Prion Disease: That sheep may safely graze
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Vermont: unvalidated western blot goes on trial
The latest from Vermont
That sheep may safely graze
Sick mice point to sheep link in mad cow disease
Scrapie diagnosed in one Montana ram
Deaths from human BSE reveal "statistically significant rising trend"
Woolly thinking: BSE in American sheep?
BSE alarm after cow's head is found on sale
Future uncertain for reliable nvCJD screening tests
Proper disposal of non-regulated medical waste: prion protein-polluted medical waste

Vermont: unvalidated western blot goes on trial

22 Jul 00 webmaster opinion
The government is in big trouble in Vermont; a humiliating settlement is likely before the trial resumes on Thursday. The judge has allowed expert cross-examination of the western blot used to impugn the sheep, saying the government's seizure order may have been arbitrary and capricious. Indeed.

There will be a very tough line of questioning put together by Thursday. Some people say Dr. Pierluigi Gambetti (director of CDC's lab at Case Western), others say Dr. Glenn Telling (professor at U. Kentucky) will direct the questioning. Both are experts on western blots. Dr. Bruno Oesch of Switzerland's Prionics is another suspect; he developed the only validated immunological test; it uses monoclonal antibody 6H4, which recognizes both PrP-C and PrP-Sc (the two isoforms are readily distinguished by their size following PK digestion). An unvalidated non-specific polyclonal test was used at Staten Island.

If there is one thing that really draws scientists into a fray, it is bad science. If there is another that puts them in an absolute froth, it is their lab or their test not being considered. The western blot at Staten Island is simply not ready to run with the big dogs.

The 2-page report to USDA is very sketchy on detailed protocols such sample handling and history, control sheep lanes, and negative antigen and antibody controls. Defense experts will look closely at the lab notebook itself for irregularities and novel or anomalous procedures. The western blot test is not even close to being a validated procedure as per international standards [validation manual of the Office of International Epizootics (OIE) ]

Thomas Higgins, representing the smaller flock, told the press that "our clients have been advised by the USDA that this is not a regular test, that it was enhanced somehow to give heightened sensitivity and would be more likely to give false positives."

The webmaster personally enjoys being cross-examined in federal court. Most scientists do not. Lawyers ask an interminable series of dim-witted questions seeming to go nowhere but then, like the crocodile, make a sudden lunge. It is best if you have stayed on high ground the entire time.

The bigger picture here is that if we want real risk managment of TSE in the US, we cannot have diagnostics shopped around until the government or elk game farmer or dairyman or shepherd gets the positive or negative they want.

The USDA can be applauded overall for a strong TSE diagnostics research program and extraordinary vigilance in regards to BSE entrenchment in the US. We are lucky to have someone as well-qualified as Dr. Linda Detwiler in public service. The quarantine of the Vermont sheep was, and is, appropriate. Finally, the seizure order itself was courageous, if not sufficiently vetted. But are we prepared to apply this draconian measure even-handedly to every flock and herd in North America affected by TSE?

Ultimately, TSE eradication programs cannot succeed with the cooperation and respect of both livestock producers and prion research scientists. In this instance, the agency has been overzealous, going far beyond what the precautionary principle or the scientific record warrant. The court ruling substantially weakened the powers of Extraordinary Emergency Seizure Orders, setting a permanent federal court precedent for appeals by livestock owners with flimsier cases who only seek delay.

As a byproduct of the Vermont press releases, the public is now more befuddled than ever. Are meat, milk, and cheese from asymptomatic animals possibly harboring a TSE safe to eat or not? First they are, then they are not, now they are again. How can 17 wheels of cheese be seized at the farm, but there be no recall from the stores? The agency needs to articulate a consistent science-based policy position. By sowing fear, uncertainty, and doubt in a narrowly conceived Vermont public relations campaign, USDA has hurt consumer confidence and thus livestock producers everywhere.

USDA has been a captive agency for many decades. Follow the money: USDA's three largest clients are cigarettes, clear-cuts, and cattle. Are we to believe this action was brought on by Philip Morris or Weyerhauser? Priorities for TSE risk management have been driven by the cattle producers' export agenda. These producers are understandably frustrated by endless Eurocratic delays over US hormone residues and TSEs.

The USDA needs to step back and look at the big picture of the scrapie and CWD threat to people nationwide. The best available science, upon which policy must be based, now says these two TSEs have a similar risk of transmission to humans as BSE, as measured by the in vitro conversion proxy test. The Vermont sheep, which may or may not harbor a TSE, are simply off the risk radar screen. Does it even matter which TSE, if BSE, scrapie, and CWD are all of comparable risk to humans?

The latest from Vermont

21 July 00 news reports and webmaster opinions

Update 7:00 pm Friday, Vermont. Judge refuses any sheep slaughter. Court resumes on Thursday. 20 Jul 00
USDA now has its slaughter trucks idling outside the farmhouse in Vermont, hoping that the court will deny the appeal for a short delay at the 1:30pm hearing today in Burlington, Vermont and that the sheep can be killed and taken to Plum Island today.

The question for many observers is, why the rush to judgement? Could not the western blot be repeated at CDC's National Prion Disease Pathology Surveillance Center (NPDPSC)?

Meanwhile, details from a 4 page pathology report from England have emerged. The document is dated 23 Dec 1998 and concerns apparently healthy culled sheep from Skunk Hollow Farm in Vermont, the smallest of the three. It is signed by GAH Wells, Head of Pathology, Veterinary Laboratories Agency, New Haw, Surrey UK

Some highlights [emphasis added]:

"The NVSl have also forwarded pathology reports from two other sheep from Skunk Hollow Farm, references 99RA136 and 99RA137. Review of the findings in those two cases suggests that common to both, and indeed also to the case on which I have reviewed the material, there is evidence of a diffuse astrocytic reaction. This glial cell response occurs in many neurological disorders and cannot, therefore, be regarded as specific. Nevertheless, its occurrence in these three cases suggests that sheep from this farm may have a neurological disease problem, albeit not specifically identifiable as scrapie, and not necessarily manifest as a clinical disorder...."

"Because of the generally accepted sequence of the changes, the pre-clincial diagnosis of scrapie is more dependent on the demonstration of the accumulation of the abbnormal protein PrP than on the demonstration of the vvacuolar pathology. In the sheep examined from Skunk Hollow Farm there has been a consistent failure to be able to demonstrate the accumulation of PrP in the brain."

"Thus in summary, there is no conclusive evidence from the material and reports to which I have had access that sheep from this flock are suffering from scrapie. In as much as evidence of a glial reaction has been demonstrated in these cases, there is the suggestion that these sheep are, however, suffering from a neurological disorder. This may or may not be a contagious disorder. This could be investigated further, particularly initially to substantiate the glial changes by applicatio of additionalhstopathological techniques....

"The 12 unstained sections or brain [and spinal cord] representing all areas described above were immunostained with PrP antisera (971F). This antisera is a polyclonal antisera raised to peptide sequence 230-244 of ovine PrP...The sections were stained by the ABC method and antisera was applied at two dilutions 1:8000 and 1:14000. Control sections from a confirmed case of scrapied stained positive. No immunostaining was obtained in any of the test sections."

"Morphological diagnosis: Astrocytosis, diffuse, moderate to severe through brain stem and spinal cord."

"The absence of convincing vacuolar changes in the [brains of the] sheep prevents the confirmation of a spongiform encephalopathy which [is a key] hallmark of clinical cases of scrapie. The prominence of the astrocytic change in this brain, is, nevertheless, suggestive of an underlying neurodegenerative process, although without other pathologicl changes this can not be regarded as in any way diagnostically specific. Similarly the changes described in the cuneate nucleus are also non-specific and, in fact, commonly present in adult sheep.

That sheep may safely graze

20 Jul 00  Press reports
Pictures and definitions of sheep breeds
Backgrounder on Friesian Milk Sheep
"That sheep may safely graze" JS Bach
Update: Vermont sheep farmers will be in federal court shortly seeking a temporary restraining order to delay Friday's seizure and slaughter of sheep, to allow western blot tests to be repeated. The outcome will be reported here as soon as it becomes available. The US Attorney has agreed to a 1 day delay in the hearing at the Court's request. It will begin at 1:30 pm Vermont time on Friday.

The sheep have retained counsel, one flock being represented by the law firms of Thomas Higgins and Thomas Amidon of Stowe, Vermont; the other by John Buckley.

Senator tells judge to kill sheep. In a press release sent out the day before the trial, the Vermont delegation said "...We accept the decision of the US Secretary of Agriculture, in consultation with the Governor and the commissioners of Agriculture and Health of Vermont to remove these sheep and pay fair market value to the affected owners..." (Vermont receives huge dairy price support payments from USDA; Senator Leahy leads the pork patrol. -- webmaster).

Opinion (webmaster): Imagine that a black man was on trial for his life. A international dispute arises among scientists about DNA testing used in obtaining the conviction. A brief stay of execution is sought until the DNA test can be repeated by a neutral lab.

The day before the trial, a prominent Senator sends the judge, whom he appointed, a press release saying he supports the guilty verdict and that the state should procede with lethal injection.

A lot of Americans would have a problem with this. It is prejudicial to a fair hearing.

True, the trial in Vermont is just of sheep and not even black-faced sheep at that, the type associated with scrapie. Still, the lives of 376 animals are at stake. They deserve a fair hearing, a stay of execution, and a repeat of the controversial western blot test in the face of contradictory evidence received yesterday from England's Central Veterinary Laboratory.

Three Sheep Flocks Infected With Neurological Disease

7/14/00 online edition of The Bloomberg wire
[Opinion (webmaster): This one is interesting for its totally contradictory advice given out on food safety.]

The government will buy and destroy 376 sheep in Vermont after four of the animals were confirmed positive for a fatal neurological disease, the U.S. Agriculture Department said. The sheep, three flocks in all, were diagnosed July 10 with TSE, or transmissible spongiform encephalopathy, a broader class of degenerative neurological diseases than ``mad cow'' disease, or bovine spongiform encephalopathy (BSE).

The disease isn't known to be ``very contagious,'' and isn't readily transferred to people, the USDA said. Still, animals likely will be incinerated to prevent possible contamination of other livestock. ``We're certainly acting with an abundance of caution,'' said Andy Solomon, press secretary to U.S. Agriculture Secretary Dan Glickman.

A department statement, issued late today, said the agency ``is working with other federal agencies and the state of Vermont to determine if there are any associated human health concerns.'' One of the best-known varieties of the disease is ``mad cow'' disease, which broke out in the United Kingdom in 1996 and resulted in a European Union ban on imports of British beef. The other variety is scrapie, the brain disorder found in goats and sheep.

No Risk to Humans

"Unlike BSE, there is no evidence that scrapie poses a risk to human health,'" the USDA said in a statement. Even so, the department is buying one flock of 21 sheep and has issued an order to seize two other flocks of 355 sheep. BSE hasn't been diagnosed in the U.S. Still, the discovery has lead the USDA to seek Control and Prevention, and the National Institutes of Health ``to ensure the health of American's livestock and the safety of its food supply,'' the USDA said.

The diseased animals are offspring of sheep imported from Belgium and the Netherlands in 1996. Both countries had confirmed cases of BSE. In 1998, the USDA said it learned that it was likely that those sheep were exposed to feed contaminated with BSE, or bovine spongiform encephalopathy. Vermont imposed a quarantine on the imported sheep at USDA's request, the statement said, and banned their slaughter or sale for breeding purposes.

The ban didn't extend to offspring, though, and ``some of these animals were slaughtered for human consumption,'' the department said. In addition, milk from sheep was sold, and some of the milk was used to make cheese, which also was sold.

`"I don't think there's any cause for alarm among consumers,' said Paul Rodgers, director of animal health and safety for the American Sheep industry Association. "People ought to be relieved that these animals were found and that they're going to be destroyed.'"

A cattle industry executive said TSE, the degenerative disease, can't be spread from eating the meat or the cheese made from sheep's milk.

``If somebody ate fried sheep brains, that would be a concern; if there's an infectious agent, that's where it would be found,'' said Rick McCarty, executive director of issues management for the National Cattlemen's Beef Association in Denver.

Sick mice point to sheep link in mad cow disease

Thu, 20 Jul 2000 Reuters Online Service  Wed, Jul 19, 2000  By Ben Hirschler
Opinion (webmaster): This article and its conclusions won't please everyone, being based on Prusiner's candid assessment of the importance and unequivocal interpretability of his own unpublished research.

A mouse, carrying a cow prion gene, is oddly (but not unprecedently) more susceptible to sheep infectious prion than to cow. Usually, intra-specific infection (cow-to-mouse/cow) is more efficient. Now mice have 38,000 genes, so swapping in a single cow gene hardly makes them isogenic to bovines. In many similar amyloidoses, secondary genes are known to be involved. If this hold in prion disease, a mouse secondary gene might interact anomalously with the bovine prion. Having said this, mouse models are the best experimental system around.

"For 25 years people have tried to connect sheep prions with CJD but were unable to do so. Now it looks as if there may be three, four or five strains of prions in sheep, one of them the BSE strain which the rendering process selected for," he said.

Though it was not deemed necessary here to mention here earlier work by the Bossers and Caughey labs quantitating in vitro conversion across species, taken together it seems that this particular strain of scrapie might be of special concern in regards to direct sheep scrapie to human transmission.

There is no direct connection to the Vermont sheep situation because it more data is needed to determine what is going on with them. However, the research does provide a further impetus for eradication of scrapie and CWD in the United States and their removal from the human food chain in the interim.

Sick Mice Point to Sheep Link in Mad Cow Disease

Tests on genetically engineered mice suggest "mad cow" disease almost certainly spread to cows from sheep, a leading expert on the brain-wasting condition said Wednesday.

Stanley Prusiner of the University of California, San Francisco, said mice whose genes had been engineered to mimic cows were highly susceptible in repeated tests to sheep scrapie, a disease related to bovine spongiform encephalopathy (BSE or mad cow disease). Prusiner, on a visit to Britain to attend a biochemistry and molecular biology conference, said he and colleagues had found the mice were actually more susceptible to sheep prions -- microscopic disease-causing agents -- than to cow prions.

"This provides the first good experimental data that mad cow disease really originated in the sheep... It's extremely likely that the prions in sheep with scrapie are the cause of mad cow disease," he said in a telephone interview.

Prusiner won a Nobel Prize in 1998 for his theories that BSE and related diseases were caused by prions, which unlike bacteria and viruses, are extremely hard to destroy by cooking or with chemicals. Scientists have long speculated that BSE may have jumped the "species barrier" from sheep to cows but no conclusive evidence has yet been produced and Prusiner said more work was needed to prove the hypothesis.

BSE -- whose human form, variant Creutzfeldt-Jakob Disease (CJD), has already caused dozens of deaths in Britain -- may be caused by one of several prions carried by sheep, he said. In normal conditions, the BSE prion in sheep is harmless because it is overwhelmed by other more dominant strains, he suggested.

But the dangerous version may have come to dominate during the rendering and heating processes carried out in the 1980s when now-banned animal-to-animal feeding regimes were practised.

"For 25 years people have tried to connect sheep prions with CJD but were unable to do so. Now it looks as if there may be three, four or five strains of prions in sheep, one of them the BSE strain which the rendering process selected for," he said.

Britain has recorded 76 definite and probable cases of variant CJD, the human version of BSE, since the bovine disease swept through herds in the 1980s. CJD is normally seen only in one in a million people.

Scrapie diagnosed in one Montana ram

June 19, 2000 For more information contact:
Karen R. Cooper, APR
Public Relations Officer
Department of Livestock
[Opinion (webmaster): Montana has also experienced chronic wasting disease, another form of TSE, in captive elk on game farms. A ballot initiative seeks to get control of these facilities. This disease is perhaps too complex for Public Relations Officers; parenthetic corrections have been added to the article below in the interests of public safety.]

The first laboratory confirmed case of scrapie in Montana has been found in a 3 year-old ram located on a small farm in southwestern Montana, according to Montana State Veterinarian Dr. Arnold Gertonson. "Transmittal of the disease within the flock or from the flock to other animals is not expected," Gertonson said. "The animal has been destroyed and the epidemiology investigation is continuing to determine if other sheep in Montana are at risk." [Horizontal transmission is well-documented in sheep -- webmaster]

A flock plan has been developed with the flock owner that included the destruction of the affected animal. Rams are not known to transmit the disease. [Sheep flocks are overwelmingly ewes and lambs, as flocks of rams are not a viable concept. Where did this ram get it if not from a ewe? -- webmaster].

Infected females have a high probability for transmission. There is no treatment for the disease, and once an animal is affected, there is no cure. The disease is confirmed by histological examination of the brain from animals that have shown clinical signs of the disease. "There is no officially recognized test for the presence of scrapie in live animals," Gertonson said.

Owners of infected or source flocks must either conduct a postexposure monitoring and management plan for five years after the last scrapie-positive- or high-risk animal is removed, or participate in the National Voluntary Scrapie Flock Certification Program (VSFCP), complete monitored category, and remain in compliance with the standards for exposed flocks for five years after the last scrapie-positive- or high-risk animal is removed.

The VSFCP is administered by the Animal and Plant Health Inspection Service of the United States Department of Agriculture, and cooperating state animal health authorities. "The owner has already complied with the state and federal requirements," Gertonson said. Montana is a Scrapie Compliant State.

"Livestock producers, hobby farmers and ranchers need to make sure they purchase sheep from certified scrapie-free flocks," Gertonson added. [If there is no approved test, how does the farmer know that the source flock is really scrapie-free? -- webmaster]

Scrapie is a slowly progressive disease that causes a degeneration of the central nervous system. It was first recognized as a disease of sheep in Great Britain and other countries of Western Europe more than 250 years ago. Since then, the disease has been reported throughout the world.

The first case of scrapie in the United States was diagnosed in 1947 in a Michigan flock. That Michigan flock owner had imported sheep of British origin through Canada for several years. In 1999, there were 29 confirmed cases of scrapie reported in the United States. [Voluntary reporting may massively understate the extent of scrapie. -- webmaster]

Over 900 flocks in the United States have been diagnosed with the disease since it was introduced in 1947, the majority occurring in the eastern portion of the country. Scrapie has been diagnosed in flocks in 45 of the 50 states.

In the United States, scrapie has primarily been reported in the Suffolk breed. It has also been diagnosed in Cheviots, Corriedales, Dorsets, Hampshires, Finn sheep, Merinos, Shropshires, Montadales, Southdowns, Rambouillets, and a number of crossbreeds. Cases of scrapie have also been reported in goats raised in contact with sheep. There is no scientific evidence that scrapie of sheep and goats is transmitted to humans. [The best available science now says scrapie and CWD pass equally as well to humans as BSE, that is, inefficiently but not zero. -- webmaster]

Clinical signs for scrapie vary widely among individual animals and develop very slowly. Early signs include subtle changes in behavior or temperament, incoordination, and muscle tremors; and may be followed by scratching and rubbing against fixed objects, apparently to relieve itching. Several other problems can cause clinical signs similar to scrapie in sheep, including the diseases ovine progressive pneumonia, listeriosis, and rabies; the presence of external parasites; pregnancy toxemia; and toxins.

Deaths from human BSE reveal "statistically significant rising trend"

20 July 2000 By Richard Tyler Human BSE Foundation and World Socialist Web Site
Two more deaths in the last fortnight have brought to 69 the total number of fatalities in the UK from variant Cretzfeld Jakob Disease (vCJD). So far this year 14 people have died from this brain-wasting disorder related to BSE (Bovine Spongiform Encephalopathy) or Mad Cow disease, equalling the 1999 total. Another seven are known to be currently suffering from this incurable disease, also known as Human BSE.

Government scientists warned Monday that there was a "statistically significant rising trend in the number of vCJD victims. The government's Spongiform Encephalopathy Advisory Committee (SEAC), set up in the wake of the emergence of BSE during the mid-1980s, put the increase at between 20 and 30 percent a year.

The World Socialist Web Site spoke to a number of relatives of Human BSE victims. Gerard Callaghan's brother Maurice died of the disease in November 1995. He said the rising trend was "very worrying. It is something that as a group of families has concerned us greatly.

The Labour government has earmarked just 26 million for research into CJD and BSE, a fraction of the amount that has been paid to farmers in compensation for cattle that were culled. In March, Prime Minister Tony Blair announced that over 200 million in further assistance would be paid to UK farmers. This comes on top of over 270 million in compensation paid to farmers in 1998 and 1999 alone.

Asked what he thought of the measures that had been introduced since Labour came to power in 1997, Gerhard Callaghan said, "I have little or no confidence in them. The fact is that we still have widespread abuses. An Irish farmer was recently prosecuted for deliberately importing an BSE-infected animal to get government compensation. The system is really open to abuse."

John Middleton, whose son Mathew Parker died of Human BSE in March 1997 at the age of 19, said he thought the government was still playing down the true level of the disease. "They don't want to damage the beef industry. It seems to me that animals are better thought of than humans. They are spending all that money on compensation to farmers and nothing for the families of victims of Human BSE. Personally, I would rather have my son back, but it's the principle of the thing.

Frances Hall of the Human BSE Foundation, whose son Peter was among the first victims of the disease, said, "It has been apparent to us for some time now that the numbers were going up. I run a help line and it has been obvious from the number of calls that the figures were increasing. She said that support and care provisions for victims and their families were "very patchy really. In some areas it's like a postcode lottery, things just aren't available when they're needed. The illness progresses very quickly; there just isn't time to wait around. We have been asking the government for months for a centralised care package, so that victims have consistent support.

Following the recent announcement of a "cluster of five vCJD cases around the Leicestershire village of Queniborough, a SEAC statement said it was "unlikely to have occurred by chance, but added that "this cannot be completely ruled out.

Like the majority of Human BSE victims, those who died in Queniborough (population 2,297) in 1998 were young people, and included teenage mother Stacey Robinson, 19. Van driver Glen Day, 35, and 24-year-old finance administrator Pamela Bayless both succumbed to the disease in the same month. Ms. Balyless's father said, "When Glen, Stacey and Pam all died within months of each other, I spoke to Glen's dad and we discussed how strange it was that it was all in Queniborough. It's such a rare disease.

A 19-year-old man from the area died in June this year, and a 25-year-old presently being nursed at home is another probable victim.

Dr. Robert Will, director of the government's CJD Surveillance Unit, said, "Statistical evidence of a cluster might be of importance in identifying further information on the causes of vCJD. But I am a bit cautious about it. We have previously identified clusters which in the end turned out not to be significant. That is the problem with rare phenomena I am still not sure we will find anything definite from this statistical anomaly.

Unlike conventional CJD, which is most frequent in those over the age of 60 and is very rare in those below 50, vCJD has mainly affected young people. To account for the high incidence in this age group, Dr. Will said that meat processing methods in the 1980s might have led to contaminated meat ending up on children's plates. "One possible explanation for the age distribution is that young people tend to eat these products more than the adult population, he commented.

In an effort to boost profits, the beef industry introduced a process known as "mechanically recovered meat. This method employs high-pressure hoses to obtain small amounts of tissue from animal carcasses. Despite the fact that mechanically recovered meat could have contained the remnants of the spinal cord, where BSE infectivity was known to be concentrated, the process was only outlawed in 1995. The recovered meat scraps largely ended up in cheap pies, sausages, burgers and ready-cooked meals. Such products were mainly bought by those on low incomes, but could also be found in school meals and infant foods.

However, not all scientists agree. Dr. Philip Monk, consultant in communicable diseases for Leicestershire Health Authority, stated, "baby food and school dinners were not a factor in the Queniborough cluster. Initial attention would be focused on the movement of cattle into the county. Local abattoirs and meat processing plants will also be investigated to establish if their products were sold regularly in local outlets. "We have been looking into what patterns of slaughtering took place in this area of Leicestershire and where meat from these slaughters entered the food chain, Dr. Monk said.

Over 10,000 tonsils and appendixes removed in hospital operations carried out in Leicestershire since 1985 may be tested for signs of CJD as part of a national survey prompted by the Queniborough cluster. CJD is known to incubate in these tissues in the early stages of the disease, however tests on tonsils and appendixes carried out elsewhere in the UK have so far failed to uncover signs of the disease.

There are indications that BSE also may have spread to other animals, including sheep. After three flocks of sheep imported into the US from Europe displayed signs of fatal brain disease, the sheep are to be destroyed. It is not yet known if the animals had contracted a form of BSE, or a novel strain of scrapie, which has existed in sheep for centuries.

The Food Standards Agency released a report Tuesday warning that present safety measures were not tight enough to prevent "high risk material from sheep possibly containing a BSE agent from entering the human food chain. According to the report, evidence that BSE has entered the national flock "might emerge at any time in the next year or two.

The number of eventual victims of Human BSE is still an unknown. Epidemiologist Roy Anderson said that the total number of vCJD cases this year "was likely to be greater than any previous year, so this epidemic is just starting. It may be a small epidemic, and all of us hope it will be, but this disease has such a long incubation period, where exposure was probably in the late 1980s, that it's far too early to say whether it will be small, medium or large.

Woolly thinking: BSE in American sheep? It's "far-fetched speculation" say experts

22 July 2000 Deborah McKenzie New Scientist 
CLAIMS that abormal prion proteins have been found in American sheep are setting alarm bells ringing in the US. But BSE experts are unimpressed.

The US government ordered the incineration of 376 sheep from Vermont, after suggestions that four of the flock were infected with BSE-the brain disease in cows that causes deadly new variant CJD (vCJD) in people. If the four cases are confirmed as BSE, they will be the first sheep known to be infected by farm feed, and would raise the spectre of more human infection.

Larry Faillace, a former animal disease researcher, imported Belgian and Dutch milking sheep to his Vermont farm in 1996. The US Department of Agriculture (USDA), fearing the imported sheep could have eaten Belgian feed contaminated with BSE, tested animals culled from Faillace's flock for prion disease. This month it announced test results indicating that seven of the sheep had brain damage of the type associated with prion disease. The animals had not shown symptoms of brain disease.

Sheep brains can be damaged in this way by both BSE and scrapie-a prion disease that affects sheep but is not thought to harm humans. Antibodies used to test the sheep for scrapie did not bind to the brains of these sheep, however. Yet four came up positive for prions in two other tests: a new assay developed by Mary Jo Schmerr of the USDA laboratory in Ames, Iowa, and a Western blot analysis by Richard Rubenstein of the Institute for Basic Research in Developmental Disabilities, Staten Island.

On 14 July, this led US agriculture secretary Dan Glickman to order the animals to be destroyed because they had prion disease "of foreign origin", which might be BSE.

Sheep deliberately fed BSE-contaminated feed will develop prion disease. While no one has ever shown that this happens on farms, some scientists say it's possible that BSE has appeared in sheep only to be mistaken for scrapie.

However, many experts doubt whether the Vermont sheep have BSE. "The connection to BSE is far-fetched speculation," says Tom Pringle of the Sperling Foundation in Oregon, which monitors prion research. The two tests used gave inconsistent results, and the imported animals were supposed to have been strictly grass-fed.

Scrapie and BSE can only be reliably distinguished by injecting brain tissue into mice, then waiting months for the result. Ian McConnell of Cambridge University, an adviser to the British government on nvCJD/BSE, told New Scientist: "I have no idea how they would make this distinction. It's a shambles."

Cases of nvCJD have risen sharply in Britain this year. Because the infection can lie dormant for many years, the fear is that thousands of cases might eventually emerge.

BSE alarm after cow's head is found on sale

AN AFRICAN delicacy containing the cheeks, snout and lips of cattle has been found on sale in Britain, breaking strict food safety rules on BSE.

The illicit trade in cattle heads has triggered an urgent investigation by the Food Standards Agency (FSA) to halt their supply for human consumption. The meat in the pomos - a Nigerian and West African beef speciality - contains possible BSE-infected material and could be harmful to health. The heads are thought to have come from British cattle.

Food safety officers in London uncovered the illegal market in pomos a few weeks ago and alerted the FSA. A head of a cow was found packed in a box and stored in a fridge at a butcher's shop in Tooting, South London. Two other cases have since been reported to the agency.

The Times found the banned meat on open sale in five ethnic food shops in Brixton, South London, yesterday. The meat was selling at 1.50 per lb. All shopkeepers removed the meat from sale yesterday when they learnt that it was illegal, and Lambeth council launched an investigation.

Local authorities are now working with the agency to establish the scale of the trade and to identify the source. Heads are routinely removed from beef carcasses in Britain, rendered and then stored for incineration. Officials now fear that heads are being smuggled out of an abattoir and that cow heads are being deliberately sold to supply this speciality food market.

A senior FSA official last night said that pomos contained specified risk material and there was a risk of BSE. He said: "We are trying very hard to identify the source and to halt the supply. Cases are being sought by local authorities and we have had at least three firm reports from London. Other authorities have been alerted to watch for the meat."

Senior officials in Whitehall are concerned about the illegal trade given the latest rise in confirmed cases of the human form of "mad cow" disease and the forecast that the cases could rise by up to 30 per cent in future years. Peter Smith, acting chairman of the Government's BSE advisory committee, the Spongiform Encephalopathy Advisory Committee, said that there had been a "statistically significant" increase in the number of cases of variant Creutzfeldt-Jakob disease. Professor Smith said it could claim thousands of lives but did not think that it would now be an epidemic.

The trade in pomos was uncovered by food safety officers working for Wandsworth Borough Council. A council spokesman said: "The butcher has been issued with a formal written warning."

All the butchers selling the meat yesterday said that they had bought it in good faith. Riaz Muhammad Friez, the leaseholder of Brixton Foods, at 39 Electric Avenue, said: "If the face is illegal we will remove it from the shelves."

Other shops selling the meat were Kashmir Halal Butchers, M. M. Quality, Faiz Quality Meat and Fab Fresh.

UK BSE born after ban: 4 owners

COMTEX Newswire Opinion Piece Wed, Jul 12, 2000 By David Walker, agricultural economist
Comment (webmaster): The highlights of this article are:

Within two days "Not only was it possible to find the diseased cow's record among more than 4.6 million registered passports, but its movement between four owners had been fully reported." meaning that the passport database is not on computer and that three additional trace-back farms are involved.

"The cow in question was born on Aug. 25, 1996, three and a half weeks after the feed ban was imposed and on a farm that also raised pigs. The chance that the cow, as a calf, was inadvertently fed pig ration containing infected meat and bone meal produced before Aug. 1, 1996, seems as credible as the first confirmed case of maternal transmission. The mother, although not diagnosed as having BSE, was slaughtered just three months after she calved.

The British State Veterinary Service is investigating the latest case but is unlikely to unearth convincing evidence almost four years after the event. The farmer is reported as not remembering why the mother of the cow was slaughtered."

Britains Passports-for-Cows System Proves Effective

NORWICH, England--Of all the hoops that British cattle farmers have jumped through to restore confidence in beef since the mad-cow disease epidemic, the system of individual cattle passports has been the most maligned.

But there is justice, now that this identification system has played an important role in tracking down the kinfolk of a cow recently found to have the disease despite being born after precautions were put in place to prevent its spread through contaminated feed.

This is a critical time for the British beef industry. It is working to regain the public confidence it has lost since the epidemic of mad cow disease, or bovine spongiform encephalopathy (BSE).

It is generally accepted that BSE is transmitted through the feeding of meat and bone meal produced from infected cattle. The recent discovery of the diseased cow has been particularly worrying for the industry, because it is the first case among cattle born after a complete ban on the feeding of meat and bone meal was introduced on Aug. 1, 1996.

The government announced the case a scant two days after the diagnosis had been made, fearing a repeat of past accusations of cover-up and incompetence. During those two days, it had been possible through the records of the cattle passport office -- the British Cattle Movement Service -- to identify and locate the cow's mother and offspring, her date of birth and original owner.

This was a triumph for Britain's cattle-tracing program. All British cattle have 30-page individual passports, about the same size as a person's European Union passport. It is, however, a much more comprehensive document, because it records all movements or changes in ownership of an animal, which are in turn reported to a central agency.

Naturally, some cattle farmers have doubted the value and effectiveness of so much paperwork. It must have been a surprise to some and a relief to others that the proverbial needle in the haystack was found so promptly. Not only was it possible to find the diseased cow's record among more than 4.6 million registered passports, but its movement between four owners had been fully reported.

The media were unusually accepting of scientific opinion that the case did not post a risk to food and that isolated cases of this nature were to be expected. The speed and precision with which the tracing system had operated could only have created confidence that the British government was on top of the situation. This is reassuring evidence that the unfortunate saga is, indeed, coming to an end.

BSE reached epidemic proportions in Britain in the early 1990s. A possible link with new variant Creutzfeldt-Jakob disease (nvCJD), a rare but fatal human disease, was suggested in March 1996. An immediate ban on British cattle and beef exports was imposed and cattle prices everywhere dropped out of sight as beef was left on retail counters in the face of very adverse publicity.

The ban on feeding meat and bone meal and the passport system were two programs in an elaborate web of safety measures put in place. These programs were set up to ensure that there was no risk of human infection (even if such a link with nvCJD did exist) and to allay consumers' fears and meet EU food safety requirements.

While the link between BSE and the feeding of meat and bone meal is generally accepted, there has always been concern that the disease also could be transmitted from cow to calf. Research has not closed the door on this possibility, particularly if the cow developed BSE symptoms soon after it had calved. The French have even raised the possibility of a mysterious "third way" of transmitting the disease.

The cow in question was born on Aug. 25, 1996, three and a half weeks after the feed ban was imposed and on a farm that also raised pigs. The chance that the cow, as a calf, was inadvertently fed pig ration containing infected meat and bone meal produced before Aug. 1, 1996, seems as credible as the first confirmed case of maternal transmission. The mother, although not diagnosed as having BSE, was slaughtered just three months after she calved.

The British State Veterinary Service is investigating the latest case but is unlikely to unearth convincing evidence almost four years after the event. The farmer is reported as not remembering why the mother of the cow was slaughtered.

In retrospect, it was too neat to be credible that no cattle born after the 1996 feed ban had been diagnosed with BSE fully two years after they could be expected to begin to show symptoms. As many as 19 such cases had been forecast to occur before the end of 2000. This suggests that either maternal transmission is less of a factor than earlier thought, or that the removal of infected meat and bone meal from farms had been more effective than expected.

Less than a week after the latest case, British Agriculture Minister Nick Brown was able to say that it "confirms my confidence in the public-protection measures we currently have in place and in our surveillance systems." He also reaffirmed plans to seek a relaxation of EU restrictions on the export of bone-in beef from Britain.

Although the incidence of BSE in Britain has been on the decline for almost 10 years, any news of domestic BSE cases has until now been bad news for the British cattle industry. The most recent incident confirms a positive change in the British public's attitude, first evident last year when the nation's sympathy was with its cattle farmers over France's refusal to lift its illegal ban on British beef imports.

There is hope that this change will be reflected in increased consumer confidence in beef, greater demand, and in beef regaining its status as the preferred meat. But more important is the public's apparent acceptance of scientific opinion.

Recognition of the role that the scientific community played in turning the BSE situation around would improve public confidence in its ability to contribute to society at large -- something that has suffered greatly since the epidemic began.

Two New Cases Of Mad Cow Disease Found In France

Mon, Jul 17, 2000 AP
Two new cases of mad cow disease have been discovered in two separate herds in western and central France and a total of 224 cows were slaughtered, the Ministry of Agriculture said in a communique Monday.

The animals were found in herds in the departments of Maine-et-Loire in the west and in Loir-et-Cher in central France. They were the 27th and 28th cases of the year.

In 1999, French authorities discovered 31 cases of mad cow disease, or bovine spongiform encephalopathy. Mad cow disease is believed to cause a similarly brain-wasting ailment in humans known as Creutzfeld-Jacob disease.

New cases of the disease are expected to appear in France until 2002, five years after authorities took rigorous measures to prevent more outbreaks. Mad cow disease has an average incubation period of five years.

Future uncertain for reliable nvCJD screening tests

Lancet 2000; 356: 229 - 232  15 July 2000 Dorothy Bonn
The realisation of an epidemic of variant Creutzfeldt-Jakob disease n(vCJD) would be a nightmare scenario for UK health-care planners. So far there have been only 63 confirmed cases of the disease in the UK (plus four more awaiting necropsy and a further seven probable cases), and one in France. [Ironically, the same issue of Lancet has a detailed account of the second French nvCJD case, see below, while the newspapers talk of yet more known cases in England. -- webmaster]

But fears persist that a large proportion of the human population may be harbouring the misfolded, protease-resistant prion protein (PrPSc) that causes both nvCJD and bovine spongiform encephalopathy and that an epidemic of vCJD is yet to come. "Only 4 years after the recognition of nvCJD, we must be cautious about making optimistic predictions", says John Collinge (Imperial College School of Medicine, London, UK). "What we need is a simple, reliable blood test for population screening", he suggests.

Unfortunately, no assay has yet proved sensitive enough to detect PrPSc in human blood samples. However, because PrPSc accumulates in lymphoreticular tissue, the UK National CJD Surveillance Centre in Edinburgh have decided to sample 18 000 archived tonsil and appendix samples in an attempt to estimate numbers at risk. The inability to detect PrPSc in the first 3170 samples is reassuring. But the immunohistochemical tests used could miss PrPSc detectable with more sensitive tests such as western blotting that are unsuitable for use on fixed material. "The possibility of large-scale epidemics can only be excluded if a very large number of tissue samples are tested or if we can be certain that the tests are highly sensitive early in the incubation period", says Roy Anderson (University of Oxford, UK).

A blood test for nvCJD?

Testing of fresh lymphoreticular tissue with a sensitive assay should be revealing; in a study of 2000 fresh tonsils, Collinge's group is using a western blot technique to detect the PrPSc glycoform associated with cCJD. But there will still be unknowns, according to Richard Knight (UK National CJD Surveillance Centre). "We don't know how early in the disease PrPSc accumulates in lymphoreticular tissue or whether lymphoreticular positivity inevitably leads to clinical nvCJD", he says. "We would have to follow up people with a positive result for years to answer these questions".

The same reservations apply to blood tests, but a reliable estimate of numbers affected would at least be a starting point for contingency planning. There are several possible approaches to enhance assay sensitivity to detect PrPSc in blood, including a so-called optimised chemiluminescent western blot and a high-throughput dissociation-enhanced fluoroimmunoassay. But all have some way to go before they can be applied to population screening.

First past the winning post is likely to be Mary Jo Schmerr, from the US National Animal Disease Center (Dayton, IA, USA), who has developed a highly sensitive test that can detect abnormal prion protein in the blood of animals infected with transmissible spongiform encephalopathies. The test was developed to detect prions in the blood of sheep infected with scrapie and elks infected with chronic wasting disease, but Schmerr says it could be applied to vCJD too. Schmerr has overcome the biggest hurdle in the development of blood tests by using organic solvents and hydrophilic-interaction chromatography to concentrate the abnormal prion protein from the buffy-coat fraction of blood. She then uses capillary electrophoresis to detect the protein.

"This assay system is unique in that it involves the direct binding of a fluorescent peptide by a specific antibody in a separation system that measures both bound and free peptide", explains Schmerr. "The equilibrium of the assay is disturbed when a competitor, the abnormal prion protein, is present, and the disturbance can easily be measured by a change in the peak heights of bound and free peptide". The assay can measure about 300 000 molecules of bound peptide, equivalent to about 15 femtograms of abnormal prion protein.

Schmerr predicts that her test will make a practical preclinical test possible for vCJD, as well as for the animal transmissible spongiform encephalopathies for which it was developed.

Knight warns, however, that Schmerr's test is not yet validated for symptomatic testing of human CJD. "It could be assessed relatively quickly, but we don't yet know if it will work reliably in humans", he says. "Evaluation for presymptomatic testing would be complex and would take considerable time", he adds. "I cannot see it as a presymptomatic test in the near future."

But Schmerr is encouraged by her latest findings. To find out when PrPSc becomes detectable in sheep's blood she sequentially sampled blood from lambs born to scrapie-infected ewes and found PrPSc in their blood from age 4 weeks. "Several of the clinically normal but PrPSc-positive sheep I tested have since developed clinical scrapie and died", she says.

In the absence of large-scale screening with a reliable test for preclinical disease, we can only rely on trends in vCJD deaths for estimates of the size of the future epidemic. With 14 cases confirmed in 1999, and assuming that vCJD affects only the 40% of the population who are homozygous for methionine at codon 129 of the prion-protein gene (all cases of vCJD so far have been homozygotes), Anderson predicts a maximum epidemic size of 500 000 cases. If no more than 15 cases are confirmed this year, the maximum, he estimates, will be about 14 000. However, there have been 12 confirmed cases already this year, and another seven suspected. The prospect of a contained epidemic does not look good: if between 30 and 49 cases are confirmed in 1999-2000, then, by Anderson's calculations, the maximum number of cases could still reach 500 000.

When a reliable screening test becomes available, determination of preclinical disease will pose "huge questions", says Knight. "There are public-health risks as well as benefits", he explains. Until we know much more about the natural history of the disease, he says, public-health planning can only be based on assumptions. "And we won't be able to tell an individual with a positive test result when, or even whether, symptoms are likely to appear."

MRI and the second French case of nvCJD

Lancet 2000; 356: 247 - 258  15 July 2000
Catherine Oppenheim, Jean-Philippe Brandel, Jean-Jacques Hauw,Jean-Philippe Deslys, Bertrand Fontaine
Sir--Martin Zeidler and colleagues (April 22) 1 have described a bilaterally increased pulvinar signal on T2-weighted magnetic resonance imaging (MRI) of patients from the UK with variant Creutzfeldt-Jakob disease2 (vCJD). Here, we report similar routine MRI features in a French patient with nvCJD. We also present a description of diffusion-weighted imaging (DWI) inn vCJD.

A woman aged 36 years presented with emotional and behavioural changes associated with severe depression. The psychiatric signs worsened despite use of antidepressive drugs, and were followed by progressive dementia, unsteadiness of gait, and cerebellar and pyramidal signs. 7 months after onset, she also developed drowsiness, progressive immobility, unresponsiveness, involuntary movements, and myoclonus. Cerebrospinal fluid examination (including the dosage of 14-3-3 protein) was normal. The electroencephalogram showed bilateral aperiodic slow waves...

The patient died 14 months after disease onset and the family gave consent for a necropsy to be done. Neuropathological examination disclosed spongiform changes, diffuse astrogliosis, and numerous florid plaques immunolabelled with monoclonal antibody. Western-blot analysis showed the presence of type 4 proteinase K resistant PrP, confirming this diagnosis of vCJD.

This constitutes the second French case of vCJD. The patient had never travelled abroad, therefore confirming that continental European and UK vCJD share similar clinical, histopathological, and neuroimaging features.

...The widespread use of MRI in patients with persistent early psychiatric features despite appropriate psychiatric treatment could provide a valuable source of epidemiological data on the emerging epidemic of vCJD, and therefore has public-health implications.

[Measures for the disposal of non-regulated alternative medical wastes--prion protein-polluted medical waste].

Rinsho Byori 2000 May;Suppl 112:104-14 [Article in Japanese]
Haishima Y  
Transmissible spongiform encephalopathy (TSE), sometimes known as prion diseases, are fatal degenerative brain diseases. From epidemiological evidence and many investigations of data, the risk that TSE agents will be transmitted from TSE patients to other humans, is very low, but TSE agents comprise one of the very severe bio-medical hazards. Although government agencies, world organization and other institutions have distributed some guidances for safe working and prevention of infection, these guidances are not compulsory and no globally harmonized guidelines is present to date. Therefore, medical staff particularly in hospitals individually take countermeasures for safety against TSE agents by using these guidelines, and both the level and method differ in each hospital. In this chapter, transmission of TSE and related parts of guidelines from the Advisory Committee on Dangerous Pathogens and Spongiform Encephalopathy Advisory Committee in the United Kingdom recommending relatively strict standards are described.

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