Atypical BSE variant found in cattle in South Holland

[Terry S. Singeltary Sr.]

Netherlands - Bovine spongiform encephalopathy - Immediate notification
Bovine spongiform encephalopathy prion, atypical strain, L-type

wahis.woah.org/#/in-review/4876

Atypical BSE variant found in cattle in South Holland

News item | 01-02-2023 | 5:13 pm

A positive case of BSE ('Mad Cow Disease') was found this week in the cadaver of an 8-year-old cow in South Holland. Wageningen Bioveterinary Research (WBVR) has investigated which variant of BSE it concerns. The result of WBVR indicates that this is an atypical variant.

Atypical cases of BSE occur sporadically in older cows, a type of 'old-age BSE'. The last time this occurred in the Netherlands was 2011. Scientists believe that the atypical variants can arise spontaneously. So far, four atypical cases have been identified in the Netherlands.

Minister Piet Adema: It is really shocking when you hear that a cow has tested positive for BSE, because we have not had a BSE case for a long time. I am relieved that this is now the so-called 'atypical variant', which means that the consequences are mainly limited to the company in question. It is of course very bad for the livestock farmer in question. 13 cattle that are related to this cow because they are descendants or have been raised together will be taken away to be killed and tested. This case has been resolved with these measures. Food safety is not at risk. It is good to note that our monitoring system for BSE does work.

Continuation
The company of the holder of the positive case is immediately blocked. The Dutch Food and Consumer Product Safety Authority (NVWA) has carried out source and contact research in which the offspring of this cow younger than 2 years old are killed and tested. In order to perform BSE tests on brain material, the animal must first be killed.

The NVWA's source and contact investigation showed that the infected bovine had five offspring, one of which is still alive on the same farm. This bovine is less than 2 years old. This one is killed and tested. The remaining four offspring are older than two years, making it unlikely that transmission from mother to these calves could have taken place. They therefore pose no risk to public health.

All cattle born on the same farm as the infected bovine within twelve months before or after the birth of this bovine will also be killed and tested, as well as all bovines that were kept together with this infected bovine in their first year of life. and who, according to the study, received the same potentially contaminated feed during that period.

A total of 13 cattle have been tracked down and are being transported to be killed and tested. As a result, the products of these animals do not enter the food chain and therefore pose no risk to food safety. The measures will be implemented as soon as possible.

What is BSE?
BSE (Bovine Spongiform Encephalopathy (BSE)) is a fatal disease that occurs in cattle affecting the central nervous system. It is also a zoonosis that can cause the deadly brain disease variant Creutzfeldt-Jacob in humans. Infection can occur through consumption of infected cattle. There is therefore a European monitoring program in which all cadavers in certain risk groups are tested for the presence of BSE.The bovine that has now been found positive has been traced through this active surveillance.

There are two variants: the atypical variant, which is now the case, and the 'classic variant', which led to the BSE crisis in Europe in the 1980s. Reuse of animal proteins in animal feed was an important cause of the spread of classical BSE. This was followed by a ban on the use of certain types of processed animal proteins in animal feed for cattle.

Documents
Letter to parliament on final result BSE-positive cattle
Minister Adema (LNV) informs the House of Representatives about the final test result of a bovine with Bovine Spongiforme ...

Parliamentary Paper: Letter to Parliament | 01-02-2023

www.rijksoverheid.nl/binaries/rijksoverheid/documenten/kamerstukken/2023/02/01/bevestiging-uitslag-bse-positief-rund/bevestiging-uitslag-bse-positief-rund.pdf

www.rijksoverheid.nl/actueel/nieuws/2023/02/01/atypische-variant-bse-aangetroffen-bij-rund-in-zuid-holland

google language translated, so could be errors...terry

Ministerie van Landbouw, Natuur en Voedselkwaliteit

> Retouradres Pastbus 20401 2500 EK Den Haag

Directoraat-generaal Agro

De Voorzitter van de Tweede Kamer

der Staten Generaal Bezoekadres : Bezuidenhoutseweg 73 Prinses Irenestraat 6 2594 AC Den Haag

2595 BD DEN HAAG Postadres

Postbus 20401 2500 EK Den Haag

Overheidsidentificatienr 00000001858272854000

T 070 379 8911 (algemeen) F 070 378 6100 (algemeen) www. rijksoverheid.nl/Inv

, Ons kenmerk Datum 1 februari 2023 DGA-DAD / 26214888

Betreft Bevestiging uitslag BSE positief rund Geachte Voorzitter,

Zoals toegezegd in mijn brief van 1 februari 2023 informeer ik u, mede namens de minister van VWS, over de definitieve testuitslag naar aanleiding van het aantreffen van Bovine Spongiforme Encephalopathie (BSE) bij een kadaver van een achtjarige koe afkomstig van een bedrijf in Zuid-Holland.

Zoals ik in mijn vorige brief heb gemeld, heeft Wageningen Bioveterinary Research (WBVR) onderzocht welke variant van BSE het betreft. Het resultaat van WBVR geeft aan dat het hier een atypische variant betreft.

Atypische gevallen van BSE komen sporadisch voor bij oudere koeien, een soort “ouderdoms BSE”. En dat geldt ook voor deze positief geteste achtjarige koe. Wetenschappers denken dat de atypische varianten spontaan kunnen ontstaan. In Nederland zijn tot nu toe vier atypische gevallen vastgesteld van de 88 gevallen die in Nederland zijn geconstateerd sinds 1997. In de afgelopen vijf jaar zijn er in de ‘EU’ drie meldingen geweest van een atypische BSE-besmetting; in 2021 twee meldingen (Duitsland en Italié) en in 2017 één melding (Zwitserland).

In het geval van een atypische BSE worden onderstaande maatregelen genomen conform Europese regelgeving:

1. De nakomelingen <2 jaar worden gedood en getest!. Uit het bron- en contactonderzoek van de NVWA is gebleken dat het besmette rund vijf nakomelingen heeft gekregen, waarvan er nog één op hetzelfde bedrijf in leven is. Dit rund is jonger dan 2 jaar. De overige vier nakomelingen waren ouder dan twee jaar, waardoor het niet waarschijnlijk is dat overdracht van moeder op deze kalveren heeft kunnen plaatsvinden. Zij vormen een verwaarloosbaar risico voor de volksgezondheid.

2. Het geboortecohort wordt gedood en getest. Dat zijn alle runderen die op hetzelfde bedrijf als het besmette rund binnen twaalf maanden voor of na de geboorte van het besmette rund zijn geboren. In dit geval bestaat het geboortecohort uit vier runderen, waarvan drie op hetzelfde bedrijf aanwezig zijn en één rund op een ander bedrijf.

3. Het voedercohort wordt gedood en getest. Dat zijn alle runderen die in hun eerste levensjaar samen met het besmette rund in haar eerste

1 Om BSE testen te kunnen doen op hersenmateriaal moet het dier eerst gedaod worden.

Pagina 1 van 2 Directoraat-generaal Agro

Ons kenmerk

levensjaar zijn gehouden in hetzelfde bedrijf en die blijkens onderzoek in DGA-DAD/ 26214888

die periode hetzelfde potentieel besmette voeder gekregen hebben. In dit geval bestaat het voedercohort uit elf runderen. Drie van deze runderen behoren ook tot het geboortecohort.

Met het doden, testen en afvoeren voor destructie van deze 13 runderen wordt de positieve besmetting met de atypische variant afgehandeld conform Europese regelgeving. Hiermee komen de producten van deze dieren niet in de voedselketen en zijn daarmee geen risico voor de volksgezondheid. Deze maatregelen worden zo spoedig mogelijk afgehandeld door de NVWA die hierbij de regie voert. Tot die tijd blijft het betreffende bedrijf geblokkeerd.

Hieruit blijkt het belang van een goede monitor in het totaal pakket van maatregelen die genomen worden voor de preventie en bestrijding van BSE.

Piet Adema Minister van Landbouw, Natuur en Voedselkwaliteit

Pagina 2 van 2

Regarding Confirmation result BSE positive round Geachte Voorzitter,

Zoals toegezegd in mijn brief van 1 februari 2023 informer ik u, mede namens the minister of VWS, over the definitive test results when necessary encounter of Bovine Spongiform Encephalopathie (BSE) in a carcass an eight-year-old cow from a company in Zuid-Holland.

As I said in my previous brief, Wageningen Bioveterinary Research (WBVR) investigated which variant of BSE was involved. The result won WBVR indicates that this is an atypical variant.

Atypical cases of BSE occur sporadically in older cows, een soort "old age BSE". A dat also applies to this positively tested eight-year-old cow. Wetenschappers think that the atypical variant can spontaneously arise. In The Netherlands zijn tot nu toe vier atypische gävlen settet van de de 88 gävlen die in Nederland zijn geconstateerd since 1997. In the last five years zijn is in de 'EU' drie melding geweest van een atypische BSE besmetning; in 2021 twee the message (Germany and Italy) and in 2017 one message (Switzerland).

In the event of an atypical BSE, the following measures are taken according to European regulations:

1. De nakomelingen <2 jaar worden gedood en getest!. Out het the bridge contactonderzoek van de NVWA is gebleken dat het besmetste rund vijf the nakomelingen heeft gerecht, of which there is still one on the same company life is ice. Around here is younger than 2 years. The rest devote the offspring waren ouder dan twee jaar, so het niet waarschijn is dat the transfer of mother to this calf has been able to take place. Zij vormen een verwaarloosbaar risico voor de volksgezondheid.

2. The birth cohort is tested. Dat zijn alle rounderen die op the same company as the infected rund binnen twaalf maaden voor of na de geboorte van het besmeste rund zijn geboren. In dit geval bestat het birthcohort uit vier rounderen, waaran drie op semeldabe bedrijf aanwezig zijn en een round op een ander bedrijf.

3. The feeding cohort is tested. Dat zijn alle rounderen die in her first life year samen met het besmetste round in haar eerste

1 If the BSE test te kunnen doen op hersenmaterial moet het dier eerst gedaod worden.

Page 1 of 2 Directorate General Agro

Our reference

year of life have been held in the same company and according to research in DGA-DAD/ 26214888

received the same potentially contaminated feed during that period. In this case, the feed cohort consists of eleven cattle. Three of these cattle also belong to the birth cohort.

With the killing, testing and removal for destruction of these 13 cattle, the positive infection with the atypical variant handled in accordance with European regulations. This means that the products of these animals do not end up in the food chain and are therefore not a risk to public health. This one measures will be dealt with as soon as possible by the NVWA, which is hereby responsible for the directs. Until then, the company in question will remain blocked.

This shows the importance of a good monitor in the total package of measures taken for the prevention and control of BSE.

Peter Adema Minister of Agriculture, Nature and Food Quality

Page 2 of 2

www.rijksoverheid.nl/binaries/rijksoverheid/documenten/kamerstukken/2023/02/01/bevestiging-uitslag-bse-positief-rund/bevestiging-uitslag-bse-positief-rund.pdf

Ministry of Agriculture, Nature and Food Quality

Directorate-General for Agriculture

To the Minister of Agriculture, Nature and Food Quality Author PS IN DECISION

Date February 1, 2023

Feature Nn ota memorandum accompanying letter to Parliament BSE positively tested cattle |

Attachments) 1

Initial route

a mua [5 le

Cause

On Monday 30 January a bovine tested positive for Bovine Spongiforme Encephalopathy (BSE), also known as 'mad cow disease'. As in your previous letter of 1 February to the House of Representatives, Wageningen Bioveterinary Research (WBVR) investigated which variant of BSE it concerns this infected cow.

The result of WBVR indicates that this is an atypical variant.

Advised decision

To inform the House about the situation, please see the enclosed letter to Parliament sign.

Key points

e The letter informs the House of the outcome of the investigation and about the measures taken/to be taken.

Page 1 of 1

www.rijksoverheid.nl/binaries/rijksoverheid/documenten/beleidsnotas/2023/02/01/beslisnota-bij-kamerbrief-bevestiging-uitslag-bse-positief-rund/beslisnota-bij-kamerbrief-bevestiging-uitslag-bse-positief-rund.pdf

Letter to parliament on final result BSE-positive cattle
Parliamentary Paper: Letter to Parliament | 01-02-2023
www.rijksoverheid.nl/binaries/rijksoverheid/documenten/kamerstukken/2023/02/01/bse-positief-getest-rund/bse-positief-getest-rund.pdf


www.rijksoverheid.nl/actueel/nieuws/2023/02/01/atypische-variant-bse-aangetroffen-bij-rund-in-zuid-holland


www.rijksoverheid.nl/actueel/nieuws/2023/02/01/atypische-variant-bse-aangetroffen-bij-rund-in-zuid-holland


NETHERLANDS LAST REPORTS OF BSE OIE

Bovine spongiform encephalopathy Recurrence of an eradicated disease 2011/01/04 2011/01/21

wahis.woah.org/#/in-review/991

Bovine spongiform encephalopathy Recurrence of an eradicated disease 2010/10/06 2010/10/20

wahis.woah.org/#/in-review/945

Bovine spongiform encephalopathy Recurrence of an eradicated disease 2010/08/28 2010/09/09

wahis.woah.org/#/in-review/922

PLEASE NOTE, OIE ET AL HAVE NOW WARNED THAT FEEDING OF ATYPICAL STRAINS OF BSE TO CATTLE RISK TRANSMISSION OF ATYPICAL BSE...SEE;

***>The current situation does not pose a serious threat to public health, the ministry said.

atypical L type BSE

A previous study of L-BSE in transgenic mice expressing human PrP suggested an absence of any transmission barrier between cattle and humans for this particular strain of the agent of BSE, in contrast to findings for the agent of classical BSE (9). Thus, it is imperative to maintain measures that prevent the entry of tissues from cattle possibly infected with the agent of L-BSE into the food chain.

atypical H type BSE

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.

''This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. 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.''

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

Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD

Date: Thu, 28 Nov 2002 10:23:43 -0000

From: "Asante, Emmanuel A" [e-mail]

To: "'[e-mail]'" [e-mail]

Dear Terry,

I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.

Thank you for your interest in the paper.

In respect of your first question, the simple answer is, ***yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.

I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

Emmanuel Asante

<<Asante et al 2002.pdf>>

____________________________________

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: [phone] Fax: [phone] email: [e-mail] (until 9/12/02) New e-mail: [e-mail] (active from now)

____________________________________

''This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. 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.''

***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.***

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.

www.nature.com/articles/srep11573

Netherlands BSE

www.woah.org/en/disease/bovine-spongiform-encephalopathy/

www.woah.org/en/?s=&_search=BOVINE+SPONGIFORM+ENCEPHALOPATHY

PLEASE NOTE, OIE ET AL HAVE NOW WARNED THAT FEEDING OF ATYPICAL STRAINS OF BSE TO CATTLE RISK TRANSMISSION OF ATYPICAL BSE...SEE;

WOAH Members Official BSE Risk Status Map Last Updated May 2022

www.woah.org/app/uploads/2022/05/bse-world-eng.png

www.woah.org/en/disease/bovine-spongiform-encephalopathy/#ui-id-2

Conclusions on transmissibility of atypical BSE among cattle

Given that cattle have been successfully infected by the oral route, at least for L-BSE, it is reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle are exposed to contaminated feed. In addition, based on reports of atypical BSE from several countries that have not had C-BSE, it appears likely that atypical BSE would arise as a spontaneous disease in any country, albeit at a very low incidence in old cattle. In the presence of livestock industry practices that would allow it to be recycled in the cattle feed chain, it is likely that some level of exposure and transmission may occur. As a result, since atypical BSE can be reasonably considered to pose a potential background level of risk for any country with cattle, the recycling of both classical and atypical strains in the cattle and broader ruminant populations should be avoided.

see full report;

REPORT OF THE MEETING OF THE OIE AD HOC GROUP ON BOVINE SPONGIFORM ENCEPHALOPATHY RISK ASSESSMENT AND SURVEILLANCE

Paris, 18-21 March 2019

snip...

3. Atypical BSE

The Group discussed and endorsed with minor revisions an overview of relevant literature on the risk of atypical BSE being recycled in a cattle population and its zoonotic potential that had been prepared ahead of the meeting by one expert from the Group. This overview is provided as Appendix IV and its main conclusions are outlined below.

With regard to the risk of recycling of atypical BSE, recently published research confirmed that the L-type BSE prion (a type of atypical BSE prion) may be orally transmitted to calves1 . In light of this evidence, and the likelihood that atypical BSE could arise as a spontaneous disease in any country, albeit at a very low incidence, the Group was of the opinion that it would be reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle were to be exposed to contaminated feed. Therefore, the recycling of atypical strains in cattle and broader ruminant populations should be avoided.

The Group acknowledged the challenges in demonstrating the zoonotic transmission of atypical strains of BSE in natural exposure scenarios. Overall, the Group was of the opinion that, at this stage, it would be premature to reach a conclusion other than that atypical BSE poses a potential zoonotic risk that may be different between atypical strains.

snip...

In contrast, there have not been any substantiated reports of the successful oral transmission of H-BSE in cattle. Initial reports from Dudas et al., 2014 based on RT-QuIC pointed to the possibility of oral transmission following a very high dose (100 grams of brain material), although the individual did not display clinical signs and the findings from standard molecular or immunohistochemical assays were all negative. Investigations are ongoing in an attempt to clarify these findings.

Although significant uncertainty remains regarding the origin of C-BSE, several studies involving the serial passage of H-BSE and L-BSE in transgenic and wild-type mice have revealed their potential to lead to the emergence of a C-BSE-like phenotype (Baron et al., 2011; Torres et al., 2011; Bencsik et al., 2013) or other novel strains (Masujin et al., 2016). Whether or not one or both of these atypical strains led to the emergence of C-BSE remains speculative; however, the similarities between transmissible mink encephalopathy (TME), first reported in the USA in 1947 (Hartsough and Burger, 1965), and L-BSE indicate that TME may have been a surrogate indicator for the presence of L-BSE in cattle populations in those countries such as the USA, Canada, Germany, Finland and Russia where outbreaks of TME had been reported decades before C-BSE was first recognised in the United Kingdom in 1986 (Hadlow and Karstad, 1968; Marsh et al., 1991; McKenzie et al., 1996; Baron et al., 2007; Comoy et al., 2013). Although TME was originally thought to have occurred as a result of feeding mink with scrapie infected sheep carcases, oral challenge studies did not confirm this (Marsh et al., 1991). Importantly, in an outbreak reported in the USA in 1985, mink had never been fed sheep products; instead they had been fed on products derived from dead and sick dairy cattle (March et al., 1991). Similarly, from an outbreak in Canada in 1963, mink had reportedly been fed with products derived from cattle but not sheep (Hadlow and Karstad, 1968).

Although, as discussed above, the passage of H-BSE or L-BSE has been proposed as a possible explanation for the origin of C-BSE, transformation of L-BSE or H-BSE to C-BSE has not been observed so far in transmission studies in cattle. That being said, it is likely that, compared to various rodent models, an insufficient number of passages have been undertaken.

It is worth noting that sheep and goats are susceptible to L-BSE following intracerebral inoculation without lymphoid involvement in most individuals (Simmons et al., 2016; Gielbert et al., 2018; Vallino-Costassa et al., 2018). As discussed by Houston and Andreoletti (2018), C-BSE appears to increase in virulence for humans if it is first passaged in sheep. Whether or not this is the same for atypical strains remains to be determined.

Conclusions on transmissibility of atypical BSE among cattle

Given that cattle have been successfully infected by the oral route, at least for L-BSE, it is reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle are exposed to contaminated feed. In addition, based on reports of atypical BSE from several countries that have not had C-BSE, it appears likely that atypical BSE would arise as a spontaneous disease in any country, albeit at a very low incidence in old cattle. In the presence of livestock industry practices that would allow it to be recycled in the cattle feed chain, it is likely that some level of exposure and transmission may occur. As a result, since atypical BSE can be reasonably considered to pose a potential background level of risk for any country with cattle, the recycling of both classical and atypical strains in the cattle and broader ruminant populations should be avoided.

www.oie.int/fileadmin/SST/adhocreports/Bovine%20spongiform%20encephalopathy/AN/A_AhG_BSEsurv_RiskAss_Mar2019.pdf

***> Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.

***> As a result, since atypical BSE can be reasonably considered to pose a potential background level of risk for any country with cattle, the recycling of both classical and atypical strains in the cattle and broader ruminant populations should be avoided.

***> 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.

Atypical L-type BSE

Emerg Infect Dis. 2017 Feb; 23(2): 284–287. doi: 10.3201/eid2302.161416 PMCID: PMC5324790 PMID: 28098532

Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle

Hiroyuki Okada, corresponding author Yoshifumi Iwamaru, Morikazu Imamura, Kohtaro Miyazawa, Yuichi Matsuura, Kentaro Masujin, Yuichi Murayama, and Takashi Yokoyama Author information Copyright and License information Disclaimer This article has been cited by other articles in PMC. Go to: Abstract To determine oral transmissibility of the L-type bovine spongiform encephalopathy (BSE) prion, we orally inoculated 16 calves with brain homogenates of the agent. Only 1 animal, given a high dose, showed signs and died at 88 months. These results suggest low risk for oral transmission of the L-BSE agent among cattle.

Keywords: atypical bovine spongiform encephalopathy, cattle, L-type, prion, oral transmission, L-BSE, prions and related diseases, zoonoses The epidemic of bovine spongiform encephalopathy (BSE) in cattle is thought to be caused by oral infection through consumption of feed containing the BSE agent (prion). Since 2003, different neuropathologic and molecular phenotypes of BSE have been identified as causing ≈110 cases of atypical BSE worldwide, mainly in aged cattle. Although the etiology and pathogenesis of atypical BSE are not yet fully understood, atypical BSE prions possibly cause sporadic cases of BSE (1).

The L-type BSE (L-BSE) prion has been experimentally transmitted to cattle by intracerebral challenge, and the incubation period was is shorter than that for classical BSE (C-BSE) prions (2–6). The origin of transmissible mink encephalopathy in ranch-raised mink is thought to be caused by ingestion of L-BSE–infected material (7). Although L-BSE has been orally transmitted to mouse lemurs (8), it remains to be established whether L-BSE can be transmitted to cattle by oral infection. We therefore investigated the transmissibility of L-BSE by the oral route and tissue distribution of disease-associated prion protein (PrPSc) in cattle. All experiments involving animals were performed with the approval of the Animal Ethical Committee and the Animal Care and Use Committee of the National Institute of Animal Health (approval nos. 07–88 and 08–010).

snip...

The neuroanatomical PrPSc distribution pattern of orally challenged cattle differed somewhat from that described in cattle naturally and intracerebrally challenged with L-BSE (2–6,11,13,14), The conspicuous differences between the case we report and cases of natural and experimental infection are 1) higher amounts of PrPSc in the caudal medulla oblongata and the spinal cord coupled with that in the thalamus and the more rostral brainstem and 2) relatively low amounts of PrPSc in the cerebral cortices and the olfactory bulb. Furthermore, fewer PrPSc deposits in the dorsal motor nucleus of the vagus nerve may indicate that the parasympathetic retrogressive neuroinvasion pathway does not contribute to transport of the L-BSE prion from the gut to the brain, which is in contrast to the vagus-associated transport of the agent in C-BSE (15). PrPSc accumulation in the extracerebral tissues may be a result of centrifugal trafficking of the L-BSE prion from the central nervous system along somatic or autonomic nerve fibers rather than centripetal propagation of the agent (4,6,9). Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.

www.ncbi.nlm.nih.gov/pmc/articles/PMC5324790/

Our study clearly confirms, experimentally, the potential risk for interspecies oral transmission of the agent of L-BSE. In our model, this risk appears higher than that for the agent of classical BSE, which could only be transmitted to mouse lemurs after a first passage in macaques (14). We report oral transmission of the L-BSE agent in young and adult primates. Transmission by the IC route has also been reported in young macaques (6,7). A previous study of L-BSE in transgenic mice expressing human PrP suggested an absence of any transmission barrier between cattle and humans for this particular strain of the agent of BSE, in contrast to findings for the agent of classical BSE (9). Thus, it is imperative to maintain measures that prevent the entry of tissues from cattle possibly infected with the agent of L-BSE into the food chain.

www.ncbi.nlm.nih.gov/pmc/articles/PMC3310119/

Atypical H-type BSE

Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge

Author item Greenlee, Justin item MOORE, S - Orise Fellow item WEST-GREENLEE, M - Iowa State University

Submitted to: Prion

Publication Type: Abstract Only

Publication Acceptance Date: 5/14/2018

Publication Date: 5/22/2018

Citation: Greenlee, J.J., Moore, S.J., West Greenlee, M.H. 2018.

The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge.

Prion 2018, May 22-25, 2018, Santiago de Compostela, Spain. Paper No. P98, page 116. Interpretive Summary:

Technical Abstract: 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 H-type 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.

www.ars.usda.gov/research/publications/publication/?seqNo115=353094

Spatial analysis of BSE cases in the Netherlands

Lourens Heres, Dick J Brus & Thomas J Hagenaars

BMC Veterinary Research volume 4, Article number: 21 (2008) Cite this article

Abstract Background

In many of the European countries affected by Bovine Spongiform Encephalopathy (BSE), case clustering patterns have been observed. Most of these patterns have been interpreted in terms of heterogeneities in exposure of cattle to the BSE agent. Here we investigate whether spatial clustering is present in the Dutch BSE case data.

Results

We have found three spatial case clusters in the Dutch BSE epidemic. The clusters are geographically distinct and each cluster appears in a different birth cohort. When testing all birth cohorts together, only one significant cluster was detected. The fact that we found stronger spatial clustering when using a cohort-based analysis, is consistent with the evidence that most BSE infections occur in animals less than 12 or 18 months old.

Conclusion

Significant spatial case clustering is present in the Dutch BSE epidemic. The spatial clusters of BSE cases are most likely due to time-dependent heterogeneities in exposure related to feed production.

snip...

Discussion

We have found three spatial case clusters in the Dutch BSE epidemic. The clusters are geographically distinct and each cluster appears in a different birth cohort. The fact that we found stronger spatial clustering when using a cohort-based analysis, is consistent with the evidence that most BSE infections occur in animals less than 12 or 18 months old [24, 25]. As a result of the infection at a young age, temporal changes in BSE exposure are seen most clearly by comparing cohort-wise incidence levels. The fact that each of the three significant clusters in the cohort-based analysis occurs in a different birth cohort, suggests that the causes of the enhanced infection levels each occurred within a limited time frame of at most about a year.

In the Introduction we discussed the possible mechanisms that may produce clustering of BSE cases. The candidate mechanisms that could underlie the observed spatial clusters in the Netherlands are feeding practice and on-farm cross-contamination, and heterogeneities in rendering and feed processing. Local recycling is not likely as the number of rendering plants in the Netherlands was as low as two and each of these supplied nationwide to feed producers. Population heterogeneity is unlikely because in previous work [1] neither genetic differences between regions have been found nor differences in management. Population heterogeneity as a cause of spatial clustering is also unlikely in view of the limited time frame in which the causes of the clusters seem to have been present.

In the same previous work, the factor "group of feed producers" was found to be a significant risk factor in a non-temporal, non-spatial analysis of case-control data [1]. Based on this previous result we therefore interpret the observed clustering to be at least in part due to regional differences in feed production. As the information from the previous study suggested, the feed-production heterogeneities have most likely arisen due to both origin of MBM and production on mixed production lines. Feed producers were different in their sourcing of MBM and the use of mixed or dedicated production lines. Separation of production lines was not obligatory up until 1999 (Table 4), and both producers A and K have used mixed production lines up until then. Variation in feeding practice (i.e. between-farm variation in the per-animal feed uptake) is a less likely mechanism to have contributed to the clustering, as the amount of feed fed was not significantly associated with BSE in the previous study. Furthermore, a contribution due to on-farm cross-contamination as a consequence of mixed farming has not been detected. Indications against such a contribution are the fact that the 1997 cluster is in an area with small numbers of pigs and the observation that the southern part of the Netherlands with dense populations of pigs has a relatively small number of BSE cases.

Also in some other European countries where spatial clusters of BSE have been found, the most likely mechanisms were suggested to be related to exposure heterogeneity [4, 10–19, 23]. The feature of different spatial clustering occurring in different birth cohorts has also been observed elsewhere in Europe [10, 12, 14, 15]. In Switzerland, France and Great Britain it was difficult to distinguish effects due to feed processing differences from those arising from differences in feeding practices between mixed farms and farms with only ruminants, because typically feed producers with mixed production lines and mixed farms were spatially correlated. In a recent analysis of Swiss data for the period after the introduction of a ban on MBM in cattle feed, Schwermer et al. [31] found evidence of spatial association between BSE cases and feed producers where cattle feed was found MBM positive by cross-contamination. Cross-contamination in the feed-production process was also implicated in a recent study by Paul et al. [23], in which a spatial analysis of the French feed industry and BSE case data showed that BSE risk in France after a ban on MBM in ruminant feed is spatially linked to the use of MBM in non-ruminant feed.

Conclusion

We have identified three spatial case clusters in the Dutch BSE epidemic. The clusters are geographically distinct and each cluster appears in a different birth cohort. In a former study the factor "group of feed producers" was found to be a significant risk factor in a non-temporal, non-spatial analysis of case-control data [1

bmcvetres.biomedcentral.com/articles/10.1186/1746-6148-4-21

J Neurol. 2007 July; 254(7): 958–960. Published online 2007 April 21. doi: 10.1007/s00415-006-0360-3. PMCID: PMC2779429

Copyright © Steinkopff-Verlag 2007

The first case of variant Creutzfeldt-Jakob disease in the Netherlands

www.ncbi.nlm.nih.gov/pmc/articles/PMC2779429/

Eurosurveillance, Volume 11, Issue 26, 29 June 2006 Articles C van Duijn1, H Ruijs2, A Timen2

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

Citation style for this article: van Duijn C, Ruijs H, Timen A.

Second probable case of vCJD in the Netherlands.

Euro Surveill. 2006;11(26):pii=2991.

Available online: www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2991

Date of submission:

Second probable case of vCJD in the Netherlands

www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2991

TO DATE, 3 CASES OF nvCJD have been documented in the Netherlands ;

vCJD cases Worldwide (Netherlands = 3 cases nvCJD documented to date August 2010)

Country 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Alive Total

Netherlands 1 1 1 3

www.eurocjd.ed.ac.uk/surveillance%20data%204.htm

Total Cases of Sporadic CJD (Deaths)

Sporadic CJD: Definite and probable cases

Country 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Total

Netherlands 12 18 8 14 18 17 19 10 14 18 12 20 20 22 15 16 11 264

www.eurocjd.ed.ac.uk/surveillance%20data%203.htm

WOAH Members Official BSE Risk Status Map Last Updated May 2022

www.woah.org/app/uploads/2022/05/bse-world-eng.png

www.woah.org/en/disease/bovine-spongiform-encephalopathy/#ui-id-2

Subject:
Bovine spongiform encephalopathy, atypical BSE (L-type). Netherlands Information received on 21/01/2011

From:
"Terry S. Singeltary Sr." <[e-mail]>
Reply To:
Bovine Spongiform Encephalopathy <[e-mail]>
Date:
Sat, 22 Jan 2011 22:51:56 -0600
Content-Type:
multipart/alternative
Parts/Attachments:
text/plain (3105 bytes) , text/html (6 kB)

Bovine spongiform encephalopathy, Netherlands

Information received on 21/01/2011 from Dr Christianne Bruschke, Chief Veterinary Officer , Ministry of Agriculture, Nature and Food Quality, Ministry of Agriculture, Nature and Food Quality, The Hague, Netherlands

Summary

Report type Immediate notification (Final report) Start date 04/01/2011 Date of first confirmation of the event 11/01/2011 Report date 21/01/2011 Date submitted to OIE 21/01/2011 Date event resolved 11/01/2011 Reason for notification Reoccurrence of a listed disease Date of previous occurrence 15/10/2010 Manifestation of disease Clinical disease Causal agent Bovine spongiform encephalopathy agent Nature of diagnosis Laboratory (basic) This event pertains to the whole country

New outbreaksOutbreak 1 Lippenhuizen, FRIESLAND Date of start of the outbreak 04/01/2011 Outbreak status Resolved (11/01/2011) Epidemiological unit Farm Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Cattle 119 1 0 1 0

Summary of outbreaks Total outbreaks: 1 Outbreak statistics Species Apparent morbidity rate Apparent mortality rate Apparent case fatality rate Proportion susceptible animals lost* Cattle 0.84% 0.00% 0.00% 0.84%

* Removed from the susceptible population through death, destruction and/or slaughter

EpidemiologySource of the outbreak(s) or origin of infection Unknown or inconclusive

Epidemiological comments Result of a monitoring sample taken at a rendering plant. The animal was euthanized by a veterinary practitioner. There are no animals alive belonging to the birth cohort and the feed cohort and there are no animals alive belonging to the off-spring younger than 2 years. This is a case of atypical BSE (L-type).

Control measuresMeasures applied Modified stamping out No vaccination No treatment of affected animals

Measures to be applied No other measures

Diagnostic test resultsLaboratory name and type Central Veterinary Institute (CVI) (Regional Reference Laboratory) Tests and results Species Test Test date Result Cattle immunohistochemical test 11/01/2011 Positive Cattle western blotting 11/01/2011 Positive

Future ReportingThe event is resolved. No more reports will be submitted.

Map of outbreak locations

www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=10152

FRIDAY, SEPTEMBER 3, 2010
Dutch report positive test for mad cow disease

Subject: Dutch report positive test for mad cow disease

Dutch report positive test for mad cow disease

AMSTERDAM, Sept 3 Fri Sep 3, 2010 7:00am EDT

AMSTERDAM, Sept 3 (Reuters) - A 10-year-old cow in the Netherlands has tested positive for BSE, more commonly known as "mad cow" disease, the first such result in more than two years, the Dutch government said on Friday.

The government ministry responsible for food quality said the animal tested positive for the brain-wasting disease bovine spongiform encephalopathy at a slaughterhouse.

It was the first positive test for BSE in the country since May 2008, the ministry said in a statement.

A spokesman for the ministry told Reuters the cow's meat was withdrawn from the food chain after a first positive test, while a second test confirmed the result.

All cows sent to slaughter in the country are tested and held aside for the results before their meat enters the system.

Mad cow disease is of particular concern because it has been known to cause a related brain-wasting disease in humans who have eaten contaminated meat.

Three people have died in the Netherlands from Creutzfeldt-Jakob disease after eating meat from a BSE positive cow. The last reported death was in January 2009. (Reporting by Ben Berkowitz; editing by James Jukwey)

www.reuters.com/article/idUSLDE6820VK20100903


Na twee jaar weer BSE-koe aangetroffen Persbericht 03-09-2010

Er is een geval van BSE vastgesteld. Het gaat om een ruim tien jaar oude koe die op het slachthuis is getest. Dit past in de verwachting van het Centraal Veterinair Instituut in Lelystad dat Nederland in de komende jaren af en toe een besmette koe zal tegenkomen.

Het ministerie van LNV is blij dat Nederland ondanks een zeer intensief testprogramma gedurende een periode van ruim twee jaar geen enkel geval van BSE aantrof. Het laatste geval was in mei 2008. In 2009 testte Nederland 405.000 runderen op BSE.

www.minlnv.nl/portal/page?_pageid=116,1640333&_dad=portal&_schema=PORTAL&p_news_item_id=2007820


BSE For some years now the Netherlands has been taking measures to prevent BSE (Bovine Spongiforme Encephalopathy) in its cattle herd. All EU measures were implemented, though the Netherlands has also anticipated European regulation and introduced additional measures of its own.

In spite of all these efforts the Netherlands has not been free of BSE. It was first diagnosed in the Netherlands in 1997.

Measures taken by the Dutch Government Over the years a broad package of measures has been built up to combat BSE. This is partly aimed at food safety, partly at the eradication of BSE. These measures follow the recommendations of the Office International des Epizoties (OIE), and Decisions of the EU.

The measures involve:

Tracking down diseased or suspect cattle. Since 1989 it is been compulsory for owners and veterinarians to report any cattle that show symptoms of BSE to the authorities. Evaluation of the animal's health at the slaughterhouse, prior to slaughter. Compulsory removal of risk material on slaughter; This measure was introduced in the Netherlands in 1997. It has applied to all European Member States since 1 October 2000. Treatment of animal by-products used in animal feed at 133°C and 3 bar during 20 min. since the seventies. A ban on the use of animal protein in animal feed for domestic farm animals (such as cattle). Testing for BSE on all slaughtered cattle older than 30 months. Further information on the most important measures is given below.

Removal of risk material The most important measure taken to protect the consumer against BSE is the decision that so-called risk material must be removed in the slaughterhouse. The disease-causing prions do not occur in the whole animal. They are concentrated in the brains, spinal cord and some other risk material. This material is removed on slaughter and incinerated, and so eliminated from the food chain. Disease-causing organisms have never been found in meat taken from cattle muscle (steak, etc.). The removal of risk material has been compulsory since 1997.

Ban on animal protein The aim is to eliminate BSEby removing the most important source of infection (infected animal protein).

Since 1989 there has been a ban in the Netherlands on the use of remains of ruminants in ruminant feed (cattle, sheep and goats). This ban has been tightened on a number of occasions. Since 1994 no animal protein originating from mammals (previously ruminants) may be used in ruminant feed. Since 1999 the production of feed for ruminants and feed for non-ruminants containing animal protein is totally separated. This measures prevents any contamination of feed for ruminants with animal protein. Since 1 January 2001 feed containing animal protein from mammals is not only banned for ruminants, but also for all domestic farm animals, such as pigs and chickens. Compulsory BSE test From 1 January 2001 all cattle older than 30 months presented for slaughter are subjected to a rapid BSE test, approved by the European Commission. In order to carry out these tests a piece of brain tissue is removed from the cattle. If the result is positive the final diagnosis is made by traditional microscopic study of brain tissue, according to OIE.

In addition to the testing of cattle older than 30 months, risk material is removed from slaughtered cattle intended for human consumption.

www.minlnv.nl/portal/page?_pageid=116,1640387&_dad=portal&_schema=PORTAL&p_document_id=111059&p_node_id=5550285&p_mode=


www.minlnv.nl/portal/page?_pageid=116,1640440&_dad=portal&_schema=PORTAL&p_node_id=8887325


J Neurol. 2007 July; 254(7): 958–960. Published online 2007 April 21. doi: 10.1007/s00415-006-0360-3. PMCID: PMC2779429

Copyright © Steinkopff-Verlag 2007

The first case of variant Creutzfeldt-Jakob disease in the Netherlands


www.ncbi.nlm.nih.gov/pmc/articles/PMC2779429/


Eurosurveillance, Volume 11, Issue 26, 29 June 2006 Articles C van Duijn1, H Ruijs2, A Timen2

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

Citation style for this article: van Duijn C, Ruijs H, Timen A.


Second probable case of vCJD in the Netherlands.

Euro Surveill. 2006;11(26):pii=2991.

Available online: www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2991

Date of submission:

Second probable case of vCJD in the Netherlands

www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2991


TO DATE, 3 CASES OF nvCJD have been documented in the Netherlands ;

vCJD cases Worldwide (Netherlands = 3 cases nvCJD documented to date August 2010)

Country 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Alive Total

Netherlands 1 1 1 3

www.eurocjd.ed.ac.uk/surveillance%20data%204.htm


Total Cases of Sporadic CJD (Deaths)

Sporadic CJD: Definite and probable cases

Country 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Total

Netherlands 12 18 8 14 18 17 19 10 14 18 12 20 20 22 15 16 11 264

www.eurocjd.ed.ac.uk/surveillance%20data%203.htm
THURSDAY, OCTOBER 14, 2010
Netherlands reports 2nd BSE case this year 14 October 2010
Netherlands reports 2nd BSE case this year

14 October 2010

THE HAGUE (BNO NEWS) -- A 13-year-old cow in the Netherlands on Thursday was found to be infected with BSE, which is commonly known as 'mad-cow disease', according to the country's Ministry of Agriculture, Nature and Food Quality.

Thursday's case is the second case of BSE in the Netherlands since May 2008. The other case was reported on September 3 when a cow was diagnosed with BSE at a farm in Tilburg, near the border with Belgium.

The ministry on Thursday said the cow had died on a farm in country, but did not reveal where the farm was located. "We can expect to see several more BSE-cases during the next few years," the ministry said in a statement.

This is because a number of cows are still alive from before a European Union feed ban went into effect on January 1, 2001. That ban prohibits certain animal products from being fed to cows, which can lead to BSE being spread among cows.

The Netherlands tested around 405,000 cattle in 2009, while around 7.5 million cattle were tested throughout the European Union. A total of 67 BSE cases were found, all of which were outside of the Netherlands.

The ministry said there is no need to take action because cows cannot infect each other with BSE. "But, as usual, the animals who were born on the same farm around the same time as the infected animal or ate the same food will be examined, as well as their offspring."

(Copyright 2010 by BNO News B.V. All rights reserved. Info: [e-mail].)


channel6newsonline.com/2010/10/netherlands-reports-2nd-bse-case-this-year/


PLEASE SEE FULL REPORT HERE ;


www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=9852

Spatial analysis of BSE cases in the Netherlands
Lourens Heres, Dick J Brus & Thomas J Hagenaars
BMC Veterinary Research volume 4, Article number: 21 (2008) Cite this article

4572 Accesses

8 Citations

Metricsdetails




Abstract
Background
In many of the European countries affected by Bovine Spongiform Encephalopathy (BSE), case clustering patterns have been observed. Most of these patterns have been interpreted in terms of heterogeneities in exposure of cattle to the BSE agent. Here we investigate whether spatial clustering is present in the Dutch BSE case data.

Results
We have found three spatial case clusters in the Dutch BSE epidemic. The clusters are geographically distinct and each cluster appears in a different birth cohort. When testing all birth cohorts together, only one significant cluster was detected. The fact that we found stronger spatial clustering when using a cohort-based analysis, is consistent with the evidence that most BSE infections occur in animals less than 12 or 18 months old.

Conclusion
Significant spatial case clustering is present in the Dutch BSE epidemic. The spatial clusters of BSE cases are most likely due to time-dependent heterogeneities in exposure related to feed production.


snip...

Discussion

We have found three spatial case clusters in the Dutch BSE epidemic. The clusters are geographically distinct and each cluster appears in a different birth cohort. The fact that we found stronger spatial clustering when using a cohort-based analysis, is consistent with the evidence that most BSE infections occur in animals less than 12 or 18 months old [24, 25]. As a result of the infection at a young age, temporal changes in BSE exposure are seen most clearly by comparing cohort-wise incidence levels. The fact that each of the three significant clusters in the cohort-based analysis occurs in a different birth cohort, suggests that the causes of the enhanced infection levels each occurred within a limited time frame of at most about a year.

In the Introduction we discussed the possible mechanisms that may produce clustering of BSE cases. The candidate mechanisms that could underlie the observed spatial clusters in the Netherlands are feeding practice and on-farm cross-contamination, and heterogeneities in rendering and feed processing. Local recycling is not likely as the number of rendering plants in the Netherlands was as low as two and each of these supplied nationwide to feed producers. Population heterogeneity is unlikely because in previous work [1] neither genetic differences between regions have been found nor differences in management. Population heterogeneity as a cause of spatial clustering is also unlikely in view of the limited time frame in which the causes of the clusters seem to have been present.

In the same previous work, the factor "group of feed producers" was found to be a significant risk factor in a non-temporal, non-spatial analysis of case-control data [1]. Based on this previous result we therefore interpret the observed clustering to be at least in part due to regional differences in feed production. As the information from the previous study suggested, the feed-production heterogeneities have most likely arisen due to both origin of MBM and production on mixed production lines. Feed producers were different in their sourcing of MBM and the use of mixed or dedicated production lines. Separation of production lines was not obligatory up until 1999 (Table 4), and both producers A and K have used mixed production lines up until then. Variation in feeding practice (i.e. between-farm variation in the per-animal feed uptake) is a less likely mechanism to have contributed to the clustering, as the amount of feed fed was not significantly associated with BSE in the previous study. Furthermore, a contribution due to on-farm cross-contamination as a consequence of mixed farming has not been detected. Indications against such a contribution are the fact that the 1997 cluster is in an area with small numbers of pigs and the observation that the southern part of the Netherlands with dense populations of pigs has a relatively small number of BSE cases.

Also in some other European countries where spatial clusters of BSE have been found, the most likely mechanisms were suggested to be related to exposure heterogeneity [4, 10–19, 23]. The feature of different spatial clustering occurring in different birth cohorts has also been observed elsewhere in Europe [10, 12, 14, 15]. In Switzerland, France and Great Britain it was difficult to distinguish effects due to feed processing differences from those arising from differences in feeding practices between mixed farms and farms with only ruminants, because typically feed producers with mixed production lines and mixed farms were spatially correlated. In a recent analysis of Swiss data for the period after the introduction of a ban on MBM in cattle feed, Schwermer et al. [31] found evidence of spatial association between BSE cases and feed producers where cattle feed was found MBM positive by cross-contamination. Cross-contamination in the feed-production process was also implicated in a recent study by Paul et al. [23], in which a spatial analysis of the French feed industry and BSE case data showed that BSE risk in France after a ban on MBM in ruminant feed is spatially linked to the use of MBM in non-ruminant feed.

Conclusion

We have identified three spatial case clusters in the Dutch BSE epidemic. The clusters are geographically distinct and each cluster appears in a different birth cohort. In a former study the factor "group of feed producers" was found to be a significant risk factor in a non-temporal, non-spatial analysis of case-control data [1
bmcvetres.biomedcentral.com/articles/10.1186/1746-6148-4-21

***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.***

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.

www.nature.com/articles/srep11573

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.

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

PRION 2015 CONFERENCE

www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/

***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.

www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

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

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.

www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

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.

www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

Sunday, January 10, 2021

APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission June 17, 2019

APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission

Greetings APHIS et al,

I would kindly like to comment on APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], and my comments are as follows, with the latest peer review and transmission studies as references of evidence.

THE OIE/USDA BSE Minimal Risk Region MRR is nothing more than free pass to import and export the Transmissible Spongiform Encephalopathy TSE Prion disease. December 2003, when the USDA et al lost it's supposedly 'GOLD CARD' ie BSE FREE STATUS (that was based on nothing more than not looking and not finding BSE), once the USA lost it's gold card BSE Free status, the USDA OIE et al worked hard and fast to change the BSE Geographical Risk Statuses i.e. the BSE GBR's, and replaced it with the BSE MRR policy, the legal tool to trade mad cow type disease TSE Prion Globally. The USA is doing just what the UK did, when they shipped mad cow disease around the world, except with the BSE MRR policy, it's now legal.

Also, the whole concept of the BSE MRR policy is based on a false pretense, that atypical BSE is not transmissible, and that only typical c-BSE is transmissible via feed. This notion that atypical BSE TSE Prion is an old age cow disease that is not infectious is absolutely false, there is NO science to show this, and on the contrary, we now know that atypical BSE will transmit by ORAL ROUTES, but even much more concerning now, recent science has shown that Chronic Wasting Disease CWD TSE Prion in deer and elk which is rampant with no stopping is sight in the USA, and Scrapie TSE Prion in sheep and goat, will transmit to PIGS by oral routes, this is our worst nightmare, showing even more risk factors for the USA FDA PART 589 TSE PRION FEED ban.

The FDA PART 589 TSE PRION FEED ban has failed terribly bad, and is still failing, since August 1997. there is tonnage and tonnage of banned potential mad cow feed that went into commerce, and still is, with one decade, 10 YEARS, post August 1997 FDA PART 589 TSE PRION FEED ban, 2007, with 10,000,000 POUNDS, with 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. you can see all these feed ban warning letters and tonnage of mad cow feed in commerce, year after year, that is not accessible on the internet anymore like it use to be, you can see history of the FDA failure August 1997 FDA PART 589 TSE PRION FEED ban here, but remember this, we have a new outbreak of TSE Prion disease in a new livestock species, the camel, and this too is very worrisome.

WITH the OIE and the USDA et al weakening the global TSE prion surveillance, by not classifying the atypical Scrapie as TSE Prion disease, and the notion that they want to do the same thing with typical scrapie and atypical BSE, it's just not scientific.

WE MUST abolish the BSE MRR policy, go back to the BSE GBR risk assessments by country, and enhance them to include all strains of TSE Prion disease in all species. With Chronic Wasting CWD TSE Prion disease spreading in Europe, now including, Norway, Finland, Sweden, also in Korea, Canada and the USA, and the TSE Prion in Camels, the fact the the USA is feeding potentially CWD, Scrapie, BSE, typical and atypical, to other animals, and shipping both this feed and or live animals or even grains around the globe, potentially exposed or infected with the TSE Prion. this APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], under it's present definition, does NOT show the true risk of the TSE Prion in any country. as i said, it's nothing more than a legal tool to trade the TSE Prion around the globe, nothing but ink on paper.

AS long as the BSE MRR policy stays in effect, TSE Prion disease will continued to be bought and sold as food for both humans and animals around the globe, and the future ramifications from friendly fire there from, i.e. iatrogenic exposure and transmission there from from all of the above, should not be underestimated. ...

www.regulations.gov/comment/APHIS-2018-0087-0002

downloads.regulations.gov/APHIS-2018-0087-0002/attachment_1.pdf

APHIS Indemnity Regulations [Docket No. APHIS-2021-0010] RIN 0579-AE65 Singeltary Comment Submission

Comment from Singeltary Sr., Terry

Posted by the Animal and Plant Health Inspection Service on Sep 8, 2022

www.regulations.gov/comment/APHIS-2021-0010-0003

downloads.regulations.gov/APHIS-2021-0010-0003/attachment_1.pdf

usdasearch.usda.gov/search?utf8=%E2%9C%93&affiliate=usda&query=2005+bse&commit=Search

SPECIFIED RISK MATERIALS DOCKET NUMBER DOCKET NO. FSIS-2022-0027 SINGELTARY SUBMISSION ATTACHMENT

www.regulations.gov/comment/FSIS-2022-0027-0002

downloads.regulations.gov/FSIS-2022-0027-0002/attachment_1.pdf

SO, WHO'S UP FOR SOME MORE TSE PRION POKER, WHO'S ALL IN $$$

SO, ATYPICAL SCRAPIE ROUGHLY HAS 50 50 CHANCE ATYPICAL SCRAPIE IS CONTAGIOUS, AS NON-CONTAGIOUS, TAKE YOUR PICK, BUT I SAID IT LONG AGO WHEN USDA OIE ET AL MADE ATYPICAL SCRAPIE A LEGAL TRADING COMMODITY, I SAID YOUR PUTTING THE CART BEFORE THE HORSE, AND THAT'S EXACTLY WHAT THEY DID, and it's called in Texas, TEXAS TSE PRION HOLDEM POKER, WHO'S ALL IN $$$

***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.

SNIP...SEE;

THURSDAY, JULY 8, 2021

EFSA Scientific report on the analysis of the 2‐year compulsory intensified monitoring of atypical scrapie

efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2021.6686

efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2021.6686

efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2021.6686

efsaopinionbseanimalprotein.blogspot.com/2021/07/efsa-scientific-report-on-analysis-of.html

TUESDAY, MAY 31, 2022

USA Bovine Spongiform Encephalopathy BSE: description of typical and atypical cases

bovineprp.blogspot.com/2022/05/usa-bovine-spongiform-encephalopathy.html

TUESDAY, SEPTEMBER 07, 2021

Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom

bse-atypical.blogspot.com/2021/09/atypical-bovine-spongiform.html

TUESDAY, SEPTEMBER 13, 2022

BSE pathogenesis in the ileal Peyer’s patches and the central and peripheral nervous system of young cattle 8 months post oral BSE challenge

bovineprp.blogspot.com/2022/09/bse-pathogenesis-in-ileal-peyers.html

TUESDAY, SEPTEMBER 07, 2021

Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom

bse-atypical.blogspot.com/2021/09/atypical-bovine-spongiform.html

Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA

bovineprp.blogspot.com/2021/10/bovine-spongiform-encephalopathy-bse.html

WEDNESDAY, JANUARY 12, 2022

Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA, what if?

bovineprp.blogspot.com/2022/01/bovine-spongiform-encephalopathy-bse.html

PLOS ONE Journal

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;

journals.plos.org/plosone/article/comment?id=10.1371/annotation/4f9be886-69fe-4c7c-922b-85b0ecbe6d53

IBNC Tauopathy or TSE Prion disease, it appears, no one is sure

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

***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 ***

www.plosone.org/annotation/listThread.action?root=86610

MONDAY, SEPTEMBER 19, 2022

589.2001 BSE TSE regulations which prohibits the use of high-risk cattle material in feed for all animal species 2022

animalhealthreportpriontse.blogspot.com/2022/09/5892001-bse-tse-regulations-which.html

SATURDAY, SEPTEMBER 24, 2022

Transmission of CH1641 in cattle

transmissiblespongiformencephalopathy.blogspot.com/2022/09/transmission-of-ch1641-in-cattle.html

FRIDAY, APRIL 1, 2022

USDA TAKES THE C OUT OF COOL, what's up with that?

naiscoolyes.blogspot.com/2022/04/usda-takes-c-out-of-cool-whats-up-with.html

MONDAY, JUNE 6, 2022

APHIS USDA History Highlight: APHIS Combats Bovine Spongiform Encephalopathy Published Jun 1, 2022

bovineprp.blogspot.com/2022/06/aphis-usda-history-highlight-aphis.html

MONDAY, NOVEMBER 30, 2020

***> REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES Paris, 9–13 September 2019 BSE, TSE, PRION

see updated concerns with atypical BSE from feed and zoonosis...terry

animalhealthreportpriontse.blogspot.com/2020/11/report-of-meeting-of-oie-scientific.html

WEDNESDAY, DECEMBER 8, 2021

Importation of Sheep, Goats, and Certain Other Ruminants AGENCY: Animal APHIA, USDA, FINAL RULE [Docket No. APHIS–2009–0095] RIN 0579–AD10

animalhealthreportpriontse.blogspot.com/2021/12/importation-of-sheep-goats-and-certain.html

WEDNESDAY, MARCH 24, 2021

USDA Animal and Plant Health Inspection Service 2020 IMPACT REPORT BSE TSE Prion Testing and Surveillance MIA

animalhealthreportpriontse.blogspot.com/2021/03/usda-animal-and-plant-health-inspection.html

SUNDAY, MARCH 21, 2021

Investigation Results of Texas Cow That Tested Positive for Bovine Spongiform Encephalopathy (BSE) Aug. 30, 2005 Singeltary's Regiew 2021

animalhealthreportpriontse.blogspot.com/2021/03/investigation-results-of-texas-cow-that.html

THURSDAY, AUGUST 20, 2020

Why is USDA "only" BSE TSE Prion testing 25,000 samples a year?

animalhealthreportpriontse.blogspot.com/2020/08/why-is-usda-only-bse-tse-prion-testing.html

THURSDAY, JANUARY 23, 2020

USDA Consolidates Regulations for NAHLN Laboratory Testing USDA Animal and Plant Health Inspection Service

sent this bulletin at 01/23/2020 02:15 PM EST

madcowusda.blogspot.com/2020/01/usda-consolidates-regulations-for-nahln.html

WEDNESDAY, APRIL 24, 2019

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019

bse-atypical.blogspot.com/2019/04/usda-announces-atypical-bovine.html

Saturday, July 23, 2016

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html

Tuesday, July 26, 2016

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html

Monday, June 20, 2016

Specified Risk Materials SRMs BSE TSE Prion Program

specifiedriskmaterial.blogspot.com/2016/06/specified-risk-materials-srms-bse-tse.html

*** PLEASE SEE THIS URGENT UPDATE ON CWD AND FEED ANIMAL PROTEIN ***

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

www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052506.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery

SEE MAD COW FEED VIOLATIONS AFER MAD COW FEED VIOLATIONS ;

chronic-wasting-disease.blogspot.com/2016/03/docket-no-fda-2003-d-0432-formerly-03d.html

Tuesday, April 19, 2016

Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission

www.regulations.gov/#!documentDetail;D=FDA-2003-D-0432-0011

17 years post mad cow feed ban August 1997

Monday, October 26, 2015

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015

madcowusda.blogspot.com/2015/10/fda-part-589-substances-prohibited-from.html

Tuesday, December 23, 2014

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION

madcowusda.blogspot.com/2014/12/fda-part-589-substances-prohibited-from.html

16 years post mad cow feed ban August 1997 2013

Sunday, December 15, 2013

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

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

Saturday, August 29, 2009

FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009

madcowfeed.blogspot.com/2009/08/foia-request-feed-recall-2009-product.html

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

madcowfeed.blogspot.com/2009/09/foia-request-on-feed-recall-product.html

Thursday, March 19, 2009

MILLIONS AND MILLIONS OF POUNDS OF MAD COW FEED IN COMMERCE USA WITH ONGOING 12 YEARS OF DENIAL NOW, WHY IN THE WORLD DO WE TO TALK ABOUT THIS ANYMORE $$$

madcowfeed.blogspot.com/2009/03/millions-and-millions-of-pounds-of-mad.html

madcowusda.blogspot.com/2009/10/cvm-annual-report-fiscal-year-2008.html

SATURDAY, OCTOBER 8, 2022

Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation

bovineprp.blogspot.com/2022/10/cattle-with-ek211-prnp-polymorphism-are.html

MONDAY, AUGUST 29, 2022

Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies 2021 Annual Report

transmissiblespongiformencephalopathy.blogspot.com/2022/08/pathobiology-genetics-and-detection-of.html


Terry S. Singeltary Sr., Bacliff, Texas, USA, 77518 [e-mail]


WEDNESDAY, FEBRUARY 1, 2023

Atypical BSE variant found in cattle in South Holland

bovineprp.blogspot.com/2023/02/atypical-bse-variant-found-in-cattle-in.html