ON the question of Sporadic or Atypical BSE and CJD

[flatfish]

PERSPECTIVE

On the Question of Sporadic

or Atypical Bovine SpongiformEncephalopathy and

Creutzfeldt-Jakob Disease

Paul Brown,* Lisa M. McShane,† Gianluigi Zanusso,‡ and Linda Detwiler§

Strategies to investigate the possible existence of sporadic

bovine spongiform encephalopathy (BSE) require

systematic testing programs to identify cases in countries

considered to have little or no risk for orally acquired disease,

or to detect a stable occurrence of atypical cases in

countries in which orally acquired disease is disappearing.

To achieve 95% statistical confidence that the prevalence

of sporadic BSE is no greater than 1 per million (i.e., the

annual incidence of sporadic Creutzfeldt-Jakob disease

[CJD] in humans) would require negative tests in 3 million

randomly selected older cattle. A link between BSE and

sporadic CJD has been suggested on the basis of laboratory

studies but is unsupported by epidemiologic observation.

Such a link might yet be established by the discovery

of a specific molecular marker or of particular combinations

of trends over time of typical and atypical BSE and various

subtypes of sporadic CJD, as their numbers are influenced

by a continuation of current public health measures that

exclude high-risk bovine tissues from the animal and

human food chains...........

SEE FULL TEXT ;


http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm?s_cid=eid06_0965_e



3:00 Afternoon Refreshment Break, Poster and Exhibit Viewing in the Exhibit Hall

3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse Models
Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve University
Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain discovered recently in Italy, and similar or different atypical BSE cases were also reported in other countries. The infectivity and phenotypes of these atypical BSE strains in humans are unknown. In collaboration with Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have inoculated transgenic mice expressing human prion protein with brain homogenates from BASE or BSE infected cattle. Our data shows that about half of the BASE-inoculated mice became infected with an average incubation time of about 19 months; in contrast, none of the BSE-inoculated mice appear to be infected after more than 2 years. These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than classical BSE in humans.


6:30 Close of Day One



http://www.healthtech.com/2007/tse/day1.asp




SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...


http://www.cjdsurveillance.com/resources-casereport.html


There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.




http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm


http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf




[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine
Spongiform Encephalopathy (BSE)


http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf





[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk
Materials for Human Food and Requirement for the Disposition of
Non-Ambulatory Disabled Cattle

03-025IFA
03-025IFA-2


http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf





THE SEVEN SCIENTIST REPORT ***


http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf





Full Text

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.



http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=dignosing+and+reporting+creutzfeldt+jakob +disease&searchid=1048865596978_1528&stored_search=&FIRSTINDEX=0&journalcode=jama




http://www.neurology.org/cgi/eletters/60/2/176#535


BRITISH MEDICAL JOURNAL


BMJ


http://www.bmj.com/cgi/eletters/319/7220/1312/b#EL2



BMJ


http://www.bmj.com/cgi/eletters/320/7226/8/b#EL1




Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518

[flatfish]

New Mad-Cow Variant Is Suspected
February 17, 2004 The Wall Street Journal by ANTONIO REGALADO

Italian scientists have discovered that cattle may harbor a new form of mad-cow disease.
The research by scientists at the University of Verona, in Italy, builds on earlier work that raised the possibility of unusual cases of the fatal brain-wasting disease, formally known as bovine spongiform encephalopathy. The findings pose new questions about the risk of consuming tainted meat.

"If you eat cattle with this new strain, you could get a disease in humans," said Salvatore Monaco, a biologist who made the finding with colleague Gianluigi Zanusso.

Dr. Monaco said he found that the brains of certain infected animals looked similar to human brains destroyed by Creutzfeldt-Jakob disease, a neurological disorder that is believed to arise spontaneously and hadn't previously been linked to tainted meat. The human form of mad-cow disease is called variant Creutzfeldt-Jakob disease, which manifests itself differently. Now the question is whether the new form of BSE could be responsible for other Creutzfeldt-Jakob cases.

About 150 cases of variant Creutzfeldt-Jakob disease -- nearly all of them in Britain -- have been linked to eating infected cattle. But the majority of cases of Creutzfeldt-Jakob, which strikes about one in a million people each year, are termed "sporadic" because they don't have any known cause.

Consumer groups are likely to leap at the Italian finding, published in the Proceedings of the National Academy of Science. Some activists have long contended that humans are contracting mad-cow disease in the U.S., contrary to what public-health officials say.

"I have been waiting for this," said Terry S. Singeltary, a Bacliff, Texas, resident whose mother died in 1997 of Creutzfeldt-Jakob disease. Mr. Singeltary and others suspect that some cases of sporadic Creutzfeldt-Jakob are caused by something in the environment, perhaps contaminated meat.

BSE is believed to be caused by misshapen proteins called prions that can be spread by consumption of contaminated tissue. The U.S. found its first case of the cattle disease in December, after a Holstein in Washington state tested positive for the condition.

The Italian findings give some support to the theory that BSE could be responsible for some cases of Creutzfeldt-Jakob disease, Dr. Monaco said. The Italian group studied the brains of eight cattle that had tested positive for BSE using standard tests. Six of the animals' brains showed the usual signs, but the brains of two animals showed unusual deposits of prions. The distinctive patterns of deposits may indicate a new strain of mad-cow disease, which the Italian scientists have dubbed BASE, for bovine amyloidotic spongiform encephalopathy.

Linda Detweiler, a former senior veterinarian for the U.S. Department of Agriculture, said the finding isn't a complete surprise. Studies in the U.K., France and Japan have hinted that some cattle may have been suffering from atypical cases of mad-cow disease.

A related disease in sheep, called scrapie, is known to come in many different strains.

Dr. Detweiler said more research will be needed to confirm whether there is in fact a new strain of BSE. One possibility is that the disease simply looks different in the specific cattle breeds in the Italian study. "I think there are still a lot of questions," Dr. Detweiler said.

Stanley Prusiner, a leading researcher at the University of California, San Francisco, who is the discoverer of the prion and who reviewed the Italian report, has said the possibility of unusual BSE cases is an argument in favor of more comprehensive testing of cattle destined for human consumption.

Currently, the Agriculture Department tests only a tiny fraction of cattle for mad-cow disease. Its policy is to target animals that aren't able to walk, known as downer animals, based on the theory that those are most likely to have BSE.

But Dr. Monaco said his findings argue strongly for more testing in the U.S. The two animals found to have the new strain were 11 and 15 years old, "weren't acting abnormal, and were apparently free of neurological problems," Dr. Monaco said.

In Europe, all cattle slaughtered that are more than 30 months of age are tested for BSE. In Japan, all cattle turned into food are tested for the disease.

Scientists first discovered that BSE could affect humans in 1996, when doctors in Britain -- where mad-cow disease was ravaging herds -- found young people succumbing to Creutzfeldt-Jakob disease, which mainly strikes older people. Further research showed the disease, which remains extremely rare, was being caused by the same strain of prion as BSE -- the pattern of damage to the brain was similar in humans and cattle, as were the molecular signatures of the prions.

The existence of a second strain of BSE could mean some people are contracting it, but that the cases aren't being diagnosed properly.

Write to Antonio Regalado at antonio.regalado@wsj.com


http://online.wsj.com/public/us


tss

[flatfish]

----- Original Message -----
From: "Terry S. Singeltary Sr." <flounder9@VERIZON.NET>
To: <SANET-MG@LISTS.IFAS.UFL.EDU>
Sent: Friday, January 19, 2007 11:09 AM
Subject: Re: [SANET-MG] [BLOODCJD] Fourth case of transfusion-associated vCJD infection in the United Kingdom




18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7
December 2006 are now available.


snip...

4. Members had received information about the notification by the Health
Protection Agency (HPA) of recipients of four batches of plasma products
that had been produced from blood donated by individuals that had later
developed variant Creutzfeldt Jakob Disease (vCJD). THESE batches HAD NOT
been included in a similar notification exercise in 2004, as the fate of
these products COULD NOT BE TRACED at that time. The fourteenth annual
report of the National CJD Surveillance Unit had been published. The
European Food Safety Authority (EFSA) had issued a consultation on a revised
methodology for geographical bovine spongiform encephalopathy (BSE) risk
assessment. Members could submit individual responses. Submission of a SEAC
response was under consideration.

snip...

ITEM 9 - ANY OTHER BUSINESS

snip...

***$$$***

64. A member noted that at the recent Neuroprion meeting, a study was
presented showing that in transgenic mice BSE passaged in sheep may be more
virulent and infectious to a wider range of species than bovine derived BSE.
Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the
prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A
MUTATION FOUND IN CASES OF SPORADIC CJD. A study also demonstrated that in a
mouse model it was possible to alleviate the pathological changes of prion
disease by suppressing expression of the prion protein gene after infection.


http://www.seac.gov.uk/minutes/95.pdf


TSS



Subject: Fourth case of transfusion-associated vCJD infection in the United
Kingdom
Date: January 18, 2007 at 8:32 am PST


Fourth case of transfusion-associated vCJD infection in the United Kingdom

Editorial team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance
editorial office

A suspected case of variant Creutzfeldt-Jakob disease (vCJD) has recently
been diagnosed in a patient in the United Kingdom (UK), who received a blood
transfusion from a donor who later developed vCJD [1]. This is the fourth
case of probable transfusion transmission of vCJD infection in the UK. Three
of the four recipients developed symptoms of vCJD.
The first symptomatic case of vCJD associated with blood transfusion was
identified in December 2003. This individual developed vCJD six and a half
years after transfusion of red cells donated by an individual who developed
symptoms of vCJD three and a half years after donation.

A second case of vCJD 'infection' was identified a few months later in a
person who had received red cells from a donor who developed symptoms of
vCJD 18 months after donation. This patient (the second case) died from
causes unrelated to vCJD five years after transfusion. Post-mortem
investigations found abnormal prion protein in the spleen and a cervical
lymph node., However, prion protein was not found in the brain, and no
pathological features of vCJD were found.

A third case developed symptoms of vCJD six years after receiving a
transfusion of red blood cells, and died two years and eight months later.
The donor of the blood involved developed vCJD about 20 months after
donating it.

These three cases have been published as case reports and in the findings of
the ongoing collaborative study between the National Blood Services, the
National CJD Surveillance Unit, and the Office for National Statistics. This
study aims to collect evidence about transmission of CJD or vCJD via the
blood supply [2,3,4,5].

The new, fourth case is in a patient who developed symptoms of vCJD eight
and a half years after receiving a transfusion of red blood cells from a
donor who developed vCJD about 17 months after this blood was donated [1].
The donor to this case also donated the vCJD-implicated blood transfused to
the third case. As for all other reported clinical vCJD cases that have been
tested for genotype, this patient is a methionine homozygote at codon 129 of
the prion protein gene. The patient is currently alive.

All four cases had received transfusions of non-leucodepleted red blood
cells between 1996 and 1999. Since October 1999, leucocytes have been
removed from all blood used for transfusion in the UK. The effect of
leucodepletion on the reduction of the risk of transmission of vCJD from an
infective donation is uncertain.

This fourth case of vCJD infection associated with blood transfusion further
increases the level of concern about the risk of vCJD transmission between
humans by blood transfusion, although much remains unknown. This reinforces
the importance of the existing precautions that have been introduced to
reduce the risk of transmission of vCJD infection by blood and blood
products [6]. No cases of vCJD have been associated with fractionated plasma
products. The small group of living recipients of vCJD-implicated blood
transfusion in the UK have been informed of their potential exposure to vCJD
by blood transfusion, asked to take certain precautions to reduce the risk
of onward person-to-person transmission of vCJD during health care, and
offered specialist neurological evaluation and advice.

This article has been adapted from reference 1


References:
Health Protection Agency. Fourth case of variant CJD associated with blood
transfusion (press release). Press release, 18 January 2007.
(http://www.hpa.org.uk/hpa/news/articles/press_releases/2007/070118_vCJD.htm
)
Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, et al.
Possible transmission of variant CJD disease by blood transfusion. Lancet
2004; 363:417-21.
Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after
blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004 ;
364: 527-9.
Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, et al Clinical
presentation and pre-mortem diagnosis of blood transfusion-associated
variant CJD. Lancet 2006;368:2061-67.
Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and
blood transfusion: results of the UK Transfusion Medicine Epidemiology
review study. Vox Sang. 2006;91(3):221-230.
Department of Health [London]. Further precautions to protect blood supply.
Press release 2004/0104, 16 March 2004.
(http://www.dh.gov.uk/PublicationsAndStatistics/PressReleases/PressReleasesN
otices/fs/en?CONTENT_ID=4076608&chk=MTwE%2Bl)

http://www.eurosurveillance.org/ew/2007/070118.asp#4


FDA NVCJD BLOOD LATEST RECALLS

http://www.fda.gov/bbs/topics/enforce/2007/ENF00987.html



TSS