USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
USDA National Scrapie Program FY 2025 Third Quarter Progress Report: July 2025
https://www.aphis.usda.gov/sites/default/files/scrapie-quarterly-report.pdf
Scrapie
Last Modified: August 18, 2025
Scrapie is a fatal, degenerative disease that affects the central nervous system of sheep and goats. It is classified as a transmissible spongiform encephalopathy. Infected flocks typically experience significant production losses. The U.S. sheep and goat industry continues to experience export losses and increased production and disposal costs because the United States is not free of scrapie.
Scrapie is difficult to detect. It can take 2 to 5 years for an animal to show signs of disease, and current diagnostic tests require brain or lymphoid tissue. Animals typically live 1 to 6 months after they begin to show signs. Most are infected as young lambs or kids, but adult animals can get it, too. Apparently healthy animals infected with the disease agent can spread it.
https://www.aphis.usda.gov/livestock-poultry-disease/sheep-goat/scrapie
2025 USDA EXPLANATORY NOTES – ANIMAL AND PLANT HEALTH INSPECTION SERVICE
In 2023, APHIS collected samples from more than 26,000 sheep and goats for scrapie testing. Out of the total number of animals tested in 2023, no animals tested positive for classical scrapie and one sheep tested positive for non-classical scrapie (Nor98-like). Unlike classical scrapie, non-classical scrapie is either not laterally transmissible or is transmissible at a very low rate. The WOAH and APHIS determined that it is not a disease of trade concern.
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Bovine spongiform encephalopathy
BSE, widely referred to as “mad cow disease,” is a progressive and fatal neurologic disease of cattle. The disease is caused by a transmissible abnormal prion protein. BSE is not a contagious disease and therefore is not spread through casual contact between cattle or with other species. BSE detections are separated into 2 distinct categories, classical and atypical. Classical BSE occurs through the consumption of contaminated feed. While classical BSE was identified as a significant threat in the 1990s, most years there are no detections made worldwide. This is a result of the successful implementation of effective control measures on an international scale. Atypical BSE refers to naturally and sporadically occurring forms, which are believed to occur in all bovine populations at a very low rate, and which have only been identified in older bovines when conducting surveillance. APHIS works with the USDA Food Safety and Inspection Service and the Food and Drug Administration to conduct ongoing BSE surveillance, allowing the United States to maintain BSE Negligible Risk status per the World Organisation for Animal Health’s (WOAH) standards to facilitate trade.
The WOAH evaluates countries that submit a request for disease freedom and assigns a points-based risk status for BSE. The BSE surveillance program uses WOAH's weighted surveillance points system, which reflects that the best BSE surveillance programs focus on obtaining quality samples from targeted populations rather than looking at the entire adult cattle population. The WOAH’s surveillance points system also incorporates a country’s history with the disease, the implementation and enforcement of cattle feed regulations, and their overall BSE surveillance. In 2023, the Agency tested for BSE in 22,835 cattle, resulting in 239,648 points, exceeding the WOAH’s international surveillance standards (21,429 points per year) by 11 times. No cases of classical BSE were detected in 2023; however, an atypical BSE case was detected at slaughter as part of the BSE surveillance program. An epidemiologic investigation was conducted in accordance with the BSE Response Plan
https://www.usda.gov/sites/default/files/documents/22-APHIS-2025-ExNotes.pdf
Outbreaks The United Kingdom
The first two cases of BSE were identified in cows in 1986 in the United Kingdom. The cows were likely infected in the 1970s.
The U.K. quickly became the epicenter of the outbreak. Overall, more than 184,000 cows in the U.K. died from BSE between 1986 and 2015. The outbreak was widespread, with more than 35,000 U.K. herds affected.
Cases peaked in 1993 at nearly 1,000 new cases per week. Cases deceased drastically after control measures were implemented. BSE cases are still reported occasionally but are very rare.
Other Countries
Outside the U.K., BSE was first reported in Ireland in 1989 and Portugal and Switzerland in 1990.
By 2005, the number of countries reporting BSE among native cattle increased to 24, with the majority in Europe.
North America
The first North American BSE case was reported in 1993 in a cow imported into Canada from the UK. Rendered cohorts of this cow may have been responsible for 19 additional Canadian BSE cases beginning in 2003.
In addition, animal health officials have identified 6 BSE cases in cows in the United States.
One was imported from Canada and is believed to have been infected there. The others were diagnosed with atypical BSE, which many researchers believe to be a sporadic illness not caused by contaminated feed.
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https://www.cdc.gov/mad-cow/php/animal-health/index.html
https://www.aphis.usda.gov/livestock-poultry-disease/cattle/bse
PLEASE BE ADVISED OF UPDATED SCIENCE ON BOTH ATYPICAL NOR98 SCRAPIE, AND ATYPICAL BSE, spontaneous vs sporadic BSE, and oral transmission studies there from, OIE should be very concerned with, imo (see below these reports, toward the end of this report, the last documented atypical L-type Bovine Spongiform Encephalopathy aka Mad Cow Case in 2023 History)…terry
2024 USDA EXPLANATORY NOTES – ANIMAL AND PLANT HEALTH INSPECTION SERVICE
In 2022, APHIS collected samples from more than 23,000 sheep and goats for scrapie testing. Out of the total number of animals tested in 2022, no animals tested positive for classical scrapie and one sheep tested positive for non-classical scrapie (Nor98-like). Unlike classical scrapie, non-classical scrapie is either not laterally transmissible or is transmissible at a very low rate. The WOAH and APHIS determined that it is not a disease of trade concern.
https://www.usda.gov/sites/default/files/documents/23-2024-APHIS.pdf
2023 USDA EXPLANATORY NOTES – ANIMAL AND PLANT HEALTH INSPECTION SERVICE
In FY 2021, APHIS collected samples from more than 30,000 sheep and goats for scrapie testing. Out of the total number of samples processed and reported in FY 2021, one sheep tested positive for classical scrapie and one sheep tested positive for non-classical scrapie (Nor98-like). Unlike classical scrapie, non-classical scrapie is either not laterally transmissible or is transmissible at a very low rate. The OIE and APHIS determined that it is not a disease of trade concern.
https://www.usda.gov/sites/default/files/documents/23-2023-APHIS.pdf
Scrapie cases USA 2023
https://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/sheep-sampling-minimums-fy2023.pdf
2022 USDA EXPLANATORY NOTES – ANIMAL AND PLANT HEALTH INSPECTION SERVICE
In FY 2020, APHIS collected samples from 33,839 sheep and goats for scrapie testing. This number represents sample results reported by October 15, 2020 and is expected to slightly increase as the remaining results are processed and reported. No animals tested positive for classical scrapie. Two sheep tested positive at slaughter for non-classical scrapie (Nor98-like). Unlike classical scrapie, non-classical scrapie is either not laterally transmissible or is transmissible at a very low rate. The OIE and APHIS determined that it is not a disease of trade concern.
https://www.usda.gov/sites/default/files/documents/22APHIS2022Notes.pdf
2021 USDA EXPLANATORY NOTES – ANIMAL AND PLANT HEALTH INSPECTION SERVICE
In FY 2019, APHIS collected samples from 34,730 sheep and goats for scrapie testing, detecting 7 classical scrapie positive animals. Of these animals, five sheep and one goat were from a source flock in Pennsylvania that was found in August 2018, depopulated in October 2018, and tested for scrapie in November 2018. A second goat, which was from an Indiana herd, was sampled at slaughter in June 2019. The source flock completed a cleanup plan and was placed on a 5-year monitoring plan. The source herd of the positive Indiana goat no longer contained any exposed animals and was also placed on a 5-year monitoring plan. A trace-back investigation narrowed the goat’s birth herd to two possible herds. Animals in both herds tested negative for scrapie and were placed on 5-year monitoring plans. There were no classical scrapie cases detected in slaughter sheep in FY 2019.
Also in FY 2019, two sheep tested positive at slaughter for non-classical scrapie (Nor98-like) and were traced back to Colorado flocks. Unlike classical scrapie, non-classical scrapie is either not laterally transmissible or is transmissible at a very low rate,and the OIE and APHIS determined that it is not a disease of trade concern.
https://www.usda.gov/sites/default/files/documents/20aphis2021notes.pdf
2020 USDA EXPLANATORY NOTES – ANIMAL AND PLANT HEALTH INSPECTION SERVICE
Sheep and Goat The National Scrapie Eradication Program (NSEP) focuses on improving the health of the national sheep flock and goat herd, reducing scrapie-associated economic losses and increasing international marketing opportunities. Regulatory scrapie slaughter surveillance efforts began in FY 2003, and were designed to identify scrapie infected flocks and herds by sampling animals at slaughter. Since the surveillance program began, the program has collected more than 600,000 samples at slaughter. When first measured in FY 2002, the rate of cull sheep sampled at slaughter that tested positive for classical scrapie was 1 in 500 (0-2%).
In FY 2018, APHIS collected samples from 43,625 sheep and goats for scrapie testing, detecting three positive (0.0068%) cases. These figures are based on sample submissions and testing completed by September 30, 2018. FY 2018 values are expected to change when testing is completed for all animals sampled in FY 2018.
In October 2017, a non-classical scrapie case was detected in a sheep from Virginia sampled at slaughter. As a result, the non- classical scrapie affected flock was placed on a 5-year monitoring plan. Unlike classical scrapie, non-classical scrapie (Nor98-like) is either not laterally transmissible or is transmissible at a very low rate and the OIE and APHIS have determined that it is not a disease of trade concern.
In April 2018, scrapie was detected in a sheep from North Carolina sampled at slaughter. There was insufficient positive tissue available to conclusively determine if the case was classical or non-classical scrapie using standard testing. The flock was depopulated and no other sheep in the flock subsequently tested positive for scrapie.
In August 2018, classical scrapie was detected through slaughter surveillance in a goat from Pennsylvania. All scrapie susceptible sheep and goats exposed to that goat are awaiting depopulation, and APHIS will monitor the herd of origin for five years.
The NSEP has a voluntary flock certification component, the Scrapie Free Flock Certification Program (SFCP). Participation in the SFCP enables producers to enhance the marketability of their animals by protecting them from scrapie and provides participants an avenue to export sheep and goats. At the end of FY 2018, 264 flocks were enrolled in the SFCP. Of these, 47 were export certified (scrapie-free), 54 were export monitored (working toward scrapie freedom), and 163 were select monitored (reduced scrapie risk).
https://www.usda.gov/sites/default/files/documents/20aphis2020notes.pdf
2019 President’s Budget Animal and Plant Health Inspection Service
Sheep and Goats
The National Scrapie Eradication Program (NSEP) focuses on improving the health of the national sheep flock and goat herd, relieving sheep and goat producers of scrapie-associated economic losses and increasing international marketing opportunities. Since 2003, the percentage of cull sheep sampled at slaughter that tested positive for classical scrapie has decreased by 100 percent. In FY 2017, APHIS collected samples from 42,030 sheep and goats for scrapie testing. As of September 30, 2017, the percent of cull sheep tested that were found positive at slaughter and adjusted for face color was 0 percent, compared to 0.001 percent in FY 2016. Based on the goats sampled at slaughter since FY 2003 and tested as of September 30, 2017, the prevalence of scrapie in U.S. cull goats is 0.002 20-70 percent.
With the exception of one goat from a long-standing herd under quarantine, no sheep or goats have tested positive for classical scrapie since April 2016.
In FY 2017, the program depopulated the last known classical scrapie infected herd, and two premises are still under herd plans pending disinfection. Unlike classical scrapie, nonclassical scrapie is either not laterally transmissible or is transmissible at a very low rate and the World Animal Health Organisation and APHIS have determined that it is not a disease of trade concern.
In FY 2017, slaughter surveillance detected two nonclassical scrapie cases. The nonclassical scrapie affected flocks will be placed on a 5-year monitoring plans.
The NSEP has a voluntary flock certification component, the Scrapie Free Flock Certification Program (SFCP). Participation in the SFCP enables producers to enhance the marketability of their animals by protecting them from scrapie and provides participants an avenue to export sheep and goats. At the end of FY 2017, 333 flocks were enrolled in the SFCP. Of these, 46 were export certified (scrapie-free), 67 were export monitored (working toward scrapie freedom), and 220 were select monitored (reduced scrapie risk).
https://www.usda.gov/sites/default/files/documents/20aphis2019notes.pdf
2018 President’s Budget Animal and Plant Health Inspection Service
Sheep and Goats
In FY 2016, the program identified one flock infected with classical scrapie and one infected with Nor98-like scrapie through slaughter surveillance, and two flocks infected with classical scrapie through on-farm surveillance.
Two of these classical scrapie infected flocks, as well as one identified in FY 2015, completed flock cleanup plans in FY 2016. The other classical scrapie infected flock completed depopulation of high-risk exposed animals with disinfection to be completed in the first quarter of FY 2017.
An additional 10 sheep were confirmed with classical scrapie through testing of sheep depopulated from these infected flocks as part of flock clean-up activities conducted in FY 2016.
The Nor98-like scrapie affected flock will be placed on a 5-year monitoring plan. The NSEP has a voluntary flock certification component, the Scrapie Free Flock Certification Program (SFCP).
Participation in the SFCP enables producers to enhance the marketability of their animals by protecting them from scrapie and provides participants an avenue to export sheep and goats. At the end of FY 2016, 409 flocks were enrolled in the SFCP. Of these, 34 were export certified (scrapie-free), 98 were export monitored (working toward scrapie freedom), and 277 were select monitored (reduced scrapie risk).
On September 10, 2015, APHIS published a proposed rule in the Federal Register to amend NSEP regulations. The main changes include aligning similar identification and recordkeeping requirements for sheep and goat owners; formalizing the use of genetic testing to assign risk levels to sheep; and providing the APHIS Administrator with the authority to relieve requirements for sheep and goats exposed to scrapie types that do not pose a significant risk of transmission. APHIS took comments on the proposed rule through December 9, 2015. The Agency anticipates that a more flexible approach to disease investigations and affected flock management, and more consistent animal identification and recordkeeping requirements, will increase the effectiveness of the eradication program. APHIS also took comments on the draft NSEP standards through December 9, 2015. These standards contain cooperative procedures and standards that APHIS has adopted for eradicating classical scrapie from the United States. They are intended to help State and Federal animal health personnel implement the NSEP consistently and equitably. APHIS has reviewed the comments and is in the process of developing the final rule.
https://www.usda.gov/sites/default/files/documents/20aphisexnotes2018.pdf
2017 Explanatory Notes Animal and Plant Health Inspection Service
The National Scrapie Eradication Program (NSEP) focuses on improving the health of national sheep flocks and goat herds, relieving sheep and goat producers of scrapie-associated economic losses and increasing international marketing opportunities. Since 2003, the percentage of positive scrapie sheep found at slaughter has decreased by 98 percent. In FY 2015, APHIS tested 40,862 samples from sheep and goats for scrapie, compared to 48,102 samples tested in FY 2014. This decrease was largely due to APHIS’ redirection of field personnel as part of the highly pathogenic avian influenza response.
Also in that response, this program assisted in the epidemiological investigation and cleanup of four flocks in which the program traced scrapie-positive animals and associated trace forward flocks.
At the end of FY 2015, the percent of cull sheep found positive at slaughter and adjusted for face color was 0.004 percent compared to 0.019 percent in FY 2014.
In addition, the first positive goats were found through slaughter surveillance in FY 2015.
Based on the goats sampled at slaughter and tested as of September 30, 2015, the prevalence of scrapie in U.S. cull goats is 0.004. At the end of FY 2015, 441 flocks were enrolled in the Scrapie Free Flock Certification Program (SFCP). Of these, 22 were export certified (i.e., the flock demonstrated it was free of scrapie), 142 were export monitored (i.e., the producers were working to demonstrate freedom from scrapie), and 277 were select monitored (i.e., the producers were observing animals for signs of scrapie and testing a specified number to demonstrate reduced risk for scrapie). Participation in the SFCP enables producers to enhance the marketability of their animals by protecting them from scrapie. The transition to the revised SFCP program, initiated in June 2013, is complete, and the program is now providing a greater amount of flock level surveillance for the eradication program.
On September 10, 2015, APHIS published a proposed rule in the Federal Register to amend NSEP regulations. The main changes include aligning similar identification and recordkeeping requirements for sheep and goat owners; formalizing the use of genetic testing to assign risk levels to sheep; and providing the APHIS Administrator with the authority to relieve requirements for sheep and goats exposed to scrapie types that do not pose a significant risk of transmission. APHIS is seeking comments on the proposed rule through November 9, 2015. The Agency anticipates that a more flexible approach to disease investigations and affected flock management, and more consistent animal identification and recordkeeping requirements, will increase the effectiveness of the eradication program. APHIS is also seeking comments on the draft NSEP standards through November 9, 2015. These standards contain cooperative procedures and standards that APHIS has adopted for eradicating classical scrapie from the United States. They are intended to help State and Federal animal health personnel implement the NSEP consistently and equitably. They are designed for the prevention, monitoring, and eradication of classical scrapie disease from domestic sheep flocks and goat herds.
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https://www.usda.gov/sites/default/files/documents/20aphis2017notes.pdf
2016 Explanatory Notes Animal and Plant Health Inspection Service
https://www.usda.gov/sites/default/files/documents/20aphis2016notes.pdf
2015 Explanatory Notes Animal and Plant Health Inspection Service
https://www.usda.gov/sites/default/files/documents/20aphis2015notes.pdf
2014 Explanatory Notes Animal and Plant Health Inspection Service
https://www.usda.gov/sites/default/files/documents/18aphis2014notes.pdf
Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep.
In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan.
With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.
http://gain.fas.usda.gov/Recent%20GAIN%20Publications/This%20Week%20in%20Canadian%20Agriculture%20%20%20%20%20Issue%2028_Ottawa_Canada_11-6-2009.pdf
SATURDAY, DECEMBER 04, 2021
Final rule on the Importation of Sheep, Goats, and Certain Other Ruminants (APHIS-2009-0095) Scrapie, BSE, CWD, TSE Prion
https://scrapie-usa.blogspot.com/2021/12/final-rule-on-importation-of-sheep.html
THURSDAY, JANUARY 7, 2021
Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021
Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021
Nor98 cases Diagnosed in the US. To Date
Nor98 cases Diagnosed in the US.
Flock of Origin State FY
Wyoming 2007
Indiana 2007
Pennsylvania 2008
Oregon 2010
Ohio 2010
Pennsylvania 2010
Untraceable 2010
California 2011
Montana 2016
Utah 2017
Montana 2017
Virginia 2018
Colorado 2019
Colorado 2019
Wyoming 2020
Montana 2020
Pennsylvania 2021
Personal Communication from USDA et al Mon, Jan 4, 2021 11:37 am...terry
TUESDAY, SEPTEMBER 22, 2020
APHIS USDA MORE SCRAPIE ATYPICAL Nor-98 Confirmed USA September 15 2020
17 cases of the Nor98 in the USA to date, location, unknown...tss
17 Nor98-like cases since the beginning of RSSS.
https://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_report.pdf
17 Nor98-like cases since the beginning of RSSS. No animals have tested positive for classical scrapie in FY 2021.
https://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_report.pdf
TUESDAY, SEPTEMBER 22, 2020
APHIS USDA MORE SCRAPIE ATYPICAL Nor-98 Confirmed USA September 15 2020
https://scrapie-usa.blogspot.com/2020/09/aphis-usda-more-scrapie-atypical-nor-98.html
MONDAY, JULY 27, 2020
APHIS USDA Nor98-like scrapie was confirmed in a sheep sampled at slaughter in May 2020
https://nor-98.blogspot.com/2020/07/aphis-usda-nor98-like-scrapie-was.html
MONDAY, JULY 13, 2020
Efficient transmission of classical scrapie agent x124 by intralingual route to genetically susceptible sheep with a low dose inoculum
https://scrapie-usa.blogspot.com/2020/07/efficient-transmission-of-classical.html
WEDNESDAY, MAY 29, 2019
***> Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures
https://nor-98.blogspot.com/2019/05/incomplete-inactivation-of-atypical.html
THURSDAY, DECEMBER 31, 2020
Autoclave treatment of the classical scrapie agent US No. 13-7 and experimental inoculation to susceptible VRQ/ARQ sheep via the oral route results in decreased transmission efficiency
https://scrapie-usa.blogspot.com/2020/12/autoclave-treatment-of-classical.html
Snip…see full text;
https://nor-98.blogspot.com/2021/01/atypical-nor-98-scrapie-tse-prion-usa.html
Date: Mon, 9 Dec 2002 21:21:10 -0600
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: SCRAPIE 'USA' ANNUAL REPORT (105 newly infected flocks 2002) & CWD IN USA
As of September 30, 2002, there were 45 scrapie infected and source flocks (figure 3).
There were 105 newly infected flocks, reported in FY2002 (figure 4).
In addition, 379 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2002 (figure 5) and (figure 6).
Five cases of scrapie in goats were reported in FY 2002 (figure 7), the last of which was confirmed in August 2002.
New infected and source flocks numbers and the number of these flocks released in FY 2002 are depicted in chart 4.
One hundred (100) flocks which is 67 percent of the scrapie infected and source flocks present in FY 2002 were released or put on clean-up plans in FY2002. Slaughter Surveillance Slaughter Surveillance is currently in Phase II which is intended to determine the prevalence of scrapie in the US culled sheep population.
Through September 2002 samples from 3,269 sheep were submitted to NVSL for testing. Samples from a total of 6,795 sheep have been submitted since the beginning of Phase II on April 1, 2002. Surveillance regions are depicted in (figure 8).
Scrapie Testing During FY 2002 11,751 animals have been tested for scrapie which includes: 2,711 regular necropsy cases, 1,343 third eyelid biopsies for the test validation project, 546 third eyelid biopsies for the regulatory program, and approximately 7,151 animals for Phase I & II of SOSS (chart 5).
Laboratory testing has been taking 10 - 11 days on average with a range of 3 - 34 days. Ear Tag Orders During FY 2002 9.9 million plastic and 6.0 million metal tags were distributed by APHIS (chart 6).
http://www.aphis.usda.gov/vs/nahps/scrapie/annual_report/annual-report.html
NEW SCRAPIE INFECTED AND SOURCE FLOCKS
http://www.aphis.usda.gov/vs/nahps/scrapie/annual_report/figure04.gif
Epidemiology of Scrapie in the United States
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Scrapie Field Trial was developed at Mission, Texas, what if?
Scrapie Field Trial was developed at Mission, Texas, on 450 acres of pastureland, part of the former Moore Air Force
EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES
Academic Preg
James Hourriganl, Albert Klingsporn2, Edited by » Peast
W. W. Clark3, and M, de Camp4
United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services
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METHODS
A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission,
Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods
to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.
The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas:
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RESULTS
Table 1 indicated that previously exposed sheep brought to the Station at various times and ages (1 to 89 months old) included 333 Suffolks at risk. Of these, 98 (29%) developed scrapie. This demonstrated the necessity to slaughter such sheep to prevent further Spread of the disease, These pre- viously exposed Suffolks were bred at the Station and produced 446 progeny at risk. Of these 153 (34%) developed scrapie.
Although the minimum and average ages when scnapied were similar for both groups, some of the previously exposed Suffolks brought to the Station developed scrapie when much older--ewes 60 to 142 months old and rams 67 to 102 months old. O£ the 153 Suffolks born at the Station, only 3 were more than 60 months of age (65, 66, and 69 months old).
This difference in age scrapied was attributed to the fact that the Suffolks born at the Station may have been sub- ject to a greater exposure from birth.
It was also observed that when both dam and progeny were scrapied, the progeny nearly always developed clinical disease at a younger age than their respective dam. Thirty- two dams were scrapied at an average of 60 months of age. Forty-six of their progeny developed the disease at an average of 38 months (range 25 to 53 months). Thirty-seven of the 46 progeny were younger than the dam (average 20 months younger, range 2 to 99 months younger). Two were scrapied at the same age as their dams, and 8 were older (average 5 months, range 1 to 13 months older).
++. Although the incidence of scrapie was considerably Greater in the progeny of scrapied compared to free dams, the progeny of either scrapied or free dams manifested scrapie at the typical age and irrespective of the age their respective dams were scrapied. The differences in ages that dams and progeny were scrapied was believed due to difference of exposure, particularly whether they were exposed at an early age,
Table 2 summarized the data on exposed Suffolks and was Prepared so as to show scrapie incidence in the progeny of dams and sires of known Scrapie status. The scrapie incidence in the progeny of Free X Free parents was 25%, progeny of scrapied Sires 39%, and scrapied dams 42%. When both sire and dam were scrapied, the scrapie incidence in 18 Progeny at risk was 78%.
When the scrapie status of the sire was ignored, scrapie incidence in th- progeny of free dams was 34% and in pre y of scrapied da as 62%. When the scrapie status of the dam was ignored, scrapie incidence in the progeny of free sires was 26% and in the progeny of scrapied sires was 452.
Although the scrapie incidence was nearly double in the progeny of scrapied compared to free dams, the latter con- tributed a greater number of scrapied progeny, 116, compared to only 51 cases which had scrapied dams. This was because free dams made a considerably heavier contribution to the progeny at risk4-342 compared to 82. It was felt that in farm flocks a similar situation could exist.
It was possible that free dams could have been mis- classified; however, this was unlikely to have been significant, unless "nonclinical or carrier" dams exist. In this Suffolk group, the ages of 100 free dams of scrapied progeny ranged from 25 to 160 (average 97) months. These free dams did not show clinical signs of scrapie,”and there were no histopathological lesions suggesting scrapie in those which died, If one cannot classify as free, ewes which have reached 97 months (average) and did not develop the disease, from a practical standpoint, it is not possible to classify sheep as free, at least on the basis of clinical signs and histology. The free dams of 50% of the scrapied progeny were more than 100 months of age, averaging 126 months.
Upon arrival at the Mission Station at 3 to 9 months of age, the 140 previously unexposed sheep and goats were placed in infected pastures and corrals and were subjected to con- tact with a succession of natural cases of scrapie in sheep, and eventually also in goats. These animals were bred only within their respective groups and were not crossbred to other breeds of sheep or those brought to the Station from infected flocks or their progeny. The male or female animals mixed freely with animals of their respective sex of the infected Flock and were similarly identified and subjected to similar flock management and diagnostic procedures.
Table 3 indicated that natural scrapie had occurred in 5 of the 140 previously unexposed sheep. One case each occurred in Rambouillet, Targhee, and Hampshire ewes at 88, 89, and 89 months of age and in % Suffolk ewes at 73 and 102 months of age, and 85, 82, 80, 64, and 93 months following initial natural exposure. This represented a natural situation involving lateral spread, under the circumstances involved, when sheep were not exposed when very young. Scrapie was not detected clinicaliy or histologically in any of the dairy or Angora goats brought to the Station. The disease occurred in an average of 27% of the progeny of previously unexposed sheep or goats born at the Station and included cases in progeny of all breeds of sheep or goats taken there, The incidence in the progeny ranged from 14% in Rambouillet sheep to 61% in dairy goats. ~
These data showed that scrapie spread laterally, by contact exposure, from scrapied te previously free animals, but at an apparently lower rate when exposure was first received at the age of 3 to 9 months. These animals were presumed to be susceptible to the disease, as their progeny developed scrapie at rates and ages similar (on the average) to the progeny, pf previously exposed Suffolk sheep born and reared in the same environment.
It was suggested that the progeny of previously unexposed animals developed scrapie at a much higher rate than their parents, and at a younger age, because they were subjected to exposure from birth. The data did not rule out the possibility that the animals born at the Station could have also received the virus from their dams "vertically" prior te, at, or following birth.
Table 4 summarized the scrapie incidence in #he progeny, born at the Station, of previously unexposed dairy goats.
The data were prepared so as to show scrapie incidence in the progeny of dams and sires of known scrapie status.
The 58% incidence in the progeny (24 at risk) of Free X Free parents was more than twice the 25% seen in the Suffolk group (Table 2). Scrapied sires did not increase the incidence in goat progeny (it was 44%); scrapied dams increased the incidence to 71%. When both sire and dam were scrapied the incidence was 89%, with only 9 goat progeny at risk.
When the scrapie status of the sire was ignored, the scrapie incidence in the progeny of free dams was 56% and in the progeny of scrapied dams it was 74%.
Free dams contributed 34 progeny at risk and scrapied dams 31 progeny.
When the scrapie status of the dam was ignored, scrapie incidence was 64% in the progeny of free sires and a similar 66% in the progeny of scrapied sires.
A total of 244 sheep (127 Suffolk, 59 Rambouillet, and 58 Targhee) were removed from scrapie exposure within a few hours of birth or at 4, 9, or 20 months of age and placed in isolation pens. Removal of sheep from exposure at these ages was selected as being representative of usual flock operations when sheep might be sold from an infected flock at weaning, the first fall or the second fall after their birth.
Table 5 reflected the fate of such animals. Four of the 6 scrapied sheep which had been isolated at birth were Suffolks and the 2 older animals were Targhees. The first case in the group isolated at birth was a Targhee, progeny of a ewe that did not develop clinical scrapie. The scrapie incidence in 36 at risk Suffolks removed from exposure at birth was 11%, con- siderably less -“en that expected had these animals remz d in an infected en ment.
Table 6 reflected the status of 51 goats isolated from scrapie exposure at birth, and at 6, 8 to 10, 20, 32 to 59 and 60 to 82 months of age.
None of the goats removed at birth developed scrapie, although all 5 of those alive at 5 years of age had scrapied dams and 1 also had a scrapied sire. The sire of the remaining 4 had sired 7 scrapied progeny. Under such circumstances, had they remained in an infected environment nearly all of these goats would have been expected to develop scrapie. With the exception of the 20 month group, scrapie occurred at an incidence of 25 to 100% in ali other groups and at the expected age. A further observation was that 4 of the progeny of these dairy goats, born and kept apart from any sheep, developed scrapie which suggested that goats were not "dead- end hosts" insofar as scrapie was concerned.
Table 7 recorded the fate of progeny of certain selected scrapied or free Suffolk sheep or dairy goat dams.’
Suffolk ewe G298 was scrapied at 46 months of age. She had twin lambs in 1969 and 1 lamb in 1970. All 3 lambs developed scrapie. Suffolk ewe G27a was scrapied at 39 months. Her lamb born in 1966 was scrapied at 53 months; however, her lambs born in 1967 and 1968 remained free--lived to 102 months of age.
Suffolk ewe G25a died at 131] months of age and was nega- tive clinically and histologically. Mice remained negative following intracerebral inoculation of brain, spleen, and lymph nodes from this ewe. This ewe had 9 progeny at risk, of which 4 developed scrapie and 5 did not. There was no dis- cernible pattern to the cases. In two instances, 1 twin was scrapied and 1 remained free.
Goat B259 was scrapied when 43 months old. All of her 6 progeny at risk developed scrapie.
Goat B14a remained free and died at 101 months of age. Of her 11 progeny at risk, 7 were scrapied and 4 were not.
It was observed at the Station that when scrapied dams had several progeny at risk, 1 or more progeny usually developed the disease. However, many such scrapied dams also had progeny which lived, or are living, considerably beyond the age of their dams and beyond the age animals born at the Station manifested the disease.
It was also observed that individual free dams had free progeny in earlier years followed by scrapied progeny when they were older, or had scrapied progeny when young followed by free progeny when older, or scrapie and free progeny dis- persed throughout the dam's breeding life. The same situation occurred in progeny of scrapied dams; however, the pattern was less irregular due to the smaller number of progeny from each scrapied dam and the higher incidence of scrapie in such progeny. Circumstances prevented breeding all ewes ary year and, thus, many had only 1 progeny at risk. Scrapie developed in 100% of the single progeny at risk of 11 scrapied and 15 free dams. The 26 scrapied progeny were equally divided between ewes and rams.
Table 8 reflected the difference in age scrapied of - sheep brought to the Station compared to the age scrapied of those born there. Although the average age of previously exposed sheep (Suffolks) brought to the Station did not differ greatly from the overall average, several animals brought to the Station developed the disease at quite advanced ages. The previously unexposed scrapied animals brought to the Station were also considerably older than animals born there. Progeny of scrapied dams developed the disease at a slightly younger age than did progeny of free dams. The average age was nearly the same for males and females.
DISCUSSION
snip...see full text;
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
Scrapie Field Trial was developed at Mission, Texas, on 450 acres of pastureland, part of the former Moore Air Force Base
EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
SUNDAY, JANUARY 19, 2025
Scrapie Field Trial was developed at Mission, Texas, what if?
Epidemiology of Scrapie in the United States 1979
https://chronic-wasting-disease.blogspot.com/2025/01/scrapie-field-trial-was-developed-at.html
EFSA atypical Scrapie
***> 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
***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2021.6686
https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2021.6686
https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2021.6686
https://efsaopinionbseanimalprotein.blogspot.com/2021/07/efsa-scientific-report-on-analysis-of.html
Experimental transmission of ovine atypical scrapie to cattle
Timm Konold, John Spiropoulos, Janet Hills, Hasina Abdul, Saira Cawthraw, Laura Phelan, Amy McKenna, Lauren Read, Sara Canoyra, Alba Marín-Moreno & Juan María Torres
Veterinary Research volume 54, Article number: 98 (2023)
Abstract
Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.
snip...
This is the first study in cattle inoculated with naturally occurring scrapie isolates that found the presence of prions resembling classical BSE in bovine brain although this was limited to detection by the ultrasensitive PMCA. The results from thermostability assay confirmed that the isolates were as thermoresistant as the BSE agent as proven in other studies [36, 48]. Previous PMCA studies with various British atypical scrapie isolates did not find any evidence of amplification [49, 50]. This may be explained by the use of ovine brain as substrate rather than brain from Bov-Tg110 mice, which may facilitate conversion to classical BSE prions.
Two hypotheses for prion strain propagation in cross-species transmission experiments have been proposed: conformational selection favours a particular strain conformation out of a mixture of conformations in a scrapie isolate whilst mutation results in the conformational shift of one conformation into another [51]. Following on from the study in mice [17], it has been subsequently suggested that classical BSE properties that arise in atypical scrapie isolates transmitted to cattle may be due to conformational mutation in a new host [52]. It does not confirm that the atypical scrapie agent is the origin of the classical BSE epidemic and further transmission studies would be required to see whether classical BSE can be generated.
Would PMCA applied to brains from cattle exposed to TSE agents other than classical BSE and atypical scrapie also produce a classical BSE-like molecular phenotype? The PMCA product obtained in the thermostability test using a thermosensitive classical scrapie control showed a profile unlike classical BSE. Atypical BSE has been linked to the origin of classical BSE because of its conversion into classical BSE following serial passages in wild-type mice (L-type BSE [11]) and bovine transgenic mice (H-type BSE [53]). Although we have not tested PMCA products of atypical BSE isolates as part of this study, there is no evidence that PMCA products from atypical BSE convert into classical BSE, at least for H-type BSE using bovine brain as substrate [54]. In fact, we were unable to propagate H-type BSE using the same methodology (S Canoyra, A Marín-Moreno, JM Torres, unpublished observation).
The study results support the decision to maintain the current ban on animal meal in feedstuffs for ruminants, particularly as atypical scrapie occurs world-wide, and eradication is unlikely for a sporadic disease.
In summary, experimental inoculation of cattle with the atypical scrapie agent may produce clinical disease indistinguishable from classical BSE, which cannot be diagnosed by conventional diagnostic tests, but prions can be amplified by ultrasensitive tests in both clinically affected and clinically unremarkable cattle, which reveal classical BSE-like characteristics. Further studies are required to assess whether a BSE-like disease can be confirmed by conventional tests, which may initially include a second passage in cattle.
https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-023-01224-3
=====
Abstract for Prion 2023
Title: Transmission of atypical BSE: a possible origin of Classical BSE in cattle
Authors: Sandor Dudas1, Samuel James Sharpe1, Kristina Santiago-Mateo1, Stefanie Czub1, Waqas Tahir1,2, *
Affiliation: 1National and WOAH reference Laboratory for Bovine Spongiform Encephalopathy, Canadian Food inspection Agency, Lethbridge Laboratory, Lethbridge, Canada. 2Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
*Corresponding and Presenting Author: waqas.tahir@inspection.gc.ca
Background: Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease of cattle and is categorized into classical and atypical forms. Classical BSE (CBSE) is linked to the consumption of BSE contaminated feed whereas atypical BSE is considered to be spontaneous in origin. The potential for oral transmission of atypical BSE is yet to be clearly defined.
Aims: To assess the oral transmissibility of atypical BSE (H and L type) in cattle. Should transmission be successful, determine the biochemical characteristics and distribution of PrPSc in the challenge cattle.
Material and Methods: For oral transmission, calves were fed with 100 g of either H (n=3) or L BSE (n=3) positive brain material. Two years post challenge, 1 calf from each of the H and L BSE challenge groups exhibited behavioural signs and were euthanized. Various brain regions of both animals were tested by traditional and novel prion detection methods with inconclusive results. To detect infectivity, brain homogenates from these oral challenge animals (P1) were injected intra-cranially (IC) into steer calves. Upon clinical signs of BSE, 3/4 of IC challenged steer calves were euthanized and tested for PrPSc with ELISA, immunohistochemistry and immunoblot.
Results: After 6 years of incubation, 3/4 animals (2/2 steers IC challenged with brain from P1 L-BSE oral challenge and 1/2 steer IC challenged with brain from P1 H-BSE oral challenge) developed clinical disease. Analysis of these animals revealed high levels of PrPSc in their brains, having biochemical properties similar to that of PrPSc in C-BSE.
Conclusion: These results demonstrate the oral transmission potential of atypical BSE in cattle. Surprisingly, regardless of which atypical type of BSE was used for P1 oral challenge, PrPSc in the P2 animals acquired biochemical characteristics similar to that of PrPSc in C-BSE, suggesting atypical BSE as a possible origin of C-BSE in UK.
Presentation Type: Oral Presentation
Funded by: CFIA, Health Canada, Alberta Livestock and Meat Agency, Alberta Prion
Research Institute
Grant Number: ALMA/APRI: 201400006, HC 414250
Abstract for Prion 2023
Acknowledgement: TSE unit NCAD, Lethbridge (Jianmin Yang, Sarah Bogart, Rachana Muley, Yuanmu Fang, Keri Colwell, Renee Anderson, John Gray, Rakhi Katoch) (CFIA, Canada), Dr. Catherine Graham (NSDA, Canada), Dr. Michel Levy (UCVM, Canada), Dr. Martin Groschup (FLI, Germany), Dr. Christine Fast (FLI, Germany), Dr. Bob Hills (Health Canada, Canada)
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
SUNDAY, APRIL 06, 2025
Failure to prevent classical scrapie after repeated decontamination of a barn Failure to prevent classical scrapie after repeated decontamination of a barn
Published: 25 March 2025
Timm Konold, John Spiropoulos, Peter Bellerby & Hugh A Simmons BMC Research Notes volume 18, Article number: 126 (2025) Cite this article
Prions, the causative agent of scrapie in sheep, are extremely resistant to disinfection and can remain biologically active for years, which makes it challenging to prevent re-infection of susceptible animals on farms after a scrapie outbreak. The present study investigated the effectiveness of disinfection of a barn that previously housed scrapie-affected sheep as part of the husbandry of scrapie infected sheep on the farm. The barn was decontaminated with sodium hypochlorite for four times the recommended exposure time. Two cohorts, consisting of 25 and 21 sheep, with susceptible prion protein genotypes (VRQ/VRQ), born 2 years apart, were housed in the barn and infection monitored by examination of rectal biopsies.
Results
One sheep from the first cohort and four from the second were found to be infected from 775 (first cohort) and 550 days (second cohort) post exposure. It is concluded that decontamination with sodium hypochlorite at the recommended concentration and longer exposure time did not prevent re-infection of susceptible sheep. Disinfection of contaminated premises to eradicate scrapie continues to be a challenge.
Snip…
In conclusion, this study has shown that repeated disinfection with sodium hypochlorite, even using extended decontamination times, did not prevent re-infection so that there is a risk of re-infection if sheep with susceptible genotypes are re-introduced. It is not known whether decontamination was ineffective or recontamination occurred from various sources.
https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-025-07188-1
I remember what “deep throat” told me about Scrapie back around 2001, this was right after my Mom died from confirmed hvCJD around Christmas 1997, a few years later, when I was corresponding with officials in England, early BSE Inquiry days, and I never forgot, and it seems it’s come to pass;
***> Confidential!!!!
***> As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!
---end personal email---end...tss
and so it seems…so, this is what we leave our children and grandchildren?
Rapid recontamination of a farm building occurs after attempted prion removal
First published: 19 January 2019 https://doi.org/10.1136/vr.105054
The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.
snip...
This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapie positive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.
https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1136/vr.105054
***>This is very likely to have parallels with control efforts for CWD in cervids.
https://pubmed.ncbi.nlm.nih.gov/30602491/
Front. Vet. Sci., 14 September 2015 | https://doi.org/10.3389/fvets.2015.00032
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination.
http://journal.frontiersin.org/article/10.3389/fvets.2015.00032/full
"Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation."
15 YEARS!
Detection of prions in soils contaminated by multiple routes
Results: We are able to detect prion seeding activity at multiple types of environmental hotspots, including carcass sites, contaminated captive facilities, and scrapes (i.e. urine and saliva). Differences in relative prion concentration vary depending on the nature and source of the contamination. Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation.
Conclusions: Detection of prions in the environment is of the utmost importance for controlling chronic wasting disease spread. Here, we have demonstrated a viable method for detection of prions in complex environmental matrices. However, it is quite likely that this method underestimates the total infectious prion load in a contaminated sample, due to incomplete recovery of infectious prions. Further refinements are necessary for accurate quantification of prions in such samples, and to account for the intrinsic heterogeneities found in the broader environment.
Funded by: Wisconsin Department of Natural Resources
Prion 2023 Abstracts
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Comparing the Distribution of Ovine Classical Scrapie and Sporadic Creutzfeldt-Jakob Disease in Italy: Spatial and Temporal Associations (2002-2014)
Ru G1 ., Pocchiari M2 ., Bertolini S. 1, Pite L.1 , Puopolo M.2 , Ladogana A.2 , Perrotta M.G.3 , Meloni D 1 . (1) National reference center for the study and research on animal encephalopathies and comparative neuropathologies (CEA). Experimental Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, Torino, Italy.
(2) Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy. (3) Office 3 National center for the fight and emergency against animal diseases. Ministry of Health, Roma, Italy.
Aim: This study aims to investigate potential spatial and temporal associations between Creutzfeldt-Jakob disease (CJD) in humans (2010-2014) and ovine classical scrapie (CS) (2002- 2006) in Italy, serving as a proxy for exposure.
Materials and Methods: National data from prion disease surveillance in humans (sporadic CJD) and small ruminants (CS) in Italy were utilized. A descriptive geographic analysis was conducted for each disease individually. Subsequently, an ecological study was performed to compare the occurrence of both diseases at the district and regional levels. Standardized incidence ratios (SIR), adjusted for confounders, were calculated for CJD and CS by district and region, respectively, representing the outcome and proxy of exposure. Considering a possible long incubation period of CJD, two study periods were analysed: 2010-2014 for CJD and 2002-2006 for CS. Eight alternative linear regression models were developed using SIR in humans as the dependent variable and SIR in sheep as the independent variable. These models varied in the scale of SIR data (continuous vs. categorical), geographical level (district vs. region), and the potential past exposure of sheep in specific areas to a known source of infection (via a contaminated vaccine).
Results: The analysis of data at the district level revealed no significant association. However, when considering aggregated regional data, all four models consistently indicated a statistically significant positive association, suggesting a higher incidence of the disease in humans as the regional incidence of sheep scrapie increased.
Conclusions: While the results are intriguing, it is important to acknowledge the inherent limitations of ecological studies. Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively.
Funded by: Italian Ministry of Health Grant number: Realizzazione del programma epidemiologico finalizzato a dare evidenza del potenziale zoonotico delle TSE animali diverse dalla BSE. Prot. N. 0018730-17/07/2015-DGSAFCOD_UO-P
''Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively.''
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
=====
Transmission of Idiopathic human prion disease CJD MM1 to small ruminant mouse models (Tg338 and Tg501).
Enric Vidal1,2, Samanta Giler1,2, Montse Ordóñez1,2, Hasier Eraña3,4, Jorge M. Charco3,4, Guillermo Cantero1,2, Juan C. Espinosa5 , Juan M. Torres5 , Vincent Béringue6 , Martí Pumarola7 and Joaquín Castilla3,8,9
Aims: About 90% of Creutzfeldt-Jakob disease cases are classified as sporadic (sCJD), that is, occur infrequently, randomly and without a known cause. It is a fatal neurodegenerative disease with an incidence of 1-1.5 cases per million per year. Epidemiological studies have been so far unable to establish a causal relationship between sCJD and prion diseases in animals.
The zoonotic potential of sheep scrapie was demonstrated in 2014 (Cassard et al., Nature Communications) through inoculation of transgenic mice overexpressing the human prion protein with scrapie isolates. The resulting prion disease was indistinguishable from that occurring after sCJD inoculation in the same model and, while these results do not demonstrate that sCJD is caused by scrapie prions, they do show that the transmission barrier between ovine and human prions is not absolute. Our aim is to further assess this zoonotic risk.
Materials and methods: we have prepared inocula from 3 sCJD cases (MM1, MV2 and VV2) and 2 VPSPr cases (MM and MV) to verify if it is possible to recover the scrapie phenotype upon inoculation in Tg338 and Tg501 ovinized mouse models. Additionally, two different inocula gCJD (E200K) and GSS (A117V) have been also included in the bioassays as controls for classical and atypical genetic human prions, respectively.
Results: No evidence of transmission was found on a first passage in Tg338 nor Tg501 ovinized mice, but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed.
Funded by: MINECO grant number AGL2017-88535-P and PID2021-1222010B-C22 and by Interreg POCTEFA grant number EFA148/16 (RedPRION)
''but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12 Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed.''
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
*** 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.
==============
PRION 2015 CONFERENCE
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-68961933-690X
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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
***> “The WOAH and APHIS determined that it is not a disease of trade concern.” <***
Remember that!…terry
Classical BSE emergence from Nor98/atypical scrapie: Unraveling the shift vs. selection dichotomy in the prion field
Sara Canoyra https://orcid.org/0000-0001-6371-8122, Alba Marín-Moreno https://orcid.org/0000-0002-4023-6398, Juan Carlos Espinosa https://orcid.org/0000-0002-6719-9902, +5 , and Juan María Torres https://orcid.org/0000-0003-0443-9232jmtorres@inia.csic.esAuthors Info & Affiliations Edited by Byron Caughey, National Institute of Allergy and Infectious Diseases (National Institutes of Health), Hamilton, MT; received January 17, 2025; accepted June 7, 2025 by Editorial Board Member Lila M. Gierasch
July 15, 2025 122 (29) e2501104122 https://doi.org/10.1073/pnas.2501104122
Significance
Classical bovine spongiform encephalopathy (c-BSE) is a fatal cattle prion disease transmissible to humans as variant Creutzfeldt–Jakob Disease (vCJD). Understanding how c-BSE emerges is crucial for preventing future outbreaks and protecting public health. Two main hypotheses explain prion adaptation during cross-species transmission: “conformational shift or deformed templating,” where the species barrier forces a change to a different pathological prion protein, and “conformational selection,” where the species barrier filters preexisting conformers. Our results demonstrate that the conformational shift mechanism explains the emergence of c-BSE when Nor98/atypical scrapie (AS) is transmitted to cattle. This is significant because AS, found in sheep and goats worldwide, can convert to c-BSE. Preventing AS from entering the food chain is crucial to reduce c-BSE/vCJD risks.
Abstract
Prion diseases can manifest with distinct phenotypes in a single species, a phenomenon known as prion strains. Upon cross-species transmission, alterations in the disease phenotype can occur, interpreted as the emergence of a new strain. Two main and non–mutually exclusive evolutionary hypotheses have been proposed to explain this phenomenon: the “conformational shift” or “deformed templating” and the “conformational selection.” The conformational shift hypothesis proposes that the introduction of a new host prion protein (PrPC) forces a change in the conformation of the pathological prion protein (PrPSc), causing the new prion strain emergence. On the contrary, the conformational selection model postulates that prion isolates are a conglomerate of PrPSc conformations with relative distribution frequencies, wherein the species barrier acts as a filter selecting the one fittest for the new species environment. Previous studies reported the emergence of the classical bovine spongiform encephalopathy agent (c-BSE) upon transmission of Nor98/atypical scrapie (AS) onto a bovine PrP. This study investigates the evolutionary dichotomy of this c-BSE emergence by using prion strain thermostability combined with protein misfolding cyclic amplification to distinguish between both strains. Our results suggest that the conformational shift could be the principal mechanism responsible for the c-BSE emergence. Furthermore, the selection model was dismissed as the key mechanism based on the analysis of an artificial c-BSE and AS mixture. The ability of the AS conformers to shift conformation to a c-BSE one supports the hypothesis that the epidemic c-BSE prion may have originated from the transmission of AS in cattle.
https://www.pnas.org/doi/abs/10.1073/pnas.2501104122?download=true
Published: 04 October 2023
Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie
Abstract The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.
Snip…
However, in conclusion, our findings show that the propagation of atypical scrapie in cattle leads to the emergence of BSE-like seeding activity. This is a concerning issue with far-reaching implications for public health and food safety. The possibility of interspecies transmission of prion diseases and the emergence of new prion strains highlight the critical need for continued surveillance and monitoring of these diseases in both animal and human populations. Early detection of prion diseases is crucial, and highly sensitive detection techniques such as PMCA can play an important role in this regard.
https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-023-01225-2
Volume 17, Number 5—May 2011
Research
Experimental Oral Transmission of Atypical Scrapie to Sheep
Marion M. SimmonsComments to Author , S. Jo Moore1, Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos
Author affiliations: Author affiliation: Veterinary Laboratories Agency–Weybridge, Addlestone, UK Cite This Article
Abstract
To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals’ peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.
Snip…
Discussion This study is still ongoing and will not be completed until 2012. However, the current interim report documents the successful oral transmission of atypical scrapie, confirms that the disease phenotype is retained following transmission by this route in AHQ/AHQ sheep, and indicates that infectivity can be demonstrated in the gut in the absence of detectable PrPSc at least as early as 12 months after exposure.
Snip…
How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantified, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confirmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected.
https://wwwnc.cdc.gov/eid/article/17/5/10-1654_article
See updated studies on AS
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
AS
https://intcwdsympo.wordpress.com/wp-content/uploads/2023/06/final-agenda-with-abstracts.pdf
Updates on the WOAH activities in the field of TSEs
Natalie MOYEN Disease Status Officer
Status Department
May 14 th , 2024
2
Outline 1. Revised BSE standards (Terrestrial Code)
a) b) Transition process: where are we?
Official recognition of BSE risk status
i. Members/zones recognised as having a negligible or controlled BSE risk status
ii. New applications
iii. Annual reconfirmations
2. Revision of Scrapie standards (Terrestrial Code
https://www.eurl.craw.eu/wp-content/uploads/2024/06/07_WOAH_Updates-on-the-WOAH-activities-in-the-field-of-TSEs.pdf
APHIS USDA BSE
6.8.Bovine spongiform encephalopathy (Chapter 11.4.), Application for official recognition by the OIE of risk status for bovine spongiform encephalopathy (Chapter 1.8.) and Glossary definition for ‘protein meal’
Background
In February 2018, following preliminary work and scientific exchanges, the Code Commission and the Scientific Commission agreed to an in-depth review of Chapter 11.4. Bovine spongiform encephalopathy (BSE). The OIE convened three different ad hoc Groups between July 2018 and March 2019: i) an ad hoc Group on BSE risk assessment, which met twice, ii) an ad hoc Group on BSE surveillance, which met once, and iii) a joint ad hoc Group on BSE risk assessment and surveillance, which met once. The Code Commission, at its September 2019 meeting, reviewed the four ad hoc Group reports and the opinion of the Scientific Commission regarding the draft revised chapter and circulated a revised draft Chapter 11.4. for comments.
In February 2020, the Code Commission considered comments received on the revised draft Chapter 11.4. and requested that the joint ad hoc Group on BSE risk assessment and surveillance be reconvened to address comments of a technical nature. In June 2020, the joint ad hoc Group was convened to address relevant comments and was also requested to review Chapter 1.8. Application for official recognition by the OIE of risk status for bovine spongiform encephalopathy to ensure alignment with the proposed changes in Chapter 11.4.
In September 2020, the Code Commission reviewed the joint ad hoc Group report and the revised draft Chapters 11.4. and 1.8. and made some additional amendments and circulated the revised chapters for comments in its September 2020 report. In February 2021, the Commission considered comments received and amended the chapters, as appropriate, and circulated the revised chapters for a third round of comments.
In preparation for the September 2021 meetings, some members of the Code Commission and the Scientific Commission met to discuss key aspects of the revision of Chapters 11.4. and 1.8. to ensure a common understanding of the main concerns raised by Members, the decisions made on the revised chapters and their impact on the official status recognition, as well as on the adapted procedures that will be required. During this meeting, it was agreed that each Commission would address the issues relevant to its meeting and document discussions in their respective reports.
Discussion
Snip…see;
https://www.aphis.usda.gov/sites/default/files/Sep-2021-Full-Comm-Report.docx
US BSE testing <25K annually…
Samples Tested by Fiscal Year
Fiscal Year v Total Samples Tested as Valid WOAH Points per Fiscal Year BSurvE Points
2024 22,848 207,808 468,946
2023 22,838 239,695 570,345
2022 21,816 360,553 842,517
2021 23,124 398,508 962,010
2020 21,441 331,561 795,183
2019 18,627 395,732 948,602
2018 21,809 540,960 1,305,585
2017 24,229 577,494 1,383,678
2016 26,564 547,959 1,314,579
2015 40,902 592,353 1,414,630
Updates on the WOAH activities in the field of TSEs
Natalie MOYEN Disease Status Officer
Status Department
May 14 th , 2024
2
Outline 1. Revised BSE standards (Terrestrial Code)
a) b) Transition process: where are we?
Official recognition of BSE risk status
i. Members/zones recognised as having a negligible or controlled BSE risk status
ii. New applications
iii. Annual reconfirmations
2. Revision of Scrapie standards (Terrestrial Code
https://www.eurl.craw.eu/wp-content/uploads/2024/06/07_WOAH_Updates-on-the-WOAH-activities-in-the-field-of-TSEs.pdf
Atypical BSE in cattle
THE recent diagnosis of two atypical bovine spongiform encephalopathy (BSE) cases in Great Britain (March 2023 in Cornwall and December 2024 in Dumfries and Galloway) and one in the Republic of Ireland (in November 2023) warrants a reminder about this notifiable disease.
Since 2005, a total of 17 cases have been detected in Great Britain.1 Unlike classical BSE, which resulted in over 180,000 cases in Great Britain and was predominantly associated with the consumption of feed contaminated with the BSE agent, and where the last case was confirmed in Ayrshire in May 2024, atypical BSE is believed to be a spontaneous disease in cattle found in approximately one in 1,000,000 tested cattle based on French data,2 similar to the sporadic Creutzfeldt- Jakob disease in people. There is currently no evidence that atypical BSE causes a disease in people, although it can be transmitted experimentally to other species by intracerebral inoculation, including primates.3–5 The World Organisation for Animal Health does not include atypical BSE in its geographical BSE risk status assessment.
Despite differences in terms of epidemiological, molecular and biological phenotype compared with classical BSE, atypical BSE is currently treated as if it were classical BSE in accordance with EU and UK legislation: once a case is identified, all cohort animals born and reared with the affected animal during the first 12 months of its life, and all offspring born within 24 months of its clinical onset, are culled and tested for BSE, which does seem to be at odds with the hypothesis that it is a spontaneous disease. This is more a precautionary measure to maintain confidence in the beef trade and protect consumers while more knowledge about this disease is obtained.
Almost all current knowledge on atypical BSE is based on experimental infection because this spontaneous
VET RECORD | 29 March–12 April 2025
disease has generally only been found in aged downer cows, which is difficult to replicate experimentally in the host species. Intracerebral inoculation of brain tissue from an affected cow causes disease in cattle in less than two years, unlike the natural disease that usually occurs in animals over eight years of age.
The vast majority of cases have been identified by active monitoring of fallen stock or emergency slaughter of cattle, where only the brain sample of various stages of autolysis is generally available. Little is known of where the atypical BSE agent can be found in natural disease, other than in the brain, because all the cases confirmed have been identified after death through active surveillance, by which time most peripheral tissue has been disposed of. Limited material from a single case of a naturally affected cow was tested in Italy by mouse bioassay, which found infectivity in muscle.6 In experimental disease generated by intracerebral inoculation of cattle, infectivity can be detected in the brain and spinal cord, ganglia, peripheral nerves and skeletal muscles, similar to classical BSE, but not in peripheral lymphoid tissue.6–8
Early reporting of clinical suspects is needed so that the live animal or the whole carcase can be delivered to an APHA regional laboratory for tissue sampling. This is made more difficult due to the subtlety of clinical signs based on experimental disease. Clinical cases may not be as over- reactive or nervous as classical BSE cases; some may, in fact, be dull, but what most cases have in common is that they have difficulty getting up and eventually end up as downer cows, and only the clinical history may reveal some prior behavioural or locomotor changes. High creatinine kinase serum levels and nibbling in response to scratching the tail head or back were some features in experimental disease,8, 9 but it is not known whether this is also seen in natural disease.
In general, BSE should be considered as a differential diagnosis in all downer cows that do not respond to treatment, where the blood results do not support the presence of a metabolic disease and where the cause cannot be determined with confidence.
Since BSE is a notifiable disease, suspected cases of BSE in Great Britain must be reported to the local APHA office.
Changes are imminent in the reporting of fallen stock cattle, which will require the owner to state whether the animal displayed signs of changes in behaviour, sensation or locomotion before death, in addition to the likely cause of death or disease. This is to obtain a better profile of the clinical history, if cattle are retrospectively diagnosed as BSE cases, which has happened in all BSE cases confirmed since 2010: none has been reported as a clinical suspect.
“BSE should be considered as a differential diagnosis in all downer cows that do not respond to treatment”
Timm Konold, TSE lead scientist
Brenda Rajanayagam, workgroup leader for the data systems group
APHA Weybridge, New Haw, Addlestone, Surrey KT15 3NB email: timm.konold@apha.gov.uk
Keith Meldrum, former chief veterinary officer The Orchard, Swaynes Lane, Guildford, Surrey GU1 2XX
References
1 APHA. Cattle: TSE surveillance statistics. Overview of Great Britain statistics. 2025. https://bit.ly/4ho5Nds (accessed 19 March 2025)
Atypical BSE In Cattle
https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1002/vetr.5400?campaign=woletoc
Classical BSE emergence from Nor98/atypical scrapie: Unraveling the shift vs. selection dichotomy in the prion field
Sara Canoyra https://orcid.org/0000-0001-6371-8122, Alba Marín-Moreno https://orcid.org/0000-0002-4023-6398, Juan Carlos Espinosa https://orcid.org/0000-0002-6719-9902, +5 , and Juan María Torres https://orcid.org/0000-0003-0443-9232jmtorres@inia.csic.esAuthors Info & Affiliations
Edited by Byron Caughey, National Institute of Allergy and Infectious Diseases (National Institutes of Health), Hamilton, MT; received January 17, 2025; accepted June 7, 2025 by Editorial Board Member Lila M. Gierasch
July 15, 2025 122 (29) e2501104122
Classical bovine spongiform encephalopathy (c-BSE) is a fatal cattle prion disease transmissible to humans as variant Creutzfeldt–Jakob Disease (vCJD). Understanding how c-BSE emerges is crucial for preventing future outbreaks and protecting public health. Two main hypotheses explain prion adaptation during cross-species transmission: “conformational shift or deformed templating,” where the species barrier forces a change to a different pathological prion protein, and “conformational selection,” where the species barrier filters preexisting conformers. Our results demonstrate that the conformational shift mechanism explains the emergence of c-BSE when Nor98/atypical scrapie (AS) is transmitted to cattle. This is significant because AS, found in sheep and goats worldwide, can convert to c-BSE. Preventing AS from entering the food chain is crucial to reduce c-BSE/vCJD risks. Abstract
Prion diseases can manifest with distinct phenotypes in a single species, a phenomenon known as prion strains. Upon cross-species transmission, alterations in the disease phenotype can occur, interpreted as the emergence of a new strain. Two main and non–mutually exclusive evolutionary hypotheses have been proposed to explain this phenomenon: the “conformational shift” or “deformed templating” and the “conformational selection.” The conformational shift hypothesis proposes that the introduction of a new host prion protein (PrPC) forces a change in the conformation of the pathological prion protein (PrPSc), causing the new prion strain emergence. On the contrary, the conformational selection model postulates that prion isolates are a conglomerate of PrPSc conformations with relative distribution frequencies, wherein the species barrier acts as a filter selecting the one fittest for the new species environment. Previous studies reported the emergence of the classical bovine spongiform encephalopathy agent (c-BSE) upon transmission of Nor98/atypical scrapie (AS) onto a bovine PrP. This study investigates the evolutionary dichotomy of this c-BSE emergence by using prion strain thermostability combined with protein misfolding cyclic amplification to distinguish between both strains. Our results suggest that the conformational shift could be the principal mechanism responsible for the c-BSE emergence. Furthermore, the selection model was dismissed as the key mechanism based on the analysis of an artificial c-BSE and AS mixture. The ability of the AS conformers to shift conformation to a c-BSE one supports the hypothesis that the epidemic c-BSE prion may have originated from the transmission of AS in cattle.
https://www.pnas.org/doi/10.1073/pnas.2501104122
Six of the seven cases of BSE identified in the United States have been diagnosed as atypical BSE. In most cases, the animals were 10 years of age or older. Two of the six detections of atypical BSE involved animals aged approximately 5 years or older.
https://www.aphis.usda.gov/sites/default/files/fs-bse.pdf
WEDNESDAY, AUGUST 13, 2025
Revised Bovine Spongiform Encephalopathy BSE TSE Prion Standards
https://bovineprp.blogspot.com/2025/08/revised-bovine-spongiform.html
https://prpsc.proboards.com/thread/177/revised-bovine-spongiform-encephalopathy-standards
Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE
Friday, May 19, 2023 | 04:12pm NASHVILLE — The Tennessee State Veterinarian is confirming a case of atypical bovine spongiform encephalopathy (BSE) in a cow with ties to Tennessee.
The cow appeared unwell after arriving at a packing company in South Carolina. In alignment with the United States Department of Agriculture’s BSE surveillance program, the animal was isolated and euthanized. It did not enter the food supply. Preliminary investigation has determined the cow originated in southeast Tennessee.
“We are working closely with our federal partners and animal health officials in South Carolina for this response,” State Veterinarian Dr. Samantha Beaty said. “That includes determining prior owners and locations where the affected cow lived in Tennessee and tracing siblings and offspring for testing.”
BSE is a chronic degenerative disease affecting the central nervous system of cattle. It is caused by an abnormal prion protein. The atypical form occurs spontaneously at very low levels in all cattle populations, particularly in older animals. Atypical BSE poses no known risk to human health. It is different from the classical form of BSE, which has not been detected in the U.S. since 2003.
BSE is not contagious and therefore is not spread through contact between cattle or with other species. There is no treatment for or vaccine to prevent BSE. The U.S. has a strong surveillance program in place for early detection and to prevent suspect cattle from entering the food supply chain.
Cattle owners are always advised to monitor their herds for health. Cattle affected by BSE may display changes in temperament, abnormal posture, poor coordination, decreased milk production, or loss of condition without noticeable loss of appetite. Owners should report any herd health concerns to their veterinarian or to the State Veterinarian’s office at 615-837-5120.
The Tennessee Department of Agriculture Animal Health Division is responsible for promoting animal health in Tennessee. The State Veterinarian’s office seeks to prevent the spread of disease through import and movement requirements, livestock traceability, disaster mitigation, and the services of the C.E. Kord Animal Health Diagnostic Laboratory. The division collaborates with other health-related stakeholders, academic institutions, and extension services to support One Health, an initiative to improve health for people and animals.
https://www.tn.gov/agriculture/news/2023/5/19/state-veterinarian-alerts-cattle-owners-to-disease-detection.html
USDA Announces Atypical L-Type Bovine Spongiform Encephalopathy BSE Detection
The U.S. Department of Agriculture (USDA) is announcing an atypical case of Bovine Spongiform Encephalopathy (BSE), a neurologic disease of cattle, in an approximately five-year-old or older beef cow at a slaughter plant in South Carolina. This animal never entered slaughter channels and at no time presented a risk to the food supply or to human health in the United States. Given the United States’ negligible risk status for BSE, we do not expect any trade impacts as a result of this finding.
USDA Animal and Plant Health Inspection Service’s (APHIS) National Veterinary Services Laboratories (NVSL) confirmed that this cow was positive for atypical L-type BSE. The animal was tested as part of APHIS’s routine surveillance of cattle that are deemed unsuitable for slaughter. The radio frequency identification tag present on the animal is associated with a herd in Tennessee. APHIS and veterinary officials in South Carolina and Tennessee are gathering more information during this ongoing investigation.
Atypical BSE generally occurs in older cattle and seems to arise rarely and spontaneously in all cattle populations.
This is the nation’s 7th detection of BSE. Of the six previous U.S. cases, the first, in 2003, was a case of classical BSE in a cow imported from Canada; the rest have been atypical (H- or L-type) BSE.
The World Organization for Animal Health (WOAH) recognizes the United States as negligible risk for BSE. As noted in the WOAH guidelines for determining this status, atypical BSE cases do not impact official BSE risk status recognition as this form of the disease is believed to occur spontaneously in all cattle populations at a very low rate. Therefore, this finding of an atypical case will not change the negligible risk status of the United States, and should not lead to any trade issues.
The United States has a longstanding system of interlocking safeguards against BSE that protects public and animal health in the United States, the most important of which is the removal of specified risk materials - or the parts of an animal that would contain BSE should an animal have the disease - from all animals presented for slaughter. The second safeguard is a strong feed ban that protects cattle from the disease. Another important component of our system - which led to this detection - is our ongoing BSE surveillance program that allows USDA to detect the disease if it exists at very low levels in the U.S. cattle population.
More information about this disease is available in the BSE factsheet.
#
https://www.aphis.usda.gov/aphis/newsroom/stakeholder-info/sa_by_date/sa-2023/bse
May 2, 2023
Two weeks before the detection of atypical L-Type BSE, I submitted this to the Docket No. APHIS–2023–0027 about BSE…terry
Docket No. APHIS–2023–0027 Notice of Request for Revision to and Extension of Approval of an Information Collection; National Veterinary Services Laboratories; Bovine Spongiform Encephalopathy Surveillance Program Singeltary Submission
ONLY by the Grace of God, have we not had a documented BSE outbreak, that and the fact the USDA et al are only testing 25K cattle for BSE, a number too low to find mad cow disease from some 28.9 million beef cows in the United States as of Jan. 1, 2023, down 4% from last year. The number of milk cows in the United States increased to 9.40 million. U.S. calf crop was estimated at 34.5 million head, down 2% from 2021. Jan 31, 2023.
ALL it would take is one BSE positive, yet alone a handful of BSE cases, this is why the Enhanced BSE was shut down, and the BSE testing shut down to 25k, and the BSE GBRs were replaced with BSE MRRs, after the 2003 Christmas Mad cow, the cow that stole Christmas, making it legal to trade BSE, imo.
Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission
https://www.regulations.gov/comment/APHIS-2023-0027-0002
see full submission;
https://downloads.regulations.gov/APHIS-2023-0027-0002/attachment_1.pdf
let's be perfectly clear what science is saying today, and especially what the WAHIS/WOAH/OIE et al are saying about the atypical BSE strains...
OIE Conclusions on transmissibility of atypical BSE among cattle…terry
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.
https://www.oie.int/fileadmin/SST/adhocreports/Bovine%20spongiform%20encephalopathy/AN/A_AhG_BSEsurv_RiskAss_Mar2019.pdf
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.
4. Definitions of meat-and-bone meal (MBM) and greaves
http://web.oie.int/downld/PROC2020/A_SCAD_Sept2019.pdf
Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324790/
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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310119/
''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.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=353094
Canadian 2021 H-type Bovine Spongiform Encephalopathy case associated with a novel E211K polymorphism in prion protein gene novel E211K polymorphism in prion protein gene
Waqas Tahir , Sandor Dudas , Renee Anderson , Jianmin Yang , Sarah Bogart , Kristina Santiago-Mateo, Yuanmu Fang & Roberta Quaghebeur
Pages 36-49 | Received 20 Feb 2025, Accepted 22 May 2025, Published online: 04 Aug 2025 Cite this article https://doi.org/10.1080/19336896.2025.2511933
ABSTRACT
Bovine Spongiform Encephalopathy (BSE) is a fatal neurodegenerative disease in cattle which can be either classical BSE (C-BSE) or atypical BSE (including H-BSE and L-BSE). Here, we report the results of our analyses of an H-BSE case found in Canada in 2021, indicating restriction of the pathological agent (PrPSc) mainly to the central nervous system with no or occasional weak involvement of peripheral tissues. Importantly, a non-synonymous mutation at codon 211 of the PRNP gene was detected and confirmed to be present as a germline mutation. This is the first case of BSE in Canada with a predisposing E211K mutation.
Snip…
Based on the results of this study, and the 2006 H-BSE case in the USA, there is an expanded spectrum of aetiologies for bovine prion diseases similar to what is observed in humans, including sporadic, genetic and acquired versions.
Supplemental material Canadian 2021 H-type Bovine Spongiform Encephalopathy case associated with a novel E211K polymorphism in prion protein gene
KEYWORDS:
Atypical BSEBovine Spongiform Encephalopathycentral nervous systemE211K mutationprion diseasesprion protein genesynonymous mutation
https://www.tandfonline.com/doi/full/10.1080/19336896.2025.2511933#d1e1606
Component 6: Transmissible Spongiform Encephalopathies (TSEs)
Problem Statement 6A: Determine pathobiology of prion strains.
The naturally occurring lysine to glutamic acid substitution (E211K in the bovine prion protein) results in short incubation periods for H-type bovine spongioform encephalopathy (BSE).
Virus and Prion Research Unit, National Animal Disease Center, Ames, Iowa
Classical BSE (C-BSE) is a prion disease of cattle that was responsible for the "mad cow disease" epizootic in Europe in the 1980s. C-BSE was determined to cause the human prion disease vCJD. Since then, atypical spontaneous strains of BSE were identified. H-BSE is one of those strains. Much research has explored the origins of C-BSE, and strain emergence from atypical H-BSE is one hypothesis. An H-BSE case was determined to have a germline mutation, an E211K substitution in the prion protein gene, which is analogous to a hereditary human prion disease. ARS scientists in Ames, Iowa reported the transmission of H-BSE from cattle, with and without the germline prion protein amino acid substitution, to cattle with various prion genotypes: EE211 (wild-type), EK211, and KK211. Results indicated a significantly shorter incubation period in K containing cattle compared to prion wild-type cattle. The scientists also explored the possibility that the C-BSE strain might have occurred after serial passages of EK211 and KK211 containing H-BSE in cattle, but results did not support this concept. This information is important to prion researchers, veterinary diagnostic laboratories, and those involved with establishing regulatory guidelines.
https://www.ars.usda.gov/ARSUserFiles/np103/AnnualReports/Final%20NP103%20FY2024%20Annual%20Report.updated%205.30.25.pdf
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation
Author item Greenlee, Justin item Cassmann, Eric item MOORE, SARA JO - Oak Ridge Institute For Science And Education (ORISE) item WEST GREENLEE, HEATHER - Iowa State University
Submitted to: Meeting Abstract Publication Type: Abstract Only Publication Acceptance Date: 6/24/2022 Publication Date: 9/16/2022 Citation: Greenlee, J.J., Cassmann, E.D., Moore, S., West Greenlee, H.M. 2022.
Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation.
Prion 2022 Conference abstracts: pushing the boundaries. 16(1):150. https://doi.org/10.1080/19336896.2022.2091286.
DOI: https://doi.org/10.1080/19336896.2022.2091286 Interpretive Summary:
Technical Abstract: In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure. Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with the H-BSE agent from either the US 2004 case (wild type donor; n=3) or from the US 2006 case with the E211K polymorphism (n=4). Cattle were observed daily throughout the course of the experiment for the development of clinical signs. When signs were noted, animals were euthanized and necropsied. Cattle were confirmed positive for abnormal BSE prions by enzyme immunoassay (EIA; Idexx HerdChek BSE Ag Test), anti-PrP immunohistochemistry (IHC) on brainstem, and microscopic examination for vacuolation. Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211 steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57-4.0) in the brainstem, and IHC demonstrated PrPSc throughout the brain. All cattle in the EE211 recipient group remain asymptomatic for the duration of the experiment (approximately 7 years post-inoculation).
This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=395351
Highlights
This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=395351
Title: A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation
Author item MOORE, S - Orise Fellow item WEST GREENLEE, M - Iowa State University item Smith, Jodi item Vrentas, Catherine item Nicholson, Eric item Greenlee, Justin
Submitted to: Frontiers in Veterinary Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: 8/30/2016 Publication Date: 9/15/2016 Citation: Moore, S.J., West Greenlee, M.H., Smith, J.D., Vrentas, C.E., Nicholson, E.M., Greenlee, J.J. 2016.
A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation.
Frontiers in Veterinary Science. 3:78. Interpretive
Summary: Cases of bovine spongiform encephalopathy (BSE) or mad cow disease can be subclassified into at least 3 distinct disease forms with the predominate form known as classical BSE and the others collectively referred to as atypical BSE. Atypical BSE can be further subdivided into H-type and L-type cases that are distinct from classical BSE and from each other. Both of the atypical BSE subtypes are believed to occur spontaneously, whereas classical BSE is spread through feeding contaminated meat and bone meal to cattle. Work by other research groups suggests that the stability of the distinguishing features of atypical BSE cases (phenotypical stability) can change to closely resemble classical BSE after experimental passage implicating atypical BSE as a possible origin of classical BSE. Interestingly, one case of H-type BSE in the US was associated with an inherited mutation in the prion protein gene referred to as E211K. The purpose of this work was to compare wild type and cattle with the E211K mutation after experimental inoculation with either classical BSE or H-BSE from the original E211K case. This study demonstrates that the disease features of E211K BSE-H remain stable when transmitted to cattle without the K211 polymorphism. In addition, passage of classical BSE to cattle with the K211 polymorphism results in disease with features consistent with classical BSE and not a switch to atypical BSE-H as a result of the K211 polymorphism. As the origin of classical, feedborne BSE remains unknown and low numbers of atypical BSE are diagnosed each year, parties with interest in the cattle and beef industries and regulatory officials responsible for safe feeding practices of cattle will be interested in this work.
Technical Abstract: In 2006, a case of H-type bovine spongiform encephalopathy (BSE-H) was diagnosed in a cow that was associated with a heritable polymorphism in the bovine prion protein gene (PRNP) resulting in a lysine for glutamine amino acid substitution at codon 211 (called E211K) of the prion protein. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele may be predisposed to rapid onset of BSE-H when exposed or to the potential development of a genetic BSE. This study was conducted to better understand the relationship between the K211 polymorphism and its effect on BSE phenotype. BSE-H from the US 2006 case was inoculated intracranially (IC) in one PRNP wild type (EE211) calf and one EK211 calf. In addition, one wild type calf and one EK211 calf were inoculated IC with brain homogenate from a US 2003 classical BSE case. All cattle developed clinical disease. The survival times of the E211K BSE-H inoculated EK211 calf (10 months) was shorter than the wild type calf (18 months). This genotype effect was not observed in classical BSE inoculated cattle (both 26 months). Significant changes in retinal function were observed in H-type BSE challenged cattle only. Cattle challenged with the same inoculum showed similar severity and neuroanatomical distribution of vacuolation and disease-associated prion protein deposition in the brain, though differences in neuropathology were observed between E211K BSE-H and classical BSE inoculated animals. Western blot results for brain tissue from challenged animals were consistent with the inoculum strains. This study demonstrates that the phenotype of E211K BSE-H remains stable when transmitted to cattle without the K211 polymorphism, and exhibits a number of features that differ from classical BSE in both wild type and heterozygous EK211 animals.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=326785
Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA?, what if?
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues
Author item CASSMANN, ERIC - Oak Ridge Institute For Science And Education (ORISE) item MOORE, SARA - Oak Ridge Institute For Science And Education (ORISE) item SMITH, JODI - Iowa State University item Greenlee, Justin
Submitted to: Frontiers in Veterinary Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/14/2019 Publication Date: 11/29/2019 Citation: Cassmann, E.D., Moore, S.J., Smith, J.D., Greenlee, J.J. 2019.
Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues.
Frontiers in Veterinary Science. 6:430. https://doi.org/10.3389/fvets.2019.00430. DOI: https://doi.org/10.3389/fvets.2019.00430
Interpretive Summary: Prion diseases are protein misfolding diseases that are transmissible between animals. The outcome of prion infection is irreversible brain damage and death. Transmission can occur between animals of the same or different species, however, transmission between different species is usually less efficient due to the species barrier, which results from differences in the amino acid sequence of the prion protein between the donor and recipient species. The present work evaluated whether transmissible mink encephalopathy (TME) can infect sheep. Our results demonstrate that sheep are susceptible to the TME agent and that the TME agent has similar properties to the agent of L-type atypical bovine spongiform encephalopathy (L-BSE). This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.
Technical Abstract: Transmissible mink encephalopathy (TME) is a food borne prion disease. Epidemiological and experimental evidence suggests similarities between the agent of TME and L-BSE. This experiment demonstrates the susceptibility of four different genotypes of sheep to the agent of TME by intracranial inoculation. The four genotypes of sheep used in this experiment had polymorphisms corresponding to codons 136 and 171 of the prion gene: VV136QQ171, AV136QQ171, AA136QQ171, and AA136QR171. All intracranially inoculated sheep without comorbidities (15/15) developed clinical scrapie and had detectable PrPSc by immunohistochemistry, western blot, and enzyme immunoassay (EIA). The mean incubation periods in TME infected sheep correlated with their relative genotypic susceptibility. There was peripheral distribution of PrPSc in the trigeminal ganglion and neuromuscular spindles; however, unlike classical scrapie and C-BSE in sheep, ovine TME did not accumulate in the lymphoid tissue. To rule out the presence of infectious, but proteinase K susceptible PrPSc, the lymph nodes of two sheep genotypes, VV136QQ171 and AA136QQ171, were bioassayed in transgenic ovinized mice. None of the mice (0/32) inoculated by the intraperitoneal route had detectable PrPSc by EIA. Interestingly, mice intracranially inoculated with RPLN tissue from a VV136QQ171 sheep were EIA positive (3/17) indicating that sheep inoculated with TME harbor infectivity in their lymph nodes. Western blot analysis demonstrated similarities in the migration patterns between ovine TME and the bovine TME inoculum. Overall, these results demonstrate that sheep are susceptible to the agent of TME, and that the tissue distribution of PrPSc in TME infected sheep is distinct from classical scrapie.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=363305
https://www.ars.usda.gov/research/publications/publication/?seqNo115=360665
https://www.ars.usda.gov/research/publications/publication/?seqNo115=373668
Previous work has shown that the Stetsonville, WI outbreak of TME could have been precipitated by feeding mink a downer cow with atypical BSE; therefore, it very well may have originated from a cow with L-BSE. The agent of TME appears to remain stable, and it has a high transmission efficiency after a sequence of interspecies transmission events. Although C-BSE is the archetypal foodborne TSE, our findings indicate that L-BSE and bTME have greater transmission efficiencies in bovinized mice. Previous work has demonstrated that L-BSE also is more virulent than C-BSE in mice expressing the human prion protein [46, 55]. Although the documented incidence of L-BSE is low, the propensity of L-BSE and the TME agent to cross species barriers support the continued monitoring for atypical BSE.
https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-020-02611-0
***>This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.<***
1985
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
https://web.archive.org/web/20090506002258/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
https://web.archive.org/web/20090506001031/http://www.bseinquiry.gov.uk/files/mb/m09a/tab01.pdf
https://web.archive.org/web/20090506024922/http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf
Specified Risk Materials DOCKET NUMBER Docket No. FSIS-2022-0027 Singeltary Submission Attachment
https://www.regulations.gov/comment/FSIS-2022-0027-0002
https://downloads.regulations.gov/FSIS-2022-0027-0002/attachment_1.pdf
Title: Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ
Author Cassmann, Eric MOORE, SARA, J, SARA - Orise Fellow KOKEMULLAR, ROBYN - Non ARS Employee BALKEMA-BUSCHMAN, A - Friedrich-Loeffler-institute GROSCHUP, M - Friedrich-Loeffler-institut Nicholson, Eric Greenlee, Justin
Submitted to: BMC Veterinary Research Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/2/2020 Publication Date: 10/8/2020
Citation: Cassmann, E.D., Moore, Sara, J, S.J., Kokemullar, R.D., Balkema-Buschman, A., Groschup, M., Nicholson, E.M., Greenlee, J.J. 2020. Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ. BMC Veterinary Research. 16. Article 383. https://doi.org/10.1186/s12917-020-02611-0.
DOI: https://doi.org/10.1186/s12917-020-02611-0
Interpretive Summary: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal brain diseases that affect livestock species. A prion disease of cattle known as Mad Cow Disease, or classical bovine spongiform encephalopathy (C-BSE), broke out in the UK from 1986-1998. The disease affected millions of cattle and over 180,000 were confirmed positive. Food products from affected cattle that were consumed by humans led to a disease in people called variant Creutzfeldt-Jakob disease. Another example of cross-species transmission occurs in mink. Mink that are fed prion contaminated food results in a disease called transmissible mink encephalopathy (TME). The present study was designed to determine the effect of cross-species transmission of prion diseases in livestock on the ability to infect mice expressing the cattle prion protein. We found that passing cattle adapted TME prions from cattle to sheep changed the ability of the prions to infect mice. These results were compared to atypical BSE (L-BSE type) and Classical BSE. Depending on the genotype of sheep used, the disease in mice appeared similar to either L-BSE or C-BSE. These results indicate a shift in the disease outcome based on transmission through sheep with different genotypes. This information gives insight into the genesis of new prion strains. It also supports the hypothesis that TME can originate from feeding mink protein from cattle afflicted with L-BSE.
Technical Abstract: Transmissible mink encephalopathy (TME) is a fatal neurologic disease of farmed mink. Epidemiological and experimental evidence indicates that TME and L-BSE are similar and may be linked in some outbreaks of TME. We previously transmitted bovine adapted TME (bTME) to sheep; the present study compared ovine bTME (o-bTME) to C-BSE and L-BSE in transgenic mice expressing wild type bovine prion protein (TgBovXV). Sheep donor genotype elicited variable disease phenotypes in bovinized mice. Inoculum derived from a sheep with the VRQ/VRQ genotype (o-bTMEVV) resulted in an attack rate, incubation period, immunoblot profile, and neuropathology most similar to bTME and L-BSE. Conversely, sheep with the VRQ/ARQ genotype (o-bTMEAV) elicited a phenotype distinct from the bTME and L-BSE. Instead, o-bTMEAV led to a disease phenotype with partial similarity to C-BSE. To determine the transmission efficiency of all TSEs in this study, we considered attack rate, mean incubation period, and the relative quantity of PrPSc in the samples. The TSE with the highest transmission capability in bovinized mice was L-BSE. The tendency to efficiently transmit to TgBovXV mice decreased in the following order bTME, C-BSE, o-bTMEVV, and o-bTMEAV. The transmission efficiency of L-BSE was approximately 1.3 times higher than o-bTMEVV and 4 times higher than o-bTMEAV. Our findings provide insight on how sheep host genotype modulates strain genesis and influences interspecies transmission characteristics. Given the similarities between TME and L-BSE, their efficient interspecies transmission capabilities, and previous reports of L-BSE transmission to mice expressing the human prion protein, continued monitoring for atypical BSE is advisable in order to prevent occurrences of interspecies transmission that may affect humans or other species.
“Given the similarities between TME and L-BSE, their efficient interspecies transmission capabilities, and previous reports of L-BSE transmission to mice expressing the human prion protein, continued monitoring for atypical BSE is advisable in order to prevent occurrences of interspecies transmission that may affect humans or other species.”
https://www.ars.usda.gov/research/publications/publication/?seqNo115=373668
Wednesday, May 24, 2023
***> WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
https://wahis.woah.org/#/in-review/5067
TUESDAY, AUGUST 26, 2025
Transmissible Spongiform Encephalopathy TSE Prion Disease UPDATE AUGUST 2025
https://transmissiblespongiformencephalopathy.blogspot.com/2025/08/transmissible-spongiform-encephalopathy.html
WEDNESDAY, AUGUST 13, 2025
Revised Bovine Spongiform Encephalopathy BSE TSE Prion Standards
https://bovineprp.blogspot.com/2025/08/revised-bovine-spongiform.html
https://prpsc.proboards.com/thread/177/revised-bovine-spongiform-encephalopathy-standards
FRIDAY, DECEMBER 22, 2023
The Mad Cow That Stole Christmas, 23 Years Later
The Mad Cow That Stole Christmas, 23 Years Later, What Has Changed, Nothing
THE USA has systematically covered up mad cow disease, in my honest opinion, the USA mad cow disease today, is Chronic Wasting Disease CWD TSE Prion disease in Cervid, they can't cover that up.
https://animalhealthreportpriontse.blogspot.com/2023/12/the-mad-cow-that-stole-christmas-23.html
Volume 31, Number 1—January 2025
Dispatch
Detection of Prions in Wild Pigs (Sus scrofa) from Areas with Reported Chronic Wasting Disease Cases, United States
Abstract
Using a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.
Snip…
Conclusions In summary, results from this study showed that wild pigs are exposed to cervid prions, although the pigs seem to display some resistance to infection via natural exposure. Future studies should address the susceptibility of this invasive animal species to the multiple prion strains circulating in the environment. Nonetheless, identification of CWD prions in wild pig tissues indicated the potential for pigs to move prions across the landscape, which may, in turn, influence the epidemiology and geographic spread of CWD.
https://wwwnc.cdc.gov/eid/article/%2031/1/24-0401_article
Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.
2. Determined that pigs naturally exposed to chronic wasting disease (CWD) may act as a reservoir of CWD infectivity. Chronic wasting disease is a naturally occurring, fatal, neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of CWD disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Pigs were assigned to 1 of 3 groups: intracranially inoculated; orally inoculated; or non-inoculated. At market weight age, half of the pigs in each group were tested ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by multiple diagnostic methods. Brain samples from selected pigs were bioassayed in mice expressing porcine prion protein. Some pigs from each inoculated group were positive by one or more tests. Bioassay was positive in 4 out of 5 pigs assayed. Although only small amounts of PrPSc were detected using sensitive methods, this study demonstrates that pigs can serve as hosts for CWD. Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.
The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP
https://www.ars.usda.gov/research/publications/publication/?seqNo115=353091
Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.
https://www.ars.usda.gov/research/project/?accnNo=432011&fy=2017
Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105
This study demonstrates that pigs can serve as potential hosts for CWD, although with low attack rates and scant PrPcwd accumulation. Detection of infectivity in orally challenged pigs using mouse bioassay raises the possibility that naturally exposed pigs act as a reservoir of CWD infectivity, even though affected pigs do not develop overt clinical signs or readily detectable PrPcwd.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=326166
***> Price of TSE Prion Poker goes up substantially, all you cattle ranchers and such, better pay close attention here...terry <***
Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure
Justin Greenlee, Jifeng Bian, Zoe Lambert, Alexis Frese, and Eric Cassmann Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA
Aims: The purpose of this study was to determine the susceptibility of cattle to chronic wasting disease agent from elk.
Materials and Methods: Initial studies were conducted in bovinized mice using inoculum derived from elk with various genotypes at codon 132 (MM, LM, LL). Based upon attack rates, inoculum (10% w/v brain homogenate) from an LM132 elk was selected for transmission studies in cattle. At approximately 2 weeks of age, one wild type steer (EE211) and one steer with the E211K polymorphism (EK211) were fed 1 mL of brain homogenate in a quart of milk replacer while another 1 mL was instilled intranasally. The cattle were examined daily for clinical signs for the duration of the experiment. One steer is still under observation at 71 months post-inoculation (mpi).
Results: Inoculum derived from MM132 elk resulted in similar attack rates and incubation periods in mice expressing wild type or K211 bovine PRNP, 35% at 531 days post inoculation (dpi) and 27% at 448 dpi, respectively. Inoculum from LM132 elk had a slightly higher attack rates in mice: 45% (693 dpi) in wild type cattle PRNP and 33% (468) in K211 mice. Inoculum from LL132 elk resulted in the highest attack rate in wild type bovinized mice (53% at 625 dpi), but no K211 mice were affected at >700 days. At approximately 70 mpi, the EK211 genotype steer developed clinical signs suggestive of prion disease, depression, low head carriage, hypersalivation, and ataxia, and was necropsied. Enzyme immunoassay (IDEXX) was positive in brainstem (OD=4.00, but non-detect in retropharyngeal lymph nodes and palatine tonsil. Immunoreactivity was largely limited to the brainstem, midbrain, and cervical spinal cord with a pattern that was primarily glia-associated.
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript.
*****>>> "Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material." <<<*****
=====end
Strain characterization of chronic wasting disease in bovine-PrP transgenic mice
Nuria Jerez-Garrido1, Sara Canoyra1, Natalia Fernández-Borges1, Alba Marín Moreno1, Sylvie L. Benestad2, Olivier Andreoletti3, Gordon Mitchell4, Aru Balachandran4, Juan María Torres1 and Juan Carlos Espinosa1. 1 Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Madrid, Spain. 2 Norwegian Veterinary Institute, Ås, Norway. 3 UMR Institut National de la Recherche Agronomique (INRA)/École Nationale Vétérinaire de Toulouse (ENVT), Interactions Hôtes Agents Pathogènes, Toulouse, France. 4 Canadian Food Inspection Agency, Ottawa, Canada.
Aims: Chronic wasting disease (CWD) is an infectious prion disease that affects cervids. Various CWD prion strains have been identified in different cervid species from North America and Europe. The properties of the infectious prion strains are influenced by amino acid changes and polymorphisms in the PrP sequences of different cervid species. This study, aimed to assess the ability of a panel of CWD prion isolates from diverse cervid species from North America and Europe to infect bovine species, as well as to investigate the properties of the prion strains following the adaptation to the bovine-PrP context.
Materials and Methods: BoPrP-Tg110 mice overexpressing the bovine-PrP sequence were inoculated by intracranial route with a panel of CWD prion isolates from both North America (two white-tailed deer and two elk) and Europe (one reindeer, one moose and one red deer).
Results: Our results show distinct behaviours in the transmission of the CWD isolates to the BoPrP-Tg110 mouse model. Some of these isolates did not transmit even after the second passage. Those able to transmit displayed differences in terms of attack rate, survival times, biochemical properties of brain PrPres, and histopathology.
Conclusions: Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study.
Funded by: MCIN/AEI /10.13039/501100011033 and by European Union NextGeneration EU/PRTR
Grant number: PCI2020-120680-2 ICRAD
"Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study."
=====end
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
2001 Singeltary on CJD
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
https://jamanetwork.com/journals/jama/article-abstract/1031186
***> Creutzfeldt Jakob Disease CJD TSE Prion Cases Increasing March 2025
https://creutzfeldt-jakob-disease.blogspot.com/2025/03/creutzfeldt-jakob-disease-tse-prion.html
***> Creutzfeldt Jakob Disease CJD, BSE, CWD, TSE, Prion, December 14, 2024 Annual Update
https://creutzfeldt-jakob-disease.blogspot.com/2024/12/creutzfeldt-jacob-disease-cjd-bse-cwd.html
THURSDAY, MAY 15, 2025
Cadaveric Human Growth Hormone–Associated Creutzfeldt-Jakob Disease with Long Latency Period, United States
https://creutzfeldt-jakob-disease.blogspot.com/2025/05/cadaveric-human-growth.html
Creutzfeldt Jakob Disease CJD TSE Prion
https://creutzfeldt-jakob-disease.blogspot.com/
VPSPr
https://vpspr.blogspot.com/
nvCjd or vCJD
https://vcjd.blogspot.com/
https://vcjdblood.blogspot.com/
https://vcjdtransfusion.blogspot.com/
MONDAY, SEPTEMBER 11, 2023
***> see Alzheimers;
Professor John Collinge on tackling prion diseases sCJD around 1 in 5000 deaths worldwide
“The best-known human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia which accounts for around 1 in 5000 deaths worldwide.”
https://www.ucl.ac.uk/brain-sciences/research/dementia-ucl-priority/professor-john-collinge-tackling-prion-diseases
Singeltary sCJD
https://creutzfeldt-jakob-disease.blogspot.com/2023/09/professor-john-collinge-on-tackling.html
Iatrogenic Transmissible Spongiform Encephalopathy TSE Prion
https://itseprion.blogspot.com/
so, this is what we leave our children and grandchildren?
“Those that fail to learn from history are doomed to repeat it.”
Terry S. Singeltary Sr.
Tuesday, September 30, 2025
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
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