
c) Tucker Milling, LLC #31232 Game Bird Grower,
50 lb. bags, Recall # V-123-6;
d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD
Medicated, 50 lb bags, Recall # V-124-6;
e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags,
Recall # V-125-6;
f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags,
Recall # V-126-6;
g) Tucker Milling, LLC #30116, TM Broiler Finisher,
50 lb bags, Recall # V-127-6
CODE
All products manufactured from 02/01/2005 until 06/20/2006
RECALLING FIRM/MANUFACTURER
Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and visit
on June 20, 2006, and by letter on June 23, 2006.
Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated
recall is ongoing.
REASON
Poultry and fish feeds which were possibly contaminated with ruminant based
protein were not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE
7,541-50 lb bags
DISTRIBUTION
AL, GA, MS, and TN
END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006
###
Subject: MAD COW FEED RECALL MI MAMMALIAN PROTEIN VOLUME OF PRODUCT IN
COMMERCE 27,694,240 lbs
Date: August 6, 2006 at 6:14 pm PST
PRODUCT
Bulk custom dairy feds manufactured from concentrates, Recall # V-113-6
CODE
All dairy feeds produced between 2/1/05 and 6/16/06 and containing H. J.
Baker recalled feed products.
RECALLING FIRM/MANUFACTURER
Vita Plus Corp., Gagetown, MI, by visit beginning on June 21, 2006. Firm
initiated recall is complete.
REASON
The feed was manufactured from materials that may have been contaminated
with mammalian protein.
VOLUME OF PRODUCT IN COMMERCE
27,694,240 lbs
DISTRIBUTION
MI
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125
TONS Products manufactured from 02/01/2005 until 06/06/2006
Date: August 6, 2006 at 6:16 pm PST
PRODUCT
a) CO-OP 32% Sinking Catfish, Recall # V-100-6;
b) Performance Sheep Pell W/Decox/A/N, medicated,
net wt. 50 lbs, Recall # V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;
d) CO-OP 32% Sinking Catfish Food Medicated,
Recall # V-103-6;
e) "Big Jim's" BBB Deer Ration, Big Buck Blend,
Recall # V-104-6;
f) CO-OP 40% Hog Supplement Medicated Pelleted,
Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6;
g) Pig Starter Pell II, 18% W/MCDX Medicated 282020,
Carbadox -- 0.0055%, Recall # V-106-6;
h) CO-OP STARTER-GROWER CRUMBLES, Complete
Feed for Chickens from Hatch to 20 Weeks, Medicated,
Bacitracin Methylene Disalicylate, 25 and 50 Lbs,
Recall # V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying
Chickens, Recall # 108-6;
j) CO-OP LAYING CRUMBLES, Recall # V-109-6;
k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED,
net wt 50 Lbs, Recall # V-110-6;
l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs,
Recall # V-111-6;
m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs,
Recall # V-112-6
CODE
Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER
Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and
visit on June 9, 2006. FDA initiated recall is complete.
REASON
Animal and fish feeds which were possibly contaminated with ruminant based
protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE
125 tons
DISTRIBUTION
AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
Subject: MAD COW FEED RECALL KY VOLUME OF PRODUCT IN COMMERCE ?????
Date: August 6, 2006 at 6:19 pm PST
PRODUCT
Bulk custom made dairy feed, Recall # V-114-6
CODE
None
RECALLING FIRM/MANUFACTURER
Burkmann Feeds LLC, Glasgow, KY, by letter on July 14, 2006. Firm initiated
recall is ongoing.
REASON
Custom made feeds contain ingredient called Pro-Lak, which may contain
ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE
?????
DISTRIBUTION
KY
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
CJD WATCH MESSAGE BOARD
TSS
MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE
Sun Jul 16, 2006 09:22
71.248.128.67
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II
______________________________
PRODUCT
a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals,
Recall # V-079-6;
b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg),
Recall # V-080-6;
c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL
FEED, Recall # V-081-6;
d) Feather Meal, Recall # V-082-6
CODE
a) Bulk
b) None
c) Bulk
d) Bulk
RECALLING FIRM/MANUFACTURER
H. J. Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and
by press release on June 16, 2006. Firm initiated recall is ongoing.
REASON
Possible contamination of animal feeds with ruminent derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE
10,878.06 tons
DISTRIBUTION
Nationwide
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
USDA 2004 ENHANCED BSE SURVEILLANCE PROGRAM AND HOW NOT TO FIND BSE CASES (OFFICIAL DRAFT OIG REPORT)
snip...
CATTLE With CNS Symptoms Were NOT Always Tested
snip...
Between FYs 2002 and 2004, FSIS condemned 680 cattle of all ages due to CNS symptoms. About 357 of these could be classified as adult. We could validate that ONLY 162 were tested for BSE (per APHIS records. ...
snip...
WE interviewed officials at five laboratories that test for rabies. Those officials CONFIRMED THEY ARE NOT REQUIRED TO SUBMIT RABIES-NEGATIVE SAMPLES TO APHIS FOR BSE TESTING. A South Dakota laboratory official said they were not aware they could submit rabies-negative samples to APHIS for BSE testing. A laboratory official in another State said all rabies-negative cases were not submitted to APHIS because BSE was ''NOT ON THEIR RADAR SCREEN." Officials from New York, Wisconsin, TEXAS, and Iowa advised they would NOT submit samples from animals they consider too young. Four of the five States contacted defined this age as 24 months; Wisconsin defined it as 30 months. TEXAS officials also advised that they do not always have sufficient tissue remaining to submit a BSE sample. ...
snip...
FULL TEXT 54 PAGES OF HOW NOT TO FIND BSE IN USA ;
SEE A FEW MAD COW FEED BAN VIOLATIONS SINCE AUGUST 1997 BSE 21 CFR 589.2000 OAI VIOLATIONS
2001 Purina
RECALLS AND FIELD CORRECTIONS: VETMED -- CLASS II
RECALL NO.ID NO.PRODUCT
V-033-1 1186 OMOLENE #300 V-034-1 4987 PURINA HORSE PELLET 14 V-035-1 27690 CATTLE COMPLETE #4 V-036-1 10602 HORSEMAN'S EDGE 12 COARSE V-037-1 5541 GRAIN LND CRS CRKD CRM V-038-1 1194 HORSE CHOW #100 V-039-1 27313 SHOWCHOW LEAN 50 L160 V-040-1 1199 HORSE CHARGE V-041-1 6214 CALF STARTER (COARSE) OTC 6 V-042-1 1384 GAME FLIGHT CONDÖÖ-- V-043-1 14971 PREPARE COMP II 18% V-044-1 28493 CU BRND A/L PLT PK V-045-1 1381 GAME BIRD STARTENA W/O ETTS V-046-1 27459 LN GN ST S2 CPSTZ V-047-1 7375 SHOW CHOW PREMIUM DEV DTC 7 V-048-1 28394 CU 1 CATTLE HOLDING V-049-1 28383 RANGE CAKE 20.SM CKR V-050-1 1505 START & GROW W/O ETTS V-051-1 39335 ACCURATION CTL DEV- V-052-1 28515 CU CAKE CUBE N V-053-1 38056 COMM CATTLE ST CTC140 V-054-1 37883 RANGE CAKE 20N 5/32 V-055-1 36668 CATTLE GROWER 32 RM 175 V-056-1 28450 WILD TURKEY CON MP.025% V-057-1 28443 PURINA ELK CHECKERS 20% V-058-1 28452 BB SCRATCH GRAIN V-059-1 39356 ACCURATION CTL COND. V-060-1 39747 NATURAL BEEF BUILDER COARSE V-061-1 26753 HORSEMAN'S EDGE PELLET 14% V-062-1 1506 START & GROW MP 0.0125% 50# V-063-1 1386 GAMEBIRD BRDR LAYENa ETTS V-064-1 27917 SWEET GRAIN MIX 9 V-065-1 19283 COMM CATTLE ST CTSM V-066-1 27310 SHWCHPIG G17-XL L160 V-067-1 18346 COMP SOW OVAL V-068-1 28255 HOG FINISHER LND W/O V-069-1 27140 CALF GROWENA 16% BVT 60 V-070-1 27460 SH CH PIG ST20-XL L140 V-071-1 28103 MAZ OSTRICH BREEDER V-072-1 5540 GRAIN LAND WHOLE CORN V-073-1 1195 HORSE CHOW #200 V-074-1 28340 LAMB SHOW RATION CTC50 V-075-1 43289 OMOLENE #300 GROWTH V-076-1 28387 FORAGE BALANCER 20N 3/8 V-077-1 43771 HFC SHOW PIG 20% T 100 V-078-1 28863 CS ACU-MN VEG PS#1, 2 RM300 V-079-1 28555 CU STANDRIDGE GRW RM700 V-080-1 43660 HF&C SHOW CHOW PIG STR W/O V-081-1 38255 PHEASANT FLIGHT COND HM BMD50 V-082-1 37504 COMM TX CATTLE STR CTSM 77.7 V-083-1 28451 BB WHOLE MILO V-084-1 28448 WILD TU COND. MP-BMD V-085-1 28441 HI-PRO DEER CHECKERS V-086-1 43661 HF&C SHOW CHOW PIG STR T100 V-087-1 39357 HI-ENERGY BEEF CKR V-088-1 40849 NATURAL BEEF BREEDER V-089-1 16647 PHEAS FLIGHT COND BMD 50 V-090-1 1822 EQUINE ADULT V-091-1 16645 PHEASANT FLIGHT COND W/O V-092-1 11040 ACCU CONCENTRATE V-093-1 9798 CATTLE FINISHER 40 W/O.. V-094-1 23778 ACCU - CREEP V-095-1 19353 CATTLE FIN 40 RM1200 V-096-1 19293 LAMB SHOW GRO/FIN CRS V-097-1 26720 SW DROUGHT CUBE V-098-1 6912 PURINA ELK CHECKERS 20% 5/32 V-099-1 24566 FOR BAL ML4 1:3 CTC70 V-100-1 28310 SOUTHWEST 14N BVT 80 V-101-1 28304 SOUTHWEST 12N HI - F V-102-1 28296 SOUTHWEST 14 N CTC28 V-103-1 44627 SHOW CH PIG ST/GR L1 200 V-104-1 28332 SOUTHWEST 12N RM 25 V-105-1 27357 FORAGE BALANCER 20M 3/4 V-106-1 28292 SOUTHWEST 14N 3/8" V-107-1 28291 SOUTHWEST 14N 1/4" V-108-1 25035 STABLE STAR SWEET 12 V-109-1 9803 RABBIT COMP BLEND 50 % V-110-1 27923 STABLE STAR SWEET GRAIN 9 V-111-1 5639 LAYENA CRUMBLES LG ETT V-112-1 1185 OMOLENE #200 V-113-1 1209 EQUINE SENIOR V-114-1 27354 RANGE CAKE 20 3/4 V-115-1 9732 SHOW CHOW PREMIUM GLD FN CTC7 V-116-1 28293 SW 14N 3/4" W/O V-117-1 27312 LEAN GEN 110 L140 V-118-1 4701 PRE - COND - REC CHOW DO .0025% V-119-1 28021 FEEDLOT 40 W/O MEAL V-120-1 11415 WHOLE CORN V-121-1 16283 ACCU CONCENTRATE RM150 V-122-1 19383 ACCU - CHICKEN BLEND GSÖ V-123-1 17632 STOCKYARDS CHOW V-124-1 24544 FORAGE BAL ML 4 1:3 V-125-1 25064 MAZ OSTRICH GR/MAINT V-126-1 24745 WILD TU STARTER MP - BMD V-127-1 28106 HI - PRO DEER CHRS - WC V-128-1 28308 SOUTHWEST 38N V-129-1 28299 BB STEER RATION V-130-1 28311 SOUTHWEST 38N RM 200 V-131-1 28338 SOUTHWEST 14N BVT 60 V-132-1 27352 RANGE CAKE 20N 3/4 V-133-1 4998 STRATEGY - GX V-134-1 1102 PRECONDITION/RECEIVING CTSM 1/4 V-135-1 28405 STABLE STAR SWEET GRAIN 14 V-136-1 1206 EQUINE JUNIOR V-137-1 28348 CATTLE COMPLETE #3ÖÖ V-138-1 1184 OMOLENE #100 V-139-1 5628 LAYENA PELLETS V-140-1 28376 RANGE CAKE 20N 3/8" V-141-1 388 COMPLETE SOW III W/O V-142-1 5887 SHOW CHOW LAMB G/F CRSE CTC50 V-143-1 10603 HORSEMAN'S EDGE 14% COARSE V-144-1 1403 GOAT CHOW V-145-1 1560 SCRATCH GRAINS V-146-1 19319 HORSE & MULE V-147-1 28245 HOG GROWER OTC50 V-148-1 28321 SOUTHWEST 14N DO.0037% V-149-1 28236 LN GN STR S1 CPSTZ - 250 V-150-1 28207 PREP PLUS COMP HL 18 V-151-1 28240 SHOW CHOW PIG ST.20-XL V-152-1 28290 SOUTHWEST 14N 5/32" V-153-1 1480 MAZURI EMU STARTER V-154-1 1189 PURE PRIDE #200 V-155-1 1508 MEATBUILDER MP 0.0125% V-156-1 27921 SWEET GRAIN MIX 12 V-157-1 26671 GOLDEN MILK B16 V-158-1 28397 B.B. HORSE & MULE V-159-1 28456 BB WHOLE OATS V-160-1 1371 ADV- NUT PROF FORM RABBIT V-161-1 40996 MAZURI PRIMATE MAINTENANCE BISCUIT V-162-1 43288 OMOLENE #200 PERFORMANCE V-163-1 28601 HORSEMAN'S EDGE 14% V-164-1 28612 BEEF PROMIX#100 CTSM V-165-1 28419 SOUTHWEST 12N RM 150 V-166-1 28371 GRASS STR 16 NÖÖÖ. V-167-1 28361 CTL LIM RTN #4 RM110 V-168-1 28360 CTLE LIM RTN #3 RM70 V-169-1 27326 PUR-LYX 21 V-170-1 672 HOG CHOW 40 MEAL V-171-1 28287 COMM CATTLE ST W/O V-172-1 28322 CS SW 14 N, TRM V-173-1 28239 MEAL V-174-1 28235 PIG STARTENA - 61900 V-175-1 1488 MAZ EMU MAINTENANCE V-176-1 1165 ACCURATION 2 HL MEAL V-177-1 1461 GRAIN LAND WHOLE OATS V-178-1 28241 SHOW CHOW PIG GROW-17-XL V-179-1 1493 PURINA OSTRIGRO COMPLETE V-180-1 28246 PIG STARTENA CP-STZ V-181-1 1190 PURE PRIDE #300 V-182-1 26957 CTLE LIM RAT #1 RM40 V-183-1 26860 COM CALF S/G CRS BVT60 V-184-1 27325 COMM CATTLE ST DO V-185-1 12837 CATTLE FINISHER 50 W/O.. V-186-1 43287 OMOLENE #100 PLEASURE V-187-1 43770 HFC SHOW PIG 20% V-188-1 28615 SOUTHWEST 12N V-189-1 28616 SOUTHWEST 12N V-190-1 28408 BEEF PRO MIX 50 V-191-1 28363 CTLE LIM TRN #5 RM180 V-192-1 43337 HF&C SHOW CHOW PIG STR CDX 50 V-193-1 28372 FRG BAL ML4 1:3 CTC750
CODE: 70YY-99, 69YY-99.
MANUFACTURER: Purina Mills, Oklahoma City, OK 73106.
RECALLED BY: The manufacturer initiated the recall by letter dated 2/16/01 flagged "URGENT RECALL" to all direct accounts. Firm-initiated recall ongoing.
DISTRIBUTION: OK, AR, KA.
QUANTITY: 161 Units.
REASON: The products have missing or incomplete labeling; items lacking include statement of ingredients, lot number, place of manufacture, percent fat & protein, etc. Most products are bagged into bags with a pre-printed unique product name, less than 5% are not.
END OF ENFORCEMENT REPORT FOR MAY 23, 2001.
####
Warning Letter Issued to Rendering Operation
On May 7, 2002, FDA's Seattle District Office issued a Warning Letter to Darling International, Inc., Tacoma, Washington. FDA conducted an inspection of the rendering operation on February 22 26, 2002. The inspection revealed a significant deviation from 21 CFR Part 589.2000 Animal Proteins in Ruminant Feed. The inspection disclosed that the firm failed to consistently label the meat and bone meal product with the required cautionary statement: "Do Not Feed to Cattle or Other Ruminants." The meat and bone meal contained beef offal along with other ingredients including chicken, fish, and pork.
SNIP...
Warning Letter Issued to Feed Manufacturer
FDA's Seattle District Office issued a Warning Letter to All American Feed & Tractor, Sandpoint, Idaho, for deviations from 21 CFR Part 589.2000, Animal Proteins Prohibited in Ruminant Feed. The firm failed to maintain sufficient records to track prohibited animal proteins throughout the receipt, processing, and distribution. In addition, the firm failed to maintain sufficient records and written procedures to prevent cross contamination. The firm also failed to maintain written procedures for cleaning out or flushing equipment after mixing feeds containing prohibited material, or for separating products that might contain prohibited material from ingredients used in ruminant feeds.
SNIP...
Bovine Spongiform Encephalopathy (BSE)
Ruminant Feed Enforcement Activities
FDA Enforcement Plan Includes Education, Inspections and Compliance Actions for Non-Compliance
To help prevent the establishment and amplification of BSE through feed in the United States, 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, became effective on August 4, 1997. To date, active monitoring by the U.S. Department of Agriculture (USDA) has found no cases of bovine spongiform encephalopathy (BSE) in U.S. cattle.
FDA's enforcement plan for the ruminant feed regulation includes education, as well as inspections, with FDA taking compliance actions for intentional or repeated non compliance. The following firms received Warning Letters for violations of FDA's regulation which prohibits the use of most mammalian protein in feeds for ruminant animals:
All American Feed & Tractor April 1, 2002
Dixon Feeds, Inc. October 24, 2001
Finlayson Ag Center November 8, 2001,
Van Dyke Grain Elevators, Inc. April 17, 2002
The Feed Bucket December 11. 2001
Bakery Trading Company July 29, 2002
Darling International, Inc. May 7, 2002
Tyson Foods February 12, 2002
Warning Letters Issued for CGMP Violations
On March 8, 2001, the FDA’s New Orleans District Office issued a Warning Letter to Prestage Farms, Inc., West Point, Mississippi. The firm manufactures medicated and non-medicated feeds for its own integrated swine enterprise. An FDA inspection of the facility on February 21 - 22, 2001, disclosed significant deviations from the Current Good Manufacturing Practice (CGMP) requirements for Medicated Feeds. These deviations included: failure to perform assays for the active drug ingredient in one product since 1999; failure to perform appropriate investigations and/or corrective actions for out of limit assays; and failure to have master production records.
The FDA’s Dallas District Office issued a Warning Letter to Purina Mills, St. Louis, Missouri, on March 23, 2001. The Warning Letter followed the an FDA inspection of Purina Mills, Oklahoma City, Oklahoma, on February 2-6, and 13-14, 2001. The firm failed to follow Purina's SOP for Drug Sequencing Requirements. The SOP provides for sequencing production (without flushing the mixer) of animal feeds for a species for which a drug component of a prior medicated feed is not approved. Additionally, the firm had distributed bagged medicated feeds since June 2000, with faulty tagging equipment and no control to ensure that all bagged feeds were completely labeled.
Bovine Spongiform Encephalopathy (BSE)
To help prevent the establishment and amplification of BSE in the Unites States, FDA implemented a final rule that prohibits the use of most mammaliam protein in feeds for ruminant animals. This rule, Title 21 Part 589.2000 of the Code of Federal Regulations, became effective on August 4, 1997.
On August 23, 2001, Department of Health and Human Services (DHHS) Secretary Tommy Thompson unveiled a department-wide action plan outlining new steps to improve scientific understanding of BSE, commonly known as "mad cow disease," and related diseases known as TSEs. The plan incorporates a comprehensive approach to further strengthen surveillance, increase research resources, and expand existing inspection efforts to prevent BSE and TSEs from entering or taking hold in the U.S.
Warning Letters for BSE Violations
FDA Inspection Finds Numerous Violations of BSE Regulations
On August 8, 2001, the FDA’s Seattle District Office issued a Warning Letter to the owner of an animal feed manufacturing facility located in Tualatin, Oregon. FDA investigators conducted an inspection on July 12, 2001, which disclosed violations of the bovine feed ingredient regulations. The inspection revealed that the firm failed to separate the receipt, processing, and storage of products containing prohibited material from non-prohibited material; failed to establish a written system, including clean-out and flushing procedures, to avoid commingling and cross-contamination of equipment; and failed to maintain records sufficient to track the materials. In addition, the firm failed to label products with the required cautionary statement, “Do Not Feed to Cattle or Other Ruminants.”
Gamecock Feedmill Found Violating BSE Regulations
On July 12, 2001, the FDA’s Cincinnati District Office issued a Warning Letter to the Carrollton Farmers Exchange, Carrollton, Ohio, a feed mill. FDA investigators conducted an inspection on June 25, 2001, which found the firm was manufacturing gamecock feed containing prohibited proteins. The firm was not labeling the gamecock feed with the cautionary statement, “Do not Feed to Cattle or Other Ruminants;” was not flushing or sequencing after manufacturing the feed, and was not maintaining distribution information.
Warning Issued for Lack of Required BSE Cautionary Statement
The FDA’s New Orleans District Office issued a Warning Letter to Shields Feed and Supply, Coffeeville, Alabama, on March 7, 2001. An inspection conducted on February 1, 2001, of Shields’ animal feed operation showed the finished product label lacked the required ruminant cautionary statement. In addition, mixing and distribution records were not maintained; no written procedures were established for mixer cleaning; and the corn used for the mixer cleaning was not labeled and quarantined.
Firm Warned for No Measures to Avoid Commingling of Feed
On May 3, 2001, the FDA’s Minneapolis District Office issued a Warning Letter to Adrian Elevator, Inc., a Butterfield, Minnesota, a manufacturer of animal feeds. On March 16, 2001, an inspection conducted by the State of Minnesota (on behalf of FDA) found significant deviations from the BSE regulations. The firm failed to provide adequate measures to avoid commingling or cross-contamination and failed to maintain adequate records to assure that prohibited animal proteins were not incorporated into feeds that may be used for ruminants. For example, there was no documentation to verify that the amount of "flush" being used was sufficient, and there were no procedures or documentation to verify that production was properly sequenced and that flushes were performed.
Warned Issued for Failure to Take Adequate Steps to Prevent BSE
The FDA’s Seattle District Office issued a Warning Letter on May 14, 2001, to Wallowa County Grain Growers, Inc., Enterprise, Oregon, for violations FDA regulations regarding Animal Proteins Prohibited in Ruminant Feed. An inspection of the firm on April 11 - 12, 2001, disclosed that the firm was not taking adequate steps to prevent the establishment and amplification of Bovine Spongiform Encephalopathy (BSE) in that they failed to separate the receipt, processing, and storage of the product containing prohibited materials from non-prohibited material; failed to establish a written system, including clean-out, and flushing procedures to avoid commingling and cross-contamination of common equipment; and failed to maintain records sufficient to track the materials throughout the receipt, processing, and distribution of product.
Contract Feed Manufacturer Found Violating BSE Regulations
On May 1, 2001, the FDA’s Chicago District Office issued a Warning Letter to Material Resources, a contract feed manufacturer in Washington Park, Illinois. An inspection of the firm in March 2001, disclosed several deviations from the BSE regulation. These included failure to maintain written procedures and provide adequate means to prevent commingling between feeds containing prohibited protein and all other protein products. The firm also lacked adequate records to track products that contained prohibited protein throughout their receipt and processing.
Firm Warned for Lack of Written Procedures for Clean-Out to Prevent Commingling
On June 6, 2001, the FDA’s Seattle District issued a Warning Letter to Superior Feeds, Chester, Montana. The firm is an animal feed manufacturing operation. An inspection of this firm on April 25, 2001, revealed that the firm failed to label their product with the required statement, “Do Not Feed to Cattle or other Ruminants.” In addition, the facility failed to maintain written procedures specifying the clean-out or sequencing procedures used to prevent commingling or cross-contamination of ruminant and non-ruminant containing feeds.
FDA Inspection Discloses Hog Feed Lacks BSE Statement
The FDA’s Minneapolis District Office issued a Warning Letter on May 30, 2001, to Round Lake Farmers Coop, Round Lake, Minnesota. The firm manufacturers animal feeds. An inspection by the State of Minnesota (on behalf of FDA) on March 30, 2001, found significant deviations from the requirements for Animal Proteins Prohibited in Animal Feed. The firm failed to label a hog feed with the required BSE caution statement. In addition, they failed to establish and implement procedures for handling prohibited animal proteins and failed to maintain records sufficient to track the receipt of products containing prohibited animal proteins. Import Detentions
Possible Contamination of Fish Food Leads to Detention
The week of March 7, 2001, the FDA’s New York District Upstate Import Operations Branch detained three entries of fish food under Import Alert 99-25 (Detention Without Physical Examination of Animal Feed, Animal Feed Ingredients And Other Products For Animal Use Consisting Or Containing Ingredients of Animal Origin) due to possible contamination with the infectious agent for BSE. The country of origin for the fish food was the Federal Republic of Germany. The local USDA/Philadelphia/PPQ Office was notified.
Vitamin Supplement for Pets Detained
The week of February 14, 2001, the FDA’s Atlanta District reported the detention of 8,777 cartons of vitamin supplements for cats, kittens, puppies, and older dogs. The detention included both dog and cat treats. The detention was based on Import Alert 99-25 (BSE). The products were manufactured by Beaphar, Raalte, Netherlands, and were valued at approximately $63,000. Calf Ration Detained
The FDA’s New York District Office reported that during the week of March 21, 2001, FDA investigators detained an entry of Calf Starter Ration and Calf Finisher Ration under Import Alert 99-25, since some of the ingredients originated from France and The Netherlands (both of which are listed on IA 99-25 as BSE susceptible countries). The manufacturer of the feed was Grober Inc., Cambridge, Ontario, Canada, and the consignee was Majestic View Farms in Milan, Pennsylvania. The USDA/APHIS/PPQ Buffalo, New York office was contacted.
Recall of Various Animal Feed Products
The FDA’s Cincinnati District Office reported that The Hyland Company, Coalton, Kentucky, conducted a recall of various animal feed products, including Ultra Bloom and Endurance Plus horse feeds, due to cross-contamination with prohibited bovine material. The firm's corrective action involved the application of a sticker-label that contained the required BSE warning statement on the labels of their affected products. The firm initiated the recall by telephone on July 25, 201, and letters on July 31, 2001.
During an FDA inspection by the Cincinnati District Office investigators determined that Central Farm Supply of Kentucky, Inc., Louisville, Kentucky, had received poultry feed manufactured by Burkmann Mills, Bowling Green, Kentucky, that contained prohibited protein, but lacked the required caution statement. On May 3, 2001, the district and the University of Kentucky Regulatory Services Division met with the responsible parties of the mill's parent firm, Burkmann Mills London, London, Kentucky. During the meeting the firm volunteered to recall all feed products manufactured at the Bowling Green mill due to the lack of the required caution statement.
FDA Announces Animal Feed Recall
On January 30, 2001, FDA issued a Press Release announcing the results of tests taken on feed used at a Texas feedlot that was suspected of containing meat and bone meal from other domestic cattle -- a violation of FDA's 1997 prohibition on using ruminant material in feed for other ruminants. The results indicated that a very low level of prohibited material was found in the feed fed to cattle.
FDA determined that each animal could have consumed, at most and in total, five-and-one-half grams - approximately a quarter ounce -- of prohibited material. These animals weigh approximately 600 pounds. It is important to note that the prohibited material was domestic in origin (therefore not likely to contain infected material because there is no evidence of BSE in U.S. cattle), fed at a very low level, and fed only once. The potential risk of BSE to such cattle was therefore exceedingly low, even if the feed were contaminated.
According to Dr. Bernard Schwetz, FDA's Acting Principal Deputy Commissioner, "The challenge to regulators and industry is to keep this disease out of the United States. One important defense is to prohibit the use of any ruminant animal materials in feed for other ruminant animals. Combined with other steps, like U.S. Department of Agriculture's (USDA) ban on the importation of live ruminant animals from affected countries, these steps represent a series of protections, to keep American cattle free of BSE."
Despite this negligible risk, Purina Mills, Inc., nonetheless announced that it was voluntarily purchasing all 1,222 of the animals held in Texas and mistakenly fed the animal feed containing the prohibited material. Therefore, meat from those animals would not enter the human food supply. FDA believes any cattle that did not consume feed containing the prohibited material was unaffected by this incident, and should be handled in the beef supply clearance process as usual.
FDA believes that Purina Mills acted responsibly by first reporting the human error that resulted in the misformulation of the animal feed supplement and then by working closely with State and Federal authorities. This episode indicates that the multi-layered safeguard system put into place is essential for protecting the food supply and that continued vigilance needs to be taken, by all concerned, to ensure these rules are followed routinely. FDA continues to work with USDA as well as State and local officials to ensure that companies and individuals comply with all laws and regulations designed to protect the U.S. food supply.
Warning Letters Issued for Violations of BSE Regulations
On May 6, 2003, the FDA’s Minneapolis District Office issued a Warning Letter to the President of Barr Animal Foods, Greenwood, Wisconsin. The FDA conducted an inspection of the firm on April 8, 2003. The inspection disclosed that the firm was not labeling their 50 pound blocks of frozen beef and bulk loads of beef bone chips and rendering waste, intended for animal feed with the required cautionary statement.
On August 25, 2003, the FDA’s Chicago District Office issued a Warning Letter to the president of Lincoln Land Livestock Co., Inc., Mascoutah, Illinois. On April 14 - 15, 2003, FDA conducted inspection of the animal feed handling facility. The investigator found that products that contained or may contain prohibited material failed to bear the caution statement, “Do not feed to cattle or other ruminants.” The inspection also disclosed that the firm did not maintain written clean-out procedures to prevent carryover of protein derived from mammalian tissues to animal protein or feeds that may be used for ruminants.
On November 7, 2002, the FDA’s Dallas District Office issued a Warning Letter to the President and Manager of Sunnymead Ranch, Inc., Idalou, Texas. An FDA inspection of this feed mill found significant deviations from 21 CFR 589.2000. FDA’s inspection revealed that the firm manufactures feed for sheep, that may contain residues of prohibited material. The sheep feed is mixed in the same equipment that is used for mixing chicken feed containing bovine meat and bone meal. In addition, the firm failed to use clean-out procedures or other means adequate to prevent carryover of protein derived from mammalian tissue to animal protein or feeds that may be used for ruminants. The Warning Letter cautioned, “As a feed manufacturer and ruminant feeder of sheep intended for slaughter as food, you are responsible for ensuring that your operations are in full compliance with the law.”
On May 22, 2003, the FDA’s New Orleans District Office issued a Warning Letter to the Manager and Owner of Millstone Agri Distributors, Maryville, Tennessee. An FDA inspection of the firm on February 13, 2003, found significant deviations from the requirements of Title 21, Code of Federal Regulations (21 CFR), Part 589.2000 - Animal Proteins Prohibited in Ruminant Feed.
FDA’s investigation found the following violations of 21 CFR 589.2000:
Failure to separate the receipt, processing, and storage of products containing prohibited material from products not containing prohibited material;
Failure to establish written procedures, including clean-out and flushing procedures, to avoid commingling and cross-contamination of common equipment;
Failure to maintain records sufficient to track prohibited materials throughout the receipt, processing, and distribution of products;
Failure to provide for measures to avoid commingling or cross-contamination of feeds intended for ruminants and feeds intended for non-ruminants that may contain prohibited materials;
Failure to label non-ruminant products with the required cautionary statement “Do not Feed to Cattle or Other Ruminants.” The investigation specifically found that dog food containing prohibited material was added as an ingredient to the product “Premium Rooster Kicker.” The failure of these feeds to bear the required BSE warning statement causes them to be misbranded.
Consent Decree of Permanent Injunction Against X-Cel Feeds, Inc. Feed Manufacturer Enjoined for Violations of the 1997 Animal Feed Rule
On July 11, 2003, FDA announced the filing of a Consent Decree of Permanent Injunction against X-Cel, Feeds Inc., and individual officers based on violations of the Federal Food, Drug, and Cosmetic Act.
X-Cel, a feed manufacturer headquartered in Tacoma, Washington, failed to comply with FDA regulations (the 1997 Animal Feed Rule) designed to prevent the establishment and spread of Bovine Spongiform Encephalopathy (BSE, also known as "Mad Cow Disease") should it ever be found in the United States and FDA regulations concerning the manufacture of medicated feeds.
The Department of Justice, Civil Division, Office of Consumer Litigation and the United States Attorney's Office of the Western District of Washington filed the Consent Decree in the United States District Court of the Western District in Tacoma, Washington. It permanently enjoins X-Cel from manufacturing animal feeds in violation of the Federal Food, Drug, and Cosmetic Act and requires the firm, its officers, and employees to take specific steps to avoid future violations including, implementing clean-out procedures, obtaining protein supplier certifications and implementing standard operating procedures for compliance until it satisfies FDA that it has corrected its problems.
SNIP...
Pet Foods
Recall of Pet Food from Canadian Manufacturer Pet Food Recalled Because “BSE” Cow May Have Been Used in Dry Dog Food
On May 26, 2003, the FDA learned from the government of Canada that rendered material from a Canadian cow that tested positive for bovine spongiform encephalopathy (BSE) also known as “mad cow disease” may have been used to manufacture pet food, specifically dry dog food, some of which was reported to have been shipped to the United States. The Canadian government prevented the BSE positive cow from being processed for human food. Therefore, consumers can be assured that their food does not contain any remnants of the BSE positive cow. There is no scientific evidence to date that dogs can contract BSE or any similar disease. In addition, there is no evidence that dogs can transmit the disease to humans.
FDA notified the U.S.pet food firm, The Pet Pantry International, of Carson City, Nevada, when FDA learned that the pet food that the firm received may have included rendered material from the BSE positive cow. The manufacturer of the pet food was Champion Pet Food, Morinville, Alberta. Even though there is no known risk to dogs from eating this dog food, as a prudent measure to help assure that the U.S. stays BSE free, The Pet Pantry International asked its customers who may have purchased the suspect product to hold it for pickup by the distributor so that the dog food would not mistakenly be mixed into cattle or other feeds if any of the dog food was discarded or otherwise not used to feed dogs.
The suspect dog food was produced by Champion Pet Food between February 4, 2003, and March 12, 2003. The Pet Pantry products were packaged in 50 pound bags, distributed to franchises around the country, and sold by home delivery only. There was no retail distribution of the product. Consumers purchase Pet Pantry products by phone or email orders. The product is then delivered by the nearest franchisee directly to the consumer’s home.
The product subject to this notification included “Maintenance Diet” labeled with a use by date of “17FEB04” and “Beef with Barley” with a use by date of “05MAR04”. Consumers who had purchased dog food from The Pet Pantry since February of this year were asked to check their present supplies and see if any match the description of the product being removed.
If so, consumers were asked to contact The Pet Pantry at 1-800-381-7387 for further information on how to return the product to The Pet Pantry for proper disposal. Consumers were asked not to destroy or discard the product themselves. The Pet Pantry also used its sales records to contact consumers who purchased the affected product. FDA worked closely with the Pet Pantry International to assure for proper disposal of the recovered product.
Subject: canine and feline spongiform encephalopathy tse prion 2019 update
EP-021 Canine Prions: A New Form of Prion Disease
Mourad Tayebi1, Monique A David2, Brian Summers3
1 University of Melbourne, Veterinary Sciences, Australia; 2Ausbiologics, Sydney, Australia; 3Royal Veterinary College, London, UK
The origin of bovine spongiform encephalopathy (BSE), which rapidly evolved into a major epidemic remains unresolved and was initially widely attributed to transmission of sheep scrapie to cattle with contaminated feed prepared from rendered sheep carcasses. Alternative transmission hypotheses also include feed contaminated with unrecognized subclinical case(s) of bovine prion disease or with prion-infected human remains. However, following the demonstration of a BSE case exhibiting the novel mutation E211 K, similar to the E200K mutation associated with most genetic CJD in humans, support for a genetic origin of prion disease in cattle is gaining momentum. In contrast to other animal species such as feline, the canine species seems to be resistant to prion disease as no canine prion cases were previously reported.
We describe here three cases of Rottweiler puppy (called RWD cases) with neurological deficits and spongiform change. We used animal bioassays and in vitro studies to show efficient interspecies transmission of this novel canidae prion isolate to other species.
Biochemical studies revealed the presence of partially proteinase K (PK)-resistant fragment and immunohistochemistry displayed staining for PrPSc in the cerebral cortex. Importantly, interspecies transmission of canine PrPSc derived from RWD3 brain homogenates following inoculation of hamsters led to signs of prion disease and replication of PrPSc in brains, spinal cords and spleens of these animals.
These findings if confirmed by further cases of prion disease in canidae and regardless of the origin of the disease would have a major impact on animal and public health.
PRION 2016 TOKYO
OR-09: Canine spongiform encephalopathy—A new form of animal prion disease
Monique David, Mourad Tayebi UT Health; Houston, TX USA
It was also hypothesized that BSE might have originated from an unrecognized sporadic or genetic case of bovine prion disease incorporated into cattle feed or even cattle feed contaminated with prion-infected human remains.1 However, strong support for a genetic origin of BSE has recently been demonstrated in an H-type BSE case exhibiting the novel mutation E211K.2 Furthermore, a specific prion protein strain causing BSE in cattle is believed to be the etiological agent responsible for the novel human prion disease, variant Creutzfeldt-Jakob disease (vCJD).3 Cases of vCJD have been identified in a number countries, including France, Italy, Ireland, the Netherlands, Canada, Japan, US and the UK with the largest number of cases. Naturally occurring feline spongiform encephalopathy of domestic cats4 and spongiform encephalopathies of a number of zoo animals so-called exotic ungulate encephalopathies5,6 are also recognized as animal prion diseases, and are thought to have resulted from the same BSE-contaminated food given to cattle and humans, although and at least in some of these cases, a sporadic and/or genetic etiology cannot be ruled out. The canine species seems to display resistance to prion disease and no single case has so far been reported.7,8 Here, we describe a case of a 9 week old male Rottweiler puppy presenting neurological deficits; and histological examination revealed spongiform vacuolation characteristic of those associated with prion diseases.9 Initial biochemical studies using anti-PrP antibodies revealed the presence of partially proteinase K-resistant fragment by western blotting. Furthermore, immunohistochemistry revealed spongiform degeneration consistent with those found in prion disease and displayed staining for PrPSc in the cortex.
Of major importance, PrPSc isolated from the Rottweiler was able to cross the species barrier transmitted to hamster in vitro with PMCA and in vivo (one hamster out of 5). Futhermore, second in vivo passage to hamsters, led to 100% attack rate (n = 4) and animals displayed untypical lesional profile and shorter incubation period.
In this study, we show that the canine species might be sensitive to prion disease and that PrPSc isolated from a dog can be transmitted to dogs and hamsters in vitro using PMCA and in vivo to hamsters.
If our preliminary results are confirmed, the proposal will have a major impact on animal and public health and would certainly lead to implementing new control measures for ‘canine spongiform encephalopathy’ (CSE).
References 1. Colchester AC, Colchester NT. The origin of bovine spongiform encephalopathy: the human prion disease hypothesis. Lancet 2005; 366:856-61; PMID:16139661; http:// dx.doi.org/10.1016/S0140-6736(05)67218-2.
2. Richt JA, Hall SM. BSE case associated with prion protein gene mutation. PLoS Pathog 2008; 4:e1000156; PMID:18787697; http://dx.doi.org/10.1371/journal. ppat.1000156.
3. Collinge J. Human prion diseases and bovine spongiform encephalopathy (BSE). Hum Mol Genet 1997; 6:1699-705; PMID:9300662; http://dx.doi.org/10.1093/ hmg/6.10.1699.
4. Wyatt JM, Pearson GR, Smerdon TN, Gruffydd-Jones TJ, Wells GA, Wilesmith JW. Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Vet Rec 1991; 129:233-6; PMID:1957458; http://dx.doi.org/10.1136/vr.129.11.233.
5. Jeffrey M, Wells GA. Spongiform encephalopathy in a nyala (Tragelaphus angasi). Vet Pathol 1988; 25:398-9; PMID:3232315; http://dx.doi.org/10.1177/030098588802500514.
6. Kirkwood JK, Wells GA, Wilesmith JW, Cunningham AA, Jackson SI. Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros). Vet Rec 1990; 127:418-20; PMID:2264242.
7. Bartz JC, McKenzie DI, Bessen RA, Marsh RF, Aiken JM. Transmissible mink encephalopathy species barrier effect between ferret and mink: PrP gene and protein analysis. J Gen Virol 1994; 75:2947-53; PMID:7964604; http://dx.doi.org/10.1099/0022-1317- 75-11-2947.
8. Lysek DA, Schorn C, Nivon LG, Esteve-Moya V, Christen B, Calzolai L, et al. Prion protein NMR structures of cats, dogs, pigs, and sheep. Proc Natl Acad Sci U S A 2005; 102:640-5; PMID:15647367; http://dx.doi.org/10.1073/pnas.0408937102.
9. Budka H. Neuropathology of prion diseases. Br Med Bull 2003; 66:121-30; PMID:14522854; http://dx.doi.org/10.1093/bmb/66.1.121.
*** DEFRA TO SINGELTARY ON HOUND STUDY AND BSE 2001 ***
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX:
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less
critical. For more details see- http://www.bseinquiry, gov.uk/files/yb/1995/06/21005001 .pdf
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================
HOUND SURVEY
I am sorry, but I really could have been a co-signatory of Gerald's minute.
I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding.
If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.
J W WILESMITH Epidemiology Unit 18 October 1991
Mr. R Bradley
cc: Mr. G A H Wells
3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, indentify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.
TSE in dogs have not been documented simply because OF THE ONLY STUDY, those brain tissue samples were screwed up too. see my investigation of this here, and to follow, later follow up, a letter from defra, AND SEE SUSPICIOUS BRAIN TISSUE SAF's. ...TSS
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
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76 pages on hound study;
snip...
39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.
40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.
41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.
Histopathological support to various other published MAFF experiments
42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).
Monday, February 14, 2011
THE ROLE OF PREDATION IN DISEASE CONTROL: A COMPARISON OF SELECTIVE AND NONSELECTIVE REMOVAL ON PRION DISEASE DYNAMICS IN DEER
NO, NO, NOT NO, BUT HELL NO !
Journal of Wildlife Diseases, 47(1), 2011, pp. 78-93 © Wildlife Disease Association 2011
Monday, March 8, 2010
Canine Spongiform Encephalopathy aka MAD DOG DISEASE
=============================
FRIDAY, DECEMBER 14, 2012
Susceptibility of domestic cats to chronic wasting disease
Candace K. Mathiason1,#, Amy V. Nalls1, Davis M. Seelig1, Susan L. Kraft2, Kevin Carnes2, Kelly R. Anderson1, Jeanette Hayes-Klug1 and Edward A. Hoover1
+ Author Affiliations
1Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523 2Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523
ABSTRACT
Domestic and non-domestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging non-domestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of n=5 cats each were inoculated intracerebrally (IC) or orally (PO) with CWD-infected deer brain. At 40 and 42 months post inoculation, two IC-inoculated cats developed signs consistent with prion disease including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors and ataxia, and progressed to terminal disease within 5 months. Brains from these two cats were pooled and inoculated into cohorts of cats by IC, PO, and IP/SQ (intraperitoneal/subcutaneous) routes. Upon sub-passage, feline CWD was transmitted to all IC-inoculated cats with a decreased incubation period of 23-27 months. Feline-adapted CWD (FelCWD) was demonstrated in the brains of all the affected cats by western blot and immunohistochemical analysis. Magnetic resonance imaging revealed abnormalities in clinically ill cats, which included multifocal T2 FLAIR signal hyperintensities, ventricular size increases, prominent sulci and white matter tract cavitation. Currently, 3 of 4 IP/SQ and 2 of 4 PO secondary passage inoculated cats have developed abnormal behavior patterns consistent with the early stage of feline CWD. These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to-feline transmission in nature.
FOOTNOTES
↵# To whom correspondence should be addressed. candace.mathiason@colostate.edu, 1619 Campus Delivery, Fort Collins, CO 80523-1619, 970 491-3975
Copyright © 2012, American Society for Microbiology. All Rights Reserved.
HOWEVER, why ignore the old science and transmission studies to date ???
Species Born Onset/Died
Ocelot May 1987 Mar 1994 Ocelot Jul 1980 Oct 1995 Puma 1986 May 1991 Puma 1980 May 1995 Puma 1978 May 1995 Lion Nov 1986 Dec 1998 Tiger 1981 Dec 1995 Tiger Feb 1983 Oct 1998 Ankole 1987 May 1995 Ankole 1986 Feb 1991 Bison 1989/90 Oct 1996
Maff data on 15 May 99
kudu 6 gemsbok 1 nyala 1 oryx 2 eland 6 cheetah 9 puma 3 tiger 2 ocelot 2 bison 1 ankole 2 lion 1
Feline Spongiform Encephalopathy (FSE) FSE was first identified in the UK in 1990. Most cases have been reported in the UK, where the epidemic has been consistent with that of the BSE epidemic. Some other countries (e.g. Norway, Liechtenstein and France) have also reported cases.
Most cases have been reported in domestic cats but there have also been cases in captive exotic cats (e.g. Cheetah, Lion, Asian leopard cat, Ocelot, Puma and Tiger). The disease is characterised by progressive nervous signs, including ataxia, hyper-reactivity and behavioural changes and is fatal.
The chemical and biological properties of the infectious agent are identical to those of the BSE and vCJD agents. These findings support the hypothesis that the FSE epidemic resulted from the consumption of food contaminated with the BSE agent.
The FSE epidemic has declined as a result of tight controls on the disposal of specified risk material and other animal by-products.
References: Leggett, M.M. et al.(1990) A spongiform encephalopathy in a cat. Veterinary Record. 127. 586-588
Synge, B.A. et al. (1991) Spongiform encephalopathy in a Scottish cat. Veterinary Record. 129. 320
Wyatt, J. M. et al. (1991) Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record. 129. 233.
Gruffydd-Jones, T. J.et al.. (1991) Feline spongiform encephalopathy. J. Small Animal Practice. 33. 471-476.
Pearson, G. R. et al. (1992) Feline spongiform encephalopathy: fibril and PrP studies. Veterinary Record. 131. 307-310.
Willoughby, K. et al. (1992) Spongiform encephalopathy in a captive puma (Felis concolor). Veterinary Record. 131. 431-434.
Fraser, H. et al. (1994) Transmission of feline spongiform encephalopathy to mice. Veterinary Record 134. 449.
Bratberg, B. et al. (1995) Feline spongiform encephalopathy in a cat in Norway. Veterinary Record 136. 444
Baron, T. et al. (1997) Spongiform encephalopathy in an imported cheetah in France. Veterinary Record 141. 270-271
Zanusso, G et al. (1998) Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy. Lancet, V352, N9134, OCT 3, Pp 1116-1117.
Ryder, S.J. et al. (2001) Inconsistent detection of PrP in extraneural tissues of cats with feline spongiform encephalopathy. Veterinary Record 146. 437-441
Kelly, D.F. et al. (2005) Neuropathological findings in cats with clinically suspect but histologically unconfirmed feline spongiform encephalopathy. Veterinary Record 156. 472-477.
TSEs in Exotic Ruminants TSEs have been detected in exotic ruminants in UK zoos since 1986. These include antelopes (Eland, Gemsbok, Arabian and Scimitar oryx, Nyala and Kudu), Ankole cattle and Bison. With hindsight the 1986 case in a Nyala was diagnosed before the first case of BSE was identified. The TSE cases in exotic ruminants had a younger onset age and a shorter clinical duration compared to that in cattle with BSE. All the cases appear to be linked to the BSE epidemic via the consumption of feed contaminated with the BSE agent. The epidemic has declined as a result of tight controls on feeding mammalian meat and bone meal to susceptible animals, particularly from August 1996.
References: Jeffrey, M. and Wells, G.A.H, (1988) Spongiform encephalopathy in a nyala (Tragelaphus angasi). Vet.Path. 25. 398-399
Kirkwood, J.K. et al (1990) Spongiform encephalopathy in an Arabian oryx (Oryx leucoryx) and a Greater kudu (Tragelaphus strepsiceros) Veterinary Record 127. 418-429.
Kirkwood, J.K. (1993) Spongiform encephalopathy in a herd of Greater kudu (Tragelaphus strepsiceros): epidemiological observations. Veterinary Record 133. 360-364
Kirkwood, J. K. and Cunningham, A.A. (1994) Epidemiological observations on spongiform encephalopathies in captive wild animals in the British Isles. Veterinary Record. 135. 296-303.
Food and Agriculture Organisation (1998) Manual on Bovine Spongiform Encephalopathy.
TSE and Surveillance Statistics Exotic species and domestic cats November 2018
Contents Number of confirmed cases of FSE in domestic cats by year
Number of confirmed cases of FSE in domestic cats by year of birth
Number of TSEs in exotic species by year reported
Transmissible Spongiform Encephalopathies in exotic species
Number of confirmed cases of FSE in domestic cats by year Data valid to 30 November 2018 Includes one case from Guernsey Year Reported No. of cases 1988 0 1989 0 1990 12 1991 12 1992 10 1993 11 1994 16 1995 8 1996 6 1997 6 1998 4 1999 2 2000 1 2001 1 2002 0 2003 0 2004 0 2005 0 2006 0 2007 0 2008 0 2009 0 2010 0 2011 0 2012 0 2013 0 2014 0 2015 0 2016 0 2017 0 2018 0 Total 89 Year of Onset No. of cases 1988 0 1989 1 1990 16 1991 11 1992 14 1993 10 1994 14 1995 4 1996 7 1997 8 1998 1 1999 1 2000 1 2001 1 2002 0 2003 0 2004 0 2005 0 2006 0 2007 0 2008 0 2009 0 2010 0 2011 0 2012 0 2013 0 2014 0 2015 0 2016 0 2017 0 2018 0 Total 89
FSE: FIRST CONFIRMED CASE REPORTED IN PORTUGAL AND POTENTIAL MAD CAT ESCAPES LAB IN USA Date: August 9, 2007 at 2:27 pm PST
DIA-45 FELINE SPONGIFORM ENCEPHALOPATHY: FIRST CONFIRMED CASE REPORTED IN PORTUGAL
J.F. Silva1, J.J. Correia, 1 J. Ribeiro2, S. Carmo2 and L.Orge3
1 Faculdade de Medicina Veterinária (UTL), Lisbon, Portugal 2 Clínica Veterinária Ani+, Queluz, Portugal 3 Laboratório Nacional de Investigação Veterinária, Unidade de BSE, Lisbon, Portugal
Feline spongiform encephalopathy (FSE), affecting domestic and captive feline species, is a prion disease considered to be related to bovine spongiform encephalopathy (BSE). Here we report the first case diagnosed in Portugal, highlighting the neuroapthological findings. In 2004 a 9-year old intact female Siamese cat was referred with chronic progressive behavioural changes, polydipsia, gait abnormalities and episodes of hypersalivation. Clinical signs progressed to tetraparesis and dementia and euthanasia was performed. At necropsy, brain and spinal cord had no significative changes. Tissue samples from brain, cerebellum, brainstem and spinal cord were collected for histopathology and immunohistochemistry for detection of PrPres. Histology revealed neuropil and neuronal perikarion vacuolation in several areas of the central nervous system together with gliosis and cell rarefaction at the granular layer of the cerebellum. Immunohistochemical detection of PrPres showed a strong and widespread PrPres accumulation as granular and linear deposits as well as associated with some neurons. These findings are supportive of FSE. To the authors knowledge this is the first confirmed case of FSE reported in Portugal.
DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability
Date: Fri, 16 May 2003 11:47:37 –0500
EMC 1 Terry S. Singeltary Sr. Vol #: 1
IN CONFIDENCE CJD TO CATS...
It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.
FELINE SPONGIFORM ENCEPHALOPATHY FSE
WEDNESDAY, JANUARY 2, 2019
canine and feline spongiform encephalopathy tse prion 2019 update
***> IMPORTS AND EXPORTS <***
***SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BAN ***
Sunday, March 20, 2016
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed ***UPDATED MARCH 2016*** Singeltary Submission
SEE MAD COW FEED VIOLATIONS AFER MAD COW FEED VIOLATIONS ;
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission
Date: March 9, 2007 at 12:13 pm PST
From: Terry S. Singeltary Sr.
Subject: STATEMENT BY DR. RON DEHAVEN REGARDING OIE RISK RECOMMENDATION
Date: March 9, 2007 at 12:13 pm PST
Karen Eggert (301) 734-7280
Jerry Redding (202) 720-4623
STATEMENT BY DR. RON DEHAVEN REGARDING OIE RISK RECOMMENDATION March 9, 2007
“In October 2006, the U.S. Department of Agriculture submitted an application and supporting documents to the World Organization for Animal Health (OIE) to formally request country classification for bovine spongiform encephalopathy (BSE) risk. The OIE undertakes a thorough review process before recommending a risk classification, and then provides an opportunity for all delegate countries to review the recommendations and present comments prior to final adoption of a country’s classification at the OIE’s General Assembly meeting in May.
“While we recognize that a final classification decision will not be made by the OIE until May, we feel it is important to be responsive to questions we are now being asked about the risk classification recommended for the United States. The OIE Scientific Commission has endorsed the recommendation from an OIE expert panel that the United States be classified as “controlled risk” for BSE.
“The controlled risk classification recognizes that OIE-recommended, science-based mitigation measures are in place to effectively manage any possible risk of BSE in the cattle population. This recommendation provides strong support that U.S. regulatory controls are effective and that U.S cattle and products from cattle of all ages can be safely traded in accordance with international guidelines, due to our interlocking safeguards.
“The OIE risk classification process is an essential step in promoting trade and understanding of this disease. We appreciate OIE’s review of our application, as well as its leadership in developing sound, science-based guidelines that will help countries standardize regulations and import requirements. We look forward to the final adoption of this classification, which will be announced at the OIE meeting in May.”
#
BSE/BASE UPDATE USA
In Reply to: MAD COW TISSUE SAMPLING FOR TESTING CONSISTS OF USDA CERTIFIED CATTLE posted by TSS on February 17, 2007 at 7:48 am: United States District Court, District of Arizona
USA v Roland Emerson Farabee 2: 07-wi-0001-01-EHC Proceeding Type: Waiver/Plea
Judge: Honorable Earl H Carroll Courtroom: Phoenix Courtroom #501, 5th Floor
Date: 01/17/2007 Court Reporter: Candy Potter Time: 01:30 PM Courtroom Deputy: Bobbi Hightower
Counts: (may not reflect all counts) 18:641 and 2 (Theft of Government Money and Adiding and Abetting) 1 18: 1341 and 2 (Mail Fruad and Aiding and Abetting) 2 18:1343 and 2 (Wire Fraud and Aiding and Abetting) - 3 U.S. Attorney: Long, Robert
--------------------------------------------------------------------------------
Defense Attorney(s): Attorney Phone: Attorney Designation: McDonald, Jr., A. Melvin retained
if my siphering is correct, that would be about another 2600 potential mad cows that went into the food chain.
add that to these ;
>It should be noted that since the enhanced surveillance program began, USDA has also conducted approximately 9,200 routine IHC tests on samples that did not first undergo rapid testing.<
AND we know IHC is the least likely to find TSE.
and not to forget that one little old mad cow in TEXAS they rendered without any test at ALL.
Statement on Texas Cow With Central Nervous System Symptoms
On Friday, April 30 th , the Food and Drug Administration learned that a cow with central nervous system symptoms had been killed and shipped to a processor for rendering into animal protein for use in animal feed.
FDA, which is responsible for the safety of animal feed, immediately began an investigation. On Friday and throughout the weekend, FDA investigators inspected the slaughterhouse, the rendering facility, the farm where the animal came from, and the processor that initially received the cow from the slaughterhouse.
FDA's investigation showed that the animal in question had already been rendered into "meat and bone meal" (a type of protein animal feed). Over the weekend FDA was able to track down all the implicated material. That material is being held by the firm, which is cooperating fully with FDA.
Cattle with central nervous system symptoms are of particular interest because cattle with bovine spongiform encephalopathy or BSE, also known as "mad cow disease," can exhibit such symptoms. In this case, there is no way now to test for BSE. But even if the cow had BSE, FDA's animal feed rule would prohibit the feeding of its rendered protein to other ruminant animals (e.g., cows, goats, sheep, bison).
FDA is sending a letter to the firm summarizing its findings and informing the firm that FDA will not object to use of this material in swine feed only. If it is not used in swine feed, this material will be destroyed. Pigs have been shown not to be susceptible to BSE. If the firm agrees to use the material for swine feed only, FDA will track the material all the way through the supply chain from the processor to the farm to ensure that the feed is properly monitored and used only as feed for pigs.
To protect the U.S. against BSE, FDA works to keep certain mammalian protein out of animal feed for cattle and other ruminant animals. FDA established its animal feed rule in 1997 after the BSE epidemic in the U.K. showed that the disease spreads by feeding infected ruminant protein to cattle.
Under the current regulation, the material from this Texas cow is not allowed in feed for cattle or other ruminant animals. FDA's action specifying that the material go only into swine feed means also that it will not be fed to poultry.
FDA is committed to protecting the U.S. from BSE and collaborates closely with the U.S. Department of Agriculture on all BSE issues. The animal feed rule provides crucial protection against the spread of BSE, but it is only one of several such firewalls. FDA will soon be improving the animal feed rule, to make this strong system even stronger.
REMINDER, CATTLE ON FEED IN TEXAS
IN TEXAS, cattle on feed for decades, fda says 5.5 grams ruminant protein, if tainted with TSE, is not enough to kill a cow. actually, it's enough to kill 100+ cows ;-)
http://www.fda.gov/bbs/topics/NEWS/2001/NEW00752.html
FDA ANNOUNCES TEST RESULTS FROM TEXAS FEED LOT
Today the Food and Drug Administration announced the results of tests taken on feed used at a Texas feedlot that was suspected of containing meat and bone meal from other domestic cattle -- a violation of FDA's 1997 prohibition on using ruminant material in feed for other ruminants. Results indicate that a very low level of prohibited material was found in the feed fed to cattle.
FDA has determined that each animal could have consumed, at most and in total, five-and-one-half grams - approximately a quarter ounce -- of prohibited material. These animals weigh approximately 600 pounds.
It is important to note that the prohibited material was domestic in origin (therefore not likely to contain infected material because there is no evidence of BSE in U.S. cattle), fed at a very low level, and fed only once. The potential risk of BSE to such cattle is therefore exceedingly low, even if the feed were contaminated.
According to Dr. Bernard Schwetz, FDA's Acting Principal Deputy Commissioner, "The challenge to regulators and industry is to keep this disease out of the United States. One important defense is to prohibit the use of any ruminant animal materials in feed for other ruminant animals. Combined with other steps, like U.S. Department of Agriculture's (USDA) ban on the importation of live ruminant animals from affected countries, these steps represent a series of protections, to keep American cattle free of BSE."
Despite this negligible risk, Purina Mills, Inc., is nonetheless announcing that it is voluntarily purchasing all 1,222 of the animals held in Texas and mistakenly fed the animal feed containing the prohibited material. Therefore, meat from those animals will not enter the human food supply. FDA believes any cattle that did not consume feed containing the prohibited material are unaffected by this incident, and should be handled in the beef supply clearance process as usual.
FDA believes that Purina Mills has behaved responsibly by first reporting the human error that resulted in the misformulation of the animal feed supplement and then by working closely with State and Federal authorities.
This episode indicates that the multi-layered safeguard system put into place is essential for protecting the food supply and that continued vigilance needs to be taken, by all concerned, to ensure these rules are followed routinely.
FDA will continue working with USDA as well as State and local officials to ensure that companies and individuals comply with all laws and regulations designed to protect the U.S. food supply.
http://www.fda.gov/bbs/topics/NEWS/2001/NEW00752.html
NEWS RELEASE
Texas Animal Health Commission
Box l2966 •Austin, Texas 78711 •(800) 550-8242• FAX (512) 719-0719
Linda Logan, DVM, PhD• Executive Director
For info, contact Carla Everett, information officer, at 1-800-550-8242, ext. 710,
or ceverett@tahc.state.tx.us
For Immediate Release--
Feed Contamination Issue Resolved by FDA
Although many of you may have heard the latest regarding the resolution of the cattle feed
contamination situation in Texas, I wanted to ensure that you received this statement issued
by the Food and Drug Administration (FDA), the agency in charge of regulating feed
components. The FDA has said the cattle involved are to be rendered and the material will not
enter ruminant or human food channels. The Texas Animal Health Commission (TAHC) will
provided assistance to the FDA as requested and needed.
FDA ANNOUNCES TEST RESULTS FROM TEXAS FEED LOT
Today (Tuesday, Jan. the Food and Drug Administration announced the results of tests taken
on feed used at a Texas feedlot that was suspected of containing meat and bone meal from
other domestic cattle -- a violation of FDA's 1997 prohibition on using ruminant material in
feed for other ruminants. Results indicate that a very low level of prohibited material was
found in the feed fed to cattle.
FDA has determined that each animal could have consumed, at most and in total,
five-and-one-half grams - approximately a quarter ounce -- of prohibited material. These
animals weigh approximately 600 pounds.
It is important to note that the prohibited material was domestic in origin (therefore not likely
to contain infected material because there is no evidence of BSE in U.S. cattle), fed at a very
low level, and fed only once. The potential risk of BSE to such cattle is therefore exceedingly
low, even if the feed were contaminated.
According to Dr. Bernard Schwetz, FDA's Acting Principal Deputy Commissioner, "The
challenge to regulators and industry is to keep this disease out of the United States. One
important defense is to prohibit the use of any ruminant animal materials in feed for other
ruminant animals. Combined with other steps, like U.S. Department of Agriculture's (USDA)
ban on the importation of live ruminant animals from affected countries, these steps represent
a series of protections, to keep American cattle free of BSE."
Despite this negligible risk, Purina Mills, Inc., is nonetheless announcing that it is voluntarily
purchasing all 1,222 of the animals held in Texas and mistakenly fed the animal feed
containing the prohibited material. Therefore, meat from those animals will not enter the
human food supply. FDA believes any cattle that did not consume feed containing the
prohibited material are unaffected by this incident, and should be handled in the beef supply
clearance process as usual.
FDA believes that Purina Mills has behaved responsibly by first reporting the human error
that resulted in the misformulation of the animal feed supplement and then by working
closely with State and Federal authorities.
This episode indicates that the multi-layered safeguard system put into place is essential for
protecting the food supply and that continued vigilance needs to be taken, by all concerned, to
ensure these rules are followed routinely.
FDA will continue working with USDA as well as state and local officials to ensure that
companies and individuals comply with all laws and regulations designed to protect the U.S.
food supply.
---30--
and add these in ;
UPI previously reported that from 2001 to 2003 the USDA collected the wrong part of the brain in more than 200 cows that were being screened as part of its BSE surveillance program.
The USDA documents also indicate the agency never was able to identify or test 52 cows that came into the United States in 2001 along with the Washington cow that tested positive in 2003. Of these, 11 were considered to be "high risk" because they were born within a year and on the same premises as the infected cow.
These cows may have gone into the food supply and been consumed by people. The concern is humans can contract a fatal brain disease from eating beef products contaminated with the mad cow pathogen.
NOT to forget what Paul Brown TSE expert at CDC said ;
THE USDA JUNE 2004 ENHANCED BSE SURVEILLANCE PROGRAM WAS TERRIBLY FLAWED ;
CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006
The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade.
The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old.
These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen.
"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that."
Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive.
USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general. "Everything they did on the Texas cow makes everything USDA did before 2005 suspect," Brown said. ...snip...end
CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... Dr. Paul Brown is Senior Research Scientist in the Laboratory of Central Nervous System ... Address for correspondence: Paul Brown, Building 36, Room 4A-05, ...
PAUL BROWN COMMENT TO ME ON THIS ISSUE Tuesday, September 12, 2006 11:10 AM
"Actually, Terry, I have been critical of the USDA handling of the mad cow issue for some years, and with Linda Detwiler and others sent lengthy detailed critiques and recommendations to both the USDA and the Canadian Food Agency."
OR, what the Honorable Phyllis Fong of the OIG found ;
Audit Report
Animal and Plant Health Inspection Service
Bovine Spongiform Encephalopathy (BSE) Surveillance Program – Phase II and Food Safety and Inspection Service
Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat Recovery Products - Phase III
Report No. 50601-10-KC January 2006
Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain
Greetings list members,
IF you remember correctly, i posted this ;
Subject: Re: USDA/APHIS JUNE 2004 'ENHANCED' BSE/TSE COVER UP UPDATE DECEMBER 19, 2004 USA
Date: Thu, 30 Dec 2004 12:27:06 -0600
From: "Terry S. Singeltary Sr.
BSE-L
snip...
>
> OH, i did ask Bio-Rad about this with NO reply to date;
>
>
> -------- Original Message --------
> Subject: USA BIO-RADs INCONCLUSIVEs
> Date: Fri, 17 Dec 2004 15:37:28 -0600
> From: "Terry S. Singeltary Sr."
> To: susan_berg@bio-rad.com
>
>
>
> Hello Susan and Bio-Rad,
>
> Happy Holidays!
>
> I wish to ask a question about Bio-Rad and USDA BSE/TSE testing
> and there inconclusive. IS the Bio-Rad test for BSE/TSE that complicated,
> or is there most likely some human error we are seeing here?
>
> HOW can Japan have 2 positive cows with
> No clinical signs WB+, IHC-, HP- ,
> BUT in the USA, these cows are considered 'negative'?
>
> IS there more politics working here than science in the USA?
>
> What am I missing?
>
>
>
> -------- Original Message --------
> Subject: Re: USDA: More mad cow testing will demonstrate beef's safety
> Date: Fri, 17 Dec 2004 09:26:19 -0600
> From: "Terry S. Singeltary Sr."
> snip...end
>
>
> Experts doubt USDA's mad cow results
snip...END
WELL, someone did call me from Bio-Rad about this, however it was not Susan Berg.
but i had to just about take a blood oath not to reveal there name. IN fact they did not want me to even mention this, but i feel it is much much to important. I have omitted any I.D. of this person, but thought I must document this ;
Bio-Rad, TSS phone conversation 12/28/04
Finally spoke with ;
Bio-Rad Laboratories 2000 Alfred Nobel Drive Hercules, CA 94547 Ph: 510-741-6720 Fax: 510-741-5630 Email: XXXXXXXXXXXXXXXXXX
at approx. 14:00 hours 12/28/04, I had a very pleasant phone conversation with XXXX XXXXX about the USDA and the inconclusive BSE testing problems they seem to keep having. X was very very cautious as to speak directly about USDA and it's policy of not using WB. X was very concerned as a Bio-Rad official of retaliation of some sort. X would only speak of what other countries do, and that i should take that as an answer. I told X I understood that it was a very loaded question and X agreed several times over and even said a political one. my question;
Does Bio-Rad believe USDA's final determination of False positive, without WB, and considering the new atypical TSEs not showing positive with -IHC and -HP ??? ask if i was a reporter. i said no, i was with CJD Watch and that i had lost my mother to hvCJD. X did not want any of this recorded or repeated.
again, very nervous, will not answer directly about USDA for fear of retaliation, but again said X tell me what other countries are doing and finding, and that i should take it from there.
"very difficult to answer"
"very political"
"very loaded question"
outside USA and Canada, they use many different confirmatory tech. in house WB, SAF, along with IHC, HP, several times etc. you should see at several talks meetings (TSE) of late Paris Dec 2, that IHC- DOES NOT MEAN IT IS NEGATIVE. again, look what the rest of the world is doing. said something about Dr. Houston stating; any screening assay, always a chance for human error. but with so many errors (i am assuming X meant inconclusive), why are there no investigations, just false positives?
said something about ''just look at the sheep that tested IHC- but were positive''. ...
TSS
-------- Original Message --------
Subject: Your questions
Date: Mon, 27 Dec 2004 15:58:11 -0800
From: To: flounder@wt.net
Hi Terry: ............................................
snip
Let me know your phone number so I can talk to you about the Bio-Rad BSE test. Thank you Regards Bio-Rad Laboratories 2000 Alfred Nobel Drive Hercules, CA 94547 Ph: 510-741-6720 Fax: 510-741-5630 Email:
=================================
END...TSS
######### https://listserv.kaliv.uni-karlsruhe.de/warc/bse-l.html ##########
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
9/13/2005
Docket No. 03-080-1 -- USDA ISSUES PROPOSED RULE TO ALLOW LIVE ANIMAL IMPORTS FROM CANADA 11/03/2003 01:19 PM
Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS 07/11/2004 09:34 PM
Importation of Whole Cuts of Boneless Beef From Japan [Docket No. 05-004-2] RIN 0579-AB93
snip...
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 comment regarding the manner by which APHIS intends to treat this new scientific finding.
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\2\ Bushmann, A., and Gruschup, 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.
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\3\ Westaway, D., et al.; (1994) Degeneration of Skeletal Muscle, Peripheral Nerves, and the Central Nervous System in Transgenic Mice Overexpressing Wild-type Prion Proteins. Cell 76, 117-129.
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Blood
Issue: Two commenters expressed concern that there has been a limited amount of research conducted on BSE infectivity in blood. One of these commenters cited a report that discussed, among other things, the detection of infectivity in sheep experimentally infected with BSE via blood transfusions.\4\ This commenter also stated that the agent that causes Creutzfeldt-Jakob disease (CJD), a chronic and fatal neurodegenerative disease of humans, was detected in blood, and questioned whether the BSE agent could be detected in blood as well. The other commenter cited a study that detected infectivity in hamsters experimentally infected with scrapie.\5\ This commenter requested that APHIS ban the use of blood in cattle feed.
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\4\ Pattison, J., et al.; UK Strategy for Research and Development on Human and Animal Health Aspects of Transmissible Spongiform Encephalopathies, 2005-2008. Available at http://www.mrc.ac.uk/pdf-about-tse_uk_strategy_june2005.pdf. \5\ Castilla, J., et al.; Detection of Prions in Blood. Nature Medicine, doi: 10.1038/nm1286, August 28, 2005, at 3.
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Response: As stated in our risk analysis, the pathogenesis studies of naturally and experimentally infected cattle have not detected BSE infectivity in blood.
The first study mentioned by the commenter above demonstrated transmission of disease from sheep experimentally infected with BSE to another sheep via blood transfusions. We note that there are widely acknowledged differences between the distribution of BSE infectivity in the tissues of cattle and sheep. In addition, there is a significant difference in susceptibility to infection based on the route of transmission. Infection via oral consumption may be 10,000 times less efficient than infection via intravenous injection, such as a blood transfusion.
Both the United Kingdom's Department for Environment, Food and Rural Affairs' Spongiform Encephalopathy Advisory Committee (SEAC) and the European Commission's Scientific Steering Committee (SSC), which are scientific advisory committees, evaluated the findings of transmission of infectivity via blood transfusions in sheep experimentally infected with BSE and concluded that
[[Page 73907]]
these findings did not indicate that additional mitigation measures were necessary to protect public health.\6\ Therefore, based on currently available information, APHIS considers it unlikely that the experimental observations in sheep reflect a biologically significant event for cattle or affect the safety of whole cuts of boneless beef derived from cattle born, raised, and slaughtered in Japan.
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\6\ Spongiform Encephalopathy Advisory Committee, Oct. 19, 2000, Summary of SEAC Committee Meeting 29 September 2000. Available at http://www.defra.gov.uk/news/seac/seac500.htm. European Commission Scientific Steering Committee; The Implications of the Recent Papers on Transmission of BSE by Blood Transfusion in Sheep (Houston et al., 2000; Hunter et al., 2002), Adopted by the SSC at its Meeting of 12-13 September. Available at http://europa.eu.int/comm/food/fs/sc/ssc/out280_en.pdf.
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The study on scrapie-infected hamsters noted by the commenter describes a process by which the abnormal prion protein can be amplified and detected using current testing methods, such as a Western blot. In this study, blood from hamsters experimentally infected with a scrapie strain was collected when the animals demonstrated clinical signs of disease. These blood samples were incubated with excess normal prion protein from brain tissue for multiple cycles. If abnormal protein is present in blood, it will convert the normal brain prion to abnormal prion, yielding an increased amount of abnormal prion that can be more easily detected. In this manner, the presence of abnormal prion protein in the initial blood samples, which was present in levels too low to detect using routine test methods, was demonstrated. While this finding has many possibilities related to the development of diagnostic tests, it does not demonstrate BSE infectivity in blood. We also note that the international community largely considers that studies using transmissible spongiform encephalopathies (TSEs) other than BSE in non- bovine animals cannot be directly extrapolated to BSE in cattle because of the significant interactions between the host species and the prion strain involved.
Feed regulations in the United States are under the authority of the Food and Drug Administration (FDA), not APHIS. Therefore, the commenter's request that APHIS ban the use of blood in cattle feed falls outside the scope of this rulemaking. For these reasons, we are not making any changes to the rule based on these comments.
snip...
Issue: Two commenters raised questions regarding the origin of CJD in humans. One commenter noted that there are different strains of TSEs being discovered in ruminants, and that new atypical strains of TSE in cattle look similar to sporadic CJD in humans. Another commenter asked if APHIS has considered whether sporadic CJD in humans might be caused by atypical cases of TSEs that have been found in animals. This commenter further questioned whether blood and other tissues may carry BSE infectivity in cattle infected with atypical strains of the BSE agent or other TSE agents.
Response: Sporadic CJD is the most common form of CJD. It has been found in every country in the world where it has been looked for including countries that are generally considered by the international scientific community to be free of BSE and other TSEs (for example, Australia and New Zealand). In general, it affects about one person per million. No association between sporadic CJD and consumption of animal products in general and/or infected or contaminated bovine products has ever been documented. It is currently believed that sporadic CJD arises through the spontaneous conversion of PrPC (normal cellular prion protein) to PrPSC in an individual.\13\ In contrast, atypical cases of BSE in cattle are rare and have been reported in only few countries that experience BSE, such as Italy, Belgium, Japan, and France. It has been speculated that the spontaneous or sporadic form of BSE could exist in cattle, as well as humans.\14\
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\13\ Stahl, N. and Prusiner, S.B.; (1991) FASEB-J. 5: 2799-807. \14\ Biacabe; 2004 EMBO reports, Vol. 5, No. 1. ---------------------------------------------------------------------------
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APHIS agrees with the commenter that reports indicate that some of the atypical BSE cases, in particular the bovine amyloidotic spongiform encephalopathy (BASE), and sporadic CJD have similar PrPSC patterns. APHIS evaluated the findings in the context of risk of exposure to cattle and humans. Currently, the relevance of the atypical cases is unknown, but at this time there is no indication that any control measures--such as feed bans or SRM requirements--should be modified based on these cases. Additionally, although atypical cases of BSE and sporadic CJD share similarities at this point, there is no evidence that they are linked.
Issue: One commenter expressed concern over the number of citations issued for various SRM violations during the June 2004 enhanced BSE surveillance program in the United States. This commenter questioned whether these incidents of noncompliance may have led to infective materials entering the human or animal food chains. This commenter cited the case of BSE detected in a 12-year-old cow in Texas as evidence that infective materials may have entered the food chain. The commenter suggested that noncompliance reports should be made more easily available to the public in the future.
Response: FSIS inspectors are responsible for verifying the effectiveness of an establishment's procedures. If FSIS personnel determine that an establishment's procedures are ineffective in preventing cross-contamination, the inspectors will take appropriate action. We note that none of the meat from the 12-year-old BSE-infected cow in Texas mentioned by the commenter entered the human food or animal feed chains.
snip...full text ;
Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION
Docket No. 05-004-1 RIN 0579-AB93 BSE TSS was Received
I would kindly like to comment on [Docket No. 05-004-1] RIN 0579-AB93 ; PROPOSED RULES
Exportation and importation of animals and animal products: Whole cuts of boneless beef from-Japan, 48494-48500 [05-16422]
[Federal Register: August 18, 2005 (Volume 70, Number 159)] [Proposed Rules] [Page 48494-48500] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr18au05-7] ========================================================================
Proposed Rules Federal Register ________________________________________________________________________
This section of the FEDERAL REGISTER contains notices to the public of the proposed issuance of rules and regulations. The purpose of these notices is to give interested persons an opportunity to participate in the rule making prior to the adoption of the final rules. ========================================================================
[[Page 48494]]
DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 94 [Docket No. 05-004-1] RIN 0579-AB93
Importation of Whole Cuts of Boneless Beef from Japan AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Proposed rule.
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SUMMARY:
We are proposing to amend the regulations governing the importation of meat and other edible animal products by allowing, under certain conditions, the importation of whole cuts of boneless beef from Japan. We are proposing this action in response to a request from the Government of Japan and after conducting an analysis of the risk that indicates that such beef can be safely imported from Japan under the conditions described in this proposal. DATES: We will consider all comments that we receive on or before September 19, 2005.
ADDRESSES: You may submit comments by any of the following methods: EDOCKET: Go to http://www.epa.gov/feddocket to submit or
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BSE infectivity has never been demonstrated in the muscle tissue of cattle experimentally or naturally infected with BSE at any stage of the disease. Studies performed using TSEs other than BSE in non-bovine animals have detected prions in muscle tissue. However, the international scientific community largely considers that these studies cannot be directly extrapolated to BSE in cattle because of the significant interactions between the host species and the prion strain involved.
Pathogenesis studies of naturally and experimentally infected cattle have not detected BSE infectivity in blood. However, transmission of BSE was demonstrated in sheep that received a transfusion of a large volume of blood drawn from other sheep that were experimentally infected with the BSE agent. The United Kingdom's Department for Environment, Food and Rural Affairs' Spongiform Encephalopathy Advisory Committee (SEAC) and the European Commission's Scientific Steering Committee (SSC), which are scientific advisory committees, evaluated the implication of this finding in relation to food safety.\5\ The SEAC concluded that the finding did not represent grounds for recommending any changes to the current control measures for BSE. The SSC determined that the research results do not support the hypothesis that bovine blood or muscle meat constitute a risk to human health.\6\
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BSE Risk Factors for Whole Cuts of Boneless Beef
The most significant risk management strategy for ensuring the safety of whole cuts of boneless beef is the prevention of cross- contamination of the beef with SRMs during stunning and slaughter of the animal. Control measures that prevent contamination of such beef involve the establishment of procedures for the removal of SRMs, prohibitions on air-injection stunning and pithing, and splitting of carcasses. These potential pathways for contamination and the control measures that prevent contamination are described in detail in the risk analysis for this rulemaking.
SRM Removal. Research has demonstrated that SRMs from infected cattle may contain BSE infectivity. Because infectivity has not been demonstrated in muscle tissue, the most important mitigation measure for whole cuts of boneless beef is the careful removal and segregation of SRMs. Removal of SRMs in a manner that avoids contamination of the beef with SRMs minimizes the risk of exposure to materials that have been demonstrated to contain the BSE agent in cattle.
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Variant Creutzfeldt-Jakob disease (vCJD), a chronic and fatal neurodegenerative disease of humans, has been linked since 1996 through epidemiological, neuropathological, and experimental data to exposure to the BSE agent, most likely through consumption of cattle products contaminated with the agent before BSE control measures were in place. To date, approximately 170 probable and confirmed cases of vCJD have been identified worldwide. The majority of these cases have either been identified in the United Kingdom or were linked to exposure that occurred in the United Kingdom, and all cases have been linked to exposure in countries with native cases of BSE. Some studies estimate that more than 1 million cattle may have been infected with BSE throughout the epidemic in the United Kingdom. This number of infected cattle could have introduced a significant amount of infectivity into the human food supply. Yet, the low number of cases of vCJD identified to date indicates that there is a substantial species barrier that protects humans from widespread illness due to exposure to the BSE agent.
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International Guidelines on BSE
International guidelines for trade in animal and animal products are developed by the World Organization for Animal Health (formerly known as the Office International des Epizooties (OIE)), which is recognized by the World Trade Organization (WTO) as the international organization responsible for the development of standards, guidelines, and recommendations with respect to animal health and zoonoses (diseases that are transmissible from animals to humans). The OIE guidelines for trade in terrestrial animals (mammals, birds, and bees) are detailed in the Terrestrial Animal Health Code (available on the internet at http://www.oie.int). The guidelines on BSE are contained in Chapter 2.3.13 of the Code and supplemented by Appendix 3.8.4 of the Code.
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Greetings again APHIS ET AL,
THIS is not correct. IN fact, there are several factors i would like to kindly address. .......
SNIP...
WE MUST ADHERE TO THE BSE GBR RISK ASSESSMENTS, WE MUST WORK TO ENHANCE THOSE BSE GBR RISK ASSESSMENTS TO INCLUDE ALL ANIMAL TSEs, USDA/APHIS/GW ET ALs BSE MRR (Minimal Risk Region) should be REPEALED/DISBANDED/TRASHED/NADA and done away with for good. The BSE MRR policy is nothing more than a legal tool to trade all strains of TSEs globally...
Terry S. Singeltary Sr. Bacliff, Texas USA 77518
Your Comment with Title "[Docket No. 05-004-1] RIN 0579-AB93 BSE TSS " was Received.
The Identifier Assigned is "APHIS-2005-0073-0009". An Electronic File was Attached to this Submission.
Please note that it may take between 24 and 72 hours for the EDOCKET staff to process your comment before it is available publicly through EDOCKET. You can use the identifier noted above to find your comment through the Quick or Advanced Search pages when it is available. ...........
http://www.aphis.usda.gov/lpa/news/2005/08/japanbeef_vs.html
EPA: Federal Register: Importation of Whole Cuts of Boneless Beef ...Importation of Whole Cuts of Boneless Beef From Japan , Federal Register document. ... we published in the Federal Register (70 FR 48494-48500, Docket No. ...
"[Docket No. 05-004-1] RIN 0579-AB93 BSE TSS " was Received BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 APHIS-2006-0041-0006 Comment from Terry S Singletary Sr 01/09/2007 PUBLIC SUBMISSIONS
APHIS-2006-0041-0006.1 Attachment to Singletary comment 01/09/2007 PUBLIC SUBMISSIONS
look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE;
Risk of oral infection with bovine spongiform encephalopathy agent in primates Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys
Summary The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.
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BSE bovine brain inoculum 100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg Primate (oral route)* 1/2 (50%) Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%) RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)
PrPres biochemical detection The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8
*Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%).
The accuracy of bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.
Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula
Published online January 27, 2005
P04.27
Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route
Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany
Background:
In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.
Aims:
The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.
Methods:
Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).
Results:
In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.
Conclusions:
Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian v CJD as fast as intracerebrally inoculated animals.
The work referenced was performed in partial fulfillment of the study "BSE in primates" supported by the EU (QLK1-2002-01096).
Calves were challenged by mouth with homogenised brain from confirmed cases of BSE. Some received 300g (3 doses of 100g), some 100g, 10g or 1g. They were then left to develop BSE, but were not subjected to the normal stresses that they might have encountered in a dairy herd. Animals in all four groups developed BSE. There has been a considerable spread of incubation period in some of the groups, but it appears as if those in the 1 and 10g challenge groups most closely fit the picture of incubation periods seen in the epidemic. Experiments in progress indicate that oral infection can occur in some animals with doses as low as 0.01g and 0.001g. .........
It is clear that the designing scientists must also have shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.
6. It also appears to me that Mr Bradley's answer (that it would take less than say 100 grams) was probably given with the benefit of hindsight; particularly if one considers that later in the same answer Mr Bradley expresses his surprise that it could take as little of 1 gram of brain to cause BSE by the oral route within the same species. This information did not become available until the "attack rate" experiment had been completed in 1995/96. This was a titration experiment designed to ascertain the infective dose. A range of dosages was used to ensure that the actual result was within both a lower and an upper limit within the study and the designing scientists would not have expected all the dose levels to trigger infection. The dose ranges chosen by the most informed scientists at that time ranged from 1 gram to three times one hundred grams. It is clear that the designing scientists must have also shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.
FRIDAY, JANUARY 04, 2019
TEXAS TPWD CONFIRMED CWD TSE PRION 3 WTD in Medina, Dallam, and Hartley Counties, and in 3 MD in Hudspeth, Hartley, and El Paso Counties
FRIDAY, DECEMBER 28, 2018
***> Chronic Wasting Disease CWD TSE Prion 2019 Where The Rubber Meets The Road
FRIDAY, DECEMBER 14, 2018
MAD COW USA FLASHBACK FRIDAY DECEMBER 14, 2018
THURSDAY, JANUARY 3, 2019
MAD COW USDA DISEASE BSE TSE Prion
Saturday, December 15, 2018
***> ADRD Summit RFI Singeltary COMMENT SUBMISSION BSE, SCRAPIE, CWD, AND HUMAN TSE PRION DISEASE December 14, 2018
TUESDAY, JANUARY 1, 2019
CHILDHOOD EXPOSURE TO CADAVERIC DURA
Terry S. Singeltary Sr., Bacliff, Texas, USA, Galveston Bay 77518
