Saturday, November 2, 2013

Exploring the risks of a putative transmission of BSE to new species

Exploring the risks of a putative transmission of BSE to new species

 

Enric Vidal, 1 Natalia Fernández-Borges, 2 Belén Pintado, 3 Montserrat Ordóñez, 1 Mercedes Márquez, 4 Dolors Fondevila, 4 Hasier Eraña, 2 Juan María Torres, 5 Martí Pumarola, 4 Joaquín Castilla 2, 6, *

 

Abstract

 

The prion responsible for the Bovine Spongiform Encephalopathy (BSE) shows unique features when compared with other prions. One of these features is its ability to infect almost all experimentally tested animal models. In the paper published in The Journal of Neuroscience1 we describe a series of experiments directed toward elucidating which would be the in vivo behavior of BSE if it would infect dogs and rabbits, two alleged prion resistant species. Protein misfolding cyclic amplification (PMCA) was used to generate canidae and leporidae in vitro adapted BSE prions. A characterization of their in vivo pathobiological properties showed that BSE prions were capable not only of adapting to new species but they maintained, in the case of rabbits, their ability to infect transgenic mice expressing human PrP. The remarkable adaptation ability of certain prions implies that any new host species could lead to the emergence of new infectious agents with unpredictable transmission potential. Our results suggest that caution must be taken when considering the use of any mammal derived protein in feedstuffs.

 

Perspectives

 

Bovine Spongiform Encephalopathy (BSE) is one of the most well-known animal prion diseases.2 The “mad cow disease” outbreak had unprecedented consequences regarding worldwide public health and food safety policies. The reason for this was the ability of the agent causing BSE to transmit to species other than cattle, its original host, including human beings.3 Enormous economical efforts were directed toward controlling the disease in cattle with exceptional results. Indeed, policies such as the ban on using ruminant protein on feed drastically reduced the reported BSE cases in cattle. The compulsory testing of a large number of animals allowed to accurately monitoring the success of such measures. In every country where these policies have been implemented, the BSE cases are practically down to zero. Thus, updated risk analyses point to a relaxation of the control measures. 2

 

Thanks to the research efforts directed toward this subject, many previously unknown aspects of this prion disease have came to light during the last decade, for instance, the existence of the so called atypical BSE cases.4,5 Two cattle prions strains have been identified in aged cattle and named BSE-L and BSE-H after the different electrophoretic pattern of its proteinase-K digested disease-associated BSE prion protein (PrPd) on western blotting. Epidemiology and pathological features of the diagnosed cases suggest that those are probably sporadic prion diseases and evidence suggests that they might have had a crucial role in the origin of the BSE epizooty.6,7 If these atypical presentations are indeed sporadic prion diseases, such as the ones known in humans, it implies that current BSE control measures will not be effective to eradicate them. In other words, even though passive surveillance and withdrawal of specified risk material should prevent transmission to humans and the ban on the use of ruminant meat and bone meal in feedstuffs should avoid horizontal transmission, sporadic cases will still occur so we will have to coexist with cattle prions and the risks associated to them. 4

 

With the exception of these atypical BSE strains, all BSE cases diagnosed in cattle have been classified as classical BSE, and for many years BSE was believed to be caused by a single stable agent.2 This observation was due to the homogeneity of biological and laboratorial features of the PrPd, a pathological isoform of the host encoded cellular prion protein (PrPC), which is believed to be the ethiological agent of transmissible spongiform encephalopathies (TSEs).8 BSE associated PrPd is characterized in western blotting by a three band pattern between 18 and 30 kDa, present after Proteinase-K digestion, with a predominance of a diglycosylated moiety.9 Also, BSE showed stable pathobiological features upon transmission to wild type inbred mouse lines which allowed precise identification of the strain based on brain lesions and PrPd deposition profiles when assessed by immunohistochemistry (IHC).10-12 These experiments suggested a link between vCJD and BSE.3 6

 

Experiments using transgenic mice expressing bovine PrP (TgBov mice) further supported the idea that the BSE epizootic was caused by a single agent with no strain diversity.13-16 Additionally, after interspecies transmission when sheep passaged BSE was inoculated back into TgBov mice, the disease exhibited typical features of BSE in this model, except for a reduced incubation period when compared with cattle BSE.17 Surprisingly, inoculation with atypical BSE isolates also showed features of classical BSE in this model, suggesting a possible link between these strains.6,18,19 6

 

Interspecies transmission of prions is a phenomenon worth studying since strain properties can be modified by new hosts. As an example, chronic wasting disease (CWD) prions proved not to be transmissible to hamsters20 but, upon transmission to ferrets, which were indeed susceptible, CWD prions could readily infect hamsters.21 BSE has in fact been described to change, to a certain extent, upon passage through species other than cattle, i.e., sheep. Passage through sheep resulted in an increase of BSE virulence when inoculated into TgBov mice.17 So, attention must be paid to the emergence of new prion strains or the modifications that new hosts might pose to the pathobiological properties of already known strains, particularly regarding the ability to transmit to other species, including humans. 3

 

In vitro amplification of prions22 has proven to be an effective tool to predict the in vivo behavior of certain prions.23,24 Not only does it accelerate the transmission process but it also can be used to push the system, by challenging healthy brain homogenates of different species with different prion strains at high concentration and directly in a test tube, to find out what would happen in case certain cross-species transmission of prions would occur in nature. Several publications support protein misfolding cyclic amplification (PMCA) ability to mimic potential in vivo scenarios. For instance, the susceptibility of rabbits to prion diseases was predicted by PMCA and then demonstrated in its natural host23 and, likewise, other species PrP could also be misfolded in vitro including dogs and horses.25 4

 

In the paper published in The Journal of Neuroscience1 we describe a series of experiments directed toward elucidating which would be the in vivo behavior of BSE, one of the most relevant prions in Europe, in case it managed to cross certain transmission barriers. The species chosen were dogs and rabbits for several reasons, namely both are species in close contact with human beings and no reports of prion susceptibility had been published at the time the experiments were designed, thus they were species considered to be probably prion resistant. 1

 

The experiments consisted in an initial in vitro phase in which dog and rabbit normal brain homogenates were subjected to PMCA with a BSE seed. In a second phase, the newly obtained prions were inoculated into TgBov mice and in a transgenic model expressing human PrP (TgHum)26 to assess their in vivo behavior in comparison to the original BSE seed. 1

 

Several interesting findings were obtained from that set of experiments. To start with, BSE was the only prion strain that could be propagated in vitro in both alleged resistant species, a capacity which lacked other prion strains originated in other hosts, such as scrapie. The typical BSE biochemical signature (western blotting) remained unchanged in both species even after multiple in vitro amplification cycles.

 

Interestingly, the pathobiological features of these newly in vitro obtained prions, such as their infectivity, incubation times, biochemical profile, lesion profile, and etcetera were remarkably comparable to those of BSE when bioassayed in transgenic mouse models overexpressing bovine and human PRNP. Of particular interest were the bioassay results in tgHum mice which evidenced the zoonotic potential of rabbit adapted BSE. Two out of nine inoculated TgHum mice succumbed with a prion disease as confirmed by WB and immunohistochemical techniques.

 

It is clear that the BSE strain has unique features when compared with other prions, particularly in terms of disease phenotype stability and permeability to different hosts. One can speculate that these differences must reside in an also unique PrPSc structure; so unique that its conformation is reproducible on a considerably wide range of amino acid sequences.11 This is not the case for other prions, which upon interspecies transmission are not able to maintain its strain characteristics. For instance, mouse adapted prions such as 139A and ME7 with a single species barrier crossing to the hamster model, a rather similar species, undergo profound strain changes.27 2

 

To fully understand why certain prion conformations, such as that of the BSE strain, remain unaltered in varying amino acid scenarios it is mandatory to resolve its structure, probably with a resolution of a few nanometers, and compare it to other prion strains. Only when this is achieved, a qualitative leap will be attained to better comprehend the prion propagation mechanisms.

 

Previous studies had already reported that BSE is able to retain its biochemical and biological properties upon interspecies passage through certain species such as sheep,17,28 goats,29 felidae,30 mice11 or humans.3,31 Although other authors have also reported that some biochemical features might change after certain BSE interspecies transmissions such as in deer32 or when testing certain transgenic mouse experimental models.33 9

 

Coexistence for centuries with animal prions, such as scrapie, without any apparent risks to the human population was disturbed by the emergence of a zoonotic prion disease in cattle: BSE. Of course, this new prion strain found its way into the field leaded by mankind’s artificial husbandry practices. So at this point any further intervention should be preceded by a meticulous consideration of all the possible risks involved. Regulations regarding TSE control and surveillance are being revised, predictably less surveillance will be performed and the roadmap is leading toward a reintroduction of animal derived protein in feedstuffs, provided that cannibalism does not happen, i.e., a determined species is not to be fed with formulas containing animal protein of its own species. Thus, feeding any farmed animal with mammal derived protein is to be banned yet, with the exception of pet-food [Regulation (EC) No 999/2001 in the Official Journal of the European Communities]. Our results evidence that BSE prions are capable not only of adapting to new species, even to those which apparently are more resistant than others, but in doing so they maintain their ability to infect human beings. And if, in an unlikely but yet possible case, this should occur in the field, the resulting prion, as any other infectious agent, might find its way to adapt and maybe evolve in a changing environment. Eventually it might even lead to the emergence of new infectious agents with unpredictable transmission potential. Given that spontaneous prions are out there in the field, results such as the ones presented here suggest that caution must be taken when considering the use of animal derived protein in feedstuffs.

 


 

 

A SPECIAL THANKS TO Joaquín Castilla ET AL, AND OF COURSE www.landesbioscience.com et al. ...TSS

 

NOW, let us analyze some of these findings, from previous findings that went ignored for all these years and decades, what I call ‘passing it around’. ...TSS

 

 

Subject: CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL PRION DISEASE

 

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.

 


 

 

***2005

 

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

 


 

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.

 


 

 

Monday, March 26, 2012

 

CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL PRION DISEASE

 


 

 

Friday, March 8, 2013

 

Dogs may have been used to make Petfood and animal feed

 


 

 

SEE FULL TEXT ;

 


 

 

*** IN CONFIDENCE ***

 

*** SUSPECT BSE IN A HORSE ***

 

CYO BSE 1 9

 

IN CONFIDENCE

 

SUSPECT BSE IN A HORSE

 

The Parliamentary Secretary (Mr Maclean) will wish to be aware that, in making his differential diagnosis, a veterinary surgeon in the Reading area has included the possibility of BSE in a horse under his care. Although it is unlikely to be BSE, because of the symptoms exhibited the veterinarian believes that he cannot exclude the possibility. The case was brought to the notice of one of the veterinary staff at the CVL by the owner's veterinary surgeon and liaison is being maintained.

 

The horse in question is a five-year old eventing gelding which was purchased by the present owner about four months ago. Approximately two months after purchase the animal became a little apprehensive, developed mild nervous symptoms and became over-sensitive to noise. The nervous symptoms have increased and the horse is now practically impossible to ride. Investigations by the owner's private veterinary surgeon are continuing but it is likely that the animal will have to be destroyed.

 

If the horse should die or be destroyed, a full post-mortem examination will be required for insurance purposes and will probably be carried out at a non-Ministry laboratory. However, Mr Bradley of the Pathology Department, CVL, has informed the private veterinary surgeon that he is willing to provide a second opinion on the brain histology if requested.

 

I will keep the Parliamentary Secretary informed of any further developments in the case.

 

I CRAWFORD

 

14 May 1990

 

Mr M P H Hill, PS/Parliamentary secretary (Mr Maclean) - by FAX

 

cc:

 

Private Offices

 

Mr K C Meldrum

 

Mrs E A J Attridge D J Evans Mr K C Taylor Mr R Lawson Mr R Bradley. CVL

 

(hand written notes i cannot read all (cut short) as follows...tss)

 

The Parliamentary Secretary (Mr Maclean was grateful for this. He said that we must keep very close to ...on it, and when the horse dies, or is put down we must be told immediately. He also feels it is very important that our veterinary staff be involved in the brain examination. .........(cannot read the rest .............TSS)

 

90/05.14/10.1

 


 

 

Mr A Huws Principal WOAD2A CP2

 

SUSPECT BSE IN A HORSE

 

You will wish to be aware that on Thursday afternoon 25 June the T/DVO Powys received a phone call from a veterinary Surgeon reporting his suspicion that a horse had ___contracted BSE after having been fed cattle cake___.

 

The clinical symptoms described were similar to those shown by cattle there ___being a similar case some months ago on the same premises___.

 

The owner' s name and address is:

 

Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse Brecon

 

The horse is a 12 year old gelding used for pony trekking.

 

By yesterday evening the horse was in a comatose state and on humane grounds was destroyed by the veterinary Surgeon. At his request a full post mortem and laboratory investigation will be carried out at the Carmarthen Veterinary Investigation Centre this morning to ascertain the exact cause; I have been told this will take at least two weeks. Charges to the veterinary Surgeon have been waived in this instance.

 

I will inform you immediately I receive a diagnosis.

 

26 June 1990

 

D SUMMERS DRVO

 

cc

 

Mr D R Williams, RVO

 

Mr A R Hunter, SVIO

 

90/06.26/10.1

 


 

 

Mr A Huws Principal WOAD2A CP2

 

SUSPECT BSE IN A HORSE

 

You will wish to be aware that on Thursday afternoon 25 June the T/DVO Powys received a phone call from a veterinary Surgeon reporting his suspicion that a horse had contracted BSE after having been fed cattle cake. The clinical symptoms described were similar to those shown by cattle there being a similar case some months ago on the same premises.

 

The owner' s name and address is:

 

Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse Brecon

 

The horse is a 12 year old gelding used for pony trekking.

 

By yesterday evening the horse was in a comatose state and on humane grounds was destroyed by the veterinary Surgeon. At his request a full post mortem and laboratory investigation will be carried out at the Carmarthen Veterinary Investigation Centre this morning to ascertain the exact cause; I have been told this will take at least two weeks. Charges to the veterinary Surgeon have been waived in this instance.

 

I will inform you immediately I receive a diagnosis.

 

26 June 1990

 

D SUMMERS DRVO

 

cc

 

Mr D R Williams, RVO

 

Mr A R Hunter, SVIO

 

90/06.26/10.1

 


 

 

full text ;

 


 

 

we know that horses, especially quarter horses and show horses are fed feed with high animal protein content, and it’s perfectly legal.

 

see ;

 

 

Nonprohibited Materials:

 

These feed materials CAN be fed to ruminants.

 

A. The following protein products derived from mammals, including ruminants, are exempt from the Ruminant Feed Ban rule and CAN be fed to ruminants:

 

Blood and blood products

 

Milk products (milk and milk protein)

 

Pure porcine (pork) protein

 

Pure equine (horse) protein

 

Gelatin Inspected meat products, such as plate waste, which have been cooked and offered for human food and further heat processed for animal feed.

 

snip... see full text ;

 


 

 

From: TSS

 

Subject: MAD COW/HORSE FEED BAN VIOLATIONS WARNING LETTER July 20, 2001 USA

 

Date: August 14, 2001 at 11:36 am PST

 

DEPARTMENT OF HEALTH AND HUMAN SERVICE

 

July 20, 2001

 

CERTIFIED MAIL RETURN RECEIPT REQUESTED

 

WARNING LETTER Ref. KAN 2001-028

 

Mr. Eric N. Blomkuist, CEO Farnam Companies, Inc. 301 W. Osborn P.O. Box 34820 Phoenix, AZ 85013

 

Dear Mr. Blomkuist:

 

An inspection of your Council Bluffs, Iowa facility that serves as a manufacturing/repackaging site for animal feed and as a distribution operation for animal drugs and feeds conducted on June 13-20, 2001 by an Investigator representing this office found significant deviations from the requirements set forth in Title 21, Code of Federal Regulations, Part 589.2000 - Animal Proteins Prohibited in Ruminant Feed. This regulation is intended to prevent the establishment and amplification of Bovine Spongiform Encephalophathy (BSE) within the borders of the United States. Such deviations cause products being manufactured and/or distributed by your facility to be adulterated within the meaning of Section 402(a)(4) and misbranded within the meaning of Section 403(F) of the Federal Food, Drug, and Cosmetic Act (the Act).

 

The inspection revealed the following:

 

There are no written procedures demonstrating the clean-out process used to prevent the cross- contamination of product. Your firm uses common equipment for product manufactured with prohibited material and for feed and/or drugs that are not.

 

Your firm distributes products that may contain prohibited material, specifically Flex Free, Equinyl, Generation and Max Flex, that are not labeled with the required cautionary statement "Do Not Feed to Cattle or Other Ruminants"

 

The above is not intended to be an all-inclusive list of violations. As a manufacturer of products intended for animal feed use you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance with the law. At the conclusion of the inspection Form FDA483, List of Inspectional Observations was issued to Ronald G. Adler, Plant Manager identifying these and other deviations. A copy is enclosed for your information.

 

Our Investigator reported a telephone discussion with Mr. Barry G. Harrison who identified himself as the Corporate Counsel of the Farnam Companies, Inc. During this discussion Mr. Harrison, reportedly, claimed the products in question are exempt from the cautionary statement requirement. This claimed exemption is based on the fact the products are intended only for the equine market and your firm defines horses as pets. We cannot accept this claimed exemption because while some horses may be held as pets, horses are also working animals and in some parts of North America, food animals.

 

Based on our knowledge of working ranches, horse feed is often stored in the same general area as ruminant feed making a conspicuous cautionary statenmit vital on feeds and supplements, containing prohibited materials.

 

You should take prompt action to correct the above violations and to establish procedures whereby such violations do not recur. Failure to make immediate and lasting corrections may result in regulatory actions without further notice including but not limiting to product seizure and/or injunction.

 

You should respond, in writing, Within 15 working days of the steps you have taken to bring your firm into compliance with the law. Please include all the steps you plan to take, the timeframe for completing these actions and any documentation demonstrating the action's completion.

 

Your response should be directed to Ralph J. Gray, Compliance Officer at the above address.

 

Sincerely, Charles W. Sedgwick District Director Kansas City District Office

 

Cc: Mr. John C. Williams CEO, Manufacturing and Distribution Farnam Companies, Inc, 1302 Law Ross Road Council Bluffs, IA 51501

 


 

 

Subject: Re: MAD COW/HORSE FEED BAN VIOLATIONS WARNING LETTER July 20, 2001

 

Date: Tue, 14 Aug 2001 23:43:26 –0400

 

From: "Robert A. LaBudde"

 

Reply-To: Bovine Spongiform Encephalopathy

 

To: BSE-L@uni-karlsruhe.de

 

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

 

At 01:41 PM 8/14/01 -0700, Terry wrote: >DEPARTMENT OF HEALTH AND HUMAN SERVICE > >July 20, 2001 > >Our Investigator reported a telephone discussion with Mr. Barry G. >Harrison who identified himself as the Corporate Counsel of the Farnam >Companies, Inc. During this discussion Mr. Harrison, reportedly, claimed >the products in question are exempt from the cautionary statement >requirement. This claimed exemption is based on the fact the products >are intended only for the equine market and your firm defines horses as >pets. We cannot accept this claimed exemption because while some horses >may be held as pets, horses are also working animals and in some parts >of North America, food animals. > >Based on our knowledge of working ranches, horse feed is often stored in >the same general area as ruminant feed making a conspicuous cautionary >statenmit vital on feeds and supplements, >containing prohibited materials.

 

Terry:

 

Perhaps you should pester FDA about this "loophole". Apparently, "pet food" does not have to bear the warning labels specified for food animals.

 

I can't see any serious objection to expanding the label requirement to ALL animal food, not just food animals.

 

Also, horses are "ruminants", so it's disturbing that they might escape the feed ban by being classified as "pets". Another good reason to extend the warning labels and regulation to all animal foods.

 

Perhaps you could submit a request for ruling to the FDA on this issue to propose amending the regulation to include all animal foods, including pet foods.

 

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

 

Robert A. LaBudde, PhD, PAS, Dpl. ACAFS e-mail: ral@lcfltd.com Least Cost Formulations, Ltd. URL: http://lcfltd.com/ 824 Timberlake Drive Tel: 757-467-0954 Virginia Beach, VA 23464-3239 Fax: 757-467-2947

 

"Vere scire est per causas scire"

 

=========================end...tss=====================

 

 

It has become appallingly obvious that our technology has exceeded our humanity.

 

Albert Einstein

 

Stupid is, as stupid does, and some times you just can’t fix stupid $$$

 

never say never with TSE Prions. ...TSS

 

 

Thursday, January 5, 2012 Horse Meat, slaughter for consumption USA

 

Horse slaughter in Texas and everywhere else should be against the law

 


 

 

FELINE SPONGIFORM ENCEPHALOPATHY FSE

 


 


 


 
 
From: Terry S. Singeltary Sr.
 
Sent: Friday, March 16, 2012 10:09 AM
 
 
 
Subject: [BSE-L] Rabbits are not resistant to prion infection
 
 
Rabbits are not resistant to prion infection
 
Francesca Chianinia,1, 1.. Natalia Fernández-Borgesb,c,1, 2.. Enric Vidald, 3.. Louise Gibbarda, 4.. Belén Pintadoe, 5.. Jorge de Castroc, 6.. Suzette A. Priolaf, 7.. Scott Hamiltona, 8.. Samantha L. Eatona, 9.. Jeanie Finlaysona, 10.. Yvonne Panga, 11.. Philip Steelea, 12.. Hugh W. Reida, 13.. Mark P. Dagleisha, and 14.. Joaquín Castillab,c,g,2
 
+ Author Affiliations
 
1.. aMoredun Research Institute, Penicuik, Near Edinburgh EH26 0PZ, Scotland, United Kingdom; 2.. bCIC bioGUNE, Derio 48160, Bizkaia, Spain; 3.. gIKERBASQUE, Basque Foundation for Science, Bilbao 48011, Bizkaia, Spain; 4.. cDepartment of Infectology, Scripps Florida, Jupiter, FL 33458; 5.. fLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; 6.. dCentre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; and 7.. eCentro Nacional de Biotecnología (CNB), 28049 Cantoblanco, Madrid, Spain 8.. Edited by Reed B. Wickner, National Institutes of Health, Bethesda, MD, and approved February 16, 2012 (received for review December 6, 2011)
 
 
 
Abstract
 
 
The ability of prions to infect some species and not others is determined by the transmission barrier. This unexplained phenomenon has led to the belief that certain species were not susceptible to transmissible spongiform encephalopathies (TSEs) and therefore represented negligible risk to human health if consumed. Using the protein misfolding cyclic amplification (PMCA) technique, we were able to overcome the species barrier in rabbits, which have been classified as TSE resistant for four decades. Rabbit brain homogenate, either unseeded or seeded in vitro with disease-related prions obtained from different species, was subjected to serial rounds of PMCA. De novo rabbit prions produced in vitro from unseeded material were tested for infectivity in rabbits, with one of three intracerebrally challenged animals succumbing to disease at 766 d and displaying all of the characteristics of a TSE, thereby demonstrating that leporids are not resistant to prion infection. Material from the brain of the clinically affected rabbit containing abnormal prion protein resulted in a 100% attack rate after its inoculation in transgenic mice overexpressing rabbit PrP. Transmissibility to rabbits (>470 d) has been confirmed in 2 of 10 rabbits after intracerebral challenge. Despite rabbits no longer being able to be classified as resistant to TSEs, an outbreak of “mad rabbit disease” is unlikely.
 
 
 
a.. in vitro replication b.. scrapie c.. transmissible spongiform encephalopathy
Footnotes
 
a.. ↵1F.C. and N.F.-B. contributed equally to this work.
 
b.. ↵2To whom correspondence should be addressed. E-mail: castilla@joaquincastilla.com a.. Author contributions: F.C., N.F.-B., S.A.P., and J.d.C. designed research; F.C., N.F.-B., E.V., L.G., B.P., J.d.C., S.A.P., S.H., S.L.E., J.F., Y.P., P.S., H.W.R., M.P.D., and J.C. performed research; F.C., N.F.-B., E.V., S.A.P., and J.C. contributed new reagents/analytic tools; F.C., N.F.-B., E.V., S.A.P., and J.C. analyzed data; and F.C., N.F.-B., S.A.P., H.W.R., M.P.D., and J.C. wrote the paper.
 
b.. The authors declare no conflict of interest.
 
c.. This article is a PNAS Direct Submission.
 
a.. This article contains supporting information online at
 
 
 
 
 

 

Wednesday, October 30, 2013

 

SPECIFIED RISK MATERIAL (SRM) CONTROL VERIFICATION TASK FSIS NOTICE 70-13 10/30/13

 


 

 

Saturday, November 2, 2013

 

APHIS Finalizes Bovine Import Regulations in Line with International Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type disease around the Globe

 


 

 

Friday, October 25, 2013

 

UK FSA TSE BSE Board meeting agenda: 5 November 2013

 


 

 

Thursday, June 6, 2013

 

FSA MORE BSE MAD COW CONTROL BREACHES JUNE 2013

 


 

 

Wednesday, September 25, 2013

 

Inspections, Compliance, Enforcement, and Criminal Investigations BSE TSE PRION 2013

 


 

 

Sunday, September 25, 2011

 

Clinical Heidenhain Variant Of Sporadic Creutzfeldt-Jakob Disease (CJD) With Co-occurrence Of Prion Protein Types 1 and 2

 


 

 

COEXISTENCE OF TSE PRION DISEASE

 

 

greetings cjd world,

 

I find this very interesting, this coesistence of different TSE prion strains from different TSE sources. this new/old study out reminds me of way back ;

 

 

According to Professor James Ironside of the National CJD Surveillance Unit, Miss Rimmer's case was "unique" and tests showed signs of both vCJD and new variant CJD.

 

"Our understanding of the case is not complete. It is one of the most unusual and difficult cases I have ever come across," he explained.

 

"The characteristics of the disease suffered by Miss Rimmer do not fall neatly into any category.

 

"The investigations that we have performed so far would indicate that this case, unique as it is, has more similarities to sporadic CJD than to new variant."

 

snip...

 

Mr Hughes returned a verdict of death by natural causes and concluded that Miss Rimmer died of bronchial pneumonia caused by CJD. ...

 


 

 

SEE ;

 


 

 

Wednesday, October 09, 2013

 

WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281 in compensation REVISED

 


 

 

Thursday, October 10, 2013

 

CJD REPORT 1994 increased risk for consumption of veal and venison and lamb

 


 

 

Monday, October 14, 2013

 

Researchers estimate one in 2,000 people in the UK carry variant CJD proteins

 


 

 

Friday, August 16, 2013

 

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

 


 

 

WHAT about the sporadic CJD TSE proteins ?

 

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

 

 

Sunday, August 11, 2013

 

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

 

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

 


 

 

Sunday, October 13, 2013

 

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

 


 

 

Tuesday, September 24, 2013

 

NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow TSE prion Contamination Suit Cethrin(R)

 

Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1 of 15

 


 

 

with great sadness and disgust, I must inform you that our federal government has failed us again, and chose the industry over sound science, with regards to TSE prion disease, aka mad cow type disease...tss

 

 

Saturday, November 2, 2013

 

APHIS Finalizes Bovine Import Regulations in Line with International Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type disease around the Globe

 


 

 

our society has failed terribly, to a point of being sick...very sick.

 

thanks to our fine friends at the CDC and there attempt at a sick Halloween prank with comparing this ever sickening movie world of the zombies, to our loved ones that did die from a prion disease, we have to now put up with crap like this zombie prion every year now. I think the CDC et al that came up with this should be fired. ...

 

 

Tuesday, October 29, 2013

 

CDC keeps eye on zombie disease

 

Dr. Christopher Ziebell, director of the Emergency Medical Department at University Medical Center Brackenridge says there are several diseases that cause patients to exhibit zombie-like behavior.

 

One is the human equivalent of mad cow disease called Creutzfeldt-Jakob disease.

 


 

 

 

kind regards, terry

 

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