Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America

>>>BY my records, to date, there have been 6 cases of the Nor-98-like atypical scrapie documented in the USA.<<<

>>>Maybe one of the USDA followers here on the BSE-L, that is in the Scrapie department, would be so kind as to help us clear this up?<<<

oh well, so much for the USDA followers here........ however, i did find this ;

Nor98-like Scrapie in the United States of America

was presented by Drs. Christina M. Loiacono, S. Mark Hall, and Bruce V. Thomsen, National Veterinary Services Laboratory, USDA-APHIS-VS.

This paper describes the first six sheep diagnosed with Nor98-like disease in the United States and serves to acknowledge the increased efforts of diagnosticians and the USDA program to control and eradicate scrapie disease. Classical scrapie, a fatal neurodegenerative disease affecting the central nervous system of sheep and goats, is among a number of diseases classified as transmissible spongiform encephalopathies (TSEs). Recently, a distinct strain of scrapie was diagnosed in sheep in Norway1 and has been identified in numerous countries of the European Union (EU). The disease has been identified, among other names, as Nor98 or Nor98-like scrapie. Distinctions between classical scrapie and Nor98-like scrapie are made based on signalment, clinical signs, histopathology and immunodiagnostic results. In the past, the classical scrapie disease was confirmed by examination of the brain tissue for a triad of histopathological signs – vacuolation, loss of neurons and gliosis – and, more recently, by immunohistochemical (IHC) or biochemical detection of abnormal prion protein (PrPSc) in the brain, or lymphoid tissues. In the case of Nor98-like scrapie there is generally little or no vacuolation in the brain and, to date, no lymphoid accumulation of PrPSc has been detected. Classical scrapie typically has the most intense PrPSc immunostaining at the obex (motor nucleus of the vagus), while this area is spared in Nor98-like scrapie. Alternatively, Nor98-like scrapie consistently has PrPSc immunostaining in the spinal nucleus of the trigeminal nerve and variable, but often an intense immunostaining for PrPSc in the cerebellum. Thus the diagnosis of Nor98 and Nor98-like disease can be based on immunohistochemistry identifying abnormal prion protein in regions of the brain not typically associated with classical scrapie. Additionally there is a distinct diagnostic western blot pattern for Nor98 and Nor-98 like disease consisting of three or more protein bands with the unglycosylated band being less than 15 kd, compared to classical scrapie in which the unglycosylated band is greater than 15 kd. Nor98 and Nor-98 like disease is associated with older sheep, usually greater than four years of age, while sheep in the range of three to five years of age are more commonly affected by classical scrapie. Clinical signs are uncommon with Nor98 and Nor98-like disease but when present most often include ataxia without pruritis. Genotypes known to provide sheep with resistance to classical scrapie are not spared from Nor98 and Nor98-like disease. The six U.S. cases had no clinical signs reported. Three cases were detected during slaughter surveillance, two were detected as a result of classical scrapie being found in the flock, one found during testing associated with diagnostic necropsy. Five of the 6 cases had genotypes that are susceptible to classical scrapie and one was AARR. Only one Nor98-like scrapie case was found per flock. 1. Benestad SL, Sarradin P, Thu B, Schönheit J, Tranulis MA, Bratberg B., Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet. Rec.





NOW, if there have been more of the Nor-98 documented to date, know one would know since NO MAP for the Nor-98 total cases in the USA is posted on the USDA/APHIS scrapie maps monthly report. ...TSS

P03.141 Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway

Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.




R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as “atypical” scrapie, as opposed to “classical scrapie”. Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease. 119


Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health. Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)


NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 007





Monday, December 1, 2008 When Atypical Scrapie cross species barriers


EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........


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. PMID: 6997404


Abstract 12/10/76



A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. 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.




Epidemiology of Scrapie in the United States 1977



Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease. Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America. Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...





----- Original Message ----- From: "Terry S. Singeltary Sr." To: Sent: Sunday, April 26, 2009 3:15 PM Subject: [BSE-L] SCRAPIE DETECTED IN ANOTHER GOAT USA UPDATE MARCH 2009

-------------------- BSE-L@LISTS.AEGEE.ORG --------------------





Greetings BSE-L,

I find it disturbing that the Nor-98 atypical cases of scrapie in the USA are NOT documented on the APHIS web page. this makes no sense, and i have ask about it before in the past, APHIS et al refuse to post a seperate map showing the documented Nor98-like atypical cases here in the USA, all of them ? said they would look into it years ago. it's like out of sight, out of mind, like the TSE in the USA bovine. THE ONLY mention of the Nor-98 like scrapie that has been documented in the USA to date was on CHART 3, and then it is very very misleading as to the actual number of cases. it states ;

>* Through March 31, 2009 - does not include the Nor-98-like Scrapie cases found through RSSS (2 in FY 2007 and 1 in FY 2008). <

SO, were just going to forget about the other 3 cases of the Nor-98-like scrapie in the USA ???

or, are there more ???

WHY not a seperate map showing Nor-98-like atypical Scrapie cases (all of them), state by state ???

HAVE the actual number of cases grown in the USA from the 6 cases I was aware of ???

BY my records, to date, there have been 6 cases of the Nor-98-like atypical scrapie documented in the USA. Maybe one of the USDA followers here on the BSE-L, that is in the Scrapie department, would be so kind as to help us clear this up?




No comments: