Ireland Department of Agriculture confirmed a case of Atypical BSE 18 year old cow
Tel: (01) 607 2802
http://efsaopinionbseanimalprotein.blogspot.com/
Thursday, July 24, 2014
Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA
http://bse-atypical.blogspot.com/2014/07/protocol-for-further-laboratory.html
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.
*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these countries. ***
see page 176 of 201 pages...tss
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2009/prion2009_bookofabstracts.pdf
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;
http://www.plosone.org/annotation/listThread.action;jsessionid=635CE9094E0EA15D5362B7D7B809448C?root=7143
Wednesday, July 15, 2015
Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?
http://transmissiblespongiformencephalopathy.blogspot.com/2015/07/additional-bse-tse-prion-testing.html
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***
Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53GMT
http://www.plosone.org/annotation/listThread.action?root=86610
Primate Biol., 3, 47–50, 2016 www.primate-biol.net/3/47/2016/ doi:10.5194/pb-3-47-2016 © Author(s) 2016. CC
Attribution 3.0 License.
Prions
Walter Bodemer German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany Correspondence to: Walter Bodemer (wbodemer@dpz.eu)
Received: 15 June 2016 – Revised: 24 August 2016 – Accepted:30 August 2016 – Published: 7 September 2016
SNIP...
3 Conclusion
Most importantly, early signs of an altered circadian rhythm, sleep–wake cycle, and activity and body temperature were recorded in prion-infected animals. This experimental approach would have never been feasible in studies with human CJD cases. After 4–6 years animals developed clinical symptoms highly similar to those typical for CJD. Clinicians confirmed how close the animal model and the human disease matched. Non-neuronal tissue like cardiac muscle and peripheral blood with abnormal, disease-related prion protein were detected in rhesus monkey tissues.
Molecular changes in RNA from repetitive Alu and BC200 DNA elements were identified and found to be targets of epigenetic editing mechanisms active in prion disease. To conclude, our results with the rhesus monkey model for prion disease proved to be a valid model and increased our knowledge of pathogenic processes that are distinctive to prion disease.
SEE FULL TEXT ;
http://www.primate-biol.net/3/47/2016/pb-3-47-2016.pdf
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand,Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, andJean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions.Contrarily, in the absence of obvious (epidemiological or experimental)elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atypical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen,2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
Saturday, April 23, 2016
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, Juan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed.The major issue in experimental assessment of TSEs zoonotic potential lies inthe modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. ***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
Title: Transmission of scrapie prions to primate after an extended silent incubation period
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690Xonline
http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html
http://wwwnc.cdc.gov/eid/article/22/12/16-0635_article
Press/Information Office Agriculture House Kildare Street Dublin 2 D02 WK12 Twitter:
E-mail: press@agriculture.gov.ie
Website: www.agriculture.gov.ie
If you have any queries on this press release please contact press@agriculture.gov.ie
05/17 18th January 2017
Department announces identification of an Atypical BSE case
The Department of Agriculture, Food and the Marine today confirmed that it has identified a case of ‘Atypical BSE’ in an 18 year old cow, through its surveillance of ‘fallen’ animals (died on farm) at knackeries.
The animal tested positive on a screening test carried out at a Department approved, accredited private laboratory over the weekend and was then subject to follow up confirmatory tests at the Department’s Central Veterinary Research Laboratory.
There are no associated public health risks with this event – a comprehensive set of public health controls are in place and the animal in this case was excluded from the food chain and its carcase will be incinerated.
The disclosure of this case of Atypical BSE does not have any impact of Ireland’s current OIE BSE ‘controlled risk’ status or trade status.
Note for editors 1.
There are two types of BSE recognised
a. Classical BSE which was the basis of the extensive incidence of BSE which commenced some in the 1980s, which was associated with the feeding of meat-and-bone meal, where scientific evidence indicates that BSE is acquired in the first year of life, and
b. Atypical BSE which has been identified more recently and which is thought to occur spontaneously.
2. Atypical BSE occurs sporadically in older animals with a low incidence rate. It was first recognized in the early 2000s in Europe following the large scale testing of livestock for BSE that was put in place at that time.
a. There have been 101 atypical BSE cases identified in the European Union during the period 2003 to 2015. This compares to a total of 2,999 cases of classical BSE during the same period.
b. Cases have occurred at a very low and relatively constant level over the entire period, ranging from two to eleven cases per year.
c. At the same time, the number of classical BSE cases has steadily dropped since 2003.
d. All known atypical BSE cases in the EU were detected in cattle older than six years of age.
e. We have identified 3 atypical cases occurred in Ireland, compared to 145 cases of classical BSE in that 13 year period.
In addition, retrospective analysis identified a 2002 case as atypical BSE - bringing the total number of confirmed atypical cases in Ireland to four.
f. Atypical cases of BSE have also been identified in Brazil (two cases) and the USA (three cases).
3. BSE does not transfer horizontally from animal to animal – no risk to other animals arises from this case animal.
ENDS
*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
Volume 23, Number 2—February 2017
Dispatch
Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle
Abstract
To determine oral transmissibility of the L-type bovine spongiform encephalopathy (BSE) prion, we orally inoculated 16 calves with brain homogenates of the agent. Only 1 animal, given a high dose, showed signs and died at 88 months. These results suggest low risk for oral transmission of the L-BSE agent among cattle.
The epidemic of bovine spongiform encephalopathy (BSE) in cattle is thought to be caused by oral infection through consumption of feed containing the BSE agent (prion). Since 2003, different neuropathologic and molecular phenotypes of BSE have been identified as causing ≈110 cases of atypical BSE worldwide, mainly in aged cattle. Although the etiology and pathogenesis of atypical BSE are not yet fully understood, atypical BSE prions possibly cause sporadic cases of BSE (1).
The L-type BSE prion (L-BSE) has been experimentally transmitted to cattle by intracerebral challenge, and the incubation period wasis shorter than that for classical BSE (C-BSE) prions (2–6). The origin of transmissible mink encephalopathy in ranch-raised mink is thought to be caused by ingestion of L-BSE–infected material (7). Although L-BSE has been orally transmitted to mouse lemurs (8), it remains to be established whether L-BSE can be transmitted to cattle by oral infection. We therefore investigated the transmissibility of L-BSE by the oral route and tissue distribution of disease-associated prion protein (PrPSc) in cattle. All experiments involving animals were performed with the approval of the Animal Ethical Committee and the Animal Care and Use Committee of the National Institute of Animal Health(approval nos. 07–88 and 08–010).
The Study
We divided a group of 16 Holstein female calves, 3–5 months of age, into 4 groups of 2–6 animals each. Each group of calves was orally administered 1 g (n = 4), 5 g (n = 6), 10 g (n = 4), or 50 g (n = 2) of pooled whole-brain homogenate prepared from cattle experimentally infected with L-BSE(3,6) (Table(https://wwwnc.cdc.gov/eid/article/23/2/16-1416-t1)). The end point titer of the pooled brain homogenate assayed in bovinized transgenic (TgBoPrP)mice was 106.9 of 50% lethal dose/g tissue (data not shown). As noninfected controls, 3 female calves were obtained at 3–4 months of age and euthanized at 60, 92, and 103 months of age, and samples were analyzed as for the experimental animals.
At 88 months after inoculation, 1 of the animals (91 months of age) that had received 50 g of L-BSE–infected brain homogenate was unable to get up. The animal extended her forelimbs and hind limbs rigidly forward but did not show persistent knuckling of her fetlock; she did not have difficulty eating and drinking. Seven days after appearance of clinical signs, the animal was found dead, having shown no characteristic signs of L-BSE, such as dullness,lowering of the head, and over reactivity to external stimuli, which had previously been observed after intracerebral inoculation of animals under experimental conditions (4).
Histopathologic examination of tissues from this animal revealed minimal or mild spongiform changes of the gray matter neuropil in the thalamic and brainstem nuclei; however, these changes were not visible in the cerebral and cerebellar cortices, the olfactory bulb, or the dorsal motornucleus of the vagus nerve at the obex. Higher amounts of proteinaseK–resistant PrPSc, analyzed by Western blotting with monoclonal antibody T2(9), were detected in the thalamus, brainstem, cerebellum, spinal cord, and retina (Figure 1, lanes 8–16; Figures 2, panels A, B), whereas PrPSc accumulation was lower in the cerebral cortices and the olfactory bulb (Figure 1, lanes1–6). The molecular characteristics of proteinase K–resistant PrPSc, such as the molecular weight and the glycoform profile in the brain of the animal, were identical to those observed in the inoculum. The most conspicuous PrPSc finding, obtained by using immunohistochemistry with monoclonal antibody F99/97.6.1 (VMRD, Pullman, WA, USA), was fine and coarse granular deposits in the neuropil of the thalamus, brainstem, and gray matter of the spinal cord,and in the retina. Perineuronal PrPSc staining was conspicuous in the large neurons of the thalamic and brainstem nuclei (Figure 2, panel C) but less common in other brain areas. Fewer PrPSc deposits were dispersed in the dorsal motor nucleus of the vagus nerve at the obex (Figure 2, panel A). No amyloid plaques were detectable in any brain section. In the extracerebral tissues,PrPSc was lower in most of the samples from the nerve ganglia (trigeminal,dorsal root, stellate, cervical cranial, no dose, and celiac and mesenteric), cauda equina, vagal nerve, optic nerve, neurohypophysis, ocular muscle, and adrenal medulla (Figure 1, lanes 17–33; Figures 2, panels D–H). However, noPrPSc signal was detected in most of the somatic nerve fibers (Figure 1, lanes25, 26, 29, 30), the enteric nervous system (Figure 1, lanes 32, 33), and anylymphoid organs including the remaining Peyer’s patches (data not shown).
The only other animal inoculated with 50 g of L-BSE brain material was alive and clinically healthy as of post inoculation month 94(December 2016). Calves that received 1 g, 5 g, or 10 g of L-BSE brain tissues showed no clinical signs of BSE and were euthanized and underwent necropsy 51–86 months after inoculation (Table https://wwwnc.cdc.gov/eid/article/23/2/16-1416-t1 for all of these animals and the uninfected controls, PrPSc results were negative by Western blot and immunohistochemical analysis.
Conclusions
Our results suggest that the risk for oral transmission of L-BSE among cattle may be very low; after 88 months, the only case of transmission occurred in a cow that had been inoculated with a high dose of L-BSE–infected brain homogenate. The incubation period was much longer for cattle dosed orally with L-BSE–infected brain homogenate than for cattle dosed orally with C-BSE–infected tissue (34−74 mo for C-BSE) (10). This finding may suggest that the L-BSE prion requires much longer to propagate from the gut to the central nervous system. In addition, the lack of clinical signs, except for difficulty in rising, may present a genuine clinical picture of L-BSE under natural conditions (11). In most cases of naturally occurring atypical BSE identified so far, the animals were >8 years of age, except for 3 cases: 1H-BSE and 1 L-BSE in Spain (1) and 1 H-BSE in Germany (12). Therefore, we cannot exclude the possibility that L-BSE developed sporadically/spontaneously. However, this case may not have naturally occurred, in view of the low prevalence of L-BSE in Japan during October 2001–August 2016, which was 0.065 cases/1 million tested adult animals. In our study, the remaining live animal,challenged with 50 g of L-BSE brain homogenate, will provide the further information about the oral transmissibility to cattle. Bioassays of brain sample sin TgBoPrP mice are ongoing.
The neuroanatomical PrPSc distribution pattern of orally challenged cattle differed somewhat from that described in cattle naturally and intracerebrally challenged with L-BSE (2–6,11,13,14), The conspicuous differences between the case we report and cases of natural and experimental infection are 1) higher amounts of PrPSc in the caudal medulla oblongata and the spinal cord coupled with that in the thalamus and the more rostral brainstem and 2) relatively low amounts of PrPSc in the cerebral cortices and the olfactory bulb. Furthermore, fewer PrPSc deposits in the dorsal motor nucleus of the vagus nerve may indicate that the parasympathetic retrogressive neuro invasion pathway does not contribute to transport of the L-BSE prion from the gut to the brain, which is in contrast to the vagus-associated transport of the agent in C-BSE (15). PrPSc accumulation in the extracerebral tissues may be a result of centrifugal trafficking of the L-BSE prion from the central nervous system along somatic or autonomic nerve fibers rather than centripetal propagation of the agent (4,6,9). Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
Dr. Okada is a veterinary pathologist and chief researcher at the National Institute of Animal Health, National Agriculture and Food Research Organization, Ibaraki, Japan. His research focuses on the pathogenesis of animal prion diseases in ruminants as natural hosts and in experimentally infected animals.
Acknowledgments
We thank Naoko Tabeta, Naomi Furuya, Junko Yamada, RitsukoMiwa, Noriko Shinozaki, and the animal caretakers for their expert technical assistance.
This work was supported by grants-in-aid from the BSE and Other Prion Disease project and the Improving Food Safety and Animal Health project of the Ministry of Agriculture, Forestry and Fisheries, Japan.
References
https://wwwnc.cdc.gov/eid/article/23/2/16-1416_article
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type)and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine,and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovinePrPC were converted by PrPSc from all tested prion strains. On the other hand,human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, our findings suggest that possible transmission risk of
H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
***P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food Inspection Agency; Lethbridge, AB Canada
Keywords: Atypical BSE, oral transmission, RT-QuIC
The detection of bovine spongiform encephalopathy (BSE) has had a significant negative impact on the cattle industry worldwide. In response, governments took actions to prevent transmission and additional threats to animal health and food safety. While these measures seem to be effective for controlling classical BSE, the more recently discovered atypical BSE has presented a new challenge. To generate data for risk assessment and control measures, we have challenged cattle orally with atypical BSE to determine transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon presentation of clinical symptoms, animals were euthanized and tested for characteristic histopathological changes as well as PrPSc deposition.
The H-type challenged animal displayed vacuolation exclusively in rostral brain areas but the L-type challenged animal showed no evidence thereof. To our surprise, neither of the animals euthanized, which were displaying clinical signs indicative of BSE, showed conclusive mis-folded prion accumulation in the brain or gut using standard molecular or immunohistochemical assays. To confirm presence or absence of prion infectivity, we employed an optimized real-time quaking induced conversion(RT-QuIC) assay developed at the Rocky Mountain Laboratory, Hamilton, USA.
Detection of PrPSc was unsuccessful for brain samples tests from the orally inoculated L type animal using the RT-QuIC. It is possible that these negative results were related to the tissue sampling locations or that type specific optimization is needed to detect PrPSc in this animal. We were however able to consistently detect the presence of mis-folded prions in the brain of the H-type inoculated animal. Considering the negative and inconclusive results with other PrPSc detection methods, positive results using the optimized RT-QuIC suggests the method is extremely sensitive for H-type BSE detection. This may be evidence of the first successful oral transmission of H type atypical BSE in cattle and additional investigation of samples from these animals are ongoing.
http://www.tandfonline.com/doi/pdf/10.4161/pri.29370
http://transmissiblespongiformencephalopathy.blogspot.com/2014/06/prion-2014-typical-and-atypical-bse-and.html
http://bse-atypical.blogspot.com/2016/05/a-comparison-of-classical-and-h-type.html
Volume 23, Number 2—February 2017
Dispatch
Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle
Abstract
To determine oral transmissibility of the L-type bovine spongiform encephalopathy (BSE) prion, we orally inoculated 16 calves with brain homogenates of the agent. Only 1 animal, given a high dose, showed signs and died at 88 months. These results suggest low risk for oral transmission of the L-BSE agent among cattle.
The epidemic of bovine spongiform encephalopathy (BSE) in cattle is thought to be caused by oral infection through consumption of feed containing the BSE agent (prion). Since 2003, different neuropathologic and molecular phenotypes of BSE have been identified as causing ≈110 cases of atypical BSE worldwide, mainly in aged cattle. Although the etiology and pathogenesis of atypical BSE are not yet fully understood, atypical BSE prions possibly cause sporadic cases of BSE (1).
The L-type BSE prion (L-BSE) has been experimentally transmitted to cattle by intracerebral challenge, and the incubation period wasis shorter than that for classical BSE (C-BSE) prions (2–6). The origin of transmissible mink encephalopathy in ranch-raised mink is thought to be caused by ingestion of L-BSE–infected material (7). Although L-BSE has been orally transmitted to mouse lemurs (8), it remains to be established whether L-BSE can be transmitted to cattle by oral infection. We therefore investigated the transmissibility of L-BSE by the oral route and tissue distribution of disease-associated prion protein (PrPSc) in cattle. All experiments involving animals were performed with the approval of the Animal Ethical Committee and the Animal Care and Use Committee of the National Institute of Animal Health(approval nos. 07–88 and 08–010).
The Study
We divided a group of 16 Holstein female calves, 3–5 months of age, into 4 groups of 2–6 animals each. Each group of calves was orally administered 1 g (n = 4), 5 g (n = 6), 10 g (n = 4), or 50 g (n = 2) of pooled whole-brain homogenate prepared from cattle experimentally infected with L-BSE(3,6) (Table(https://wwwnc.cdc.gov/eid/article/23/2/16-1416-t1)). The end point titer of the pooled brain homogenate assayed in bovinized transgenic (TgBoPrP)mice was 106.9 of 50% lethal dose/g tissue (data not shown). As noninfected controls, 3 female calves were obtained at 3–4 months of age and euthanized at 60, 92, and 103 months of age, and samples were analyzed as for the experimental animals.
At 88 months after inoculation, 1 of the animals (91 months of age) that had received 50 g of L-BSE–infected brain homogenate was unable to get up. The animal extended her forelimbs and hind limbs rigidly forward but did not show persistent knuckling of her fetlock; she did not have difficulty eating and drinking. Seven days after appearance of clinical signs, the animal was found dead, having shown no characteristic signs of L-BSE, such as dullness,lowering of the head, and over reactivity to external stimuli, which had previously been observed after intracerebral inoculation of animals under experimental conditions (4).
Histopathologic examination of tissues from this animal revealed minimal or mild spongiform changes of the gray matter neuropil in the thalamic and brainstem nuclei; however, these changes were not visible in the cerebral and cerebellar cortices, the olfactory bulb, or the dorsal motornucleus of the vagus nerve at the obex. Higher amounts of proteinaseK–resistant PrPSc, analyzed by Western blotting with monoclonal antibody T2(9), were detected in the thalamus, brainstem, cerebellum, spinal cord, and retina (Figure 1, lanes 8–16; Figures 2, panels A, B), whereas PrPSc accumulation was lower in the cerebral cortices and the olfactory bulb (Figure 1, lanes1–6). The molecular characteristics of proteinase K–resistant PrPSc, such as the molecular weight and the glycoform profile in the brain of the animal, were identical to those observed in the inoculum. The most conspicuous PrPSc finding, obtained by using immunohistochemistry with monoclonal antibody F99/97.6.1 (VMRD, Pullman, WA, USA), was fine and coarse granular deposits in the neuropil of the thalamus, brainstem, and gray matter of the spinal cord,and in the retina. Perineuronal PrPSc staining was conspicuous in the large neurons of the thalamic and brainstem nuclei (Figure 2, panel C) but less common in other brain areas. Fewer PrPSc deposits were dispersed in the dorsal motor nucleus of the vagus nerve at the obex (Figure 2, panel A). No amyloid plaques were detectable in any brain section. In the extracerebral tissues,PrPSc was lower in most of the samples from the nerve ganglia (trigeminal,dorsal root, stellate, cervical cranial, no dose, and celiac and mesenteric), cauda equina, vagal nerve, optic nerve, neurohypophysis, ocular muscle, and adrenal medulla (Figure 1, lanes 17–33; Figures 2, panels D–H). However, noPrPSc signal was detected in most of the somatic nerve fibers (Figure 1, lanes25, 26, 29, 30), the enteric nervous system (Figure 1, lanes 32, 33), and anylymphoid organs including the remaining Peyer’s patches (data not shown).
The only other animal inoculated with 50 g of L-BSE brain material was alive and clinically healthy as of post inoculation month 94(December 2016). Calves that received 1 g, 5 g, or 10 g of L-BSE brain tissues showed no clinical signs of BSE and were euthanized and underwent necropsy 51–86 months after inoculation (Table https://wwwnc.cdc.gov/eid/article/23/2/16-1416-t1 for all of these animals and the uninfected controls, PrPSc results were negative by Western blot and immunohistochemical analysis.
Conclusions
Our results suggest that the risk for oral transmission of L-BSE among cattle may be very low; after 88 months, the only case of transmission occurred in a cow that had been inoculated with a high dose of L-BSE–infected brain homogenate. The incubation period was much longer for cattle dosed orally with L-BSE–infected brain homogenate than for cattle dosed orally with C-BSE–infected tissue (34−74 mo for C-BSE) (10). This finding may suggest that the L-BSE prion requires much longer to propagate from the gut to the central nervous system. In addition, the lack of clinical signs, except for difficulty in rising, may present a genuine clinical picture of L-BSE under natural conditions (11). In most cases of naturally occurring atypical BSE identified so far, the animals were >8 years of age, except for 3 cases: 1H-BSE and 1 L-BSE in Spain (1) and 1 H-BSE in Germany (12). Therefore, we cannot exclude the possibility that L-BSE developed sporadically/spontaneously. However, this case may not have naturally occurred, in view of the low prevalence of L-BSE in Japan during October 2001–August 2016, which was 0.065 cases/1 million tested adult animals. In our study, the remaining live animal,challenged with 50 g of L-BSE brain homogenate, will provide the further information about the oral transmissibility to cattle. Bioassays of brain sample sin TgBoPrP mice are ongoing.
The neuroanatomical PrPSc distribution pattern of orally challenged cattle differed somewhat from that described in cattle naturally and intracerebrally challenged with L-BSE (2–6,11,13,14), The conspicuous differences between the case we report and cases of natural and experimental infection are 1) higher amounts of PrPSc in the caudal medulla oblongata and the spinal cord coupled with that in the thalamus and the more rostral brainstem and 2) relatively low amounts of PrPSc in the cerebral cortices and the olfactory bulb. Furthermore, fewer PrPSc deposits in the dorsal motor nucleus of the vagus nerve may indicate that the parasympathetic retrogressive neuro invasion pathway does not contribute to transport of the L-BSE prion from the gut to the brain, which is in contrast to the vagus-associated transport of the agent in C-BSE (15). PrPSc accumulation in the extracerebral tissues may be a result of centrifugal trafficking of the L-BSE prion from the central nervous system along somatic or autonomic nerve fibers rather than centripetal propagation of the agent (4,6,9). Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
Dr. Okada is a veterinary pathologist and chief researcher at the National Institute of Animal Health, National Agriculture and Food Research Organization, Ibaraki, Japan. His research focuses on the pathogenesis of animal prion diseases in ruminants as natural hosts and in experimentally infected animals.
Acknowledgments
We thank Naoko Tabeta, Naomi Furuya, Junko Yamada, RitsukoMiwa, Noriko Shinozaki, and the animal caretakers for their expert technical assistance.
This work was supported by grants-in-aid from the BSE and Other Prion Disease project and the Improving Food Safety and Animal Health project of the Ministry of Agriculture, Forestry and Fisheries, Japan.
References
https://wwwnc.cdc.gov/eid/article/23/2/16-1416_article
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type)and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine,and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovinePrPC were converted by PrPSc from all tested prion strains. On the other hand,human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, our findings suggest that possible transmission risk of
H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
***P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion
Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food Inspection Agency; Lethbridge, AB Canada
Keywords: Atypical BSE, oral transmission, RT-QuIC
The detection of bovine spongiform encephalopathy (BSE) has had a significant negative impact on the cattle industry worldwide. In response, governments took actions to prevent transmission and additional threats to animal health and food safety. While these measures seem to be effective for controlling classical BSE, the more recently discovered atypical BSE has presented a new challenge. To generate data for risk assessment and control measures, we have challenged cattle orally with atypical BSE to determine transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon presentation of clinical symptoms, animals were euthanized and tested for characteristic histopathological changes as well as PrPSc deposition.
The H-type challenged animal displayed vacuolation exclusively in rostral brain areas but the L-type challenged animal showed no evidence thereof. To our surprise, neither of the animals euthanized, which were displaying clinical signs indicative of BSE, showed conclusive mis-folded prion accumulation in the brain or gut using standard molecular or immunohistochemical assays. To confirm presence or absence of prion infectivity, we employed an optimized real-time quaking induced conversion(RT-QuIC) assay developed at the Rocky Mountain Laboratory, Hamilton, USA.
Detection of PrPSc was unsuccessful for brain samples tests from the orally inoculated L type animal using the RT-QuIC. It is possible that these negative results were related to the tissue sampling locations or that type specific optimization is needed to detect PrPSc in this animal. We were however able to consistently detect the presence of mis-folded prions in the brain of the H-type inoculated animal. Considering the negative and inconclusive results with other PrPSc detection methods, positive results using the optimized RT-QuIC suggests the method is extremely sensitive for H-type BSE detection. This may be evidence of the first successful oral transmission of H type atypical BSE in cattle and additional investigation of samples from these animals are ongoing.
http://www.tandfonline.com/doi/pdf/10.4161/pri.29370
http://transmissiblespongiformencephalopathy.blogspot.com/2014/06/prion-2014-typical-and-atypical-bse-and.html
http://bse-atypical.blogspot.com/2016/05/a-comparison-of-classical-and-h-type.html
*** SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY ***
***Moreover, sporadic disease has never been observed inbreeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
http://www.nature.com/articles/srep11573
Monday, January 09, 2017
Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle CDC Volume 23, Number 2—February 2017
http://bse-atypical.blogspot.com/2017/01/oral-transmission-of-l-type-bovine.html
***Moreover, sporadic disease has never been observed inbreeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
http://www.nature.com/articles/srep11573
Monday, January 09, 2017
Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle CDC Volume 23, Number 2—February 2017
http://bse-atypical.blogspot.com/2017/01/oral-transmission-of-l-type-bovine.html
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
WEDNESDAY, JANUARY 18, 2017
EU-approved rapid tests might underestimate bovine spongiform encephalopathy infection in goats
Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA
http://bse-atypical.blogspot.com/2014/07/protocol-for-further-laboratory.html
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.
*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these countries. ***
see page 176 of 201 pages...tss
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2009/prion2009_bookofabstracts.pdf
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;
http://www.plosone.org/annotation/listThread.action;jsessionid=635CE9094E0EA15D5362B7D7B809448C?root=7143
Wednesday, July 15, 2015
Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?
http://transmissiblespongiformencephalopathy.blogspot.com/2015/07/additional-bse-tse-prion-testing.html
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***
Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53GMT
http://www.plosone.org/annotation/listThread.action?root=86610
Primate Biol., 3, 47–50, 2016 www.primate-biol.net/3/47/2016/ doi:10.5194/pb-3-47-2016 © Author(s) 2016. CC
Attribution 3.0 License.
Prions
Walter Bodemer German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany Correspondence to: Walter Bodemer (wbodemer@dpz.eu)
Received: 15 June 2016 – Revised: 24 August 2016 – Accepted:30 August 2016 – Published: 7 September 2016
SNIP...
3 Conclusion
Most importantly, early signs of an altered circadian rhythm, sleep–wake cycle, and activity and body temperature were recorded in prion-infected animals. This experimental approach would have never been feasible in studies with human CJD cases. After 4–6 years animals developed clinical symptoms highly similar to those typical for CJD. Clinicians confirmed how close the animal model and the human disease matched. Non-neuronal tissue like cardiac muscle and peripheral blood with abnormal, disease-related prion protein were detected in rhesus monkey tissues.
Molecular changes in RNA from repetitive Alu and BC200 DNA elements were identified and found to be targets of epigenetic editing mechanisms active in prion disease. To conclude, our results with the rhesus monkey model for prion disease proved to be a valid model and increased our knowledge of pathogenic processes that are distinctive to prion disease.
SEE FULL TEXT ;
http://www.primate-biol.net/3/47/2016/pb-3-47-2016.pdf
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand,Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, andJean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions.Contrarily, in the absence of obvious (epidemiological or experimental)elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atypical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen,2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
Saturday, April 23, 2016
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, Juan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed.The major issue in experimental assessment of TSEs zoonotic potential lies inthe modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. ***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
Title: Transmission of scrapie prions to primate after an extended silent incubation period
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690Xonline
http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html
http://wwwnc.cdc.gov/eid/article/22/12/16-0635_article
MONDAY, JANUARY 16, 2017
APHIS Bovine Spongiform Encephalopathy (BSE): Ongoing Surveillance Program Last Modified: Jan 5, 2017
Tuesday, September 06, 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
http://bse-atypical.blogspot.com/2016/09/a-comparison-of-classical-and-h-type.html
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE,TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
http://bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html
Tuesday, July 26, 2016
Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016
http://bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html
Monday, June 20, 2016
Specified Risk Materials SRMs BSE TSE Prion Program
http://specifiedriskmaterial.blogspot.com/2016/06/specified-risk-materials-srms-bse-tse.html
Wednesday, May 25, 2016
USDA APHIS National Scrapie TSE Prion Eradication Program April 2016 Monthly Report Prion 2016 Tokyo Update
http://scrapie-usa.blogspot.com/2016/05/usda-aphis-national-scrapie-tse-prion.html
Wednesday, December 21, 2016
TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2016 ANNUAL REPORT ARS RESEARCH
http://transmissiblespongiformencephalopathy.blogspot.com/2016/12/transmission-differentiation-and.html
Thursday, December 08, 2016
USDA APHIS National Scrapie Eradication Program October 2016Monthly Report Fiscal Year 2017 atypical NOR-98 Scrapie
http://scrapie-usa.blogspot.com/2016/12/usda-aphis-national-scrapie-eradication.html
http://scrapie-usa.blogspot.com/2016/06/scrapie-field-trial-experiments-mission.html
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
http://bse-atypical.blogspot.com/2016/09/a-comparison-of-classical-and-h-type.html
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE,TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
http://bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html
Tuesday, July 26, 2016
Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016
http://bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html
Monday, June 20, 2016
Specified Risk Materials SRMs BSE TSE Prion Program
http://specifiedriskmaterial.blogspot.com/2016/06/specified-risk-materials-srms-bse-tse.html
Wednesday, May 25, 2016
USDA APHIS National Scrapie TSE Prion Eradication Program April 2016 Monthly Report Prion 2016 Tokyo Update
http://scrapie-usa.blogspot.com/2016/05/usda-aphis-national-scrapie-tse-prion.html
Wednesday, December 21, 2016
TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2016 ANNUAL REPORT ARS RESEARCH
http://transmissiblespongiformencephalopathy.blogspot.com/2016/12/transmission-differentiation-and.html
Thursday, December 08, 2016
USDA APHIS National Scrapie Eradication Program October 2016Monthly Report Fiscal Year 2017 atypical NOR-98 Scrapie
http://scrapie-usa.blogspot.com/2016/12/usda-aphis-national-scrapie-eradication.html
http://scrapie-usa.blogspot.com/2016/06/scrapie-field-trial-experiments-mission.html
2001 FDA CJD TSE Prion Singeltary Submission
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
2016
https://www.regulations.gov/document?D=FDA-2016-N-0321-0005
https://www.regulations.gov/document?D=FDA-2013-N-0764-0008
Tuesday, August 9, 2016
Concurrence with OIE Risk Designations for Bovine SpongiformEncephalopathy [Docket No. APHIS-2015-0055]
BILLING CODE: 3410-34-P DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service
http://bovineprp.blogspot.com/2016/08/concurrence-with-oie-risk-designations.html
????: CBCnews
*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video
*** sporadic CJD linked to mad cow disease
*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
http://zoomify.uzh.ch:8080/zoomify/videos/video-004/video-004.html
new url
https://histodb11.usz.ch/Images/videos/video-004/video-004.html
1994-10-13: Scrapie Man
*** Scrapie Video
http://zoomify.uzh.ch:8080/zoomify/videos/video-011/video-011.html
new link
https://histodb11.usz.ch/Images/videos/video-011/video-011.html
1997-11-10: Panorama - The british disease
*** Human Mad Cow Video
http://zoomify.uzh.ch:8080/zoomify/videos/video-009/video-009.html
new link
https://histodb11.usz.ch/Images/videos/video-009/video-009.html
2009-08-27
PrioNet Canada_Lecture "New Findings in Prion Research"
Prof. Dr. Adriano Aguzzi
https://histodb11.usz.ch/Images/videos/video-029/video-029.html
Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis *video*
https://www.youtube.com/watch?v=zf3lfz9NrT4
Wednesday, December 14, 2016
Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples
http://creutzfeldt-jakob-disease.blogspot.com/2016/12/diagnosis-of-human-prion-disease-using.html
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP,Gajdusek DC. Laboratory of Central Nervous System Studies, National Instituteof Neurological Disorders and Stroke, National Institutes of Health, Bethesda,MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakobdisease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour,the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No.6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakobdisease (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.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB.Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA.2000;284:2322-2323.
http://jama.jamanetwork.com/article.aspx?articleid=1031186
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
2016
https://www.regulations.gov/document?D=FDA-2016-N-0321-0005
https://www.regulations.gov/document?D=FDA-2013-N-0764-0008
Tuesday, August 9, 2016
Concurrence with OIE Risk Designations for Bovine SpongiformEncephalopathy [Docket No. APHIS-2015-0055]
BILLING CODE: 3410-34-P DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service
http://bovineprp.blogspot.com/2016/08/concurrence-with-oie-risk-designations.html
????: CBCnews
*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video
*** sporadic CJD linked to mad cow disease
*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
http://zoomify.uzh.ch:8080/zoomify/videos/video-004/video-004.html
new url
https://histodb11.usz.ch/Images/videos/video-004/video-004.html
1994-10-13: Scrapie Man
*** Scrapie Video
http://zoomify.uzh.ch:8080/zoomify/videos/video-011/video-011.html
new link
https://histodb11.usz.ch/Images/videos/video-011/video-011.html
1997-11-10: Panorama - The british disease
*** Human Mad Cow Video
http://zoomify.uzh.ch:8080/zoomify/videos/video-009/video-009.html
new link
https://histodb11.usz.ch/Images/videos/video-009/video-009.html
2009-08-27
PrioNet Canada_Lecture "New Findings in Prion Research"
Prof. Dr. Adriano Aguzzi
https://histodb11.usz.ch/Images/videos/video-029/video-029.html
Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis *video*
https://www.youtube.com/watch?v=zf3lfz9NrT4
Wednesday, December 14, 2016
Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples
http://creutzfeldt-jakob-disease.blogspot.com/2016/12/diagnosis-of-human-prion-disease-using.html
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP,Gajdusek DC. Laboratory of Central Nervous System Studies, National Instituteof Neurological Disorders and Stroke, National Institutes of Health, Bethesda,MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakobdisease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour,the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No.6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakobdisease (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.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB.Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA.2000;284:2322-2323.
http://jama.jamanetwork.com/article.aspx?articleid=1031186
posted by Terry S. Singeltary Sr. at
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