Friday, March 17, 2023

Are Brazilian cervids at risk of prion diseases?

Are Brazilian cervids at risk of prion diseases?


''However, in Brazil, formal attempts to detect CWD have never been performed by governmental authorities, which summed to others factors, perhaps prevented CWD detection in this country.''

Prion. 2017; 11(1): 65–70.

Published online 2017 Feb 8. doi: 10.1080/19336896.2016.1274000

PMCID: PMC5360121

PMID: 28281927

Are Brazilian cervids at risk of prion diseases?

Caio Bruno Ribeiro Falcão,a Isabel Luiza de Melo Nunes Freire Lima,a José Maurício Barbanti Duarte,b João Ricardo Mendes de Oliveira,c Rodrigo Augusto Torres,d Artur Maia Wanderley,a José Eriton Gomes da Cunha,c and José Eduardo Garciaa

Author information Article notes Copyright and License information Disclaimer

This article has been corrected. See Prion. 2017; 11(6): 471.

ABSTRACT

Prion diseases are neurodegenerative fatal disorders that affect human and non-human mammals. Chronic Wasting Disease (CWD) is a prion disease of cervids regarded as a public health problem in North America, and polymorphisms at specific codons in the PRNP gene are associated with this disease. To assess the potential CWD susceptibility of South American free-ranging deer, the presence of these polymorphisms was examined in Mazama gouazoubira, Ozotoceros bezoarticus and Blastocerus dichotomus. Despite the lack of CWD reports in Brazil, the examined codons (95, 96, 116, 132, 225, and 226) of the PRNP gene showed potential CWD susceptibility in Brazilian deer. Low abundancy of deer in Brazil possibly difficult both CWD proliferation and detection, however, CWD surveillance may not be neglected.

KEYWORDS: Blastocerus, chronic wasting disease, Mazama, neotropical deer, Ozotocerus, PrP, prion

INTRODUCTION

Prion diseases or transmissible spongiform encephalopathies (TSEs), are a group of lethal neuronal disorders presenting common characteristics. Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats and chronic wasting disease (CWD) in cervids, present the same patterns of neuronal vacuums and cell death in the central nervous system.1 The main event in prion pathogenicity is the conformational alteration from the normal PrPC form into a non-normal PrPSc. This isoform is insoluble and partially resistant to proteases. Prion diseases present only the modified isoform (PrPSc), which is converted from α-helices portions to β-sheets.2 This structural modification is accompanied by alterations in the physical-chemistry properties of PrPC.3 Studies using transgenic mice have shown that PrPSc acts as a template which transforms PrPC into new PrPSc molecules.4

Chronic wasting disease is a disorder that affects the Cervidae family, attacking either captive or wild living animals.5 Among all TSEs, CWD is the most efficiently transmitted and can reach 30% of transmissibility in wildlife. Although not entirely understood, it is supposed that transmission occurs more efficiently in a horizontal way, via direct contact with body secretions,6 excreta7 and decomposed carcasses.8 Prevalence among captive animals can reach ∼80% because those animals are kept in restricted areas (research facilities and breeding farms) where the exchange of fluids is constant.6

The development of CWD has been commonly associated with polymorphisms at the exon 3 of the PRNP gene. Susceptibility and resistance to TSEs follow genetic patterns based on different allelic forms encoded by PRNP.9 Genetic analyses have shown that susceptibility to CWD in white-tailed deer is strongly influenced by polymorphisms at codons 95 and 96.10,11 Codon 95 encodes Glutamine or Histidine while codon 96 should be Glycine or Serine. An analysis of the codon 96 showed that heterozygosity (G96S) has low frequency in CWD-positive animals, suggesting a reduction on susceptibility or slowdown in disease progress. When both codons (95 and 96) were analyzed together, heterozygosity at codon 95 (Q95H) also presented low CWD-positive frequency, irrespective of homo or heterozygosity in codon 96.12 In addition, in white-tailed deer, alleles encoding Glycine in codon 116, and alleles encoding Lysine in codon 226 have been identified as putatively CWD-resistant.13

O'Rourke et al.14 reported a new single nucleotide polymorphism in elks at the codon 132 (M132L) associated with CWD susceptibility. In the following year, the sequence of PRNP in CWD-positive and CWD-negative animals was determined to identify any correlation with CWD susceptibility. The results demonstrated that 100% (for wild animals) and 74% (for captive animals) of CWD-positive cases presented 132MM. Animals encoding M132L were not in number significant on captive animals and did not happen on CWD-positive wild living animals. No animals encoding 132LL were CWD-positive.15 The CWD susceptibility of the M132 L and 132MM genotypes was further confirmed by orally dosing with CWD-infected brain elks with the genotypes M132L, 132MM and 132LL.16

Another well established polymorphism apparently related to CWD susceptibility is found at codon 225 of the PRNP gene. Mule deer heterozygous for Serine (S) and Phenylalanine (F) (S225F) or homozygous for Phenylalanine (225FF) are poorly represented in CWD-positive cases. Conversely, the CWD-positive cases are overrepresented (30 times higher in incidence) on homozygous to Serine (225SS).17

The incidence of CWD has been reported in the United States (USA)18 and Canada19 in mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and rocky mountain elk (Cervus elaphus nelsoni). Some cases were also reported in South Korea, but the animals were imported from infected farms in Canada.20 More recently, the first European CWD infection has been reported in Norway in a free-ranging reindeer (Rangifer tarandus tarandus).21 In the USA, CWD is considered an epidemic, whereas in Brazil there are no records of this disease. However, the potential occurrence of CWD should not be overlooked because the white-tailed deer, known to be susceptible to the disease, occurs in sympatry with Mazama spp. in the Setentrional Amazon.22

The goal of this study was to examine the potential CWD susceptibility in 3 species of Neotropical deer (Mazama gouazoubira, Blastocerus dichotomus and Ozotoceros bezoarticus), based on the occurrence of polymorphisms in the PRNP gene associated with the development of CWD in North American deer. Together with O. virginianus and O. hemionus, and other new world deer, the species examined in this study form a distinct clade separate from the old-word deer.23,24

RESULTS AND DISCUSSION

Alignment analysis demonstrated that the exon 3 of the PRNP gene from the 3 studied Brazilian deer species was highly conserved, and BLASTx (see methods) showed that the amino acid sequences in these species remained very similar or even identical to that of white-tailed deer (97–100% identity). All analyzed animals were homozygous for the 4 loci, encoding Glutamine, Glycine, Methionine and Serine at codon 95, 96, 132 and 225, respectively. All these genotypes have been reported to be associated with CWD-positive cases in white-tailed deer, and other North American deer species.10-12,14,15,17 Except for one M. gouazoubira individual, which was homozygous for the putative CWD-resistant 116G allele, all sequenced animals were 116AA. The putative CWD-resistant 226K allele was not detected in the analyzed Brazilian deer. One M. gouazoubira individual, and one O. bezoarticus individual showed the 226LL and 226QQ genotypes, respectively, whereas all the other sampled individuals of the 3 species showed the 226EE genotype.13 These results suggest a potential susceptibility to CWD in Brazilian deer.22 However, no cases of CWD have been reported in Brazil. The absence of registered cases of CWD-positive animals despite the existence of susceptibility-related genotypes was also identified by Kataoka et al.25 in Cervus nippon. Therefore, the presence of the susceptibility-associated genotypes and the lack of infected animal records in Brazil are of interest because it suggests new putative threats for the conservation of these animals in the Neotropics.

A recent CWD case has been reported in a free-ranging reindeer individual in Norway - the first case ever reported in Europe - raising the question whether it was an extremely rare (perhaps isolated) case, or whether this is a subtle disease hardly detected in free-ranging animals.21 If the second scenario is correct, it possibly explains why CWD has never been detected in Brazil, despite potential genetic susceptibility to this disease in Brazilian deer.

The very similar or even identical amino acid sequences observed in the Brazilian deer species here studied, and in CWD-positive white-tailed deer individuals, but the lack of CWD reports in Brazil may suggest the importance of other genetic factors associated with CWD-susceptibility. However, in Brazil, formal attempts to detect CWD have never been performed by governmental authorities, which summed to others factors, perhaps prevented CWD detection in this country. Except for the Pantanal region, natural deer populations show extremely low densities and no deer farming exists in Brazil. Thus, the probability of detecting CWD infected animals is very low, and CWD outbreaks may be hampered given the low abundancy of most free-ranging deer in Brazil. In contrast, although deer farms are not the cause of CWD, in North America, the high density of animals in these farms have facilitated the occasional detection of novel epidemic foci or have served as harbingers of a low prevalence epidemic in free-ranging species. Although deer have been kept in small-scale captivity for research purposes in Brazil, CWD have never been diagnosed under such conditions. However, because stress or inappropriate raising conditions are high in captivity, premature mortality before CWD development - which has a long incubation period - possibly hinder positive cases.26 Furthermore, because deer hunting in Brazil is illegal, potential hunters' reports of CWD infected animals - an important source of CWD information in the US where deer hunting is legal - may have been omitted. Also, in contrast to the US, in Brazil deer are found in remote areas far from urban areas, which also reduce chances of detecting infected animals. Another possible factor contributing for the lack of CWD reports in Brazil, despite the evidence of genetic susceptibility to this disease here presented, might be the small number of trained personnel able to identify infected animals.

The potential susceptibility to CWD in Brazilian deer species here reported also raises concerns because deer provide vital protein to subsistence hunters across the Neotropics. Redford27 estimates that 14 million mammals are killed each year in the Amazonian region, highlighting the staggering extent of subsistence hunting. Although it is not known whether CWD infected animals can transmit the disease to human populations, meat consumption of potentially CWD susceptible deer species by indigenous and traditional peoples, raises an important issue in public health and deserves further investigation. Meanwhile, it is important that public health policies take into consideration the findings here presented to reduce any potential risks of CWD transmission to human populations in South America.

MATERIALS AND METHODS

Blood samples were collected with EDTA by venopunction from Mazama gouazoubira (gray brocket deer) (N = 6); Ozotoceros bezoarticus (pampas deer) (N = 15) and Blastocerus dichotomus (marsh deer) (N = 25). Sampling a greater number of deer was not possible given the low abundancy of the studied species along their distribution range, and the high costs involving their capture, which often require the support of a helicopter and a great number of personnel.

Blood samples of the captured animals were stored in ethyl alcohol until DNA isolation. Total DNA was isolated according to Medrano et al.28 DNA quantification and quality verification was done by agarose gel electrophoresis stained with GelRed (Biotium). A fragment of ∼800 bp from the exon 3 of the PRNP gene was obtained using primers CWD-13 (5′-TTTTGCAGATAAGTCATCATGGTGAAA-3′ [forward]) and CWD-LA (5′-AGAAGATAATGAAAACAGGAAGGTTGC- 3′ [reverse]) as described by Johnson et al.10 Polymerase chain reaction amplification conditions included initial denaturation at 95°C for 5 min, amplification with Taq Polymerase (LGC Biotecnologia) for 10 cycles at 95°C (45 sec), 58°C (45 sec), and 72°C (1.5 min) followed by 25 cycles at 95°C (45 sec), 57°C (45 sec), and 72°C (1.5 min), and a final extension at 72°C (5 min) according to Johnson et al.10 Successful amplifications were verified using a 1.5% agarose gel stained with GelRed. Amplified products were purified using QIAquick PCR Purification Kit (Qiagen). Sequencing of samples was conducted at Macrogen facilities (www.macrogen.com) (Korea) under BigDyeTM terminator cycling conditions on an ABI 3730 xl automatic sequencer (Applied Biosystems, USA).

Sequences (N = 46) were aligned using BioEdit version 5.0.9,29 and submitted to the algorithm ‘BLASTn’ in GenBank to confirm whether they belonged to the exon 3 of the PRNP gene. Nucleotide sequences were translated on BioeEdit and a BLASTx was performed on GenBank also intending to confirm the nature of the sequences. Polymorphisms at the PRNP gene were detected base-to-base by eye, focusing on known polymorphisms related to CWD susceptibility. The polymorphisms mostly associated to CWD occur at codons 95, 96, 132 and 225.10,11,14,17 In addition, we examined codons 116 and 226, where putative CWD-resistant polymorphisms (116G and 226K) have recently been identified.13

DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

No potential conflicts of interest were disclosed.

FUNDING

Authors are thankful to CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) (Grant 480959/2011–0), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and FACEPE (Fundação de Amparo à Ciência e Tecnologia de Pernambuco) for financial support. 

REFERENCES

snip...see;



Sadly, Like BSE, Scrapie, and CJD in humans, surveillance for these human and animal TSE prion disease are woefully lacking in Brazil, and have been for years, decades, imo. If i were a country contemplating importing from Brazil, any product capable of containing a TSE Prion disease, i would think twice, maybe three times before putting that thought into action.

remember one thing about the infamous hijacking of the BSE GBR policy, by the BSE MRR policy, which is a rubber stamp for any country to spread the TSE Prion. AS long as the BSE MRR policy is still in place, you will never eradicate BSE, TSE, Prion disease. when the Bovine Spongiform Encephalopathy Minimal Risk Region policy was put into place, was immediately after the USA lost it's BSE Gold Card i.e. BSE Free Status, right after that happened, science policies were changed, with not very good sound science, just trade wrangling science policies, i.e. junk science. the BSE MRR policy is set up to fail. ...imo.

the OIE has been nothing more than a mouth piece for the industry in the past, one that helped spread mad cow disease around the globe. it is the USDA and the OIE, and regulations there from, that helped spread mad cow disease, scrapie, and now cwd around the globe imo., and continue to do so with the BSE, atypical BSE, atypical Scapie, CWD, policies. 

BSE early days USA...

from the inside looking out ; 

Quote: ''Maybe familirise yourself with the OIE. The primary concern is animal health of the world they are the animal version of the WHO. It is a long way down from that ivory tower but here we go, until pressured by the USA representatives a country could not export animals for 6 years after finding a BSE/BASE positive animal so under the old rules the US would not be able to export anywhere in the world for another 4 1/2 years. Who got the risk levels system put in to allow some trade - your US representatives. You guys want to change rules - OK , but you do not get special rules that only apply to the US. As i have told you before Sand h I market all my own slaughter animals and you know that, so don't do the whole holier than thow act.'' 

With all due respect, it is obvious that you know little about the OIE and how it actually works. Having been to their offices in Paris and talked personally with the Head of the Animal Test Section, you would choke if you knew how many lobby groups attend that office daily. There is a steady stream of paid lobby groups that have one goal in life and that is to sway the Section Heads of each department within the OIE to suit the needs of different jurisdictions around the world, which curiously enough, also includes the USA and Canada. Anyone can go there and chat with them - providing they can provide valid cause to be let in. To say that the only goal of the OIE is animal health is actually only part of their function. They are more than that and my discussions with Dr. Diaz there has showed me that. But to blindly make a statement regarding what they do when you have no idea what they actually do is like eating the skin of the orange and not knowing what is actually under. 

Interestingly you state that the US Government applied pressure (to the OIE) I assume and that is a great example of the lobby groups doing their job. So, at the end of the day, one can safely assume that it is the pressure applied by certain influential lobby groups that will determine a likely outcome to an apparent OIE directive. Man alive, isn't it great to live in a democracy wherein the people get to make the choices and not just some "other" interested party or group - say like........Cargill or Tyson for example? 

So, one last question, question? 

Who wags the tail of that dog?? And for what reason other than one that is purely associated with trade and international agreements and greed? 

And you think it is so simply explainable. end

THE ABOVE WAS A QUOTE FROM 'BSETESTER', Ronald Arnold Our company, BSE Prion Solutions Inc, owns the only USA Tested and Proven "Live Animal Infectious Prion Protein Urine Test" anywhere in the world that can identify the presence of PrPsc in as little as 1 ml of urine taken from a living animal.

Ron Arnold, of BSE Prion Solutions bse-tester Well-known member Joined Jul 1, 2005 Messages 517 Reaction score 0 Location Edmonton, Alberta, Canada

http://ranchers.net/forum/viewtopic.php?f=5&t=22833&p=250801&hilit=familirise#p250801

updated url;


bse-tester Well-known member Joined Jul 1, 2005 Messages517 Reaction score0 Location Edmonton, Alberta, Canada Dec 20, 2007

#47

Actually QUESTION, the guy in charge is Dr. Francois Diaz. He runs the BSE Section for the OIE and has done so for many years. As far as I know, there are no extremists there but there are some in Canada apparently.

You state:

These guys have their own agenda and it has nothing to do with consumer safety or eliminating BSE.

You obviously know nothing about the OIE and what it is really all about. But it is convenient for you to simply label them as extremists with their own agenda and that is how you view the world. You talk of being sure that you keep your cattle free of BSE. How do you do that? Do you simply go over to them and one at a time, look into their eyes and make a wish?? How the hell do you know what is living inside them on a day to day basis. Last year alone in the UK there were over 200 cases of BSE/Scrapie found prior to slaughter. These animals were not generally reported in the media because the UK Government has decided to simply do discreet surveillance and take them out of the loop wherever possible but they still admit that there is a significant risk that some animals are going through the system.

Also, in the USA, I have been advised that there are a Typical (classic PrPsc) and an A-Typical brain from animals born and raised in the USA. Do you honestly think that there are no conspiracies within the Canadian, UK and US Governments that prevent us and the rest of the world from knowing the depths to which BSE goes in their respective National herds - you can bank on it!!! The folks I have met at the OIE take their jobs extremely seriously and have shown repeatedly that they are dedicated to the ellimination of BSE, Scrapie and all known TSE's. :D :D

=====

bse-tester Well-known member Joined Jul 1, 2005 Messages 517 Reaction score0 Location Edmonton, Alberta, Canada Dec 21, 2007

#83

SRM removal is a smoke screen brought about by the packer lobbys who fought to have this angle introduced and by government officials who thought it a good idea to have something to tell the public at large when their credibility was failing at the height of the BSE crisis.

SRM removal was put forward as a means to provide a so-called scientific excuse to the general public to alleviate their fear that BSE was going to be brought into the human food chain. Removing only certain tissues from an animal is a farce when one can find PrPsc throughout the entire carcass. Just think about those poor smucks who competed on that TV show "Fear Factor" and ate cattle eye-balls and raw bovine liver and guts to make a few bucks. Mmmmmmmmm, where will they be in a few decades I wonder?

So who the hell is fooling whom??? Come on Timmy, I know you are going to wail in on this one - don't bother pal, stick to what you know and not what you think you know.

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2023 MAD COW CASES

WAHIS Brazil Bovine spongiform encephalopathy Follow up report 1 [FINAL]

Brazil - Bovine spongiform encephalopathy - Follow up report 1 [FINAL]

GENERAL INFORMATION

COUNTRY/TERRITORY OR ZONE

COUNTRY/TERRITORY

ANIMAL TYPE TERRESTRIAL

DISEASE CATEGORY OIE-listed

EVENT ID 4918

DISEASE Bovine spongiform encephalopathy

CAUSAL AGENT Bovine spongiform encephalopathy prion, atypical strain, H-type

GENOTYPE / SEROTYPE / SUBTYPE -

START DATE 2023/01/18

REASON FOR NOTIFICATION Recurrence of an eradicated disease

DATE OF LAST OCCURRENCE 2021/09/03

CONFIRMATION DATE 2023/02/22

EVENT STATUS Resolved

END DATE 2023/03/03

SELF-DECLARATION NO

REPORT INFORMATION REPORT NUMBER Follow-up report 1

REPORT ID FUR_159644

REPORT REFERENCE -

REPORT DATE 2023/03/05

REPORT STATUS Validated

NO EVOLUTION REPORT -

EPIDEMIOLOGY

SOURCE OF EVENT OR ORIGIN OF INFECTION

Unknown or inconclusive

EPIDEMIOLOGICAL COMMENTS

On March 3rd, 2023, the National Centre for Animal Diseases/Canadian Food Inspection Agency (NCAD/CFIA), Lethbridge Laboratory, WOAH reference laboratory, issued a conclusive result of the Western Blotting test with atypical H-type BSE detected. This is the sixth case of atypical H-type BSE registered in Brazil in more than 25 years of surveillance for the disease. Brazil has never diagnosed a classical BSE case, maintaining, since 2012, official recognition by the WOAH as a country of negligible risk for the disease. The investigation has been completed.

QUANTITATIVE DATA SUMMARY MEASURING UNIT Animal

Species Susceptible Cases Deaths Killed and Disposed of Slaughtered/ Killed for commercial use Vaccinated

Cattle (DOMESTIC) NEW------

TOTAL160 1 0 1 0 0 DIAGNOSTIC DETAILS CLINICAL SIGNS YES

METHOD OF DIAGNOSTIC Diagnostic test

Test name Laboratory Species sampled Number of outbreaks sampled First result date Latest result date Result

Antigen detection Western blot (Ag Western blot) Canadian Food Inspection Agency (CFIA), National Centre for Animal Disease (NCAD), Lethbridge Laboratory Cattle 1 2023/03/03 2023/03/03 Positive

Immunohistochemistry (IHC) Laboratorio Federal de Defesa Agropecuária - PE Cattle 1 2023/02/22 2023/02/22 Positive

CONTROL MEASURES AT EVENT LEVEL

CONTROL MEASURES AT EVENT LEVEL

DOMESTIC ANIMALS

WILD ANIMALS

Official disposal of carcasses, by-products and waste

Applied

Screening

Applied

Selective killing and disposal

Applied

Traceability

Applied

PREVIOUSLY REPORTED OUTBREAKS

OB_114504 - 15042080057 - MARABÁ


BRAZIL BSE START DATE 2023/01/18

BRAZIL BSE CONFIRMATION DATE 2023/02/22

BRAZIL BSE END DATE 2023/03/03


SPAIN BSE START DATE 2023/01/21

SPAIN BSE CONFIRMATION DATE 2023/02/03

SPAIN BSE END DATE 2023/02/06


NETHERLANDS BSE START DATE 2023/02/01

NETHERLANDS BSE CONFIRMATION DATE 2023/02/01

NETHERLANDS BSE END DATE 2023/03/13


WAHIS, WOAH, OIE, REPORT Switzerland Bovine Spongiform Encephalopathy Atypical L-Type

Switzerland Bovine Spongiform Encephalopathy Atypical L-Type



''H-TYPE BSE AGENT IS TRANSMISSIBLE BY THE ORONASAL ROUTE''

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.


OIE 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. 


Annex 7 (contd) AHG on BSE risk assessment and surveillance/March 2019

34 Scientific Commission/September 2019

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.

4. Definitions of meat-and-bone meal (MBM) and greaves

snip...

REFERENCES

SNIP...END SEE FULL TEXT;


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


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.


Brazil MAPA OMSA Confirms BSE TSE Prion atypical H-type

OFFICIAL NOTE - Map confirms that case of Bovine Spongiform Encephalopathy is atypical type H

Ministry is immediately adopting measures so that exports of Brazilian beef are reestablished as soon as possible

Published on 03/02/2023 22:18 Updated on 03/03/2023 00:08


Brazil Confirms BSE Mad Cow Case, Strain not known yet

OFFICIAL NOTE 

Mapa adopts measures on BSE case in Brazil 

Meat for market consumption is not affected by confirmation 

Published on 02/22/2023 8:15 pm Updated on 02/22/2023 9:51 pm 


Brazil Suspected case of bovine spongiform encephalopathy

COMUNICADO

Caso suspeito de Encefalopatia Espongiforme Bovina 

para Copiar para área de transferência Publicado em 20/02/2023 15h36 

Atualizado em 20/02/2023 15h39 O


2023/01/18

EVENT 4918

Brazil - Bovine spongiform encephalopathy


BRAZIL, BSE, SCRAPIE, CJD, TSE, HISTORY

SATURDAY, SEPTEMBER 4, 2021

Brazil Confirms TWO More Cases of Mad Cow Disease BSE States of Mato Grosso and Minas Gerais

OIE REPORT Brazil BSE 2 CASES CONFIRMED



OIE

Most recent notifications

Country/Territory Disease-Serotype/genotype/subtype Date

Brazil Bovine spongiform encephalopathy 06/09/21

Brazil Bovine spongiform encephalopathy 06/09/21



BRAZIL BSE EEB TSE PRION


CASOS EEB ATÍPICA NO BRASIL

1º CASO: de corte – 13 anos Ø Sertanópolis – Paraná; animal em decúbito – negahvo para raiva; sem alterações no histopatológico Ø 15.06.2012 – diagnóshco posihvo Imunohistoquímica – LANAGRO-PE – Nota Técnica 159/2012; Ø Animal Health and Veterinary Laboratories Agency (AHVLA), Weybridge, United Kingdom – 06.12.2012 - EEB a*pica do 0po H Vaca 2º CASO: corte 12 anos – abate 19.03.14 – vigilância abate emergência – decúbito esternal – fadiga muscular - Notas Técnicas DSA 42 e 52/2014 Ø Porto Esperidião, Mato Grosso; Ø CaracterísHcas – EEB aIpica do Hpo H Ambos no(ficados para OIE. 

CASOS EEB ATÍPICA NO BRASIL

3º CASO – 2019 Vaca de corte Nelore – 17 anos Ø Vigilância abate de emergência – animal caído – coleta em 05.04.2019 Ø Nova Canaã do Norte, Mato Grosso Ø Diagnóshco posihvo ELISA – 13.05.2019 - LFDA-PE; Ø Laboratório da Agência de Inspeção de Alimentos Canadenses (CFIA) Alberta, Canada (Laboratório de Referência da OIE) – posihvo ELISA 31.05.2019 Ø CFIA – Canadá – Western Blot – EEB aIpica do Hpo H


OFFICIAL NOTE

Update on an atypical BSE case verified in Mato Grosso Share: Published 06/03/2019 5:41 PM 1- After examining the notification of the occurrence by the International Organization for Animal Health (OIE), this body determined today (3) the closure of the case without changing the Brazilian health status, which remains an insignificant risk for the disease.

2 - The OIE also informed that there will be no supplementary reports on the case.

3 - In the case of China, the Ministry of Agriculture, Livestock and Supply of Brazil has temporarily suspended the issuance of health certificates until the Chinese authority completes its assessment of the information already transmitted about the episode, thus complying with the provisions of the protocol bilateral agreement signed in 2015.


OFFICIAL NOTE

Occurrence of an atypical case of Bovine Spongiform Encephalopathy in Mato Grosso

Published on 05/31/2019 5:20 PM Updated on 05/31/2019 5:25 PM

The Agricultural Defense Secretariat of the Ministry of Agriculture, Livestock and Supply (Mapa) confirms the occurrence, in Mato Grosso, of an atypical case of Bovine Spongiform Encephalopathy ( BSE ). This disease occurs spontaneously and sporadically and is not related to the ingestion of contaminated food.

It is a beef cow, aged 17 years. All BSE- specific risk material was removed from the animal during emergency slaughter and incinerated at the slaughterhouse. Other animal-derived products were identified, located and preventively seized, with no entry of any product into the human or ruminant food chain. Therefore, there is no risk for the population.

It should be noted that the Ministry of Agriculture and the Institute of Agricultural Defense of Mato Grosso (INDEA/MT) immediately began field investigations, with a ban on the original property. All sanitary risk mitigation actions were completed even before the issuance of the final result by a reference laboratory of the World Organization for Animal Health (OIE). After confirmation, this Friday (31), Brazil officially notified the OIE and importing countries, as provided for by international standards.

According to OIE rules, there will be no change in Brazil's risk classification for the disease, which will continue as a country with an insignificant risk, the best possible for BSE . In more than 20 years of surveillance for the disease, Brazil registered only three cases of atypical BSE and no cases of classic BSE .


 INTERNATIONAL MARKET

Brazil returns to export beef to China Sales were suspended since June 3 due to notification of an unusual case of BSE in Mato Grosso Share: Published 06/13/2019 11:04 AM Updated on 06/13/2019 1:08 PM China will resume beef imports from Brazil, which had been suspended since June 3, due to the notification of an atypical case of Bovine Spongiform Encephalopathy ( BSE ), detected in Mato Grosso.

China is the only country, among Brazil's importers, that has a sanitary protocol that requires the temporary suspension of meat imports when an atypical case of BSE is detected . The minister of Agriculture, Livestock and Supply, Tereza Cristina, received the news of the reopening of the Chinese market this morning. The minister reaffirmed that she will continue negotiating a new protocol with the Chinese health authorities.

The disease was found in a 17-year-old beef cow. All BSE- specific risk material was removed from the animal during emergency slaughter and incinerated at the slaughterhouse. Other animal-derived products were identified, located and preventively seized, with no entry of any product into the human or ruminant food chain. Therefore, there was no risk for the population.


TUESDAY, SEPTEMBER 27, 2016 

Classical Scrapie Diagnosis in ARR/ARR Sheep in Brazil 

Acta Scientiae Veterinariae, 2015. 43(Suppl 1): 69.

CASE REPORT Pub. 69

ISSN 1679-9216

1

Received: 4 August 2014 Accepted: 19 December 2014 Published: 6 February 2015

1Programa de Pós-graduação em Ciências Veterinárias (PPGCV), Faculdade de Veterinária (FaVet), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. 2Setor de Patologia Veterinária (SPV), Departamento de Patologia Clínica Veterinária (DPCV), FAVET, UFRGS, Porto Alegre, RS, Brazil. 3Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde (ICBS), UFRGS, Porto Alegre, RS. CORRESPONDENCE: J.S. Leal [julianoob@gmail.com - Tel.: +55 (51) 3308 3631]. Setor de Patologia Veterinária, FAVET, UFRGS. Av. Bento Gonçalves n. 9090, Bairro Agronomia. CEP 91540-000 Porto Alegre, RS, Brazil.

 Classical Scrapie Diagnosis in ARR/ARR Sheep in Brazil

 Juliano Souza Leal1,2, Caroline Pinto de Andrade2, Gabriel Laizola Frainer Correa2, Gisele Silva Boos2, Matheus Viezzer Bianchi2, Sergio Ceroni da Silva2, Rui Fernando Felix Lopes3 & David Driemeier2

 ABSTRACT

 Background: Scrapie is a transmissible spongiform encephalopathy (TSE) that affects sheep flocks and goat herds. The transfer of animals or groups of these between sheep farms is associated with increased numbers of infected animals and with the susceptibility or the resistance to natural or classical scrapie form. Although several aspects linked to the etiology of the natural form of this infection remain unclarified, the role of an important genetic control in scrapie incidence has been proposed. Polymorphisms of the PrP gene (prion protein, or simply prion), mainly in codons 136, 154, and 171, have been associated with the risk of scrapie. Case: One animal from a group of 292 sheep was diagnosed positive for scrapie in the municipality of Valparaíso, state of São Paulo, Brazil. The group was part of a flock of 811 free-range, mixed-breed Suffolk sheep of the two genders and ages between 2 and 7 years from different Brazilian regions. Blood was collected for genotyping (for codons 136, 141, 154 and 171), and the third lid and rectal mucosa were sampled for immunohistochemistry (IHC) for scrapie, from all 292 animals of the group. IHC revealed that seven (2.4%) animals were positive for the disease. Collection of samples was repeated for 90 animals, among which the seven individuals diagnosed positive and 83 other animals that had some degree of kinship with those. These 90 sheep were sacrificed and necropsied, when samples of brain (obex), cerebellum, third eyelid, rectal mucosa, mesenteric lymph node, palatine tonsil, and spleen were collected for IHC. The results of IHC analyses carried out after necropsy of the seven positive animals submitted to the second collection of lymphoreticular tissue and of the 83 animals with some degree of kinship with them confirmed the positive diagnosis obtained in the first analysis, and revealed that three other sheep were also positive for scrapie. Samples of 80 animals (89%) were negative for the disease in all organs and tissues analyzed. In turn, 10 sheep (11%) were positive, presenting immunoreactivity in one or more tissues. Genotyping revealed the presence of four of the five alleles of the PrP gene commonly detected in sheep: ARR, ARQ, VRQ and ARH. These allele combinations formed six haplotypes: ARR/ARR, ARR/ARQ, ARH/ARH, ARQ/ARH, ARQ/ARQ and ARQ/VRQ. Animals were classified according to susceptibility to scrapie, when 8.9% of the genotyped sheep were classified into risk group R1 (more resistant, with no restriction to breeding). In turn, 40% of the animals tested ranked in groups R4 and R5 (genetically very susceptible, cannot be used for breeding purposes). Discussion: The susceptibility of sheep flocks depends on the genetic pattern of animals and is determined by the sequence of the gene that codifies protein PrP. Additionally, numerous prion strains are differentiated based on pathological and biochemical characteristics, and may affect animals differently, depending on each individual’s genotype. Most epidemiologic data published to date indicate that animals that carry the ARR/ARR genotype are less susceptible to classical scrapie. However, in the present study, the fact that two scrapie-positive sheep presented the haplotype ARR/ARR indicates that this genotype cannot always be considered an indicator of resistance to the causal agent of the classical manifestation of the disease. The coexistence in the same environment of several crossbred animals from different flocks and farms, which characterizes a new heterogeneous flock, may have promoted a favorable scenario to spread the disease, infecting animals in the most resistant group.

 Keywords: biopsy, scrapie, TSEs, immunohistochemistry.

 DISCUSSION

 The susceptibility of sheep flocks to scrapie depends largely on the genetic pattern of the animal, and is determined mainly by the sequence of the gene that codifies the PrP protein, since there are several polymorphisms that affect the conversion of the cell protein PrPC to its pathological form, PrPSc [8, 9]. Nevertheless, it is not possible to consider the occurrence of only one form of ovine prion, since there are numerous prion strains with different pathological and biochemical characteristics that may affect animals distinctively, depending on their genotypes [1, 30]. In the present study, the frequency of codon VRQ was very low (2.2%), confirming previous findings, which revealed that the alleles ARR and ARQ prevail in Suffolk sheep, and that the allele ARH sometimes is detected [12, 32]. The high sensitivity of homozygous VRQ carriers or of individuals with ARQ haplotypes has also been reported in the literature [24]. This condition raises concerns about susceptibility from the epidemiological perspective, since the allele VRQ, which is rare or absent in breeds like Suffolk, was present in two animals, one of which was positive for scrapie. Most epidemiological and genetic data published indicate that sheep carrying the haplotype ARR/ ARR are less susceptible to classical form, while animals with the haplotype VRQ in homozygosis or with ARQ haplotypes are highly susceptible [24]. This hypothesis is supported by genotyping data for thousands of sheep with the disease around the world. For example, a study carried out in Japan described a classical scrapie case in one ARR/ARR sheep [16]. Sensitivity of ARR/ARR sheep in a scenario of oral exposure to the disease has also been reported [3]. Atypical cases were observed in ARR/ARR animals [11, 42].

 Polymorphisms at codon positions 136, 154 and 171 are not the only ones associated with resistance or susceptibility to scrapie [33]. An analysis of the variation of codon positions 136 and 171, for instance, showed that each has several adjacent polymorphic sites and may codify up to four amino acids [7, 50]. The atypical scrapie form, characterized by strain Nor98 [6], is more frequently detected in AHQ animals that carry a polymorphism in codon 141, and has not been described in Suffolk sheep in Brazil [2]. This atypical form expresses phenylalanine (F), instead of leucine (L) in the form L141F [6, 37, 46].

 However, although it is generally acceptable that classical scrapie is an infectious and contagious disease [14], contagion with the atypical form is questionable in light of the fact that the specific marker for the atypical manifestation of the disease is detected outside the central nervous system [5, 20, 29], even in cases experimentally transmitted to transgenic mice [35] and sheep [47]. Several studies have demonstrated that susceptibility to the atypical form is consistently associated with PrP codons 141 (L/F) and 154 (R/H) [6, 42]. In fact, studies have proposed the hypothesis that this form may evolve when the animal is not exposed to the infectious agent [5, 18, 29, 48], given the limited knowledge of the physiopathology of this manifestation of the disease [19].

 In the present study, two (2/8) positive animals presented the haplotype ARR/ARR, which is considered to be the least susceptible and therefore responsible for the lowest risk of scrapie. However, like all sheep that were genotyped, these animals did not present any change in lysine in codon position 141. This change (that is, when lysine is replaced by phenylalanine) has been associated with atypical scrapie in Suffolk sheep [6]. Therefore, these two ARR/ARR sheep do not fit in the genotypic characteristics of sheep that may commonly present the atypical form. It is possible that the presence of several crossbred animals of different flocks and farms in the same environment, which characterizes an heterogeneous flock, has created the favorable conditions for the disease to evolve and spread, infecting the more susceptible animals.

 The variation in the frequency of the PrP genotype between flocks has been identified as a real risk factor for the disease [4]. The introduction of adult sheep free of scrapie in contaminated flocks is believed to allow lateral transmission, even between adult animals with less susceptible genotypes [40, 45], although young sheep are more predisposed [43]. Other reasons behind differences in occurrence include the stress caused during husbandry and large population numbers [26]. Additionally, the lack of a defined epidemiological pattern and the different strains of the causal agent play an important role in inter-flock variability [40]. Several models were based on the assumption that outbreak duration is influenced by flock size and by the frequency of the PrP genotype in one flock [25, 26, 38, 51]. Commercial flocks with high genetic diversity, mainly in codons other than 136, 154 and 171, are more consistently affected. In these animals, the onset of clinical manifestations occurs at significantly different ages, with means varying from 2 to 5.7 years, due to noteworthy dissimilarities in age and PrP genotype profiles [40]. The purchase of infected animals has been pointed out as the main scrapie infection mechanism in flocks [27, 41].

 *** The diagnosis of scrapie in two homozygous ARR/ARR sheep indicates that the resistance of this genotype to the classical form of the disease is debatable. Although scrapie in these animals is rare, the cases presented in this case report lend strength to the notion that its occurrence depends on a combination of infectious factors, including differences in biological and biochemical properties in the natural hosts to this prion.

 MANUFACTURERS 1VMRD Pullman Albion Road. Pullman, WA, USA. 2Qiagen. Hilden, Germany. 3InvitrogenTM. São Paulo, Brazil. 4Life TechnologiesTM. Gaithersburg, MD, USA. 5InvitrogenTM. Carlsbad, CA, USA. 6Applied Biosystems Inc. Foster City, CA, USA. Declaration of interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.




Scrapie diagnosis in a goat and four Santa Inês sheep from the same herd in Brazil

J.S. LealG.L.F. CorreaG.S. BoosM.V. BianchiF.M. BoabaidR.F.F. LopesD. Driemeier

Diagnóstico de scrapie em um caprino e quatro ovinos Santa Inês de um mesmo rebanho no Brasil

Scrapie is a fatal and progressive transmissible spongiform encephalopathy (TSE) of natural occurrence in sheep and goats. The suspicion of scrapie may be based on clinical signs; however, the detection of pathological features of the prionic protein (PrP) in target tissues is necessary to diagnose the disease. The presence of an abnormal protein form (PrPSc) in lymphoreticular and nervous tissues is an important characteristic in diagnosis. This paper reports a case of scrapie in a flock of 55 Suffolk crossbred sheep, 19 Santa Inês sheep and 21 goats in the Mato Grosso state, midwestern Brazil. The animals were euthanized after the confirmation of a scrapie case with clinical signs in a Suffolk sheep in the same farm. Samples of brainstem at the level of the obex and lymphoid issues like palatine tonsils, mesenteric lymph nodes, third eyelid fixed in formalin 10% were processed for histological examination. Histological examination with hematoxylin and eosin did not show any microscopic changes in samples. Immunohistochemistry (IHC) examination to detect anti-prion PrPSc was performed in lymphoid tissues. Scrapie diagnosis was confirmed based on IHC positive results for PrPSc in lymphoid tissues of a crossbreed goat and four Santa Inês sheep, without any clinical scrapie signs. IHC showed positive staining in at least three lymphoid germinal centers in goat mesenteric lymph node, palatine tonsil, and third eyelid samples. The mesenteric lymph node, and tonsil samples of all sheep showed positive immunostaining, and only one sheep showed positive staining in lymphoid follicles in the third eyelid. Scrapie diagnosis using IHC in fixed samples of lymphoreticular tissue is technically feasible to detect the disease in both goats and sheep, as a form of pre-clinical diagnosis. The results indicate that the herd was infected by a sheep coming from another herd where scrapie had been diagnosed before.

scrapie; prion; diseases of small ruminants; immunohistochemistry; lymphoid tissues


WEDNESDAY, JUNE 12, 2019

FINAL REPORT OF AN AUDIT CONDUCTED IN BRAZIL MAY 15 TO JUNE 2, 2017 EVALUATING THE FOOD SAFETY SYSTEMS GOVERNING MEAT PRODUCTS EXPORTED TO THE UNITED STATES OF AMERICA


TUESDAY, MARCH 26, 2019 

Joint Statement from President Donald J. Trump USA and President Jair Bolsonaro Brazil FOREIGN POLICY BSE TSE Prion aka mad cow disease


SATURDAY, JUNE 01, 2019 

Brazil reports another cases of mad cow disease atypical BSE TSE Prion 


FINAL REPORT OF AN AUDIT CONDUCTED IN BRAZIL MAY 15 TO JUNE 2, 2017 EVALUATING THE FOOD SAFETY SYSTEMS GOVERNING MEAT PRODUCTS EXPORTED TO THE UNITED STATES OF AMERICA 

FINAL REPORT OF AN AUDIT CONDUCTED IN BRAZIL

MAY 15 TO JUNE 2, 2017

EVALUATING THE FOOD SAFETY SYSTEMS GOVERNING MEAT PRODUCTS EXPORTED TO THE UNITED STATES OF AMERICA

FINAL REPORT OF AN AUDIT CONDUCTED IN BRAZIL

MAY 15 TO JUNE 2, 2017

EVALUATING THE FOOD SAFETY SYSTEMS GOVERNING MEAT PRODUCTS

EXPORTED TO THE UNITED STATES OF AMERICA

November 6, 2017

Food Safety and Inspection Service

United States Department of Agriculture 

Executive Summary

This report describes the outcome of an onsite equivalence verification audit conducted by the Food Safety and Inspection Service (FSIS) from May 15 to June 2, 2017. The purpose of the audit was to determine whether Brazil's meat inspection system remains equivalent to that of the United States, with the ability to export products that are safe, wholesome, unadulterated, and correctly labeled and packaged. At the time of this audit, Brazil was approved to export raw intact, ready-to-eat (RTE), not ready-to-eat (NRTE) processed, and thermally processed, commercially sterile (TPCS) meat.

The audit focused on six system equivalence components: (1) Government Oversight (e.g., Organization and Administration); (2) Government Statutory Authority, Food Safety, and Other Consumer Protection Regulations (e.g., Inspection System Operation, Product Standards and Labeling, and Humane Handling); (3) Government Sanitation; (4) Government Hazard Analysis and Critical Control Points (HACCP) System; (5) Government Chemical Residue Testing Programs; and (6) Government Microbiological Testing Programs. The FSIS auditors identified the following systemic findings:

Government Oversight

 The Central Competent Authority (CCA) has not developed policies and procedures to identify potential areas where conflicts of interest could arise between inspection personnel and the regulated establishments where they work;

 The CCA does not verify that regulatory information provided to supervisory official veterinarians is consistently communicated to their subordinates;

 The CCA does not verify that in-plant inspectors perform their assigned duties in a manner that is consistent with the issued instructions; and

 The CCA has not developed procedures to standardize the assessment of competence and performance of in-plant inspection personnel assigned to United States-certified establishments. Government Statutory Authority and Food Safety and Other Consumer Protection Regulations

 The implemented post-mortem inspection procedures are inadequate to ensure that only wholesome carcasses, free of contamination and defects receive the mark of inspection;

 Brazilian TPCS product reinspected at United States point-of-entry demonstrates a trend of abnormal container violations; and

 Higher-level officials did not adequately review and follow-up on periodic supervisory reports and plans of action.

Government Sanitation

 Inspection personnel do not adequately enforce sanitation regulatory requirements to prevent the creation of insanitary conditions and direct product contamination.

Government HACCP System

 Inspection personnel do not accurately assess the design and implementation of the establishments HACCP systems, and do not conduct adequate verification sampling of products. Government Chemical Residue Testing

 The official methods of chemical analysis used by the government laboratories is inconsistent with FSIS requirements; and

 The CCA has not instructed establishments and in-plant inspectors to hold livestock carcasses selected for residue sampling until acceptable results are received.

During the audit exit meeting, the CCA committed to address the preliminary findings as presented. FSIS received a written response from the CCA addressing all outstanding concerns identified in the draft final audit report. FSIS will evaluate the adequacy of the proposed corrective actions and base its activities for future equivalence verification on the information provided. 

snip...see full text;


Post forecasts beef production in 2019 at 10.2 million metric tons, which is an increase of 3 percent. The increase is driven by solid exports, mostly to China and Hong Kong and moderate domestic demand. Posts also forecasts pork production to increase by over 3 percent and reach nearly 3.8 million metric tons, reflecting a rebound in exports, moderate domestic demand and favorable feed costs in 2019. The expected growth of the Brazilian economy in 2019, with declining inflation and unemployment rates support optimism in the animal protein sector in Brazil. Major uncertainties in the near future include the volatility of the exchange rate, end of the year elections and a new federal administration in 2019. 



USDA Halts Beef Imports from Brazil Drovers

June 22, 2017 04:59 PM

Imports of fresh beef from Brazil are being halted into the U.S. The announcement was made by Secretary of Agriculture Sonny Perdue after inspections by USDA-Food Safety and Inspection Service (FSIS) revealed concerns over safety issues.

"Ensuring the safety of our nation’s food supply is one of our critical missions, and it’s one we undertake with great seriousness," Perdue says.

Brazil’s Ministry of Agriculture self-suspended the shipment of beef from five packing plants after U.S. officials found "irregularities" in the processed carcasses this past week. However, the move by Perdue and USDA will supersede the self-suspension.

A statement from the Brazilian Association of Beef Industry Exports says the self-suspension happened "after the detection of [bovine] reactions to the vaccine for foot-and-mouth disease, that in some cases can provoke internal, and not externally visible abscesses."

The voluntary halt by Brazil appeared to be temporary while the vaccine manufacture attempted to find a solution for the abscesses. Now it could be much longer before fresh Brazilian beef enters the U.S.

"Once again the industry is inheriting a problem that it has not created," says Antonio Camardelli, president of the board of the Brazilian Association of Meat Exporters.

The Ministry of Agriculture was alerted by USDA-FSIS on June 16 and exports were stopped immediately from those plants impacted. State locations and ownership of the packing facilities include:

Owner JBS Location Mato Grosso do Sul 

Owner Minerva Location Goias 

Owner Marfrig Locations Sao Paulo Mato Grosso Rio Grande do Sul The U.S. just began exporting fresh beef from Brazil last year after a trade agreement was reached on Aug. 1. Prior to this trade deal, Brazil had not had access into the U.S. since 2003 because of foot-and-mouth disease outbreaks. Similarly, U.S. beef had not been in Brazil since 2003 when bovine spongiform encephalopathy was found.

"Although international trade is an important part of what we do at USDA, and Brazil has long been one of our partners, my first priority is to protect American consumers," Perdue says. "That’s what we’ve done by halting the import of Brazilian fresh beef. I commend the work of USDA’s Food Safety and Inspection Service for painstakingly safeguarding the food we serve our families."

There were 31 packing plants in Brazil approved to export into the U.S. prior to this suspension.

Brazil’s meat packing industry has seen a number of setbacks in the past few months after the discovery of a widespread bribery scandal. Aftershocks from the corruption scandal have included:

The stoppage of exports into a number of countries JBS owners stepping down from the board The selloff of several other JBS packing plants in South America More selloffs of different JBS businesses like Five Rivers Cattle Feeding in the U.S. In March, USDA FSIS began inspecting all meat product coming from Brazil. During that time FSIS has rejected 11% of Brazilian fresh beef imports. It adds up to 1.9 million pounds of beef from 106 lots that were rejected because of public health concerns, sanitary conditions and animal health issues. 

National Cattlemen’s Beef Association (NCBA) is in support of the decision to suspend fresh beef imports from Brazil.

"This action is the result of USDA’s strong, science-based testing protocol of imported beef and this proves that our food safety system works effectively. NCBA supports USDA’s commitment to science-based trade and its commitment to keeping our food supply as safe as possible," says Craig Uden, NCBA president.

There is no timeline for when Brazil will be eligible to again export beef to the U.S. market. 


Minvera to export beef to US

09.15.2016

By Erica Shaffer SAO PAULO, Brazil – Two meat processing facilities owned by Minerva SA have been cleared to export fresh beef to the United States.

The company’s facilities in Palmeiras de Goias and Barretos have processing capacities of 2,000 head of cattle per day and 840 head of cattle per day, respectively. In a notice to shareholders, the company explained that, “The US import system is based on specific quotas depending on the country or group of countries, and Brazil has not yet been assigned a quota. Therefore, the country will initially be included under the ‘Other’ quota (with a total equivalent to 64,800 ton/year), where countries such as Chile, Costa Rica, El Salvador, Honduras, Nicaragua and the Dominican Republic, together, are also able to export to USA.”

In August, USDA announced that Brazil had reopened its markets to US beef exports. Brazil had banned imports of US beef and beef products in 2003 after the discovery of a confirmed case of bovine spongiform encephalopathy (BSE). Brazil had its own brush with atypical BSE in 2012. Animals classified as having atypical BSE may or may not get BSE.

Minerva operates 17 slaughtering and boning plants — 11 in Brazil, three in Paraguay, two in Uruguay and one in Colombia. Slaughtering capacity is 17,330 head of cattle per day, and boning capacity is 20,300 head per day, according to the company’s website. Minerva also operates 13 distribution centers.



Brazil Kept Mad Cow Secret for Two Years

By Dan Flynn on December 10, 2012

Enough beef to feed one million Americans for a year has been imported from Brazil without the bovine spongiform encephalopathy (BSE) mitigations that are supposed to be applied to countries where BSE is known to exist. 

That’s because for the past two years, USDA was operating under the assumption that Brazil had not experienced any BSE, or Mad Cow disease as it’s commonly known. 

But Brazil–the world’s biggest beef exporting country–was keeping a secret for the past two years. 

A secret that if known might well have seen its beef banned from the U.S., or at the very least, subjected its beef to BSE controls. 

That’s because while the U.S. was importing 67 million pounds of beef from Brazil, South America’s biggest country was keeping a Mad Cow secret. But it’s not a secret anymore. 

Here’s what we know so far: 

Brazil on Dec. 6 became the 26th country in the world to report an incident of BSE, or the always-fatal Mad Cow disease that can be transmitted to humans. 

The designation stems from a 13-year-old cow that died two years ago in December 2010 in Brazil that was suffering with at least proteins common to bovine spongiform encephalopathy (BSE), but Mad Cow disease might not have killed it. 

Details finally began to emerge when Brazil filed a notification to the World Organization for Animal Health (OIE), reporting that a 13-year- old cow died in December 2010 in Parana and BSE was suspected. 

The notification said the dead cow was subjected to a histopathological test, one of two primary tests for BSE. 

It was reportedly negative. 

A second test, not conducted until June 15, 2012 at the National Reference Laboratory in Recife, was positive. 

The beef exporting Brazil claims the long delays were due to work overloads at the lab and OIE rules that cause it to give the test a low priority. 

After the positive test, Brazil also sent a brain sample to the OIE reference lab in the United Kingdom, where a second positive test for Mad Cow was conducted. 

OIE has not issued its own report. 

Countries reporting BSE cases often pay a price in having their beef banned from world markets. 

That’s what happened to the U.S. in 2003 when its first BSE case was discovered in Washington state. 

Countries around the world banned U.S. beef sales. 

Although Japan announced it was banning beef from Brazil beginning on Saturday, it is unclear how other countries are going to react, including the U.S. 

Japan is apparently not buying a second report put out by Brazil’s Agricultural Minister that the dead cow did not have BSE, but just the protein believed to cause the disease. 

BSE is a prion disease that involves folded proteins. 

The Ag minister’s story is the dead cow was experiencing a spontaneous genetic mutation that was unlikely to evolve into BSE. 

Brazil could not confirm the exact cause of death for the grass-fed cow. 

It had collapsed and died 24 hours later. 

“The two year delay in Brazil’s disease notification is a symptom of the failure of the OIE’s global system that erroneously assumes foreign countries, particularly developing countries, have the same means, commitment and capabilities as the United States to control and eradicate diseases, says Max Thornsberry, who chairs R-CALF USA’s Animal Health Committee. 

Thornsberry said USDA’s reliance on foreign countries and OIE to protect U.S. citizens from unsafe imports is “absolutely foolish” and again points up the need for country-of-origin labeling. 

USDA cutbacks in on-site review of the foreign regulatory systems that are supposed to inspect meat exported to the U.S. were reported earlier by Food Safety News. 

R-CALF USA stands for the Ranchers-Cattlemen Action Legal Fund, United Stockgrowers of America. The organization is based in Billings, MT. The only trade- rrelated beef announcement out of USDA since Dec. 6 involved Canada. The XL Foods plant at Brooks, Alberta was permitted to export beef to the U.S. for the first time since the facility’s E. coli crisis.

Tags: Brazil, BSE, Japan, mad cow disease


FRIDAY, NOVEMBER 03, 2017 

First case of V180I rare mutation in a Brazilian patient with Creutzfeldt-Jakob disease


TUESDAY, SEPTEMBER 27, 2016 

Classical Scrapie Diagnosis in ARR/ARR Sheep in Brazil 

Acta Scientiae Veterinariae, 2015. 43(Suppl 1): 69. 


MONDAY, AUGUST 1, 2016 

USDA Announces Reopening of Brazilian Market to U.S. Beef Exports and the Potential for Transmissible Spongiform Encephalopathy TSE prion disease


MONDAY, MAY 5, 2014 

Brazil BSE Mad Cow disease confirmed OIE 02/05/2014


Monday, May 5, 2014 

Brazil 2nd BSE Mad Cow disease confirmed OIE 02/05/2014 


Thursday, April 24, 2014 

Brazil investigates possible BSE mad cow case 


WEDNESDAY, JANUARY 29, 2014

Another Suspect case of Creutzfeldt-Jakob disease investigated in Brazil


THURSDAY, SEPTEMBER 26, 2013 

Brazil evaluate the implementation of health rules on animal by-products and derived products SRM BSE TSE PRION aka MAD COW DISEASE


Wednesday, December 19, 2012 

Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of Brazil 


***> Friday, December 07, 2012 

***> ATYPICAL BSE BRAZIL 2010 FINALLY CONFIRMED OIE 2012 


TUESDAY, SEPTEMBER 27, 2016 

Classical Scrapie Diagnosis in ARR/ARR Sheep in Brazil 

Acta Scientiae Veterinariae, 2015. 43(Suppl 1): 69. 


Boletim Epidemiológico Vol.53 Nº39

24/10/2022 -
 Monitoramento dos casos de arboviroses até a semana epidemiológica 41 de 2022; Perfil epidemiológico de casos da doença de Creutzfeldt-Jakob (DCJ) no Brasil, 2005 a 2021; e Informes gerais.


Dement Neuropsychol. 2007 Oct-Dec; 1(4): 347–355.

doi: 10.1590/S1980-57642008DN10400004

PMCID: PMC5619428

PMID: 29213410

Language: English | Portuguese

Prion diseases are undercompulsory notification in Brazil: Surveillance of cases evaluated by biochemicaland/or genetic markers from 2005 to 2007

Vilma Regina Martins,1 Hélio Rodrigues Gomes,2 Leila Chimelli,3 Sergio Rosemberg,4 and Michele Christine Landemberger1

Author information Article notes Copyright and License information Disclaimer

Abstract

The emergence of the new variant of Creutzfeldt-Jakob disease (vCJD) in the United Kingdom has raised concerns over the risks of this prion disease in other parts of the world. Since 2005, human prion diseases have been under compulsory notification in Brazil. It is well known that some polymorphisms within the cellular prion gene (PRNP) have been associated to a higher susceptibility to sporadic CJD (sCJD) and vCJD.

Objectives

To describe the first notified cases and to evaluate the presence of mutations and polymorphisms of the PRNP in these cases.

Methods

Thirty-five notified cases were evaluated by clinical, auxiliary exams and biochemical and/or genetic tests and classified according to the World Health Organization criteria for CJD. A control group (N=202) was included for the purpose of comparing the genetic analyses.

Results

Twenty seven cases (74%) were classified as possible sCJD while 51% fulfilled the criteria for probable sCJD. Brain tissue analysis was available in three cases, where two were classified as definite sCJD and one as unconfirmed sCJD. Mutation of the PRNP was not found, and regarding the codon 129 polymorphism, valine in both alleles (Val129Val) was more frequent in patients than in the control group (OR=4.98; 1.55-15.96; p=0.007) when all possible cases were included, but not when only probable cases were considered.

Conclusions

Our data did not show correlation of PRNP polymorphisms with probable sCJD cases. It is necessary to work toward notification of all cases of possible CJD in Brazil and to increase the rate of definitive diagnoses.

Keywords: prion, prion diseases, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, genetic polymorphism


Dementia & Neuropsychologia 2007;1(4):339-346

Gattás VL, et al. Surveillance of prion diseases 339

New variant of Creutzfeldt-Jakob (vCJD) disease and other human prion diseases under epidemiological surveillance in Brazil

Vera Lúcia Gattás1 , Antonio Silva Lima Neto2 , George Santiago Dimech3 , Denise Mancini4 , Ligia Maria Cantarino5 , José Ricardo Pio Marins6 , Expedito José Albuquerque Luna7


Risk.25: Genetic Analysis of Human Prion Diseases in Brazil from 2005 to 2011

Michele C. Landemberger,1,† Cleiton F. Machado,1 Helio R. Gomes,2 Leila Chimelli,3 Sergio Rosemberg,2 Ricardo Nitrini2 and Vilma R. Martins1 1 International Center for Research and Education Hospital A.C Camargo; Sao Paulo, SP Brazil; 2 Faculdade de Medicina da Universidade de São Paulo; Sao Paulo, SP Brazil; 3 Faculdade de Medicina da Universidade Federal do Rio de Janeiro; Rio de Janeiro, RJ Brazil † Presenting author; Email: mlandemberger@yahoo.com

Global surveillance of vCJD and other forms of CJD was recommended from the WHO for a better understanding of potential causes of iatrogenic CJD, as well as the distribution of various hereditary forms. 

Prion diseases have been under compulsory notification in Brazil since 2005. 

From August 2005 to February 2011, we received 141 blood samples from notified cases of suspected CJD. 

Among these, twenty five cases (18%) did not fulfill clinical criteria for notification or the notification form was not complete. 

Blood samples were analyzed by direct genomic sequencing to identify mutations and polymorphisms in the PRNP gene. 

Cases with mutation in direct sequencing were cloned to confirm results. 

The presence of 14.3.3 protein in Cerebrospinal Fluid (CSF) was evaluated using immunoblotting and brain tissue obtained by autopsy or biopsy was analyzed by imunohistochemistry for the presence of spongiosis and proteinase K resistant PrP. 

The average age of the 117 remaining patients was 58.8 years with a median of 61 years (range 13-82 years), males representing 52% of the cases. 

PRNP polymorphisms analysis showed that 59% of the cases were homozygous for methionine at codon 129 (M129M), 26% were heterozygous (M129V) and 15% were homozygous for valine (V129V). 

The silent polymorphism at codon 117 was detected in 10% of the patients and 4% had deletion at the octarepeat. 

E200K mutation at PRNP was found in four unrelated patients and all of them presented methionine at codon 129 in the mutated allele. 

Brain tissue of 19 patients was available (16%); 16 of them had spongiosis and were positive for proteinase K resistant PrP. After clinical evaluation, imaging exams, 14.3.3 protein presence, genetic and immunohistochemical analysis, notified cases were classified according to the WHO criteria. 

Thus, 16 cases (14%) were classified as definite sCJD, four cases (3%) as genetic CJD, 38 cases (32%) were classified as possible sCJD and 42 (36%) as probable sCJD. Fourteen cases (12%) remained suspected sCJD and three cases could not be confirmed as sCJD. 

From the 16 cases with definite sCJD, 75% were M129M, 19% M129V and 6% V129V. 

This study provides the first epidemiologic data about human prion diseases in Brazil. Similar to any other country the availability of brain tissue from these patients is a limiting factor to confirm the diagnosis of prion diseases. 

This study also represents an important tool for prion-prevention policies and is of great importance for future implementation of clinical trials.


Boletim Epidemiológico | Secretaria de Vigilância em Saúde | Ministério da Saúde 12 Volume 53 | N.º 39 | Out. 2022

Perfil epidemiológico de casos da doença de Creutzfeldt-Jakob (DCJ) no Brasil, 2005 a 2021

Coordenação-Geral de Vigilância de Zoonoses e Doenças de Transmissão Vetorial do Departamento de Imunização e Doenças Transmissíveis da Secretaria de Vigilância em Saúde (CGZV/Deidt/SVS)*.

Introdução

A Doença de Creutzfeldt-Jakob (DCJ) é uma doença priônica humana que além de rara é rapidamente progressiva e fatal. A doença que foi descrita pela primeira vez em 1920 por Hans Gerhard Creutzfeldt e Alfons Jakob na Alemanha é uma Encefalopatia Espongiforme Transmissível Humana (EETH) que provoca um conjunto de alterações neuropatológicas cuja causa está ligada com a existência e disseminação anormal de uma proteína priônica patogênica denominada (PrPsc).1-3

A DCJ é considerada uma doença cosmopolita que é responsável anualmente por uma a duas mortes por cada milhão de habitantes. Além disso, 90% dos indivíduos acometidos evoluem para óbito entre seis meses e um ano após o início dos sinais e sintomas, sendo a média de sobrevida de cinco meses.1-4

Além da DCJ, outras EETHs afetam os humanos, como a doença de Gerstmann-Sträussler-Scheinker (GSS), a Insônia Familiar Fatal (IFF) e o Kuru. Contudo, a degeneração progressiva das habilidades psicomotoras dos indivíduos acometidos pela DCJ é bem mais acelerada quando comparada com outras demências.4-6

A faixa etária de maior incidência para a DCJ é entre 55 e 70 anos, com média de 65 anos. Apresentando sintomatologia variada e inespecífica, as manifestações clínicas são semelhantes com outras classes de demências e transtornos neurológicos progressivos como Alzheimer ou a doença de Huntington. Destacam-se sinais e sintomas como dor de cabeça, fadiga, sono, falta de apetite, desordem cerebral, perda de memória, tremores, falta de coordenação motora, distúrbios de linguagem e perda visual. Já com a progressão do quadro, pode ocorrer insônia, depressão, ataques epiléticos, paralisia facial, dentre outros.1,3,6

Entre as formas de apresentação clínica existentes, a DCJ esporádica é a mais comum, porém, não há causa ou fonte infecciosa conhecida, assim como, não há registros de transmissão de pessoa a pessoa. Representando cerca de 85% dos casos confirmados por DCJ, mundialmente, apresenta uma discreta maior incidência entre pessoas do sexo feminino.1,4

A DCJ também pode se apresentar na forma clínica hereditária, decorrente de uma mutação no gene (PRNP) que codifica a produção da proteína priônica, representando entre 10% a 15% dos casos totais. Ou ainda na forma iatrogênica, que pode ser adquirida através de procedimentos cirúrgicos ou na utilização de instrumentos neurocirúrgicos contaminados. Essa forma da doença compreende 1% dos casos já relatados em todo o mundo.1-3 Para a investigação de casos é importante a realização de exames como a detecção da proteína 14-3-3 do líquido cefalorraquidiano, ressonância magnética e tomografia computadorizada, além do eletroencefalograma que pode mostrar alterações típicas de estágios avançados da doença.7-10

Segundo a Organização Mundial da Saúde (OMS), a definição de um caso suspeito de DCJ é realizado com base na avaliação de sinais e sintomas, exames laboratoriais e de imagem e história epidemiológica do paciente. Conforme recomendado pelo Centro de Controle e Prevenção de Doenças dos Estados Unidos (CDC/EUA), pelo Centro Europeu de Prevenção e Controle de Doenças (ECDC), pela OMS e indicado no Protocolo de Notificação e Investigação da Doença de Creutzfeldt-Jakob do Ministério da Saúde, a confirmação de casos requer a realização de testes neuropatológicos e/ou imunocitoquímicos para identificação da proteína do príon patogênico (PrPsc) e/ou presença de fibrilas positivas para PrPsc. No entanto, por se tratar de um procedimento muito invasivo e arriscado que requer a abertura do crânio é indicado apenas em situação post mortem.7-13

Além disso, atualmente, há a possibilidade de realização do exame de Real-Time Quaking-Induced Conversion (RT-QuIC) do líquido cefalorraquidiano para a classificação de casos suspeitos da doença. A técnica apresenta alto grau de sensibilidade (entre 69% e 93%) e especificidade (99% a 100%).7-10

Embora tenham sido estudadas diversas alternativas terapêuticas, nenhuma se mostrou efetiva para a reversão da evolução fatal da doença. Por tanto, ainda não há tratamento para nenhuma das formas da DCJ, sendo apenas recomendadas estratégias de manejo de suporte e controle das complicações.4,5

No Brasil, a DCJ passou a integrar a lista de doenças de notificação compulsória em 2005. Apesar de não ser uma zoonose, sua vigilância, em nível federal, é desenvolvida pelo Grupo Técnico de Saúde Única da Coordenação-Geral de Vigilância de Zoonoses e Doenças de Transmissão Vetorial do Departamento de Imunização e Doenças Transmissíveis (CGZV/Deidt) da Secretaria de Vigilância em Saúde (SVS), do Ministério da Saúde (MS), que busca promover a articulação intersetorial, interdisciplinar e interinstitucional nas ações de vigilância, prevenção e controle, para detecção precoce de casos da DCJ e identificação de possíveis casos da vDCJ.1-5,8,13-15

Variante da Doença de Creutzfeldt- -Jakob (vDCJ) No ano 1996 foram caracterizados os primeiros casos da Variante da Doença de Creutzfeldt-Jakob (vDCJ). Trata- -se de uma Encefalopatia Espongiforme Transmissível Humana (EETH) que está associada principalmente ao consumo de carne e subprodutos de bovinos contaminados com Encefalopatia Espongiforme Bovina (EEB) clássica, conhecida como “Doença da Vaca Louca”.13,14,16

A vDCJ é uma doença zoonótica considerada muito rara, não endêmica em nenhum país do mundo, sendo que o último caso registrado no Reino Unido aconteceu em 2016. Esta doença afeta predominantemente jovens e adultos, entre 16 e 48 anos e apresenta maior incidência em indivíduos com idade média de 29 anos.14,16,17

Conforme o Centro de Controle e Prevenção de Doenças dos Estados Unidos (CDC/EUA) a duração mediana da doença é de treze a quatorze meses após o início dos sinais e sintomas, caracterizados inicialmente por sintomas psiquiátricos proeminentes, sensoriais e comportamentais.8,13

No Brasil, desde que foi instituída a obrigatoriedade de notificação da doença em 2005, nunca houve registro de caso da vDCJ. Em mais de 20 anos de vigilância instaurada para a detecção da EEB clássica em bovinos de produção, causadora da vDCJ em humanos, jamais foram encontrados casos no país. Questão que reforça a inexistência de casos ou óbitos pela vDCJ na população humana. Neste sentido, desde 2012, o Brasil possui o reconhecimento da World Organisation for Animal Health (WOAH), como país de risco insignificante para a EEB.10,15,18,19

Justificativa

Com base no cenário apresentado, entende-se que compreender o perfil epidemiológico da DCJ pode ser um recurso potencializador para o fortalecimento da vigilância, pois, pode possibilitar a construção de informações mais fidedignas e úteis para o planejamento estratégico e o direcionamento das políticas públicas para o monitoramento e definição de medidas de prevenção e biossegurança para a orientação de condutas relacionadas ao manejo da DCJ no Brasil.

Métodos

Trata-se de um estudo observacional descritivo realizado com o uso de dados secundários provenientes das notificações de casos suspeitos de DCJ no Sistema de Informação de Agravos de Notificação (Sinan), no período de janeiro de 2005, ano em que a doença passou a integrar a lista de doenças de notificação compulsória no Brasil, a dezembro de 2021. A análise dos dados foi realizada com a utilização do programa Microsoft Excel® para tabulação e análise descritiva, e do programa QGis versão 3.22.9, para construção dos mapas utilizando base cartográfica, em formato shapefile, no sistema de projeção geográfica do Brasil disponibilizado pelo Instituto Brasileiro de Geografia e Estatística (IBGE).20

Foram realizadas a triagem e tratamento do banco de dados, excluindo as duplicidades a partir das variáveis: nome do paciente, data de nascimento, nome da mãe, data dos primeiros sintomas e data da classificação final. Também foram excluídas as notificações em que não havia o preenchimento de data de início de sintomas ou cujo registro foi realizado com data posterior às datas de nascimento ou óbito.

snip...

Resultados

Como resultado da triagem e tratamento dos dados foram excluídos 1,9% (30) dos registros de notificação por ausência de preenchimento da variável “data de início de sintomas” e por ocorrência de “duplicidades”, na Figura 1, é representado o método de triagem do banco de dados.

No período de 2005 a 2021 foram registradas no Brasil 1.576 notificações de casos suspeitos da doença de Creutzfeldt-Jakob (DCJ), encontrados com maior frequência em indivíduos residentes nas Regiões Sul, Sudeste e Nordeste. Os estados com maior número de casos notificados no período foram: São Paulo com 32,5% (512), Paraná com 12,0% (189) e Minas Gerais com 10% (158) (Figura 2). 

snip...

Considerações finais

No Brasil, com a implementação do sistema de vigilância da DCJ e sua inserção na lista de doenças de notificação compulsória no ano de 2005, foi observado um aumento progressivo do número de registros de casos suspeitos. A análise permitiu observar uma maior elevação no número de registros de casos a partir de 2012, com aumento expressivo do número de notificações, sugerindo uma maior sensibilidade da vigilância quanto à identificação e registro de casos suspeitos.9

Foi identificada também importante incompletude de dados nos registros de notificação de casos suspeitos de DCJ. Em função desta limitação de registros advinda das notificações com preenchimento na base de dados do Sinan incompletos, foi necessária a retirada de casos notificados da análise do banco de dados. Essa ausência de informações pode ser um fator determinante quanto à qualidade dos dados, visto que, diante das análises há possibilidade de serem geradas hipóteses ou conclusões que não refletem adequadamente a situação epidemiológica analisada.21

Dentre os casos confirmados para DCJ foram identificados registros de evolução para cura, porém, esse desfecho não condiz com o que é relatado na literatura, dado fato de a doença apresentar 100% de letalidade, não havendo tratamento que possibilite a reversão da evolução fatal da DCJ.9-15 Podendo ainda ser compreendido como um viés de informação decorrente da baixa qualidade dos dados.

Foram identificadas ainda notificações com ausência do registro quanto à evolução dos casos, o que não é recomendado. Contudo esse fato pode estar relacionado à dificuldade no seguimento dos casos pelos profissionais dos serviços de saúde em função do período de evolução da DCJ, que pode ser longo. Além disso, pode haver baixo conhecimento da vigilância da doença, ou ainda, a limitação de campos para registro de dados na ficha de notificação, por não ser específica para a DCJ. Essa questão também pode dificultar o processo de investigação, atualização e lançamento de informações no Sinan.4,9,10

No processo de investigação de casos suspeitos de DCJ, os diagnósticos diferenciais devem ser considerados, ao passo que há condições como a doença de Alzheimer, a demência por Corpos de Lewy, o edema cerebral, as encefalopatias metabólicas, a doença de Pick, entre outras, que podem desencadear características neuropatológicas similares.1,4,9 Porém, a qualidade dos dados clínicos registrados nos formulários de notificação, principalmente referentes à descrição de sinais e sintomas, tende a constituir um fator limitante no processo de vigilância.

Assim como é observado na literatura, com relação às características sociodemográficas, foi identificada maior frequência de casos suspeitos notificados entre indivíduos da raça/cor branca, seguido da raça/cor parda, e, quanto à zona de residência, a maior parte dos casos informou morar em áreas urbanas.

Internacionalmente é esperada uma pequena variação quanto ao sexo das pessoas que apresentam a doença, com predominância do sexo feminino.7,9 Este perfil também foi observado neste estudo, sendo identificada uma singela diferença entre os casos notificados, sendo a maioria dos casos do sexo feminino.

Foram identificadas notificações de casos suspeitos de DCJ entre pessoas com idade inferior a 25 anos, todavia, é extremamente rara a ocorrência da doença entre pessoas nessa faixa etária. A exceção ocorre nos casos da vDCJ, que é adquirida pelo consumo de carne bovina contaminada com EEB, pode se manifestar a partir dos 20 anos.1-4,21 Dessa forma, é possível a ocorrência de inconsistência no banco de dados em função da baixa qualidade no preenchimento das notificações.

Diante do exposto, compreende-se que é primordial o aprimoramento pelos municípios e estados dos registros de notificações de casos no Sinan para torná-lo capaz de gerar informações de qualidade que subsidiem as tomadas de decisão no que diz respeito a essa doença. Dessa forma, recomenda-se a adoção de estratégias que visem o aperfeiçoamento do processo de notificação da doença e melhoria da qualidade de dados, tanto por meio da oferta de treinamentos aos profissionais de saúde e melhoria dos instrumentos de registro quanto pelo monitoramento efetivo dos sistemas de vigilância visando identificar falhas e construir soluções adequadas aos processos de trabalho.

Referências

snip...see full text;

https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/edicoes/2022/boletim-epidemiologico-vol-53-no39/@@download/file/Boletim%20Epidemiol%C3%B3gico%20Vol.53%20N%C2%BA39.pdf



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 longe 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.


2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author:

‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).

In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-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.


***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.


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


***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

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. 


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. 


PLOS ONE Journal 

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


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 ***


WEDNESDAY, FEBRUARY 3, 2010

Import Alert 62-07 Sygen Injectable (Bovine-Extracted GMI Monosialoganglioside) manufactured from bovine brain starting material


Import Alert 62-07 Import Program

Import Alerts

Import Alerts by Numbers

Import Alert

(Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the manufacturer(s) and/or products(s) at issue. It does not create or confer any rights for or on any person, and does not operate to bind FDA or the public).

Import Alert # 62-07

Published Date: 10/02/2009

Type: DWPE Import Alert Name:

"Detention Without Physical Examination of Shipments of Sygen Injectable (Bovine-Extracted GMI Monosialoganglioside)"

Reason for Alert:

Sygen is an unapproved new drug manufactured by Fidia SpA, Italy, which is currently distributed under b(4) . The product presents BSE concerns because it is manufactured from bovine brain starting material. An inspection of Fidia conducted in February - March 2001, disclosed significant deficiencies regarding verification that the bovine brain source used in the manufacture of Sygen was obtained from a non-BSE country or that no commingling with any animal material from BSE risk countries had occurred. A Warning Letter was issued on June 28, 2001, to Fidia and CDER/OC is awaiting response.

The Office of Compliance has also learned that firms other than Fidia SpA are shipping Sygen to the U.S. Two such firms include TRB-Pharma of Brazil and its subsidiary, TransBussan of Switzerland. Neither of these firms has approved IND's for Sygen. Reportedly, the shipments are being offered for entry for personal treatment under FDA's procedures for Coverage of Personal Importations.

Guidance:

Districts may detain without physical examination all shipments of Sygen unless:

-they are coming directly from Fidia SpA, Padua, Italy;

and

-they are from finished product lot nos. b(4) and active pharmaceutical ingredient (API) lot no. 1(B)

and

-they are offered for entry under b(4) Districts encountering shipments of Sygen, which meet the listed criteria, contact for further instructions.

For questions concerning the new drug status of the product, please contact CDER.

Discretionary release of Sygen injectable under the Personal Importation guidance of Chapter 9 of the Regulatory Procedures Manual (RPM) is not appropriate. This drug poses an unreasonable health risk to the user due to possible exposure to Bovine Spongiform Encephalopathy (BSE) causative agents.

Product Description: Sygen, injectable

Charge: "The article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a new drug that is adulterated, misbranded, or without an effective new drug application (NDA) as required by Section 505. [Unapproved new drug, Section 505(a)]."

OASIS charge code - UNAPPROVED

and

"The article is subject to refusal of admission pursuant to Section 801(a)(1) in that it appears to be for use as a drug and may have been manufactured, processed, or packed under insanitary conditions, or the article appears to be prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health [Adulterated drug, Section 501 (a)(2)(a)]."

OASIS charge code - BSE DRUGS

and

"The article is subject to refusal of admission pursuant to Section 801(a)(1) in that it appears to be for use as a drug and may not have been manufactured, processed, packed, or held in conformity with current good manufacturing practices [Adulterated drug, Section 501 (a)(2)(B)]."

OASIS charge code - DRUG GMPS

Countries (99) MULTIPLE COUNTRIES (PODS ONLY)

(55 - - - --) Pharm Necess & Ctnr For Drug/Bio

(57 - - - --) Bio & Licensed In-Vivo & In-Vitro Diag

(60 - - - --) Human and Animal Drugs

(61 - - - --) Human and Animal Drugs

(62 - - - --) Human and Animal Drugs

(63 - - - --) Human and Animal Drugs

(64 - - - --) Human and Animal Drugs

(65 - - - --) Human and Animal Drugs

(66 U - - 01) Bone Parts (Natural Body Parts, Invivo Only)

(66 U - - 02) Cornea (Eye Parts) (Natural Body Parts, Invivo Only)

(66 U - - 03) Embryo (Natural Body Parts, Invivo Only)

(66 U - - 04) Hair (Natural Body Parts, Invivo Only)

(66 U - - 05) Heart (Natural Body Parts, Invivo Only)

(66 U - - 06) Kidney (Natural Body Parts, Invivo Only)

(66 U - - 07) Skin (Natural Body Parts, Invivo Only)

(66 U - - 08) Sperm (Natural Body Parts, Invivo Only)

(66 U - - 99) Natural Body Parts, Invivo Only, N.E.C.

(66 - - - --) Human and Animal Drugs

(73 - - - --) Anesthesiology

(74 - - - --) Cardiovascular

(75 - - - --) Chemistry

(76 - - - --) Dental

(77 - - - --) Ear,Nose And Throat

(78 - - - --) Gastroenterological & Urological

(79 - - - --) General & Plastic Surgery

(80 - - - --) General Hospital/Personal Use

(81 - - - --) Hematology

(82 - - - --) Immunology

(83 - - - --) Microbiology

(84 - - - --) Neurological

(85 - - - --) Obstetrical & Gynecological

(86 - - - --) Ophthalmic

(87 - - - --) Orthopedic

(88 - - - --) Pathology

(89 - - - --) Physical Medicine

(90 - - - --) Radiological

(91 - - - --) Toxicology

List of firms and their products that have met the criteria for exclusion from Detention without Physical Examination (DWPE) under this Import Alert (a.k.a. Green List)

(3002806986) Fidia S.p.A.Date Published : 09/10/2009 Via Ponte Della Fabbrica, 3/a , Abano Terme, Padova, IT

http://www.accessdata.fda.gov/cms_ia/importalert_170.html

PLEASE BE AWARE ;

The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.

http://www.oie.int/boutique/extrait/06heim937950.pdf

NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE

snip...

I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.

snip...

The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...

http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf

http://collections.europarchive.org/tna/20080102174454/http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf

new url;

http://web.archive.org/web/20090718143039/http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf

B.S.E. and Veterinary Medicines

Thank you very much indeed for your letter of the 26th of January outlining to me the various steps that are proposing to take in order to reduce the risk from B.S.E. in veterinary medicines. It is, as you say, and extremely difficult problem. ....

http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf

http://web.archive.org/web/20030526124448/http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf

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http://web.archive.org/web/20090718143228/http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf

(It was noted with concern that hormone extracts could be manufactured by a veterinary surgeon for administration to animals under his care without any Medicines Act Control.)

PITUITARY EXTRACT

This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.

BEEF BRAIN AND BRAIN INFUSION BROTHS

Considered to be of great risk.

http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf

http://collections.europarchive.org/tna/20080102164725/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf

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http://web.archive.org/web/20090718143053/http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf

TWA LITTLE STATEMENT 331

8 June 1988 Internal CVL meeting to discuss the implications of BSE to Biologicals Products containing bovine extracted material (Annex 6). (YB 88/06.08/11.1-11.2) Following a detailed review of situation the following recommendations were made:

1. Specific concern over use of pituitary gland products by veterinary surgeons and companies. Paper to be produced for Tolworth (Veterinary Medicines Division).

2. Urgent review of all products both immunological and pharmaceutical for possible inclusion of ingredients of bovine origin.

3. Draft guidelines to be presented in full to the National Office of Animal Health (NOAH), the trade body representing the Veterinary Medicines part of the pharmaceutical industry, at next meeting on 11 July 1988

http://www.bseinquiry.gov.uk/files/ws/s331.pdf

http://collections.europarchive.org/tna/20080102163939/http://www.bseinquiry.gov.uk/files/ws/s331.pdf

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TWA LITTLE minute

2. We have identified one problem over where we are unable to act and this is the use of gonadotrophins in embryo transfer work. Some veterinary surgeons are quite legally using this exemption from the Medicines Act contained in Section 9(2) to prepare gonadotrophins from pituitary glands from various species, including cattle. These hormones are used to stimulate superovulation in donor cows.

http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf

http://collections.europarchive.org/tna/20080102164806/http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf

new url;

http://web.archive.org/web/20090718143101/http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf

http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf

http://collections.europarchive.org/tna/20080102164811/http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf

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http://web.archive.org/web/20090718143117/http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf

COMMERCIAL IN CONFIDENCE

3.2 Minute 5.3 - 5.4 Bovine Spongiform Encephalopathy

It was reported that some replies had been received from Companies using pituitary glands in their products. Copies of the BSE document had also been sent to DHSS and NIBSC.

and then another 3 + pages of blank space. ...TSS

http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf

http://collections.europarchive.org/tna/20080102164813/http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf

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http://web.archive.org/web/20090718143134/http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf

COMMERCIAL IN CONFIDENCE

BSE - CURRENT POSITION WITH VETERINARY LICENCED PRODUCTS (MA.1968)

There are three areas of particular concern, vaccines (including emergency vaccines), pharmaceuticals which are covered by MA licences and unlicenses hormonal products produced under exemptions claimed under (Section 9(2) Medicines Act).

1) Vaccines

http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf

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NOT FOR PUBLICATION

another 6 pages of blank space. ...TSS

http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf

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Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr." 
Reply-To: Bovine Spongiform Encephalopathy 
To: BSE-L@uni-karlsruhe.de


[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.

[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]

[host Richard] could you repeat the question?

[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[not sure whom ask this] what group are you with?

[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.

[not sure who is speaking] could you please disconnect Mr. Singeltary

[TSS] you are not going to answer my question?

[not sure whom speaking] NO

from this point, i was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;

[unknown woman] what group are you with?

[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?

at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference.

snip...full text ;

http://bse-atypical.blogspot.com/2010/01/14th-international-congress-on.html

COMMERCIAL IN CONFIDENCE

NOT FOR PUBLICATION

COMMITTEE ON SAFETY OF MEDICINES

another 6 pages or so that are blank. ...TSS

http://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdf

http://collections.europarchive.org/tna/20080102185137/http://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdf

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COMMERCIAL IN CONFIDENCE

NOT FOR PUBLICATION

COMMITTEE ON SAFETY OF MEDICINES

WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY

7.2.1. Products with bovine brain/lymphoid tissue as ingredients and administered by injection...[111]

7.2.2 Products with bovine ingredients (other than brain/lymphoid tissue) and administered by injection...[135]

7.2.3 Tissue implants, open wound dressings, surgical materials, dental and opthalmic products with bovine ingredients...[27]

7.2.4. Products with bovine ingredients and administered topically...[5]

7.2.5 Products with bovine ingredients and administered orally...[9]

7.2.6 Products with other animal/insect/bird ingredients and administered:

a. by injection a: 117

b. by topically b: 6

c. orally c: 8

7.2.7 Products with materials produced from animal material by chemical processes, eg stearic acid, gelatin and lanolin...[156]

With two exceptions, the replies to date have not given any immediate cause for concern, although 176 products do not conform to the CSM/VPC guidelines.

8. The first exception was from which gave very limited information about a very large number of homoepathic medicines with material obtained from cattle and a number with material from the brain. Of these, 53 were injectable products of which 20 were derived from cattle brain. A list of these products is attached as Appendix 1 to Annex D. The second exception relates to the product, 'Surgical Catgut', which is sourced from UK bovine intestines and will contain lymphoid material...

see full text ;

http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf

http://collections.europarchive.org/tna/20080102164420/http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf

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NEVER SAY NEVER, WITH RELATIONS TO LIVE VACCINES AND THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE. VETERINARY PHARMACEUTICALS, VACCINES, AND TRANSMISSION THEREFROM TSE PRION DISEASE HAS BEEN DOCUMENTED SEVERAL TIMES IN THE FIELD. so, i hope that these products are no long available...

Subject: Louping-ill vaccine documents from November 23rd, 1946 

Date: Sat, 9 Sep 2000 17:44:57 -0700 

From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy 

To: BSE-L@uni-karlsruhe.de

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

THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946

NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND

ANNUAL CONGRESS, 1946

The annual Congress, 1946, was held at the Royal Veterinary College, Royal College Street, London, N.W.I. from September 22nd to September 27th.

Opening Meeting

[skip to scrapie vaccine issue...tss]

Papers Presented to Congress

The papers presented to this year's Congress had as their general theme the progressive work of the profession during the war years. Their appeal was clearly demonstrated by the large and remarkably uniform attendance in the Grand Hall of the Royal Veterinary College throughout the series; between 200 and 250 members were present and they showed a keen interest in every paper, which was reflected in the expression of some disappointment that the time available for discussion did not permit of the participation of more than a small proportion of would-be contributors.

In this issue we publish (below) the first to be read and discussed, that by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E., "Advances in Veterinary Research." Next week's issue will contain the paper on "Some Recent Advances in Veterinary Medicine and Surgery in Large-Animal Practice" by Mr. T. Norman Gold, M.R.C.V.S. In succeeding numbers of the Record will be reproduced, also with reports of discussions, that by Mr. W. L. Weipers, M.R.C.V.S., D.V.S.M., on the same subject as relating to small-animal practice, and the papers by Mr. J. N. Ritchie, B.SC., M.R.C.V.S., D.V.S.M., and Mr. H.W. Steele-Bodger, M.R.C.V.S., on "War-time Achievements of the British Home Veterinary Services."

The first scientific paper of Congress was read by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E. on Monday, September 23rd, 1946, when Professor J. Basil Buxton, M.A., F.R.C.V.S, D.V.H., Prinicipal of the Royal Veterinary College, presided.

Advances in Veterinary Research

by

W.S. GORDON, PH.D., M.R.C.V.S., F.R.S.E.

Agriculteral Research Council, Field Station, Compton, Berks.

Louping-ill, Tick-borne Fever and Scrapie

In 1930 Pool, Browniee & Wilson recorded that louping-ill was a transmissible disease. Greig et al, (1931) showed that the infective agent was a filter-passing virus with neurotropic characters and Browniee & Wilson (1932) that the essential pathology was that of an encephalomyelitis. Gordon, Browniee, Wilson & MacLeod (1932) and MacLeod & Gordon (1932) confirmed and extended this work. It was shown that on louping-ill farms the virus was present in the blood of many sheep which did not show clinical symptoms indicating involvement of the central nervous system and that for the perpetuation and spread of the disease these subclinical cases were probably of greater importance that the frank clinical cases because, in Nature, the disease was spread by the tick, lxodes ricinus L. More recently Wilson (1945, 1946) has described the cultivation of the virus in a chick embryo medium, the pathogenic properties of this culture virus and the preparation of louping-ill antiserum.

Between 1931 and 1934 I carried out experiments which resulted in the development of an effective vaccine for the prevention of louping-ill.* This vaccine has been in general use since 1935 and in his annual report to the Animal Diseases Research Association this year, Dr. Greig stated that about 227,000 doses of vaccine had been issued from Moredun alone.

Dr. Gordon illustrated this portion of his paper by means of graphs and diagrams projected by the epidiascope.

This investigation, however, did not begin and end with the study of louping-ill; it had, by good fortune, a more romantic turn and less fortunately a final dramtic twist which led almost to catastrope. After it had been established that a solid immunity to louping-ill could be induced in sheep, a group of immunized and a group of susceptible animals were placed together on the tick-infected pasture of a louping-ill farm. Each day all the animals were gathered and their temperatures were recorded. It was anticipated that febrile reactions with some fatalities would develop in the controls while the louping-ill immunes would remain normal. Contrary to expectation, however, every sheep, both immune and control, developed a febrile reaction. This unexpected result made neccessary further investigation which showed that the febrile reaction in the louping-ill immunes was due to a hitherto undescribed infective agent, a Rickettsia-like organism which could be observed in the cytoplasm of the grannular leucocytes, especially the neutrophil polymorphs (MacLeod (1932), Gordon, Browniee, Wilson & MacLeod. MacLeod & Gordon (1933). MacLeod (1936). MacLeod collected ticks over many widely separated parts of Scotland and all were found to harbour the infective agent of tick-borne fever, and it is probable that all sheep on tick-infested farms develop this disease, at least on the first occasion that they become infested with ticks. When the infection is passed in series through susceptible adult sheep it causes a sever, febrile reaction, dullness and loss of bodily condition but it rarely, if ever, proves fatal. It is clear, however, that it aggravates the harmful effects of a louping-ill infection and it is a serious additional complication to such infections as pyaemia and the anacrobic infections which beset lambs on the hill farms of Northern Britain.

Studying the epidemiology of louping-ill on hill farms it became obvious that the pyaemic condition of lambs described by M'Fadyean (1894) was very prevalent on tick infested farms Pyaemia is a crippling condition of lambs associated with tick-bite and is often confused with louping-ill. It is caused by infection with Staphylococcus aureus and affected animals may show abscess formation on the skin, in the joints, viscera, meninges and elsewhere in the body. It was thought that tick-borne fever might have ben a predisposing factor in this disease and unsuccessful attempts were made by Taylor, Holman & Gordon (1941) to reproduce the condition by infecting lambs subcutaneously with the staphylococcus and concurrently produceing infections with tickborne fever and louping-ill in the same lambs. Work on pyaemia was then continued by McDiarmid (1946a, 1946b, 1946c), who succeeded in reproducing a pyaemic disease in mice, guinea-pigs and lambs similar to the naturally occuring condition by intravenous inoculation of Staphylococcus aureus. He also found a bacteraemic form of the disease in which no gross pyaemic lesions were observed. The prevention or treatment of this condition presents a formidable problem. It is unlikely that staphylococcal ???oid will provide an effective immunity and even if penicillin proved to be a successful treatment, the difficulty of applying it in adequate and sustained dosage to young lambs on hill farms would be almost insurmountable.

>From 1931 to 1934 field trials to test the immunizing value and harmlessness of the loup-ill vaccine were carried out on a gradually increasing scale. Many thousands of sheep were vaccinated and similar numbers, living under identical conditions were left as controls. The end result showed that an average mortability of about 9 percent in the controls was reduced to less than 1 percent in the vaccinated animals. While the efficiency of the vaccine was obvious after the second year of work, previous bitter experience had shown the wisdom of withholding a biological product from widespread use until it had been successfully produced in bulk, as opposed to small-scale experimental production and until it had been thoroughly tested for immunizing efficiency and freedom from harmful effects. It was thought that after four years testing this stage had been reached in 1935, and in the spring of that year the vaccine was issued for general use. It comprised a 10 percent saline suspension of brain, spinal cord and spleen tissues taken from sheep five days after infection with louping-ill virus by intracerebral inoculation. To this suspension 0-35 percent of formalin was added to inactivate the virus and its safety for use as a vaccine was checked by intracerbral inoculation of mice and sheep and by the inoculation of culture medium. Its protective power was proved by vaccination sheep and later subjecting them, along with controls, to a test dose of living virus.

Vaccine for issue had to be free from detectable, living virus and capable of protecting sheep against a test dose of virus applied subcutaneously. The 1935 vaccine conformed to these standards and was issued for inoculation in March as three separate batches labelled 1, 2, and 3. The tissues of 140 sheep were employed to make batch 1 of which 22,270 doses were used; 114 to make batch 2 of which 18,000 doses were used and 44 to make batch 3 of which 4,360 doses were used. All the sheep tissues incorporated in the vaccine were obtained from yearling sheep. During 1935 and 1936 the vaccine proved highly efficient in the prevention of louping-ill and no user observed an ill-effect in the inoculated animals. In September, 1937, two and a half years after vaccinating the sheep, two owners complained that scrapie, a disease which had not before been observed in the Blackface breed, was appearing in their stock of Blackface sheep and further that it was confined to animals vaccinated with louping-ill vaccine in 1935. At that stage it was difficult to conceive that the occurrence could be associated with the injection of the vaccine but in view of the implications, I visited most of the farms on which sheep had been vaccinated in 1935. It was at this point that the investigation reached its dramatic phase; I shall not forget the profound effect on my emotions when I visited these farms and was warmly welcomed because of the great benefits resulting from the application of louping-ill vaccine, wheras the chief purpose of my visit was to determine if scrapie was appearing in the inoculated sheep. The enquiry made the position clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in a few instances that the owner was associating the occurrence with louping-ill vaccination. The disease was affecting all breeds and it was confined to the animals vaccinated with batch 2. This was clearly demonstrated on a number of farms on which batch 1 had been used to inoculate the hoggs in 1935 and batch 2 to inoculate the ewes. None of the hoggs, which at this time were three- year-old ewes. At this time it was difficult to forecast whether all of the 18,000 sheep which had received batch 2 vaccine would develop scrapie. It was fortunate, however, that the majority of the sheep vaccinated with batch 2 were ewes and therefore all that were four years old and upwards at the time of vaccination had already been disposed of and there only remained the ewes which had been two to three years old at the time of vaccination, consequently no accurate assessment of the incidence of scrapie could be made. On a few farms, however, where vaccination was confined to hoggs, the incidence ranged from 1 percent, to 35 percent, with an average of about 5 percent. Since batch 2 vaccine had been incriminated as a probable source of scrapie infection, an attempt was made to trace the origin of the 112 sheep whose tissues had been included in the vaccine. It was found that they had been supplied by three owners and that all were of the Blackface or Greyface breed with the exception of eight which were Cheviot lambs born in 1935 from ewes which had been in contact with scrapie infection. Some of these contact ewes developed scrapie in 1936-37 and three surviving fellow lambs to the eight included in the batch 2 vaccine of 1935 developed scrapie, one in September, 1936, one in February, 1937, and one in November, 1937. There was, therefore, strong presumptive evidence that the eight Cheviot lambs included in the vaccine although apparently healthy were, in fact, in the incubation stage of a scrapie infection and that in their tissues there was an infective agent which had contaminated the batch 2 vaccine, rendering it liable to set up scrapie. If that assumption was correct then the evidence indicated that:-

(1) the infective agent of scrapie was present in the brain, spinal cord and or spleen of infected sheep: (2) it could withstand a concentration of formalin of 0-35 percent, which inactivated the virus of louping-ill: (3) it could be transmitted by subcutaneous inoculation; (4) it had an incubation period of two years and longer.

Two Frenchmen, Cuille & Chelle (1939) as the result of experiments commenced in 1932, reported the successful infection of sheep by inoculation of emulsions of spinal cord or brain material by the intracerebral, epidural, intraocular and subcutaneous routes The incubation period varied according to the route employed, being one year intracerebrally, 15 months intraocularly and 20 months subcutaneously. They failed to infect rabbits but succeeded in infecting goats. Another important part of their work showed that the infective agent could pass through a chamberland 1.3 filter, thus demonstrating that the infective agent was a filtrable virus. It was a curious coincidence that while they were doing their transmission experiments their work was being confirmed by the unforeseeable infectivity of a formalinized tissue vaccine.

As a result of this experience a large-scale transmission experiment involving the use of 788 sheep was commenced in 1938 on a farm specially taken for the purpose by the Animal Diseases Research Association with funds provided by the Agricultural Research Council. The experiment was designed to determine the nature of the infective agent and the pathogenesis of the disease. It is only possible here to give a summary of the result which showed that (1) saline suspensions of brain and spinal cord tissue of sheep affected with scrapie were infective to normal sheep when inoculated intracerebrally or subcutaneously; (2) the incubation period after intracerebral inoculation was seven months and upwards and only 60 percent of the inoculated sheep developed scrapie during a period of four and a half years; (3) the incubation period after subcutaneous inoculation was 15 months and upwards and only about 30 percent of the inoculated sheep developed the disease during the four and a half years: (4) the infective agent was of small size and probably a filtrable virus.

The prolonged incubation period of the disease and the remarkable resistance of the causal agent to formalin are features of distinct interest. It still remains to determine if a biological test can be devised to detect infected animals so that they can be killed for food before they develop clinical symptoms and to explore the possibilities of producing an immunity to the disease...

snip...end...TSS

=====

source, CJ Gibbs, sent to me via US Postal, way back...terry

=====


Evidence for the transmission of scrapie to sheep and goats from a vaccine against Mycoplasma agalactiae

M. Caramelli DVetMed, PhD, G. Ru DVetMed, PhD, C. Casalone DVetMed, E. Bozzetta DVetMed, P. L. Acutis DVetMed, A. Calella PharmChem, PhD, G. Forloni BSc, PhD

Abstract

An accidental infection from a vaccine was suggested as the explanation for the sudden increase in outbreaks of scrapie in Italy in 1997 and 1998. This paper describes a recent outbreak of scrapie in sheep and goats which were exposed to the same vaccine. No ewes or goats had been imported into the herd since 1992, but a vaccine against Mycoplasma agalactiae had been administered twice, in 1995 and 1997. High rates of crude mortality and scrapie incidence were experienced by both species, all birth cohorts were involved and a large proportion of aged animals was affected. A pattern of brain lesions was observed, with slight differences between the sheep and goats, which was very similar to the pattern observed in animals previously exposed to the same vaccine but clearly different from that observed in the brains of sheep with scrapie in a flock not exposed to the vaccine. Regardless of their exposure status, genotype analysis of the sheep showed the presence of polymorphism only at codon 171. The patterns of both incidence and brain lesions provide evidence that the epidemic of scrapie was due to the use of the vaccine.


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. ...



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




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



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





Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission

Comment from Singeltary, Terry Posted by the Animal and Plant Health Inspection Service on Mar 11, 2021

Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission

Greetings APHIS et al, i would kindly like to comment on Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004.

Greetings APHIS et al, i would kindly like to comment on Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004.

***> 1st and foremost your biggest problem is 'VOLUNTARY'! AS with the BSE 589.2001 FEED REGULATIONS, especially since it is still voluntary with cervid, knowing full well that cwd and scrapie will transmit to pigs by oral route. VOLUNTARY DOES NOT WORK! all animal products should be banned and be made mandatory, and the herd certification program should be mandatory, or you don't move cervid. IF THE CWD HERD CERTIFICATION IS NOT MANDATORY, it will be another colossal tse prion failure from the start.

***> 2nd USA should declare a Declaration of Extraordinary Emergency due to CWD, and all exports of cervid and cervid products must be stopped internationally, and there should be a ban of interstate movement of cervid, until a live cwd test is available.

***> 3rd Captive Farmed cervid ESCAPEES should be made mandatory to report immediately, and strict regulations for those suspect cwd deer that just happen to disappear. IF a cervid escapes and is not found, that farm should be indefinitely shut down, all movement, until aid MIA cervid is found, and if not ever found, that farm shut down permanently.

***> 4th Captive Farmed Cervid, INDEMNITY, NO MORE Federal indemnity program, or what i call, ENTITLEMENT PROGRAM for game farm industry. NO MORE BAIL OUTS FROM TAX PAYERS. if the captive industry can't buy insurance to protect not only themselves, but also their customers, and especially the STATE, from Chronic Wasting Disease CWD TSE Prion or what some call mad deer disease and harm therefrom, IF they can't afford to buy that insurance that will cover all of it, then they DO NOT GET A PERMIT to have a game farm for anything. This CWD TSE Prion can/could/has caused property values to fall from some reports in some places. roll the dice, how much is a state willing to lose?

***> 5th QUARANTINE OF ALL FARMED CAPTIVE, BREEDERS, URINE, ANTLER, VELVET, SPERM, OR ANY FACILITY, AND THEIR PRODUCTS, that has been confirmed to have Chronic Wasting Disease CWD TSE Prion, the QUARANTINE should be for 21 years due to science showing what scrapie can do. 5 years is NOT near long enough. see; Infectious agent of sheep scrapie may persist in the environment for at least 16 to 21 years.

***> 6th America BSE 589.2001 FEED REGULATIONS CWD TSE Prion

***> 7TH TRUCKING TRANSPORTING CERVID CHRONIC WASTING DISEASE TSE PRION VIOLATING THE LACEY ACT

***> 8TH ALL CAPTIVE FARMING CERVID OPERATIONS MUST BE INSURED TO PAY FOR ANY CLEAN UP OF CWD AND QUARANTINE THERE FROM FOR THE STATE, NO MORE ENTITLEMENT PROGRAM FOR CERVID GAME FARMING PAY TO PLAY FOR CWD TSE PRION OFF THE TAX PAYERS BACK.

***> 9TH ANY STATE WITH DOCUMENTED CWD, INTERSTATE, NATIONAL, AND INTERNATIONAL MOVEMENT OF ALL CERVID, AND ALL CERVID PRODUCTS MUST BE HALTED!

***> 10TH BAN THE SALE OF STRAW BRED BUCKS AND ALL CERVID SEMEN AND URINE PRODUCTS

***> 11th ALL CAPTIVE FARMED CERVID AND THEIR PRODUCTS MUST BE CWD TSE PRION TESTED ANNUALLY AND BEFORE SALE FOR CWD TSE PRION

SEE FULL SCIENCE REFERENCES AND REASONINGS ;

***> 1st and foremost your biggest problem is 'VOLUNTARY'!

''APHIS created a cooperative, voluntary Federal-State-private sector CWD Herd Certification Program designed to identify farmed or captive herds infected with CWD.''

key word failure is 'voluntary'.

WE know for a fact now that voluntary does NOT WORK!

AS with the BSE 589.2001 FEED REGULATIONS (see , another colossal failure, and proven to be a sham, especially since it is still voluntary with cervid, knowing full well that cwd and scrapie will transmit to pigs by oral route. VOLUNTARY DOES NOT WORK! all animal products should be banned and be made mandatory, and the herd certification program should be mandatory, or you don't move cervid. IF THE CWD HERD CERTIFICATION IS NOT MANDATORY, it will be another colossal tse prion failure from the start.

***> 2nd USA should declare a Declaration of Extraordinary Emergency due to CWD, and all exports of cervid and cervid products must be stopped internationally, and there should be a ban of interstate movement of cervid, until a live cwd test is available.

***> 3rd Captive Farmed cervid ESCAPEES should be made mandatory to report immediately, and strict regulations for those suspect cwd deer that just happen to disappear. IF a cervid escapes and is not found, that farm should be indefinitely shut down, all movement, until aid MIA cervid is found, and if not ever found, that farm shut down permanently. ...snip...see full text submission with science references...TSS




Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification



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



FRIDAY, FEBRUARY 17, 2023 

TEXAS OVERVIEW OF STATE RESPONSE TO CHRONIC WASTING DISEASE CWD TSE PRION April 2019 a Review




Terry S. Singeltary Sr., Bacliff, Texas USA 77518 <flounder9@verizon.net>

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