Prions: a threat to health security and the need for effective medical countermeasures
PERSPECTIVE
Prions: a threat to health security and the need for effective medical countermeasures
Author Ying-Chiang J. Lee
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
Available online 4 February 2023.
Abstract
Prions are infectious conformations of certain naturally occurring proteins. These misfolded proteins can structurally alter healthy protein, creating misfolded copies that repeat the process and form protein aggregates that lead to neuronal cell death. Although years can pass from initial prion infection to clinical presentation of symptoms, onset of symptoms is typically followed by rapid neurological decline resulting in death. Prion diseases have been characterized in animals ranging from sheep and cattle to cervids and humans, with notable cross-species infections such as the variant Creutzfeldt-Jakob disease. Thus, prions present a health risk with the potential to disrupt major food sources as well affect human health through animal to human and human to human transmission events. While human to human prion transmission is rare and the immediate risks for a prion-facilitated pandemic are low, prions are a class of pathogens for which we are underprepared. In addition, prions, and prion disease-like approaches, have also been discussed in the context of biological weapons and toxins, adding another layer of complexity surrounding biosecurity and biodefense. These threats underscore the need for increased scrutiny and research on prions. Here, pharmaceutical and nonpharmaceutical prion-specific interventions are discussed. Recent advances in prion therapeutic development are also briefly highlighted, and a set of policy recommendations are given that aims to provide high level suggestions for the prevention and mitigation of prion diseases.
snip...
3. The Threat of Prions as Biological Weapons
Biological weapons (BWs) encompass all pathogenic and toxic biological agents that can cause morbidity and/or mortality. In the traditional sense, infectious BWs can spread in a population and causes diseases and/or death. Prions are atypical in that the lag time between infection and the first appearance of symptoms and eventual death is large – typically on the order of years to decades. Prions make for stealthy but deadly BWs, with rapid neurological decline after onset of symptoms and have a 100% case fatality rate. Their use was discussed in workshops discussing the Biological and Toxin Weapons Convention in 2015 and has drawn attention from those in defense communities.30, 31, 32, 33 Depending on the bad actors’ motivations and willingness to wait for an effect, the dosage of prions per exposure could be altered through common biotechnological approaches and facilitate faster disease progression. Prions are in many ways analogous to a class of BWs known as bioregulators. First developed by the Soviet Union, and later reported by Western scientists, bioregulators are compounds that mimic, or are copies of existing, natural proteins and compounds found in the human body.34, 35, 36 Upon exogenous delivery and exposure in certain doses using engineered bacterial producers, these proteins and compounds can result in neurological and physical symptoms analogous to late-stage prion disease and eventually cause death in exposed individuals. The possible delivery mechanisms, immunological challenges, and effects are similar in both prion and bioregulator-induced diseases, the potential for protein-based BWs should be recognized and sufficient resources dedicated to developing MCMs.
The severe health consequences of a prion BW should be of concern—for both human and animal health. Biological warfare involving prions can come in several formats that will be briefly outlined here, grouped by transmission format: animal-animal, animal-human, non-transmissible human prion attack, and human-human. While more granular methods will be purposefully avoided in this non-classified work, it is important to highlight the various possible prion BW exposure and use formats to further emphasize the need for robust medical and vaccination research programs that can respond to a prion BW attack. Animal to animal prion transmission in a BW attack is perhaps the most probable and realistic according to current knowledge around prion biology. This purposeful introduction of animal-specific prion BWs are a form of agroterrorism—an attack on livestock or plants and food sources.37 Prion diseases have already affected many animal populations in the wild, primarily in North America but also now has spread into Europe. Agroterrorism via a prion agent that spreads only among cattle, pigs, or other critical meat sources and results in rapid death would seriously affect regional, national, and even international food supply and severely impact social and economic stability. Such effects could last for years and lead to negative outcomes in food security and nutritional status among various populations. Animal to human transmission, in the case of BSE/vCJD is another route of attack with a prion BW. While this form of prion disease is not known to be contagious and require direct consumption of tainted meat, such an attack would require vast animal product recalls. Importantly, this approach will directly affect human health and result in fatalities. Similar to the animal to human prion BW attack, the non-transmissible human prion attack will also affect humans directly, but not occur through means of contaminating animals, but by directly contaminating food and drink. The last prion BW approach covered here involves human to human transmission and is perhaps the most ominous of prion BW attack methods. With a deeper understanding of prion biology, transmission, and effects, a bad actor could engineer a contagious prion disease that spreads among humans like a cold. In fact, various prion delivery vehicles could be utilized that involve common infectious diseases. Such prion diseases would spread within a population and engineered to result in death years or decades later. This would lead to a catastrophic population collapse with devastating implications for humanity.
The high-level description of potential prion BW approaches neglects the feasibility and lacks a rigorous risk assessment needed to prioritize likely prion BW use from an objective standpoint. However, taken together, the prion BW approaches highlight the broad risk to both humans and animals and underscore the importance in the research and development of prion-specific vaccines and therapeutics.
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Keywords: Prions, Medical countermeasures, Interventions, Vaccines, Biosecurity, Policy 1. Background
snip...see full text;
Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of 2002 Singeltary Submission;
Subject: Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of 2002;
Date: Mon, 27 Jan 2003 15:54:57 -0600
From: "Terry S. Singeltary Sr."
To: [log in to unmask]
Docket No: 02-088-1
Title: Agricultural Bioterrorism Protection Act of 2002; Possession, Use, and Transfer of Biological Agents and Toxins
http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2002_register&docid=fr13de02-15.pdf
Greetings,
i would like to kindly submit to this docket and warn of the potential for biological 'suitcase bombs' from civilian air-traffic populations from known BSE/FMD and other exotic animal disease pathogens coming into the USA.
please be warned;
Date: Thu, 21 Mar 2002 08:42:56 -0800
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: USA SEALED BORDERS AND THE ''USCS'' (unspecified species coding
system) MORE POTENTIAL B.S.eee
Change in Disease Status of Greece With Regard to Foot-and-Mouth
[Federal Register: March 21, 2002 (Volume 67, Number 55)]
snip...
Under Sec. 94.11, meat and other animal products of ruminants and swine, including ship stores, airplane meals, and baggage containing these meat or animal products, may not be imported into the United States except in accordance with Sec. 94.11 and the applicable requirements of the U.S. Department of Agriculture's Food Safety and Inspection Service at 9 CFR chapter III.
snip...
From an economic standpoint, the proposed rule would have little or no impact on U.S. animal stock and commodities. There are two reasons. First, the proposed rule would not remove other disease-based restrictions on the importation of ruminants or swine (and certain meat and other products from those animals) from Greece into the United States. Because bovine spongiform encephalopathy is considered to exist in Greece, the importation of ruminants and meat, meat products, and certain other products of ruminants that have been in Greece is prohibited.
snip...
http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2002_register&docid=02-6837-filed
========================
What are the U.S. imports of affected animals or animal products from the country?
Very few products that would be of risk for transmission of BSE were imported into the US from Greece during 2000 or 2001 (January - April). Due to the above mentioned import ban, no live ruminants, ruminant meat, meal made from ruminants, or other high risk products from ruminants were imported from Greece during this time period. In 2001 (January - April), 3000 kg of enzymes and prepared enzymes and 5 kg of medicants containing antibiotics for veterinary use were imported. The data do not provide a species of origin code for these products, therefore they may not contain any ruminant product.
Sources: World Trade Atlas
What is the level of passenger traffic arriving in the United States from the affected country?
Approximately 185,000 direct flights from Greece arrived to US airports in fiscal year 2000. Also, an unknown number of passengers from Greece arrived via indirect flights.
Under APHIS-PPQ's agriculture quarantine inspection monitoring, 584 air passengers from Greece were sampled for items of agricultural interest in fiscal year 2000. Of these passengers, 14 carried meat (non-pork) items that could potentially transmit pathogens that cause BSE; most passengers carried from one to two kilograms (kg) of meat, although one passenger in November 1999 carried 23 kg of meat in a suitcase. Florida, Massachusetts, and New York were the reported destinations of these passengers. None of the passengers with meat items reported plans to visit or work on a ranch or farm while in the US.
Source: US Department of Transportation, and APHIS-PPQ Agricultural Quarantine Inspection data base
http://www.aphis.usda.gov/vs/ceah/cei/bse_greece0701.htm
Greetings list members,
i just cannot accept this;
> 23 kg of meat in a suitcase (suitcase bomb...TSS)
> The data do not provide a species of origin code for these
> products, therefore they may not contain any ruminant product.
what kind of statement is this?
how stupid do they think we are?
it could also very well mean that _all_ of it was ruminant based products !
Terry S. Singeltary Sr., Bacliff, Texas USA
What is the level of passenger traffic arriving in the United States from Slovenia?
There were no direct flights from Slovenia to the US in fiscal year 2000.
APHIS-PPQ’s agriculture quarantine inspection monitoring sampled 27 air passengers from Slovenia for items of agricultural interest in fiscal year 2000. One of these 27 passengers was carrying two kilograms of a meat item that could potentially harbor pathogens that cause BSE. This passenger arrived to Elizabeth, New York, in June 2000 and declared no intention to visit a farm or ranch in the US.
Source: US Department of Transportation, and APHIS-PPQ Agricultural Quarantine Inspection data base
http://www.aphis.usda.gov/vs/ceah/cei/bse_slovenia1101.htm
What is the level of passenger traffic arriving in the United States from the affected country?
A total of 45,438 passengers arrived in the US on direct flights from the Czech Republic in fiscal year 2000. It is likely that additional passengers originating in the Czech Republic traveled to the US on non-direct flights.
As part of APHIS-PPQ’s Agriculture Quarantine Inspection Monitoring, 238 air passengers from the Czech Republic were inspected for items of agricultural interest in fiscal year 2000. Of these, 10, or 4.2%, were found to be carrying a total of 17 kg of items that could potentially present a risk for BSE. None of the passengers with items reported plans to visit or work on a farm or ranch while in the US.
Source: US Department of Transportation, and APHIS-PPQ Agricultural Quarantine Inspection data base
http://www.aphis.usda.gov/vs/ceah/cei/bse_cz0601.htm
What are the US imports of affected animals or animal products from Austria?
Between 1998 and June 2001, US imports from Austria included goat meat, animal feeds, and sausage. The sausage and animals feeds were from unspecified species.
Source: World Trade Atlas
snip...
What is the level of passenger traffic arriving in the United States from Austria?
A total of 168,598 passengers on direct flights from Austria arrived at US airports in fiscal year 2000. An undetermined number of passengers from Austria arrived in the US via indirect flights.
Under APHIS-PPQ’s agricultural quarantine inspection monitoring, 565 air passengers from Austria were sampled for items of agricultural interest in fiscal year 2000. Ten (10) of these passengers, or 1.7 percent, carried a total of 23 kg meat (non-pork) items that could potentially harbor the pathogen(s) that cause BSE. None of these passengers from whom meat items were confiscated reported plans to visit or work on a ranch or farm during their visit to the US.
Source: US Dept. of Transportation; APHIS-PPQ
http://www.aphis.usda.gov/vs/ceah/cei/bse_austria1201.htm
Greetings FDA and public,
if you go to the below site, and search all BSE known countries and check out their air traffic illegal meat they have confiscated, and check out the low number checked, compared to actual passenger traffic, would not take too much for some nut to bring in FMD/TSEs into the USA as a 'suitcase bomb'.
[[Under APHIS-PPQ's agricultural quarantine inspection monitoring, 284 air passengers from Israel were sampled for items of agricultural interest in fiscal year 2001. Seven of these passengers, or 2 percent, carried a total of 11 kg of meat items that could potentially harbor the pathogen that causes BSE. None of these passengers from whom meat items were confiscated reported plans to visit or work on a ranch or farm during their visit to the U.S.]]
if they were to have questioned the terrorist that bombed the Twin Towers with jets, if they were to have questioned them at flight school in the USA, i am sure that they would have said they did not intend to visit the Twin Towers as a flying bomb either. what am i thinking, they probably did ask this? stupid me.
[[In 1999 a small amount of non-species specific meat and offal was imported and a small amount of fetal bovine serum (FBS) was also imported. FBS is considered to have a relatively low risk of transmitting BSE.]]
more of the USA infamous 'non-species coding system', wonder how many of these species are capable of carrying a TSE?
snip...
A total of 524,401 passengers arrived on direct flights to the U.S. from Israel in fiscal year 2000. This number does not include passengers who arrived in the U.S. from Israel via indirect flights.
Under APHIS-PPQ's agricultural quarantine inspection monitoring, 284 air passengers from Israel were sampled for items of agricultural interest in fiscal year 2001. Seven of these passengers, or 2 percent, carried a total of 11 kg of meat items that could potentially harbor the pathogen that causes BSE. None of these passengers from whom meat items were confiscated reported plans to visit or work on a ranch or farm during their visit to the U.S.
http://www.aphis.usda.gov/vs/ceah/cei/bse_israel0602.htm
Source: U.S. Department of Transportation and APHIS-PPQ Agricultural Quarantine Inspection data base.
What is the level of passenger traffic arriving in the United States from Japan?
Approximately 6.84 million passengers on 29,826 direct flights from Japan arrived at US airports in fiscal year 2000. An undetermined number of passengers from Japan arrived in the US via indirect flights.
Under APHIS-PPQ's agriculture quarantine inspection monitoring, 801 air passengers from Japan were sampled for items of agricultural interest in fiscal year 2000. Of these 801 passengers, 10 carried meat (non-pork) items that could potentially harbor the pathogen(s) that cause BSE; most passengers carried an average of 1.7 kilograms of meat. None of these passengers from whom meat items were confiscated reported plans to visit or work on a ranch or farm during their visit to the US.
Source: US Department of Transportation, and APHIS-PPQ Agricultural Quarantine Inspection data base
http://www.aphis.usda.gov/vs/ceah/cei/bse_japan0901.htm
What is the level of passenger traffic arriving in the United States from the affected country?
A total of 3.3 million passengers arrived in the US on direct flights from Germany in 1998, although many of these passengers would not have originated in Germany. As part of APHIS-PPQ's Agriculture Quarantine Inspection Monitoring, 8,247 air passengers from Germany were inspected for items of agricultural interest. Of these, 198, or 2.3%, were found to be carrying a total of 304 kg of items that could potentially present a risk for BSE. Thirty (30) of the passengers with items reported plans to visit or work on a farm or ranch while in the US. Reported destination states of these 30 passengers were CA, CO, DE, FL, LA, MT, OH, VA, and WY.
Source: US Department of Transportation, and APHIS-PPQ Agricultural Quarantine Inspection data base
http://www.aphis.usda.gov/vs/ceah/cei/bse_germany1200e.htm
search archives at bottom of page of each BSE Country;
http://www.aphis.usda.gov/vs/ceah/cei/iw_archive.htm
more on non-species coding system and TSEs and potential 'suitcase bombs';
To: Bovine Spongiform Encephalopathy
Subject: Re: POLAND FINDS 4TH MAD COW CASE/USA IMPORTS FROM POLAND/non-species coding system strikes again
References: <[log in to unmask]>
Content-Type: text/plain; charset=ISO-8859-1; format=flowed
Content-Transfer-Encoding: 8bit
X-Virus-Scanner: Found to be clean
Greetings again List Members,
let me kick a madcow around here a bit.
on the imports from Poland and the infamous USA 'non-species' coding system.
the USDA/APHIS states;
> During the past four years (1998 - 2001), US imports from
> Poland included non-species specific animal products
> used in animal feeds and non-species specific sausage and offal
> products (Table 3). Given US restrictions on ruminant product
> imports, these US imports should not have contained ruminant
> material.
NOW, if you read Polands GBR risk assessment and opinion on BSE, especially _cross-contamination_, it states;
ANNEX 1
Poland - Summary of the GBR-Assessment, February 2001
EXTERNAL CHALLENGE STABILITY INTERACTION OF EXTERNAL CHALLENGE AND STABILITY
The very high to extremely high external challenge met a very unstable system and could have led to contamination of domestic cattle in Poland from 1987 onwards.
This internal challenge again met the still very unstable system and increased over time.
The continuing very high external challenge supported this development.
Not OK MBM-ban since 1997, but no feed controls. Reasonably OK Heat treatment equivalent to 133°C / 20min / 3 bar standards, but no evidence provided on compliance.
Not OK. No SRM-ban, SRM are rendered and included in cattle feed.
BSE surveillance:
Not sufficient before 2001.
Cross-contamination:
Lines for ruminant and non-ruminant feed in feed-mills only separated in time and no analytical controls carried out. Likely present since 1987 and growing.
see full text and ANNEX 1 at;
http://europa.eu.int/comm/food/fs/sc/ssc/out185_en.pdf
so in my humble opinion, the statement by the USDA/APHIS that ''these US imports _should_ not have contained ruminant materials, is a joke. a sad joke indeed.
* POLAND BSE GBR RISK ASSESSMENT
http://europa.eu.int/comm/food/fs/sc/ssc/out185_en.pdf
BSE ISRAEL change in disease status, AND THE DAMN NON-SPECIES CODING SYSTEM $$$
Subject: BSE ISRAEL change in disease status, AND THE DAMN NON-SPECIES CODING SYSTEM $$$
Date: November 1, 2002 at 8:03 am PST
[Federal Register: November 1, 2002 (Volume 67, Number 212)]
DEPARTMENT OF AGRICULTURE
Animal and Plant Health Inspection Service
9 CFR Part 94
[Docket No. 02-072-2]
Change in Disease Status of Israel Because of BSE
AGENCY: Animal and Plant Health Inspection Service, USDA.
ACTION: Affirmation of interim rule as final rule.
-----------------------------------------------------------------------
SUMMARY: We are adopting as a final rule, without change, an interim rule that amended the regulations by adding Israel to the list of regions where bovine spongiform encephalopathy exists because the disease had been detected in a native-born animal in that region. The effect of the interim rule was a restriction on the importation of ruminants, meat, meat products, and certain other products of ruminants that had been in Israel. The interim rule was necessary to help prevent the introduction of bovine spongiform encephalopathy into the United States.
EFFECTIVE DATE: The interim rule became effective on June 4, 2002.
FOR FURTHER INFORMATION CONTACT: Dr. Gary Colgrove, Chief Staff Veterinarian, Sanitary Trade Issues Team, National Center for Import and Export, VS, APHIS, 4700 River Road Unit 38, Riverdale, MD 20737- 1231; (301) 734-4356.
SUPPLEMENTARY INFORMATION:
Background
The regulations in 9 CFR parts 93, 94, 95, and 96 (referred to below as the regulations) govern the importation of certain animals, birds, poultry, meat, other animal products and byproducts, hay, and straw into the United States in order to prevent the introduction of various animal diseases, including bovine spongiform encephalopathy (BSE).
In an interim rule effective June 4, 2002, and published in the Federal Register on July 18, 2002 (67 FR 47243-47244, Docket No. 02- 072-1), we amended the regulations in Sec. 94.18 (a)(1) by adding Israel to the list of regions where BSE exists due to the detection of BSE in a native-born animal in that region.
Comments on the interim rule were required to be received on or before September 16, 2002. We did not receive any comments. Therefore, for the reasons given in the interim rule, we are adopting the interim rule as a final rule.
This action also affirms the information contained in the interim rule concerning Executive Orders 12866 and 12988 and the Paperwork Reduction Act.
Further, for this action, the Office of Management and Budget has waived its review under Executive Order 12866.
Regulatory Flexibility Act
This action affirms an interim rule that amended the regulations by adding Israel to the list of regions where BSE exists. The effect of the interim rule was a restriction on the importation of ruminants, meat, meat products, and certain other products of ruminants that had been in Israel. The interim rule was necessary to help prevent the introduction of BSE into the United States.
The following analysis addresses the economic effects of the interim rule on small entities, as required by the Regulatory Flexibility Act.
The interim rule's restrictions on the importation of ruminants and ruminant products and byproducts from Israel are not expected to have a significant impact on a substantial number of small entities due to the fact that the restricted items are either not imported from Israel or are imported in very small amounts. There are three categories of imports that may be affected, but Israel's share of U.S. imports is small in each case.
The first category of affected imported commodities is ``Meat and edible meat offal, salted in brine, dried or smoked; edible flours and meals of meat or meat offal.'' Average total yearly imports of these products by the United States over the 3-year period 1999-2001 were valued at $24.6 million. Imports from Israel in 1999 were valued at $26,000. No imports of these products from Israel were reported for 2000 or 2001.
The second category of affected commodities is ``Preparations of a kind used in animal feeding.'' Average total yearly imports of these products, 1999-2001, were valued at $93.5 million. Imports from Israel had an average yearly value over this period of about $76,000. The final category of affected commodities is ``Other prepared or preserved meat, meat offal or blood.'' Average yearly imports of these products, 1999-2001, were valued at $101.2 million. Imports from Israel had an average yearly value over this period of about $2.7 million. It is apparent that Israel is a minor supplier to the United States of the ruminant products and byproducts affected by the BSE-related restrictions resulting from the interim rule. Therefore, we do not expect that the interim rule's restrictions on ruminants and ruminant products and byproducts from Israel will substantially affect any U.S. importers, large or small, of those commodities.
Under these circumstances, the Administrator of the Animal and Plant Health Inspection Service has determined that this action will not have a significant economic impact on a substantial number of small entities.
List of Subjects in 9 CFR Part 94
Animal diseases, Imports, Livestock, Meat and meat products, Milk, Poultry and poultry products, Reporting and recordkeeping requirements.
PART 94--RINDERPEST, FOOT-AND-MOUTH DISEASE, FOWL PEST (FOWL PLAGUE), EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, HOG CHOLERA, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND RESTRICTED IMPORTATIONS
Accordingly, we are adopting as a final rule, without change, the interim rule that amended 9 CFR part 94 and that was published at 67 FR 47243-47244 on July 18, 2002.
Authority: 7 U.S.C. 450, 7711-7714, 7751, 7754, 8303, 8306, 8308, 8310, 8311, and 8315; 21 U.S.C 136 and 136a; 31 U.S.C. 9701; 42 U.S.C. 4331 and 4332; 7 CFR 2.22, 2.80, and 371.4.
Done in Washington, DC, this 28th day of October, 2002. Bobby R. Acord, Administrator, Animal and Plant Health Inspection Service. [FR Doc. 02-27812 Filed 10-31-02; 8:45 am] BILLING CODE 3410-34-P
http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2002_register&docid=02-27812-filed
greetings List members,
MORE OF THE INFAMOUS USA NON-SPECIES CODING SYSTEM.
as long as the exporting country and the importing country know not what they are exporting (play dumb/stupid), this non-species coding system allows potential BSE/TSE materials to be imported and exported freely and legally...
TSS
What are the U.S. imports of affected animals or animal products from Israel?
The U.S. imported no live ruminants or ruminant meat from Israel since 1999. In 1999 a small amount of non-species specific meat and offal was imported and a small amount of fetal bovine serum (FBS) was also imported. FBS is considered to have a relatively low risk of transmitting BSE. Other imports from Israel during the period 1998-2001 included non-species specific preparations used in animal feeds and other non-food products of unspecified animals. For the category "preparations used in animal feeding, NESOI" that was imported into the U.S., it is possible that bovine meat or bovine byproducts could have been included in this category. However, the US Food and Drug Administration prohibits feeding of meat-and-bone meal to ruminants in the U.S.
HS Code
Description
Unit
1998
1999
2000
2001
Feed - non species specific
Total
45,030
48,000
50,649
43,000
2309909500
Preparations Used in Animal Feedings, NESOI
KG
45,030
48,000
50,649
43,000
Meat & offal- non species specific
Total
5
0
0
0
300110
Dried Organs
KG
5
0
0
0
Other animal products - ruminants
Total
24
0
0
0
3002100040
Fetal Bovine Serum (FBS)
KG
24
0
0
0
Source: World Trade Atlas
What is the level of passenger traffic arriving in the United States from Israel?
A total of 524,401 passengers arrived on direct flights to the U.S. from Israel in fiscal year 2000. This number does not include passengers who arrived in the U.S. from Israel via indirect flights.
Under APHIS-PPQ?s agricultural quarantine inspection monitoring, 284 air passengers from Israel were sampled for items of agricultural interest in fiscal year 2001. Seven of these passengers, or 2 percent, carried a total of 11 kg of meat items that could potentially harbor the pathogen that causes BSE. None of these passengers from whom meat items were confiscated reported plans to visit or work on a ranch or farm during their visit to the U.S.
Source: U.S. Department of Transportation and APHIS-PPQ Agricultural Quarantine Inspection data base.
http://www.aphis.usda.gov/vs/ceah/cei/bse_israel0602.htm
TSS
Docket Management
Docket: 02N-0276 - Bioterrorism Preparedness; Registration of Food Facilities, Section 305
Comment Number: EC -254
Accepted - Volume 11
http://www.fda.gov/OHRMS/DOCKETS/DOCKETS/02n0276/02N-0276-EC-254.htm
http://web.archive.org/web/20041012090622/http://www.fda.gov/OHRMS/DOCKETS/DOCKETS/02n0276/02N-0276-EC-254.htm
2023
FRIDAY, FEBRUARY 03, 2023
Netherlands Bovine Spongiform Encephalopathy BSE, atypical strain, L-type
Thursday, February 2, 2023
EFSA OIE WOHA UPDATES ON CHRONIC WASTING DISEASE CWD TSE PrP ZOONOSIS
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.
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.
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.
P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge
Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
With the experiment currently at 55 months post-inoculation, no other cattle in this study have developed clinical signs suggestive of prion disease. This study demonstrates that the H-type BSE agent is transmissible by the oronasal route.
These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
PRION CONFERENCE 2018 CONFERENCE ABSTRACT
Published: 23 June 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
The present study demonstrated successful intraspecies transmission of H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be minimally defined by oral transmission of different TSE agents (C-type, L-type, and H-type BSE agents) [59]. Oral transmission studies with H-type BSE-infected cattle have been initiated and are underway to provide information regarding the extent of similarity in the immunohistochemical and molecular features before and after transmission. In addition, the present data will support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE.
References...END
***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.
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
WEDNESDAY, NOVEMBER 30, 2022
USDA Bovine Spongiform Encephalopathy BSE, Scrapie, CWD, Testing and Surveillance 2022 A Review of History
SUNDAY, OCTOBER 16, 2022
USDA Transmissible Spongiform Encephalopathy TSE Prion Action Plan National Program 103 Animal Health 2022-2027
TUESDAY, MAY 31, 2022
USA Bovine Spongiform Encephalopathy BSE: description of typical and atypical cases
TUESDAY, SEPTEMBER 13, 2022
BSE pathogenesis in the ileal Peyer’s patches and the central and peripheral nervous system of young cattle 8 months post oral BSE challenge
TUESDAY, SEPTEMBER 07, 2021
Atypical Bovine Spongiform Encephalopathy BSE OIE, FDA 589.2001 FEED REGULATIONS, and Ingestion Therefrom
Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA
WEDNESDAY, JANUARY 12, 2022
Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA, what if?
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