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Mystery BSE Disease Found
In Sheep - Mad Cow Mutating?

From Patricia Doyle, PhD
dr_p_doyle@hotmail.com
4-9-4


Hello, Jeff - I believe that we are now seeing all forms of prion disease mutating. Attached below is a Scrapie-LIKE disease update. Atypical Scrapie, Atypical BSE in cattle and now, an atypical BSE in sheep indicates that this is not the abnormal, but, the beginning of the norm. Until, we find out what causes the prion to misfold and figure out the "trigger" we will cotninue to be perplexed by this disease.
 
Although, scrapie was first identified in the 1700s, TSE and all of the prion diseases are really quite new. Prion disease is unlike viral disease. Antigenic drift and shifts in viral diseases, such as occur with Influenza can almost be predictable. Mechanisms of prion folding and misfolding are, truly, alien to us. We now have a new trend in prion disease or TSEs and we don't know how and why or how to stop it.
 
There is a good possibility that atypical mutations of all prion diseases has basis in an eroding genetic evolution of the victims of the disease. We may be polluting ourselves into oblivion.
 
Patricia
 
Mysterious BSE-Like Disease Found In Sheep
 
From ProMED-mail 4-9-4
 
By Debora MacKenzie] NewScientist.com news service 8 Apr 2004
 
A massive research programme to find out whether BSE is circulating in British sheep has turned up its first suspicious result. But while scientists say the sheep did not have conventional BSE, they cannot rule out the possibility that it could have had a new form of BSE (mad cow disease) that has adapted to sheep.
 
Britain's Department for Environment, Food and Rural Affairs [DEFRA] has announced that the Veterinary Laboratories Agency (VLA) in Weybridge, England, had found "a type of scrapie not previously seen in the UK". Scrapie is a sheep disease similar to BSE which is not generally thought to harm people.
 
The Department for the Environment, Food and Rural Affairs (DEFRA) said the disease-causing prion detected in the sheep's brain "had some characteristics similar to experimental BSE in sheep", but that on other tests it resembled neither BSE nor "previously recognised types of scrapie". The UK's Food Standards Agency said in a statement: "Uncertainties still remain on this issue. However, based on the best scientific evidence to date, we are not advising against eating lamb and sheep meat."
 
There have long been fears that sheep which ate cattle-derived meat and bone meal during Britain's BSE epidemic in the 1980s might have acquired BSE, although they have never been confirmed. Unlike BSE in cattle, prion diseases spread directly from sheep to sheep. So any BSE in sheep could still be circulating despite subsequent bans on animal-derived feed. Furthermore, sheep experimentally fed BSE develop a disease indistinguishable from ordinary scrapie, making detection very difficult. Yet the prion from such animals still behaves like BSE, and could cause the fatal human disease vCJD. Worse, sheep carry prions in more tissues than cattle, including the muscle that people eat, so BSE-infected sheep could cause more human disease than mad cows.
 
A previous attempt to determine whether British sheep had acquired BSE went spectacularly wrong in 2001 when sheep and cattle brains were mixed up in the lab. But since then, the VLA has tested the brains of all 1019 newly reported cases of scrapie, as well as 1125 scrapie brains dating back to 1998, with tests designed to distinguish scrapie from BSE.
 
The new result announced on Wednesday, from a sheep recently reported with scrapie symptoms, is the first to give results that resembled BSE. Danny Matthews of the VLA told New Scientist that in a prion test called a western blot, the sheep's brain did not bind an antibody called P4. P4 also does not bind prions from sheep experimentally infected with BSE, but does bind all but one forms of scrapie tested with it.
 
Also like BSE, the form of the prion without a sugar attached to it had a lower molecular weight than the form found in scrapie. But the ratio of prions with different numbers of sugars on them looked like scrapie, not BSE, says Matthews. Most conclusively, immunohistochemistry (IHC), in which thin slices of the sheep's brain were stained with various antibodies, showed prions had accumulated in different parts of the brain and different kinds of cells from BSE -- or any known form of scrapie.
 
The IHC pattern reliably indicates BSE, says Matthews, having been constant in the 100 experimentally infected sheep of different genetic varieties tested so far. But so little scrapie has been tested, he says, it is not known if one strain might give these results on the tests. One possibility, he says, is that the sheep might have been carrying a prion initially derived from BSE. Passage into new species is well known to change prions.
 
BSE from experimentally infected sheep has so far been passed to just one more round of sheep, with no apparent change. "But we don't know if passage through many sheep, of different genetic types, might change it so it no longer gives the same pattern in IHC or western blots," says Matthews. "Those experiments are underway now."
 
Any such new incarnation of BSE in sheep may -- or may not -- have lost its ability to harm humans.
 
http://www.newscientist.com/news/news.jsp?id=ns99994869
 
-- ProMED-mail <promed@promedmail.org>
 
[As rightly commented, the main current worry, related to a possible presence of BSE in sheep, is its infection routes. Cattle are thought to be infected with BSE mainly, if not only, orally -- namely by the consumption of infected meat & bone meals (MBMs). The banning of this commodity is regarded to terminate the infection cycle.
 
Scrapie spreads among sheep laterally (from one animal to another via direct or indirect contact) and maternally (from a dam to its offspring, either vertically or laterally by close post-parturient association). Thus -- provided BSE, if infecting sheep, behaves like the scrapie agent -- the discontinuation of feeding sheep with MBMs will not terminate the infection cycle. - Mod.AS]
 
 
 
Date: Fri, 9 Apr 2004 From: ProMED-mail <promed@promedmail.org> Source: NewScientist.com news service, 8 Apr 2004 [edited] <http://www.newscientist.com/news/news.jsp?id=ns99994869>
 
 
Mysterious BSE-like disease found in sheep
------------------------------------------
A massive research programme to find out whether BSE is circulating in British sheep has turned up its first suspicious result. But while scientists say the sheep did not have conventional BSE, they cannot rule out the possibility that it could have had a new form of BSE (mad cow disease) that has adapted to sheep.
 
Britain's Department for Environment, Food and Rural Affairs [DEFRA] has announced that the Veterinary Laboratories Agency (VLA) in Weybridge, England, had found "a type of scrapie not previously seen in the UK". Scrapie is a sheep disease similar to BSE which is not generally thought to harm people.
 
The Department for the Environment, Food and Rural Affairs (DEFRA) said the disease-causing prion detected in the sheep's brain "had some characteristics similar to experimental BSE in sheep", but that on other tests it resembled neither BSE nor "previously recognised types of scrapie". The UK's Food Standards Agency said in a statement: "Uncertainties still remain on this issue. However, based on the best scientific evidence to date, we are not advising against eating lamb and sheep meat."
 
There have long been fears that sheep which ate cattle-derived meat and bone meal during Britain's BSE epidemic in the 1980s might have acquired BSE, although they have never been confirmed. Unlike BSE in cattle, prion diseases spread directly from sheep to sheep. So any BSE in sheep could still be circulating despite subsequent bans on animal-derived feed. Furthermore, sheep experimentally fed BSE develop a disease indistinguishable from ordinary scrapie, making detection very difficult. Yet the prion from such animals still behaves like BSE, and could cause the fatal human disease vCJD. Worse, sheep carry prions in more tissues than cattle, including the muscle that people eat, so BSE-infected sheep could cause more human disease than mad cows.
 
A previous attempt to determine whether British sheep had acquired BSE went spectacularly wrong in 2001 when sheep and cattle brains were mixed up in the lab. But since then, the VLA has tested the brains of all 1019 newly reported cases of scrapie, as well as 1125 scrapie brains dating back to 1998, with tests designed to distinguish scrapie from BSE.
 
The new result announced on Wednesday, from a sheep recently reported with scrapie symptoms, is the first to give results that resembled BSE. Danny Matthews of the VLA told New Scientist that in a prion test called a western blot, the sheep's brain did not bind an antibody called P4. P4 also does not bind prions from sheep experimentally infected with BSE, but does bind all but one forms of scrapie tested with it.
 
Also like BSE, the form of the prion without a sugar attached to it had a lower molecular weight than the form found in scrapie. But the ratio of prions with different numbers of sugars on them looked like scrapie, not BSE, says Matthews. Most conclusively, immunohistochemistry (IHC), in which thin slices of the sheep's brain were stained with various antibodies, showed prions had accumulated in different parts of the brain and different kinds of cells from BSE -- or any known form of scrapie.
 
The IHC pattern reliably indicates BSE, says Matthews, having been constant in the 100 experimentally infected sheep of different genetic varieties tested so far. But so little scrapie has been tested, he says, it is not known if one strain might give these results on the tests. One possibility, he says, is that the sheep might have been carrying a prion initially derived from BSE. Passage into new species is well known to change prions.
 
BSE from experimentally infected sheep has so far been passed to just one more round of sheep, with no apparent change. "But we don't know if passage through many sheep, of different genetic types, might change it so it no longer gives the same pattern in IHC or western blots," says Matthews. "Those experiments are underway now."
 
Any such new incarnation of BSE in sheep may -- or may not -- have lost its ability to harm humans.
 
[byline: Debora MacKenzie]
 
-- ProMED-mail <promed@promedmail.org>
 
[As rightly commented, the main current worry, related to a possible presence of BSE in sheep, is its infection routes. Cattle are thought to be infected with BSE mainly, if not only, orally -- namely by the consumption of infected meat & bone meals (MBMs). The banning of this commodity is regarded to terminate the infection cycle.
 
Scrapie spreads among sheep laterally (from one animal to another via direct or indirect contact) and maternally (from a dam to its offspring, either vertically or laterally by close post-parturient association). Thus -- provided BSE, if infecting sheep, behaves like the scrapie agent -- the discontinuation of feeding sheep with MBMs will not terminate the infection cycle. - Mod.AS]
 
 
 
[1] Date: Wed 7 Apr 2004 From: Mary Marshall <tropical.forestry@btinternet.com> Source: FarmersWeekly Interactive (FWI), 7 Apr 2004 [edited] <http://www.fwi.co.uk/article.asp?con=14329&sec=18&hier=2>
 
 
Unusual scrapie type found
--------------------------
The Veterinary Laboratories Agency has informed the Department for Environment Food and Rural Affairs (DEFRA), the Devolved Administrations, and the Food Standards Agency, of a type of scrapie not previously seen in the UK. The VLA and other European laboratories with expertise in scrapie-like diseases have analyzed tissue samples from the sheep.
 
A meeting of the scientific experts who performed these tests concluded that this case could not be considered to be BSE in sheep, although it does not behave like known types of scrapie either. Further investigation will be needed before more can be said about how this unusual result should be described, according to DEFRA.
 
The Voluntary Scrapie Flocks Scheme, part of the National Scrapie Plan, provides free scrapie genotype testing of all sheep on the eligible farm. Scrapie susceptible animals -- NSP type 2, 3, 4 and 5 rams and type 4 and 5 females -- identified on these farms will be culled and replaced with stock that is more resistant.
 
****** [2] Date: Wed 7 Apr 2004 From: ProMED-mail <promed@promedmail.org> Source: DEFRA news release 139/04, 7 Apr 2004 [edited] <http://www.defra.gov.uk/news/2004/040407b.htm>
 
 
DEFRA investigates an unusual scrapie case
------------------------------------------
The VLA and other European laboratories with expertise in scrapie-like diseases have now applied several rapid diagnostic methods to tissue samples from a sheep with suspected scrapie. Some of the methods have indicated that the case does not appear to resemble previously recognized cases of scrapie and, although there were differences, it had some characteristics similar to experimental BSE in sheep and also to an experimental strain of sheep scrapie. More importantly, though, microscopic analysis of brain material showed that the case neither resembled previously recognized types of scrapie or experimental BSE in sheep.
 
A meeting of the scientific experts who performed these analyses, held on 30 Mar 2004, concluded that this case could not be considered to be BSE in sheep, although it does not behave like known types of scrapie either. Further investigation will be needed before more can be said about how this unusual result should be described.
 
DEFRA's chief scientific adviser, Professor Howard Dalton, said "The UK, and especially the VLA, have played an important part in improving the diagnostic methods available for identifying TSEs in sheep. As we continue to assess more samples with these improved methods, it is likely that we will continue to find samples, such as this, which fall outside our current knowledge of the disease. DEFRA, as it does with all research, will continue to consult scientific experts to ensure that we are investigating these cases using the best available techniques and methods."
 
The National Scrapie Plan remains unaffected by this new result and SEAC [Spongiform Encephalopathy Advisory Committee] will be consulted in the near future.
 
Notes for editors: 1. Scrapie is a fatal neurological sheep disease belonging to a group of diseases called transmissible spongiform encephalopathies (TSEs), including BSE in cattle and CJD in humans. It has been present in the national flock for over 250 years. It is not considered to be transmissible to humans. 2. There is a theoretical risk that BSE could be present in sheep, masked by scrapie, but it has not been found naturally occurring in sheep. 3. There is as yet no definitive diagnostic method that can rapidly distinguish different TSEs, for example, scrapie from BSE. Consequently, from time to time the scrapie surveillance programs in EU member states throw up unusual results that merit further investigations (DEFRA press release 371/03 refers <http://www.defra.gov.uk/news/2004/../2003/030911a.htm>. 4. The VLA have applied several different methods to the sample to compare it to a wide range of previously detected scrapie cases, experimental BSE in sheep, and an experimental strain of scrapie, termed CH1461. 2 main methods have been used in this analysis: a. Western blot (WB) This involves taking a sample of the brain and treating it with an enzyme -- proteinase k -- to destroy the normal prion protein (PrPC). The diseased form of the protein (PrPSc) is able to withstand this treatment and is then separated from other cellular material on a gel. A blot is taken of the gel and the PrPSc is visualized using specific antibodies. b. Immunohistochemistry (IHC) This involves taking thin slices of the brain, and by using special (antibody) markers to detect the PrPSc it is possible to see disease specific patterns of PrPSc distribution in the brain under a microscope. The Western blot method found that the sample did not appear to resemble previously recognized cases of scrapie and, although there were some differences, some characteristics were similar to experimental BSE in sheep and also the experimental strain of sheep scrapie, CH1461. IHC found that it neither resembled previously recognized types of scrapie or experimental BSE in sheep 5. The tissue sample has now been analyzed using a total of 5 different diagnostic methods claiming to be able to differentiate between scrapie and experimental BSE in sheep. 2 were performed at the VLA and 3 were performed in other European laboratories. 6. The VLA is the European Reference Laboratory for TSEs and is responsible for coordinating such investigations into unusual cases. Their findings will be considered by the European Food Safety Authority's committee of TSE experts and in the UK by the SEAC. 7. The genotype of the suspect sheep was ARQ/ARQ which is known to be susceptible to some strains of scrapie and, in experiments, to BSE. Background information on scrapie, scrapie genotyping, and the National Scrapie Plan is published on the Defra internet at <http://www.defra.gov.uk/news/2004/../../nsp>www.defra.gov.uk/nsp>. 8. For information and advice on BSE in sheep from the FSA please consult their website <http://www.foodstandards.gov.uk>
 
****** [3] Date: 6 Apr 2004 From: ProMED-mail <promed@promedmail.org> Source: The Scotsman, 6 Apr 2004 [edited] <http://business.scotsman.com/agriculture.cfm?id=388482004>
 
 
Concerns raised over fall in reported scrapie cases
---------------------------------------------------
 
Farmers could be storing up trouble for themselves in the next human food health scare by failing to report cases of the fatal sheep brain infection scrapie. Although there is a legal requirement to report scrapie, some state vets now believe that only happens for about 1 in 10 infected sheep and that more than 5000 flocks in the UK have had at least 1 case, not the 500 or so recorded. It is also understood that underreporting has become significantly worse in the run-up to a European Union scheme this summer that can include whole-flock slaughter and no sheep on a farm for 3 years. Unofficial figures indicate that during a period when, on average, reports of about 100 cases of scrapie were expected in the UK, there has been 1.
 
The long term problem with underreporting is that scrapie is a transmissible spongiform encephalopathy similar to BSE in cattle that has been linked with more than 130 cases of the fatal human variant CJD. Since BSE was identified as a human health risk more than 8 years ago, the possibility that scrapie might be "masking" BSE in sheep has been raised several times.
 
5 years ago this Apr, SEAC said: "There remains the possibility that BSE in sheep might behave like scrapie and have been sustained in some sheep." It made 20 recommendations for further research and surveillance and media headlines at the time included the possibility that the UK's 35 million to 40 million sheep might all be slaughtered and incinerated.
 
There have been several scares since then -- not helped by 1 botched large-scale test that mixed sheep brains for analysis with those of cattle -- and another "BSE in sheep" alarm always seems imminent. As well as testing hundreds of sheep brains for any sign of BSE, a national scrapie plan was introduced with the clear intention that if scrapie were eradicated, the possibility of it hiding BSE would be removed. The voluntary scheme concentrates on encouraging breeding only from ewes and rams showing genetic resistance to scrapie and slaughtering those that are susceptible.
 
On 5 Apr 2004, the latest development in this scheme, run by DEFRA, was announced, and is open to farmers who have had a case of scrapie confirmed since July 1998. Being accepted for the "voluntary scrapie flocks" scheme will provide free genotype tests, compensation for culled animals and assistance to buy scrapie-resistant rams. About 90 Scots flocks could be eligible, more than half of them on Shetland. The island virtually has a "closed flock" health policy and apparently the highest incidence of scrapie in Scotland, almost certainly because its farmers have been working to eradicate the disease for 20 years and all cases are reported.
 
[byline: Fordyce Maxwell]
 
-- ProMED-mail <promed@promedmail.org>
 
[The Scotsman's item [3], published one day before DEFRA's news release, underlines the importance of improved reporting. At present, there is no indication that BSE has infected sheep in field conditions, but such a scenario has not been refuted. One may assume that the reporting quality in other countries is similar to that of the UK. For background on BSE and sheep, the reader may refer to postings 20021119.5847 and 20020106.3180. - Mod.AS].
 
 
Patricia A. Doyle, PhD Please visit my "Emerging Diseases" message board at: http://www.clickitnews.com/ubbthreads/postlist.php?Cat=&Board=emergingdiseases Zhan le Devlesa tai sastimasa Go with God and in Good Health



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