From: Terry S. Singeltary Sr.
To: FREAS@CBER.FDA.GOV
Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov
Sent: Wednesday, November 29, 2006 1:24 PM
Subject: TSE advisory committee for the meeting December 15, 2006 [TSSSUBMISSION]November 29, 2006
Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,
a kind and warm Holiday Greetings to you all.i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derivedantihemophilic factor (FVIII) productsmanufactured from U.S. plasma donors and related communication material ;
http://a257.g.akamaitech.net/7/257/2422/01jan20061800/edocket.access.gpo.gov/2006/E6-20251.htm
i see the media picked up on this as a 'low risk', from what the gov. agency perceived to be to them;
http://www.newsday.com/news/health/ats-ap_health14nov27,0,7955259.story?coll=ny-leadhealthnews-headlines
however, i seem to disagree. from my primitive ciphering, i see it another way. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, wha tabout the mixed genotypes/mixed susceptibility?
what about the silent carriers that donated tainted blood?
what about the sporadic CJDs of UNKNOWN strain or phenotype?
this risk assessment is just more BSe to me. just another in a long line of industry fed crap. i pray that my assessment is the one that is wrong. but it is THEY who roll the dice with your life. it is THEY who refuse to regulate an industry that has run amok. just from are call aspect of potentially tainted blood, and these are just recent recalls ;
PRODUCT
Source Plasma, Recall # B-0054-7CODEUnits: 03MMNC5465, 03MMNC6361, 03MMNC6801, 03MMNC7510, 03MMNC7891,03MMNC8252, 03MMNC8801, 03MMNC9144, 03MMND1122, 03MMND1478, 03MMND1969,03MMND2350, 03MMND2825, 03MMND3211, 03MMND3708, 03MMND4072, 03MMND4588,03MMND4831, 03MMND5320, 03MMND5719, 03MMND6268, 03MMND6683, 03MMND7228,03MMND7656, 03MMND8211, 03MMND8652, 03MMND9195, 03MMND9618, 03MMNE0628,03MMNE0884, 03MMNE1597, 03MMNE1979, 03MMNE2644, 03MMNE3064, 03MMNE3707,03MMNE4122, 03MMNE4750, 03MMNE5080, 03MMNE5876, 03MMNE6218, 03MMNE7189,03MMNE7587, 03MMNE8027, 03MMNE8645, 03MMNE9029, 03MMNE9641, 03MMNE9979,03MMNF0491, 03MMNF0685, 03MMNF0937, 03MMNF1260, 04MMNA0351, 04MMNA0707,04MMNA1241, 04MMNA1650, 04MMNA2291, 04MMNA2646, 04MMNA3340, 04MMNA3719,04MMNA4312, 04MMNA4683, 04MMNA5298, 04MMNA5750, 04MMNA6407, 04MMNA6816,04MMNA7482, 04MMNA7915, 04MMNA8632, 04MMNA9076, 04MMNA9723, 04MMNB0063,04MMNB0696, 04MMNB1100, 04MMNB1845, 04MMNB2285, 04MMNB3035, 04MMNB3485,04MMNB4213, 04MMNB4672, 04MMNB5841, 04MMNB6652, 04MMNB7162, 04MMNB7930,04MMNB8453, 04MMNB9239, 04MMNB9747, 04MMNC0456, 04MMNC0931, 04MMNC1578
RECALLING FIRM/MANUFACTURER
BioLife Plasma Services, L.P., Mankato, MN, by facsimile on June 4, 2004.
Firm initiated recall is complete.
REASON
Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
89 units
DISTRIBUTION
CA and Austria
END OF ENFORCEMENT REPORT FOR October 25, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00975.html
USA FDA MAD COW BLOOD HUMANS RECALL (these are dime a dozen)RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS II
______________________________
PRODUCTSource Plasma, Recall # B-1708-6CODEUnits: MI180733, MI180927, MI181625, MI181780, MI182337, MI182519, MI183140,MI183311, MI183955, MI185006, MI185278, MI185822, MI186081, MI186855,MI187183, MI187903, MI188273, MI188695, MI189257, MI189553, MI190136,MI190473, MI191073, MI191395, MI191972, MI192303, MI193473, MI194343,04MINA0377, 04MINA0801, 05MINA7147, 05MINA7451, 05MINA8094, 05MINA8504,05MINA9548, 05MINA9883, 05MINB0489, 05MINB0875, 05MINB1469, 05MINB1874,05MINB3116, 05MINB7192, 05MINB7529, 05MINB8246, 05MINB8612, 05MINB9236,05MINB9366, 05MINB9475, 05MINB9641, 05MINC0031, 05MINC0237, 05MINC0336,05MINC0894, 05MINC0964, 05MINC1138, 05MINC1619, 05MINC1750, 05MINC1907,05MINC1977, 05MINC2375, 05MINC2774, 05MINC3113, 05MINC3484, 05MINC4277,05MINC4623, 05MINC5623, 05MINC5914, 05MINC7545, 05MINC7870, 05MINC8355,05MINC8689, 05MINC9437, 05MINC9775, 05MIND0067, 05MIND0393, 05MIND0892,05MIND0951, 05MIND1836, 05MIND2183 and 05MIND2962
RECALLING FIRM/MANUFACTURER
BioLife Plasma Services L.P., Muncie, IN, by facsimile on November 22, 2005.
Firm initiated recall is complete.
REASON
Blood products, collected from unsuitable donors based on risk factors for Creutzfeldt-Jakob Disease (CJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
80 units
DISTRIBUTION CA, NC, and MD
______________________________
PRODUCT
a) Red Blood Cells, Leukocytes Reduced, Recall # B-1714-6;b) Fresh Frozen Plasma, Recall # B-1715-6;c) Platelets, Recall # B-1716-6CODEa),
b), and c) Unit: 2443732RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by letters dated November 11, 2003 and December 18, 2003. Firm initiated recall is complete.
REASON
Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX and WI
END OF ENFORCEMENT REPORT FOR SEPTEMBER 13, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00969.html
PRODUCT
Fresh Frozen Plasma, Recall # B-1751-6
CODE
Unit: 4936623
RECALLING FIRM/MANUFACTURER
Gulf Coast Regional Blood Center, Houston, TX, by facsimile dated September 16, 2005.
Firm initiated recall is complete.
REASON
Blood product, which was collected from an unsuitable donor based on risk factors for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
TX
END OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html
Mon Aug 7, 2006 10:2471.248.132.189
PRODUCT
a) Red Blood Cells, Recall # B-1587-6;b) Cryoprecipitated AHF, Recall # B-1588-6;c) Recovered Plasma, Recal # B-1589-6
CODE
a), b) and c)
Unit: 2016719
RECALLING FIRM/MANUFACTURER
Walter Shepeard Community Blood Center, Inc., Augusta, GA, by facsimile on March 13, 2003.
Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
GA and Germany
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1590-6;b) Fresh Frozen Plasma, Recall # B-1591-6
CODE
a) and b)
Unit: 2443595
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June30, 2004.
Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1592-6;b) Fresh Frozen Plasma, Recall # B-1593-6
CODEa) and b)
Unit: 2545596
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on December 14, 2004 and January 3, 2005.
Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX
______________________________
http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1550-6;b) Fresh Frozen Plasma, Recall # B-1551-6
CODEa) and b)
Unit 2395371
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on August 20,2003.
Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1552-6;b) Platelets, Recall # B-1553-6;c) Fresh Frozen Plasma, Recall # B-1554-6
CODE
a), b) and c)
Unit 2438702
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on May 29,2003.
Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1555-6;b) Fresh Frozen Plasma, Recall # B-1556-6
CODEa) and b)
Unit 2454970
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on July 23 and December 11. 2003.
Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX
______________________________
PRODUCT
a) Red Blood Cells, Recall # B-1494-6b) Cryoprecipitated AHF, Recall # B-1495-6
CODEa) and b)
Unit 5013100
RECALLING FIRM/MANUFACTURER
Walter L. Shepeard Community Blood Center, Inc., Augusta, GA, by fax on May17, 2005. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
GA
______________________________
PRODUCT
Source Plasma, Recall # B-1450-6
CODE
Unit numbers ST0824313 and ST0824764
RECALLING FIRM/MANUFACTURER
Stillwater Plasma Center LLC, Stillwater, OK, by fax on November 21, 2003.
Firm initiated recall is complete.REASON
Blood products, which were collected from a donor whose suitability pertaining to risk factors for Creutzfeldt-Jakob Disease (vCJD) was not adequately determined, were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
UK
______________________________
PRODUCT
Plasma Frozen, Recall # B-1422-6;Recovered Plasma, Recall # B-1423-6
CODE
a) Unit 03E42218;
b) Unit 03E38153
RECALLING FIRM/MANUFACTURER
American Red Cross Blood Services, Atlanta, GA, by telephone, e-mail orletter on February 20 or 21, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
GA and Switzerland
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1374-6;
b) Recovered Plasma, Recall # B-1375-6CODEa) and b) unit 2453906
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on October 31 and November 5, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX and Austria
______________________________
PRODUCT
Source Plasma.
Recall # B-1295-6
CODE
Units: NG0046551, NG0045950
RECALLING FIRM/MANUFACTURERD
CI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002, Firm initiated recall is complete.
REASON
Blood products, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire appropriately, were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
KY
______________________________
PRODUCT
Source Plasma. Recall # B-1296-6
CODE
Unit: NG 0044520RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 12, 2002. Firm initiated recall is complete.
REASON
Blood product, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire, was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
KY
______________________________
PRODUCT
Source Plasma. Recall # B-1297-6
CODE
Units: NG0042874, NG0043139, NG0043312, NG0043618, NG0043797, NG0044020,NG0044209, NG0044507, NG0044718, NG0044977, NG0045161, NG0045412, NG0045555RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.
REASON
Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
13 units
DISTRIBUTION
KY
______________________________
PRODUCT
Source Plasma, Recall # B-1298-6
CODE
Units: NG 0046823, NG 0046671, NG 0045205, NG 0044635, NG 0043095, NG0042525, NG 0042341RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.
REASON
Blood products, collected from a donor who answered questions on the variant Creutzfeldt-Jacob disease (vCJD) questionnaire inappropriately, were distributed.
VOLUME OF PRODUCT IN COMMERCE
7 units
DISTRIBUTION
KY
______________________________
PRODUCT
Recovered Plasma, Recall # B-1299-6CODEUnit: 4357117
RECALLING FIRM/MANUFACTURER
Department of the Navy, Naval Medical Center, San Diego, CA, by fax and letter on September 25, 2003. Firm initiated recall is complete.
REASON
Blood product, collected from a donor considered to be at risk of exposure to Creutzfeldt-Jacob Disease (CJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
Germany
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html
CJD WATCH MESSAGE BOARD
TSS
FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY Fri Jul 7, 2006 09:3770.110.83.160
FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1379-6;
b) Platelets, Recall # B-1380-6;
c) Fresh Frozen Plasma, Recall # 1381-6;
d) Recovered Plasma, Recall # B-1382-6
CODE
a) Unit numbers: 2343106, 2377779, and 2403533;
b) and c) Unit numbers: 2377779;
d) Unit numbers: 2343106 and 2403533
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June12, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
7 units
DISTRIBUTIONTX and Austria
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1467-6;
b) Recovered Plasma, Recall # B-1468-6
CODE
a) and b)
Unit numbers: 2329380
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on May 8,2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTIONTX and Switzerland
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1479-6;
b) Cryoprecipitated AHF, Recall # B-1480-6;
c) Recovered Plasma, Recall # B-1481-6
CODE
a), b), and c)
Unit numbers: 2383280
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on July23 and 29, 2004. Firm initiated recall is complete.
REASONBlood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX and Switzerland
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1482-6;
b) Fresh Frozen Plasma, Recall # B-1483-6
CODE
a) and b)
Unit number: 2501452
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile onOctober 5, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX and NY
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1484-6;
b) Plasma Cryoprecipitated Reduced, Recall # B-1485-6;
c) Recovered Plasma, Recall # B-1486-6
CODE
a) and c)
Unit number: 2554077;
b) Unit number: 2415708
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on August13, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX and Austria
_____________________________________
END OF ENFORCEMENT REPORT FOR July 5, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00959.html
Greetings again Dr. Freas et al at FDA,
WITH new atypical TSE in the bovine, in the sheep, goat, and humans, and the fact that the new BASE TSE in cattle being very very similar to sporadic CJD, rather than the nvCJD, the fact that now science showing the TSE agent of the atypical cattle in Japan showing infectivity other than CNS tissue, the fact that the latest Texas mad cow and the recent Alabama mad cow both being of the atypical strain, it would seem prudent to include all human TSE in the blood ban, in my opinion. with sporadic CJD, you have many strains and or phenotypes, some of which are 'UNKNOWN', so we do not know how this will transmit, what tissues are infectious and or if blood transmits. that's the bottomline, however it has been reported that the BASE is more virulent to humans.With this, and the fact that sporadic CJD has tripled in the past few years or so, i see itas being prudent to take serious and immediate action ;
PERSPECTIVE
On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy 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. ......
PLEASE READ FULL TEXT ;
http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm?s_cid=eid06_0965_e
CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006
The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade. The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old. These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen.
"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases,"
Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United PressInternational.
"The question was, 'How many?' and we still can't answer that."
Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has
"absolutely no confidence in USDA tests before one year ago"
because of the agency's reluctance to retest the Texas cow that initially tested positive.
USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general.
"Everything they did on the Texas cow makes everything USDA did before 2005 suspect,"
Brown said. ...
snip...end
http://www.upi.com/
*** Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain
http://www.usda.gov/oig/webdocs/50601-10-KC.pdf
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 istransmissible to humans and suggest that BASE is more virulent thanclassical 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.htmhttp://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
Prion infections, blood and transfusions
Adriano Aguzzi* and Markus Glatzel
Prion infections lead to invariably fatal diseases of the CNS, including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE), and scrapie in sheep. There have been hundreds of instances in which prions have been transmitted iatrogenically among humans, usually through neurosurgical procedures or administration of pituitary tissue extracts. Prions have not generally been regarded as blood borne infectious agents, and case-control studies have failed to identify CJD in transfusion recipients. Previous understanding was, however, questioned by reports of prion infections in three recipients of blood donated by individuals who subsequently developed variant CJD. On reflection, hematogenic prion transmission does not come as a surprise, as involvement of extracerebral compartments such as lymphoid organs and skeletal muscle is common in most prion infections, and prions have been recovered from the blood of rodents and sheep. Novel diagnostic strategies, which might include the use of surrogate markers of prion infection, along with prion removal strategies, might help to control the risk of iatrogenic prion spread through blood transfusions. ...
snip...
Last, despite all epidemiological evidence to the contrary, patients who are methionine/valineheterozygous at codon 129 of the PRNP gene are susceptible to infection with vCJD prions, which raises several important questions.
Is the virulence of BSE prions enhanced when passaged from human to human, as opposed to the original bovine to human situation? Passaging experiments of scrapie infectivity between mice and hamsters indicate that this scenario is highly plausible.6 Even more importantly, can vCJD infection of heterozygous individuals establish a permanent subclinical carrier state? Although this situation might constitute a best-case scenario for the infected individuals, it could be disastrous from an epidemiological viewpoint, as it might lead to an unrecognized and possibly self-sustaining epidemic. ...
snip...
full text ;
JUNE 2006 VOL 2 NO 6 AGUZZI AND GLATZEL NATURE CLINICAL PRACTICE NEUROLOGY329
www.nature.com/clinicalpractice/neuro
FDA Fines American Red Cross $4.2 Million (BLOOD CJD)
Fri Sep 8, 2006 20:0171.248.154.242FD
A Statement
FOR IMMEDIATE RELEASE
Statement
September 8, 2006
Media Inquiries:301-827-6242
Consumer Inquiries:888-INFO-FDA
FDA Fines American Red Cross $4.2 Million for Failure to Meet Established Blood Safety Laws
http://www.fda.gov/cber/talkpapers.htm#arc
snip...
One way the Red Cross erred was by failing to ask donors about travel history that could increase the chances of having malaria or the human version of mad cow disease, FDA officials said.
snip...
http://today.reuters.co.uk/news/articlenews.aspx?type=healthNews&storyID=2006-09-08T224834Z_01_N08403053_RTRIDST_0_HEALTH-REDCROSS-DC.XML
http://today.reuters.co.uk/news/articlenews.aspx?type=healthNews&storyID=2006-09-08T224834Z_01_N08403053_RTRIDST_0_HEALTH-REDCROSS-DC.XML&pageNumber=1&imageid=&cap=&sz=13&WTModLoc=NewsArt-C1-ArticlePage1
Greetings again Dr. Freas et al at FDA,
THIS was like closing the barn door after the mad cows got loose. not only the red cross, but the FDA has failed the public in protecting them from the TSE aka madcow agent. TSE agent i.e. bse, base, cwd, scrapie, tme, and any sub strains there of. we do not know if these strains will or have transmitted to humans as subclinical TSE or clinical disease, and we do not know if they have or will transmit second, third,forth passage via friendly fire i.e. multiple potential routes via medical, surgical, pharmaceutical etc.
IF you remember correctly Dr. Freas et al, i called this long ago, almost 6 years ago ;
PDF]Freas, William TSS SUBMISSIONFile Format: PDF/Adobe Acrobat -Page 1. J Freas, William From:
Sent:
To:
Subject:
Terry S. SingeltarySr. [flounder@wt.net]
Monday, January 08,200l 3:03 PM
freas ...Freas, William
From: Terry S. Singeltary Sr. [flounder@wt.net]
Sent: Monday, January 08,200l 3:03 PM
To: freas@CBS5055530.CBER.FDA.GOV
Subject: CJDIBSE (aka madcow) Human/Animal TSE?s--U.S.--Submission
To
Scientific Advisors and Consultants Staff January 2001 Meeting (short version)
Greetings again Dr. Freas and Committee Members,
I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version).
I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, but will attempt here:
remember AIDS/HIV, 'no problem to heterosexuals in the U.S.? no need to go into that, you know of this blunder:
DO NOT make these same stupid mistakes again withhuman/animal TSE's aka MADCOW DISEASE. I lost my Mom to hvCJD, and my neighbor lost his Mother to sCJD as well (both cases confirmed). I have seen many deaths, from many diseases.I have never seen anything as CJD, I still see my Mom laying helpless, jerking tremendously, and screaming "God, what's wrong with me, why can't I stop this". I still see this, and willnever forget. Approximately 10 weeks from 1st of symptoms to death.This is what drives me. I have learned more in 3 years about not onlyhuman/animal TSE's but the cattle/rendering/feeding industry/government than i ever wished to.
I think you are all aware of CJD vs vCJD, but i don't think you all know the facts of human/animal TSE's as a whole, they are all very very similar, and are all tied to the same thing, GREED and MAN.
I am beginning to think that the endless attempt to track down and ban, potential victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually?
AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, eyelid test, anything at whatever cost, we need a test FAST.
DO NOT let the incubation time period of these TSEs fool you.
To think of Scrapie as the prime agent to compare CJD, but yet overlook the Louping-ill vaccine event in 1930's of which 1000's of sheep where infected by scrapie from a vaccine made of scrapie infected sheep brains, would be foolish. I acquired this full text version of the event which was recorded in the Annual Congress of 1946 National Vet. Med. Ass. of Great Britain and Ireland.> From the BVA and the URL is posted in my (long version).
U.S.A. should make all human/animal TSE's notifiable at all ages, with requirements for a thorough surveillance and post-mortem examinations free of charge, if you are serious about eradicating this horrible disease in man and animal.There is histopathology reports describing "florid plaques" in CJD victims in the USA and some of these victims are getting younger. I have copies of such autopsies, there has to be more.
PLUS, sub-clinical human TSE's will most definitely be a problem.THEN think of vaccineCJD in children and the bovine tissues used in the manufacturing process, think of the FACT that this agent surviving 6OO*C. PNAS -- Brown et al. 97 (7): 3418 scrapie agent live at 600*C
Then think of the CONFIDENTIAL documents of what was known of human/animal TSE and vaccines in the mid to late 8Os, it was all about depletion of stock, to hell with the kids, BUT yet they knew. To think of the recall and worry of TSE's from the polio vaccine, (one taken orally i think?), but yet neglect to act on the other potential TSE vaccines (inoculations, the most effective mode to transmit TSEs) of which thousands of doses were kept and used, to deplete stockpile, again would be foolish.
--Oral polio; up to 1988, foetal calf serum was used from UK andNew Zealand (pooled); since 1988 foetal calf serum only from NewZealand. Large stocks are held.
--Rubella; bulk was made before 1979 from foetal calf serum from UKand New Zealand. None has been made as there are some 15 years stock.
--Diphtheria; UK bovine beef muscle and ox heart is used but since theend of 1988 this has been sourced from Eire. There are 1,250 litres of stock.. .
--Tetanus; this involves bovine material from the UK mainly Scottish.There are 21,000 litres of stock.
--Pertussis; uses bovine material from the UK. There are 63,000 litres of stock.
--They consider that to switch to a non-UK source will take a minimum of 6-18 months and to switch to a non-bovine source will take a minimum offive years.
3. XXXXXXXXXXX have measles, mumps, MMR, rubella vaccines. These are sourced from the USA and the company believes that US material only is used.89/2.14/2.1
============
BSE3/1 02514.
XXXXXXXXXXX have a measles vaccine using bovine serum from the UK. there are 440,000 units of stock. They have also got MMR using bovine serum from the UK.5.
XXXXXXXXXXX have influenza, rubella, measles,' MMR vaccines likely to be used in children. Of those they think that only MMR contains bovine material which is probably a French origin.6.
XXXXXXXXXXX have diphtheria/tetanus and potasses on clinical trial. These use veal material, some of which has come from the UK and has been made by XXXXXXXXXXX (see above).
I have documents of imports from known BSE Countries,of ferments, whole blood, antiallergenic preparations, 2 human blood plasma, normal human blood sera, human immuneblood sera, fetal bovine serum, and other blood fractions not elsewhere specified or included, imported glands,catgut, vaccines for both human/animal, as late as 1998.
Let us not forget about PITUITARY EXTRACT. This was used to help COWS super ovulate. This tissue was considered to be of greatest risk ofcontaining BSE and consequently transmitting the disease.
ANNEX 6
MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TO BIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIAL
How much of this was used in the U.S.?
Please do not keep making the same mistakes.
'Absence of evidence is not evidence of absence'.
What are the U.S. rules for importing and manufacturing vaccines, medicines and medical devices?
Does the U.S.A. allow sourcing of raw material of ruminants from the U.S.A.?
U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds.?
The U.S. rendering system would easily amplify T.S.E.'s:
Have we increased the stability of the system (improved heat treatments) since the EU SSC report on the U.S.A. was published in july 2000?
What is done to avoid cross-contaminations in the U.S.A.?
How can the U.S. control absence of cross-contaminations of animal TSE's when pig and horse MBM and even deer and elk are allowed in ruminant feed, as well as bovine blood?
I sadly think of the rendering and feeding policy before the Aug. 4, 1997 'partial' feed ban, where anything went, from the city police horse, to the circus elephant, i will not mention all the scrapie infected sheep. I am surprised that we have not included man 'aka soyent green'. It is a disgusting industry and nothing more than greed fuels it.
When will the U.S.. start real surveillance of the U.S. bovine population (not passive, this will not work)?
When will U.S. start removing SRMs?
Have they stopped the use of pneumatic stunners in the U.S.?
If so, will we stop it in all U.S. abattoirs or only in those abattoirs exporting to Europe?
If not, WHY NOT?
same questions for removal of SRM in the U.S.A.,or just for export?
If not, WHY NOT?
How do we now sterilize surgical/dental instruments in the U.S.A.?
Where have we been sourcing surgical catgut? (i have copies of imports to U.S., and it would floor you)
When will re-usable surgical instruments be banned?
'Unregulated "foods" such as 'nutritional supplements' containing variousextracts from ruminants, whether imported or derived from US cattle/sheep/cervids ("antler velvet" extracts!) should be forbidden or at least very seriously regulated. (neighbors Mom, whom also died from CJD, had been taking bovine based supplement, which contained brain, eye, and many other bovine/ovine tissues for years, 'IPLEX').
What is the use of banning blood or tissue donors from Germany, France,etc... when the U.S.A. continues exposing cattle, sheep and people to SRM, refuses to have a serious feed ban, refuses to do systematic BSE-surveillance?
The FDA should feel responsible for the safety of what people eat. prohibit the most dangerous foods, not only prohibit a few more donors, the FDA should be responsible for the safe sourcing of medical devices, not only rely on banning donors "from Europe", The 'real' risks are here in the U.S. as well, and have been for sometime.
We must not forget the studies that have proven infectivity in blood from TSE's.
The Lancet, November 9, 1985
" Sir, --Professor Manuelidis and his colleagues (Ott 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from, whole blood samples of a patient (and of mice) infected with CJD.lBrain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.
snip...full text ;
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
Greetings again Dr. Freas et al at FDA,
NOW, here we are in 2006, worried and still fumbling around with what should have beendone long, long ago ;
Subject: 91ST MEETING OF THE SEAC MEETING LONDON 24TH FEB 2006
Date: March 10, 2006 at 7:36 am PST1© SEAC 2006
NINETY FIRST MEETING OF THE SPONGIFORMENCEPHALOPATHY ADVISORY COMMITTEE
The Spongiform Encephalopathy Advisory Committee held its 91stmeeting in London on 24th February 2006.
snip...
MEDICAL IMPLANTS CONTAINING BOVINE MATERIAL
SEAC considered the risk to human health from medical implants that include bovine material sourced from the USA. This material was used for a wide range of medical devices, some of which are life saving and for which there are no alternative products.SEAC considered that the source of the animal was crucial to manage the risk. The committee suggested that other precautionary steps be taken where practicable, such as using material from young animals, sourcing material from countries with good surveillance procedures and a low prevalence of disease. ......
snip...
http://www.seac.gov.uk/minutes/final90.pdf
A BIT OF HISTORY ON THIS TOPICTWA LITTLE minute
http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf
COMMERCIAL IN CONFIDENCE
http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf
NOT FOR PUBLICATION
http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf
http://www.bseinquiry.gov.uk/yb/1988/11/04003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/30001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also inthe 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...
http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf
more on the 1968 medicine act, they forgot to follow
http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
8. The Secretary of State has a number of licences. We understand thatthe inactivated polio vaccine is no longer being used. There is a stockof smallpox vaccine. We have not been able to determine the sourcematerial. (Made in sheep very unlikely to contain bovine ingredients).
http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/02/14011001.pdf
although 176 products do _not_ conform to the CSM/VPCguidelines.
http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
Draft cover letter to product licence holders (considered by Human and VetMedicines including deer)
http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
(It was noted with concern that hormone extracts could be manufactured by aveterinary surgeon for administration to animals under his care without anyMedicines Act Control.)
http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf
TWA LITTLE STATEMENT 331
http://www.bseinquiry.gov.uk/files/ws/s331.pdf
WE know about USA serum and tissue donor herds from the now infamous Jan. 9, 2001 FDA emergency 50 state BSE conference call, that in fact, USA serum and tissue donor herds were eating banned ruminant feed as well ;
Date: Sun, 7 Jan 2001 09:45:19 -0800
Reply-To: Sustainable Agriculture Network Discussion Group<[log in to unmask]>Sender: Sustainable Agriculture Network Discussion Group<[log in to unmask]>From: Beth von Gunten <[log in to unmask]>
Subject: [BSE] FDA/IMPORTANT NOTICE: 50 STATE CONFERENCE CALLIMPORTANT NOTICE: 50 STATE CONFERENCE CALL - BSE
TUESDAY, JANUARY 9, 20011:00-2:00 PM EST
CALL: 1-888-273-9887
A special "50 STATE CONFERENCE CALL" to discuss BSE (Bovine Spongiform Encephalopathy) issues for Food and Drug Administration(FDA) regulated animal feed products in the United States and imported animal feeds. The conference call will discuss the FDA proposed response to the current BSE issue and the assistance needed from state feed and agriculture programs. THIS ISSUE MAY IMPACT ALL STATES AND ALL ANIMAL FEED AND PRODUCTION INDUSTRIES.
The 50 State call is scheduled for Tuesday, January 9, 2001 from1:00-2:00 pm EST. Any state agency responsible for animal feed issues wishing to participate should call 1-888-273-9887 and ask to be connected to the "50 State BSE Call". The conference host operator will explain how to participate, including asking questions during the call. If possible, please coordinate within your state to utilize only one phone line per state agency.
We request that you forward this message to your agency management and feed coordinators or other agencies or departments who may be responsible for any animal feed issues related to FDA regulated products.The agenda will be as follows:
1. Center For Veterinary Medicine (FDA) - Discussion of the problem related to BSE events in Europe and the impact on US feed ingredients for animals and feed operations. Discussion of the proposed actions/inspections/compliance of licensed and unlicensed feed mills, commercial feed manufacturers, animal feed imports, renderer's, protein blenders, on-farm mixers, and ruminant feeders.
2. Office of Regional Operations (FDA) - Discussion ofcontracting/working with states to inspect the universe of feedmills/industry for "Animal Proteins Prohibited from Use in Animal Feed". Discussion of working with FDA field offices.
3. Questions and answers.Richard H. Barnes, DirectorDivision of Federal-State Relations (HFC-150)5600 Fishers Lane Room 1207Rockville, Md. 20857ph: (301) 827-6906 FAX: (301) 443-2143Email: [log in to unmask]
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0101&L=sanet-mg&P=13410
Subject: BSE--U.S. 50 STATE CONFERENCE CALLJan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
I was lucky enough to sit in on this BSE conference call today and evenmanaged to ask a question. that is when the trouble started. I submitted aversion of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so.
"They tell me it is a closed meeting and theywill release whatever information they deem fit. Rather infuriating." and i would have been doing just fine, until i asked my question. ...
snip...end
http://lists.iatp.org/listarchive/archive.cfm?id=121143
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE MEETING
Thursday, June 2, 1999
CHAIRMAN BROWN: My name is Dr. Paul Brown.
Welcome to the FDA traveling road show. We are asked yet once more by the FDA to consider a question of theoretical risk in the absence of sufficient knowledge on which to base any firm conclusion. The issue before us today is that of excluding categories of American blood donors who have either visited or resided for longer periods of time in Great Britain. The issue is sufficiently delicate, as you see that we have been moved outside the Beltway. (Laughter.)
snip...
"Dr. Alan Williams is employed by the American Red Cross, Holland Labs, and is Scientific Adviser for the Florida Blood Services and Canadian Blood Services. In addition, he has financial interests in firms that could be affected by the general discussions."Dr. Richard Race has financial interests in firms that could be affectedby the general discussions and is a public health science researcher. "In the event that the discussions involve specific products or specific firms for which FDA participants have a financial interest, the participants are aware of the need to exclude themselves from such involvement. And their exclusion will be noted for the public record. A copy of the waivers is available by written request under the Freedom of Information Act. "With respect to all other meeting participants, we ask in the interest of fairness that they address any current or previous financial involvement with any firm whose product they may wish to comment upon." So ends the reading of the conflict of interest statement.
Dr. Brown, I turn the meeting over to you.
snip...
DR. JACOBS: Thank you, Dr. Brown, and welcome to members of the Committee. Today we are again bringing the question of deferral from blood donation of persons with possible foodborne exposure to bovine spongiform encephalopathy, BSE, as a precautionary measure to reduce the risk of blood transmission of new variant Creutzfeldt Jakob disease. And we are asking the Committee at this time, as we did in December, to consider this in the light of possible shortages.
Next, the current status. So far there have been no cases of either BSE or new variant CJD reported in the U.S. We're aware and we discussed in December the precautionary measures which have been taken in the U.K. First, they are not using U.K.? sourced plasma; and, secondly, they are implementing universal leukoreduction.
snip...
Next. In December, we asked the Committee to vote on two votes. I'm going to go through what those votes were. The first one is:
Should FDA recommend new deferral criteria for blood donors to attempt to reduce a theoretical risk for transmitting new variant Creutzfeldt Jakob disease be excluding donors potentially exposed to the agent of bovine spongiform encephalopathy?
The Committee voted nine yes and six no.
Next overhead. Should FDA recommend excluding donors who have resided in the United Kingdom or other BSE countries?
The Committee voted 15 yes,unanimous, to remove "or other BSE countries."
snip...
I want to just put on the record and mention the other votes which were taken in December.
Should FDA recommend withdrawal for blood componentsbased on these donor deferral criteria?
The vote was seven yes, five no.
And should FDA recommend withdrawal for plasma derivatives based on these donor deferral criteria?
Voted eleven no, one yes.
Next one, please. In addition to these questions on deferral of donors, in December we also asked the Committee to consider the actions that FDA would take if there were a report of a possible case of new variant CJD. We're going to refer those to CDC, but considering our precautionary withdrawal policy for new variant CJD, we asked:
Should FDA recommend precautionary quarantine or withdrawal for plasma derivatives to which a possible new variant CJD donor contributed pending confirmation of the clinical diagnosis?
The Committee voted eight yes, one no, one abstained, but they asked us to revisit this question of our operational definition of a possible new variant CJD case.
And in the second part of today's deliberations, after the vote on deferral, we will go back to that question. The Committee also voted that a tonsil biopsy negative for protease?
resistant prion would not be sufficient to make product withdrawals unnecessary.
snip...
We now have a presentation by Dr. Philip Comer, who will give us the DetNorsk Veritas risk assessment.
Dr. Comer? MR. COMER: Thank you very much, Chairman, and thank you for the opportunity to come and talk about the study that we were asked to do by the Department of Health in the United Kingdom as a result of a recommendation from the United Kingdom's Spongiform Encephalopathy Advisory Committee.
snip...
I am just going to go very quickly over the evidence for infectivity in blood. I think probably that will have already been looked at significantly by this Committee, but it was very much part of the background for what we were doing in the study that we did. If we look at blood transfusions, we know that all attempts to transmit infectivity of blood, blood transfusion, so across a species barrier, have failed and that within animal models, as far as I am aware, the one case which has been reported by Bob Rohwer is still the only case that I have heard of in which there has been a positive transmission by the i/v routewithin an animal model.
Epidemiology studies have shown that's from sporadic CJD. There is no evidence that there has been any transmission through the blood route. And when we look at blood from human CJD cases, primarily sporadic CJD cases and certainly no variant CJD cases, and look at that, their infectivity throughthe i/c route into animal models, there have been a few experiments which have shown positive infectivity into rodents but negative results from a significant number of studies into primates and other species. And there have been some questions asked about ?? these cases, these experiments all involve very small numbers of animals and some sort of significant questions asked about those and, in particular, the fact that it is a bit odd that we have got no positive infections in the primates, which you might have expected would be more susceptible than the rodents. Then when we look at actually within animal models themselves, there have been quite a number of cases, experiments where positive infections have been reported from animals infected with some form of TSE and have been through the i/c route infected in the same species, so again with no species barrier.
snip...
page 89
CHAIRMAN BROWN: A couple of points just to bring your experimental data upto speed.
Unpublished further experiments on the mouse model have produced good news and bad news. The bad news is that we have a disappointingly large number of transmissions following intravenous inoculation of either plasma or Buffycoat. We also have a transmission using whole blood as a transfusion into these mice. So that's not good news. The other thing that is not too good is that we have now got in this particular model a ratio of five to one, as opposed to ten to one, which was also disappointing. The only piece of good news in that in terms of experimental data is that we found that, again, in this model, the level of infectivity during the entire incubation period is almost negligible compared to the level of infectivity during the clinical phase of illness. And that is very goodnews indeed. So these are data that are not yet published but ??
snip...
page 105
CHAIRMAN BROWN: Right, right. And, as I say, if it turns out to be the case with the human disease, ?? and I'm guessing it probably will be ?? with you, I think the likelihood of disease, natural disease, whether it be scrapie in sheep, BSE in cattle, or CJD in humans, is going to be quite a lot less virulent than the experimentally induced disease. Even under the experimental conditions I mentioned, however, infectivity in all components of the blood during the incubation period is so low that it virtually poses I think no risk, at least in terms of plasma derivatives.
snip...
page 106
Dr. Chansnip...So the issue that we dealt with in early May was "do variants of CJD pose arisk to blood safety?"
And we sort of divided it into the classic variant and others. The others came out of, I'm sure you're all aware, of the scare that we all had over the Utah donor was this a possible chronic wasting disease, etc. So we just put that issue on the table and let's see where it went. Our process -- we circulated a notice widely to all associations, consumergroups. We've sort of got a mailing list that's growing.
snip...
page 129
And thirdly, the question was: What is the biological plausibility, from our experimental data, that there will be other variants of CJD?
I won't go into the attempts of answering these.
snip...
page 135
The rest of the recommendations I'll go through very briefly. Health Canada had not standardized its -- not finalized its policy on classic CJD, and we advised that they do so. The blood services should provide clear statements about the reasons for believing that there are no longer concerns regarding the classic sporadic CJD;
that Health Canada and the blood services provide communication regarding all aspects of product quarantine. And that was because there's considerable confusion over the Utah donor case. Health Canada identify and provide information that all products that contain trace amounts of blood products
-- this was interesting. Many of the physicians did not even know which products that were being distributed contained blood products. We thought this was an important issue. All products can be tracked in the event of an infected donor. And that they take steps to discourage manufacturers from using blood productsin the production or formulation of other products. That mechanisms are developed to ensure that
-- oh, this is the surveillance for CJD. That criteria have to be established to determine between classic and variant forms, which I know is the topic that you are going to be discussing this afternoon.
snip...
page 138
CHAIRMAN BROWN: This afternoon's program will begin with several presentations as a part of the open public hearing.
snip...
page 145
CAPTAIN RUTHERFORD: Good afternoon. The Department of Defense would like to thank you for allowing us to offer public comment. I am Captain Bruce D. Rutherford, Medical Service Corps, United StatesNavy, the present Director of the Armed Services Blood Program. On 5 February, 1999, Dr. Sue Bailey, the Assistant Secretary of Defense for Health Affairs, forwarded a letter to Vice Admiral David Satcher, Public Health Service, the Surgeon General of the United States. In that letter, Dr. Bailey expressed her opposition and the opposition of the Surgeon Generals of the Army, Navy and Air Force on deferring individuals as blood donors based on "perception" of a "possible" risk of transfusion transmission of the agent for "new variant" CJD. There has not been a single case, repeat, single case of transfusion transmitted new variant CJD or classical CJD reported in the world in more than 55 years since transfusion of blood products became widely accepted as a treatment regime. In November of 1991, the Department of Defense issued an advisory recommending that individuals participating in Operation Desert Storm be deferred as blood donors after a number of Desert Storm troops were identified with cutaneous and visceral Leishmania tropica. Knowing that Leishmania donavani was transfusion transmissible, and now knowing the extent of infection rate of the "at risk" population, the DOD decided to defer those individuals as blood donors who participated in country in the Persian Gulf. It was not until December of 1993, or two years later, that the DOD stopped asking leishmaniasis related questions of its blood donors. The cessation was due to a concentrated effort by the military health system in identifying an extremely small number of infected individuals and the follow-on screening questions' ability in identifying an extremely small number of donors with symptoms where leishmaniasis could have been a possibility. However, a study in the survivability and infectivity of viscerotropic Leishmania tropica in human blood donors from ODS participants was later shown to support our concern and was published in the American Journal of Tropical Medicine and Hygiene in 1993. Transfusion transmission by Leishmania species was a known, not theoretical. We know the calculatable risk of being injured in a car accident, yet millions of individuals a day drive their cars with hundreds of thousands being injured per year and tens of thousands killed each year. It is the same with airplanes, lightening and other activities. In theory, anything is possible. I remember back a few years ago when the Institutes of Medicine came out with this HIV report. Yes, hindsight was better, but that has always been true. I think in this case we have hindsight, 55 years of hindsight. We do not need to institute a UK deferral policy which will only lead to further crippling of our nation's blood supply and more product shortages.
snip...
page 148
CHAIRMAN BROWN: Thank you, Captain Rutherford. Are there any questions that any of the panel would wish to address to Captain Rutherford?
The next presentation will be by Kay R. Gregory of the American Association of Blood Banks. MS. GREGORY: Good afternoon.
snip...
page 148
In conclusion, AABB notes that there is no evidence that nvCJD is transmitted by blood transfusion. There are no cases of nvCJD in the UnitedStates. It is unknown whether travel to Great Britain correlates with exposure to or infection with the agent of BSE. And there is no evidence that any proposed criteria will decrease the theoretical risk of acquiring nvCJD from transfusion. In contrast, there is good evidence that even a one to two percent loss of donors due to new deferral criteria will have a significant impact on blood availability and, hence, on the safety of those transfusion recipients who cannot tolerate a delay in receiving blood products. The country should contemplate nvCJD deferral criteria only when it is apparent that such a policy would improve blood safety more than the loss of donors and the associated decrease in blood availability would compromise blood safety. Thank you.
CHAIRMAN BROWN: Thank you, Ms. Gregory. The word theoretical has been used many, many, many times this morning and will continue to be used, and it's being used correctly. I'd just point out that, for ten years, between 1985 and 1995, the risk of new variant CJD from BSE was also theoretical. The next speaker is Dave Cavenaugh from the Government Relations Committee of Ten Thousand.
MR. CAVENAUGH: I'm the government relations person at the Committee of Ten Thousand. The organization is the Committee of Ten Thousand.
CHAIRMAN BROWN: Yes, that's fine. Thank you.
MR. CAVENAUGH: Okay, COTT, which is the Committee of Ten Thousand, is gravely concerned about the industry logic favoring UK donors over additional U.S. replacement donors even with the survey, and even with the lack of data on paid and unpaid high volume pheresis donors. This morning's discussion showed a glaring omission in the analysis to date of the impact of excluding well paid, highly educated, non-incentiveprovided pheresis donors in addition to the larger, understood group of paid pheresis donors. We've heard quite a bit in terms of the studies and in terms of some of the questions about the likely blood borne nature of this never documented entity of prion and its ability to be transmitted by blood. There's a perceived link between new variant and beef that's been raised based on proximity, but the BSE classical CJD link should not be forgotten. It should be entertained at the minimum. Living in the United Kingdom in the late '80s seemed to be a major factor, for example. What was it about living there, that's proximity. Both statistic presenters showed clear risk of new variant in the blood, not even enlarging the scope to include classical CJD. There are no nv cases in the U.S., but plenty of classical -- arguably, much more than the one in one million rate alleged. Just ask CJD Voice, the patient-family support group which spoke before you 18 months ago. Small then, its numbers have mushroomed. Something is getting transmitted. Can it all be through beef? But most disturbing is the recent news confirming a second mutated form of prions also causing death in under a year. This doubling of the number of ways prions can be malformed with fatal results raises our concern levels considerably. The explanation that it is spontaneous sounds like an early catch all. With an entity so new, so unknown and so dangerous, the committee should be providing every protection possible, not bowing to arguments of relative risk. Thank you.
CHAIRMAN BROWN: Thank you.
snip...page 154
CHAIRMAN BROWN: Well, this is exactly why we're here today. Dr. Satcherand the other groups have already decided that this is not worth significant worry with respect to classical CJD, and that new variant was an unknown. And so that's why we're considering specifically new variant because we don't have information specifically on it. I mean, everything we don't have information on becomes a subject for this committee. (Laughter.)
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DR. LEITMAN: We seem to be extrapolating the partitioning data of classical CJD -- the agent of classical CJD to the agent of new variant CJD. That mayor may not be okay. I'd like to ask Dr. Prusiner if we can at all extrapolate the lack of transmissibility through blood components of classical CJD agent to new variant?
DR. PRUSINER: I don't know that I'm qualified to answer this. I can only tell you that the little bit of work that we've done now on new variant CJD says that it is a dramatically different strain of prion. That means that the confirmation of PRP scrapie is dramatically different than anything else we've studied. So let me give you an example. We've looked at 40 different cases of sporadic CJD, and we know that there's several different confirmations there at least. And all of these are transmissible in about 200 days to either mice that have a human PRP gene or have a chimeric mouse human PRP gene. If you look at new variant CJD, it takes more than 500 days and only about 60 percent of the animals get sick. Now, as I said before, if we take new variant CJD and we passage it into a mouse that expresses a bovine PRP geneon a null background, then all the mice are getting sick in 240 days. The piece of data I don't have that you want is you want to know if I take sporadic CJD or familial CJD cases and passage those into mice with a bovinePRP gene, do they get sick? And the answer is I don't know yet.
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page 218
MS. HARRELL: Well, I asked him the question, was there a deferral ?? was there deferral criteria for blood donors for classic CJD for people who have either resided or visited the UK.
CHAIRMAN BROWN: I'm sorry. Repeat that, the question.
MS. HARRELL: Is there a deferral policy for blood donors to attempt to reduce the risk of transmitting classic CJD for people who either resided or visited the UK?
DR. SCHONBERGER: The answer is no.
MS. HARRELL: And if there is no risk, if we think that there is no risk of transmitting the whatever to ?? for CJD, what makes this different, for new variant CJD much different?
CHAIRMAN BROWN: That's the first time, Stan, you'll ever hear of prion referred to as a whatever. (Laughter.)
CHAIRMAN BROWN: I mean, I've heard it referred to as a lot of different things. I'm ??
DR. PRUSINER: You've said that many times, Paul. (Laughter.)
CHAIRMAN BROWN: It may be that ??
DR. PRUSINER: Is that in the Congressional Record?
CHAIRMAN BROWN: The issue is not about sporadic CJD. That is the issue we can sort of generically say CJD. Presumably, if the blood from a patient with new variant CJD were infectious, the disease that it would transmit would be new variant CJD. So it's not ??
MS. HARRELL: Okay. So CJD is not transmitted through the blood is what you're saying?
CHAIRMAN BROWN: We have no evidence from looking at populations that that has ever happened. The question is: since we know it can happen when we use experimental models of CJD, we can take CJD blood from one animal and produce the disease in another animal. So there is the "theoretical possibility" that this might also happen in humans, particularly with a different strain of the disease, which new variant is, about which we don't know a whole lot. That's the question.
DR. SCHONBERGER: Isn't the answer to her question that the incidence of CJD, REDS, classic CJD, is not influenced by whether or not you've lived in the UK between 1980 and 1996 ??
CHAIRMAN BROWN: Yes.
DR. SCHONBERGER: ?? but the incidence of new variant CJD is?
CHAIRMAN BROWN: Yes, 40-love. (Laughter.)
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page 240
CHAIRMAN BROWN: I agree. We're starting to vote, and we'll start with Larry. Hold on. All right. The question is: should FDA recommend new deferral criteria for donors of transfusable components, to attempt to reduce the theoretical risk of transmitting new variant CJD from transfusions based on donor exposure to BSE in the UK?
DR. SCHONBERGER: Yes.
CHAIRMAN BROWN: Incidentally, just to remind the committee, it is possible to vote punt; that is to say, you can vote yes, no, or no vote ?? abstain.
DR. HUESTON: Well, for my own benefit, I suppose, to walk through the logic ?? and maybe for the benefit of Barbara because I think she raises a good point about how we proceed ?? we have a situation with a small number of known cases of variant Creutzfeldt Jakob, all but one of which are in the UK. However, we know there is a potential for widespread exposure to BSE that has already occurred. Therefore, we expect more cases, but we really don'thave a good idea of the magnitude of the epidemic that we're going to expect. Part number 2 says, "While there is no known whole blood or blood product transmission of classical CJD in humans, variant Creutzfeldt Jakob differs substantially from classical CJD." So we recognize that there is the potential for transmission of some of the transmissible spongiform encephalopathies via blood, albeit controversial We have an animal model, and we can identify infectivity in lymphoidtissues with variant Creutzfeldt Jakob, which is different from classical Creutzfeldt Jakob. At the same time, it has been pointed out many times by a number of peoplethat there have been no observed risk ?? or no observed cases at this point of transfusion or blood product related variant Creutzfeldt Jakob cases in the UK. I think that's a little premature. One might say the absence of evidence is not evidence of absence.???????????????
http://www.fda.gov/o
At the same time, there are look-backstudies in place in the UK, and there is a natural experiment ?? a huge natural experiment ongoing in the United Kingdom, where if, in fact, there is a risk, I believe that the risk will first be apparent in the United Kingdom far before we would see it anywhere else.
At the same time, in looking at the precautionary principle ??
CHAIRMAN BROWN: Is this the preamble for a vote?
DR. HUESTON: Yes, sir. You got it. (Laughter.)
DR. HUESTON: If our goal is to be precautionary, but at the same time we have to preclude having more negative impacts for any action that we take,then positive ?? in other words, impacts on the blood supply. And I have struggled through the whole time, but I'm going to vote no at this time.
CHAIRMAN BROWN: Could I urge the remaining members of the committee ?? (Laughter.)
CHAIRMAN BROWN: ?? to vote rather than ?? I appreciate it, and I let Will, you know, chatter on because he hasn't said a whole lot, and I wanted to hear what he had to say. And so thank you, but we'll never get through if we continue to explain the reasons for our votes, each one and all. So,Susan?
DR. LEITMAN: I take the opportunity to disagree with what you just said. I think the vote at this table is so critical, it will have such a huge impact potentially on the way America collects its blood, that if we go beyond our designated time it's worth it. And I was influenced, and it was helpful to hear the last speaker'sdiscussion. So I think if any of us have discussions or points to mention now, they might be valuable. The deliberations of this committee are among the most difficult of any advisory committee I've ever been on because there are simply inadequate data upon which to base a decision. For myself, in the absence of data suggesting or, rather, documenting risk, I cannot vote yes based on assumptions, perceptions, possibilities, uncertainties, theoretical risks, and potential risks.
On the other hand, there are tangible measurable data that deferral of any percentage of donors, whether it's half, one and a half, two percent, will lead to replacement by donors by a small proportion of donors that are at increased risk for measurable diseases such as hepatitis B and C. So I vote no.
CHAIRMAN BROWN: Dr. Leitman votes no. Dr. Prusiner?
DR. PRUSINER: I would like to vote yes, and I would like to say I have 23 points that I want to go through. (Laughter.)
DR. PRUSINER: I only want to say very quickly that I don't think that economics and the availability of donors is a reason to vote yes or no in this. I think that the economy has a way of solving these problems, and I think that will happen. I think the real problem here lies that we have avery imperfect data set, and we're dealing with a disease which is universally fatal. This is really the problem that we face.
CHAIRMAN BROWN: Dr. Prusiner votes yes. Dr. Roos?
DR. ROOS: I think we're dealing with a situation in which we have no evidence of any transfusion that has transmitted either classical or new variant Creutzfeldt. And we have a situation where there are risks involved with blood transfusions that the donors accept at this point. That is, we were informed about ?? I guess about 14 percent of individuals do donate blood that have I guess the recipients. About 14 percent of individuals that donate blood have some risky behavior. And maybe I might include living in UK part of that risky behavior. And so I kind of accept this as, at the moment, acceptable risk for donated blood and I am awaiting evidence to prove that there is more danger involved. So I'm voting no here.
CHAIRMAN BROWN: Dr. Roos votes no. Dr. Belay?
DR. BELAY: I'm concerned about two issues. The first one is the studies that showed the presence of the new variant CJD agent in lymphoreticular tissues. And the second concern I have is the absence of evidence against blood-borne transmission of new variant CJD. The kind of data that's available for classic CJD is not available for new variant CJD, so I vote yes.
CHAIRMAN BROWN: Dr. Belay votes yes. Dr. Lurie?
DR. LURIE: Really, what we're doing is balancing one risk against two others. The two risks are the problem of the replacement donor, which is not zero but it is probably very small, given that we're only talking about one, two perhaps, percent replacement of donors here, depending on what happens in B if we get that far. The second has to do with the diminution in the blood supply itself. And,again, there are scenarios available to us under B that allow us to minimize that. So we really have, on the one hand, two small risks that can more or less be quantified, and on the other hand we have another risk, which may itself be small, but if we are wrong could be very, very large. And that'sreally the benefit ?? the risk benefit calculation that we're making. For me, there remain too many uncertainties, and so I vote yes.
CHAIRMAN BROWN: Dr. Lurie votes yes. Dr. Hoel?
DR. HOEL: Yes. I'm changing my vote from last time, and I'm going to vote yes, mainly because of what I see in the epidemiology data of the cases in England and the modeling work. I think this needs to be monitored further to see how it comes in because the risks could be quite large, and so I would vote yes.
CHAIRMAN BROWN: Dr. Hoel votes yes. Dr. Bolton?
DR. BOLTON: I believe that there is insufficient documentation of the risk at this time. And in light of that, I can't ?? I don't think that the information warrants changing the current policy. I vote no.
CHAIRMAN BROWN: Dr. Bolton votes no. Dr. Nelson?
DR. NELSON: Well, this is a pretty difficult vote. Last time I voted no, and I'm going to vote no again, although I am ?? really, it's disturbing that there is no really good data at this point. And I am impressed with a comment that was made earlier, and that is that there is an experiment in the UK of many people who have been exposed to UKdonors over a period of many years. And I am some what reassured that there have been no cases, and I'm also reassured with the quality of the epidemiologic surveillance and data from the UK. I think that that has been well done, carefully done, and presumably it will continue to be closely monitored. You know, if a single case had occurred, we would really need to change our policy immediately. That's number one. But the other problem I have is if I voted yes, then I would have to make a decision on 1B. And the only ?? (Laughter.)
DR. NELSON: ?? the only reasonable decision on 1B would be to remove ?? to exclude all donors who had lived in the UK. I see no basis for any arbitrary decision. Once you go down that route, then you have to exclude anybody from the UK or who visited the UK or Ireland during this period. I don't see any alternative.
CHAIRMAN BROWN: Dr. Nelson votes no. Dr. McCullough?
DR. McCULLOUGH: I agree with Susan. This is one of the most difficult groups I have had to deal with. I'm impressed by the epidemiologic data.I'm also impressed by having sat through in 1983 and 1984 discussions of there ain't been a case reported yet, and also that we are concerned about the impact on the blood supply
.hrms/dockets/ac/99/transcpt/3518t1.rtf???????????TRANSMISSIBLE SPONGIFORMENCEPHALOPATHIES ADVIS
And possibly also, I'm influenced by having been the fodder for congressional hearings and 60-minute expose on things that might have been done differently at some of those times. So I'm going to vote yes. I have tremendous confidence in the blood systems of this country that they will be able to ?? not easily ?? respond if changes are made.
CHAIRMAN BROWN: Dr. McCullough votes yes. Dr. Brown votes yes. Dr.Ewenstein?
DR. EWENSTEIN: Yes. I'm impressed by the modeling data. I believe that we have biologic data as well as at least the potential epidemiology coming out of England to suggest that this is a new disease and on that basis should be handled with a lot more caution, because we don't have the comfort that we have with the long-standing classical CJD. And so I'm going to vote yes.
CHAIRMAN BROWN: Dr. Ewenstein votes yes. Dr. Detwiler?
ORY COMMITTEE MEETING Thursday, June 3,1999???????http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t2.rtf
DR.DETWILER: I'm going to vote yes, because with these diseases, a long incubation and the lack of a pre-clinical screening test, that the day you find out there is transmission you're already years too late, and you can't easily clean up the problem. And I think they found out that even with the human transmission because that was based on there is no theoretical ?? or it's only a theoretical risk until 1996.
CHAIRMAN BROWN: Dr. Detwiler votes yes. Dr. Piccardo?
DR. PICCARDO: I would vote yes because all of the data from classical CJD cannot be extrapolated into the new variant.
CHAIRMAN BROWN: Dr. Piccardo votes yes. Dr. Williams?
DR. WILLIAMS: I'm going to vote no. I think that this is truly a balancing act, and it's a trade off between a known problem, I believe related to the blood supply, and the problems that may follow from a reduced supply and the perception of a risk of new variant CJD. And I completely agree that an experiment is going on right now. Those data are going to come in, and, obviously, there is going to be close attention paid to those data, and that surely this committee and FDA will respond should information indicate that we need to take another look at the issue.
CHAIRMAN BROWN: Dr. Williams votes no. Dr. Hollinger?
DR. HOLLINGER: I'm voting no also, for the same reasons that have been addressed. I think there is ?? by doing something now doesn't mean that everything is going to be turned around and you don't have to worry about it, if you do have a long incubation situation and one can wait to see if there is some risk down the line, and I think we do have those things going on ?? natural and experimental ?? in England. So I'm voting no.
CHAIRMAN BROWN: Dr. Hollinger votes no. Ms. Harrell??????????????P04.49??????????Case Report of V MS. HARRELL: Okay. Sitting next to my ex-learned colleague ?? (Laughter.)
MS. HARRELL: Okay. I'm voting to be prudent, and I think that this will buy us time to get the data in and have it analyzed from the UK. But right now, we don't have time, and so I vote yes.
CHAIRMAN BROWN: Ms. Harrell votes yes. Dr. Cliver?
DR. CLIVER: No. CHAIRMAN BROWN: Dr. Cliver votes no. Dr. Burke?
DR. BURKE: This is a balancing act, and I can ?? there are measurable negatives here. In the face of a theoretical, I vote no.
CHAIRMAN BROWN: Dr. Burke votes no. Dr. Tramont?
DR. TRAMONT: I vote yes.
CHAIRMAN BROWN: Dr. Tramont votes yes. Twelve yes. Nine no. Well, at the least, Dr. Epstein can come away from the day with the understanding that he has not been given a mandate. (Laughter.)
DR. FREAS: Can I just make a comment? I did verify the count. There are 21 voting people at the table. Dr. Roos is a non-voting participant. And the total does add up to 21. Excuse me. I apologize. Dr. Rohwer is ??
CHAIRMAN BROWN: I don't have to ask Bob what he would have voted, had he been allowed to vote. (Laughter.)
CHAIRMAN BROWN: But I will if you'd like to put it on the record. This is simply a question to Bob, since he's at the table. Were his vote to be counted, what would it have been?
DR. ROHWER: I'll use this soapbox opportunity.
CHAIRMAN BROWN: Uh-oh. (Laughter.)
DR. ROHWER: I am very concerned that we may be facing the grave possibility of an epidemic of new variant CJD, an epidemic that, if it occurs, could be made much worse through the mechanism of interspecies transmission, such as would occur through blood products. But I recognize the real risks of insufficient supply. However, I am impressed by Dr. Donnelly's warning that if the feed ban in the case of BSE had been delayed just one year, the epidemic would have been vastly worse than it was. And, therefore, I feel we should take what everopportunities for implementing mitigating measures that we can that do not simultaneously jeopardize the supply unduly. So I recognize that what we have ?? the opportunity we have here is very,very imperfect, but I feel like it is possible to do something, and we should do it.
CHAIRMAN BROWN: Jay, you wanted a recount, or just a reexpression?
DR. EPSTEIN: Just a reexpression.
CHAIRMAN BROWN: Okay. The vote on question 1A is 12 votes yes, nine votes no.
Therefore, the committee is obliged now to consider what deferral criteria might be recommended. And presumably, based on the evidence, the only deferral criteria that are offered us that make any sense are duration of residence in the UK.
snip...258
Dr. Scott
skip
In addition, we do know, as Dr. Prusiner has pointed out several times, that the new variant agent is biologically different from the classical CJD agent, so we can't necessarily extrapolate all of the information that we have on classical CJD to new variant. For example, he talked about the differences in the protein and its behavior, and we also know that there is enhanced expression of the new variant agent in lymphoid tissues compared with CJD. And we don't know much about its virulence or infectivity compared with the classical CJD. And, of course, we haven't had time to get or enough patients or subjects or transfused people to get the kind of epidemiologic data that we have which tells us that transmission of classical CJD by blood or blood products at worst is rare and may not occur. So, currently, the diagnosis of new variant CJD is based upon neuropathology, and these are the three most characteristic features ?? numerous wide spread kuru type amyloid plaques, which obviously can occur in a few other kinds of CJD but are quite common in new variant CJD; spongiform change, which is predominant in certain areas of the brain; and a high density prion protein accumulation, especially the cerebrum and the cerebellum by immunohistochemistry, and tonsillar biopsy may ultimately play a role in this diagnosis as well as analysis of prion glycoforms. Current age, if alive, or age at death, less than 55. Since the typical age of a new variant patient is about late 20s, and the typical age of a classical CJD patient is about 65, this is one criteria that is useful. And new variant patients tend to have persistent painful sensory symptoms early in presentation and/or psychiatric symptoms. I can go into this further if people want to know about it. But there were a couple of articles published in the Lancet from the CJD surveillance unit in September 1997, which goes into this in great detail. In addition, the patient must have dementia and a delayed development of neurologic symptoms, particularly movement disorders, about a four-month delay. And, again, this is somewhat different from classical CJD in its course. They may have a normal or abnormal EEG, but not the diagnostic EEG, which is a pseudo periodic sharp wave that's often seen in classical CJD. The duration of illness should be greater than six months. Again, this is in marked distinction to most cases of classical CJD which average four to four and a half months of duration. Whereas, the new variant case typically is around 14 months duration, although there is a spread. In addition, routine investigations will not suggest an alternate diagnosis. And this is a criteria, really, for the U.S. There should be history of possible exposure to BSE; that is, consumption of local beef products as resident or traveler to a BSE-affected country. And there is only two more. No history of iatrogenic exposures that are related to development of classical CJD, and, finally, of course, such a patient, if they had a prion protein gene mutation, it was associated with familiar CJD. That would not fall under ?? that would not be a patient that we would worry about new variant CJD in.
2012
Wednesday, August 01, 2012
Behavioural and Psychiatric Features of the Human Prion Diseases: Experience in 368 Prospectively Studied Patients
http://creutzfeldt-jakob-disease.blogspot.com/2012/08/behavioural-and-psychiatric-features-of.html
TSS
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DR. ROOS: Thanks, Dr. Scott. So we're not asked to take a vote, but just to discuss these issues. Yes?
DR. NELSON: I'm concerned a little bit about the explanation for the age criteria, and I can see that this is very useful because the one thing you do know, when somebody gets sick, you can estimate what their age is. And so that's an easy ?? you know, an easy early marker for a possible case that's not classical. And I assume that probably the reason for the classical CJD patients being much older is that the incubation period is so long that they probably had an exposure much longer. But as this epidemic ?? or as the ?? if it's exposure to the BSE agent from the epidemic, it seems like over time this age criteria will probably change, and that the under 55 may no longer be a useful criteria 10 years from now or 40 years from now. And I just wonder if Larry or anybody could comment on that.
DR. SCHONBERGER: We definitely agree, and it underscores the evolving nature of these diagnoses. All I can say is the age is an excellent and easy criteria for us to use now. All cases, as you know, in the world of new variant CJD have been under age 55. In fact, I think the oldest was ?? I think the median age is like 29 or so, 28 at onset and 29 at death. So that's why that particular criteria came into existence. However, obviously, if the epidemic should change and we should start seeing older cases, then, obviously, we would have to change. There is some semantic problems. We actually investigate every case under 55. So, in a sense, all cases under 55 in the United States could be regarded as under investigation or possible. We have not used the word "probable," in part because that's the word they use in the United Kingdom, and they count those cases as amongst the cases of new variant CJD that we count. The 40 cases in the UK, I think, includes one, is it? One probable? That was a case in a teenager whose brain tissue was unavailable for study. And they indicate that it's too early in the epidemic. Their experience is too small for them to be absolutely sure about that, but they're willing to ?? at this point to call it a case. And I've been told that with these new MRI criteria, and so on, that maybe we'll be able to call cases without necessarily having the tissue, depending on what they find the specificity and sensitivity of those to be. So all cases essentially under 55 right now are under investigation. Plus, we have established amongst pathologists the concept that any case that has the pathology of new variant CJD, regardless of age, or even regardless of whether they've diagnosed it as CJD, should be reported. And those two would count as new variant even though they are not under 55.
DR. ROOS: Just a quick question, Larry. What is your time frame of reporting, or what is the goal here? Obviously, with respect to these new guidelines, you want to identify these cases fairly quickly and make some disposition as far as blood products.
DR. SCHONBERGER: Precisely because we are looking at all cases under 55, I was encouraging FDA to encourage the blood establishments ?? or the first to identify these cases at least, and that has been the history ?? to reportto us any case of CJD under 55. Once we get that report, it may be very easy for us and very quickly making it ?? to very quickly make a determination that we're dealing with, say, a dura mater case or a human growth hormone case. But then, another part of FDA will probably become interested in that. So we think it's worth the blood establishments reporting all of their cases in donors. There just are not that many CJD cases that are going to occur among donors that the blood establishment is going to be able to identify that quickly. But if they do, we want it reported right away.
DR. ROOS: Just a quick question. So, I mean, how about if this patient donates to some large blood pool or has donated whole blood? It doesn't go back to the blood establishment. It goes to a neurologist, gets diagnosed,etcetera. What's the time frame then?
DR. SCHONBERGER: Well, frequently, our experience with the withdrawals ?? and I'll use the Utah case as an example as that came out ?? we handled that very, very rapidly. But even handling it very, very rapidly, you'll find that huge, huge numbers of recipients were exposed to this donor's bloodproducts. So the withdrawal program is relatively inefficient, compared to what we just did, which was to get deferral criteria. And I think that's why it was important to try to be preemptive in a sense and have the deferral criteria up front. The withdrawal procedure, even when you do it very quickly as in the Utah case, I would not encourage people to depend on that for considerable safety. What we will do is we will modify and ameliorate the situation.But it certainly won't eliminate even the majority of the risk.
DR. ROOS: I just think it might be good to publicize these new policies widely to the neurological community, so that they alert you, Larry, or the FDA quickly. The Utah case, in fact, was kind of a very aberrant case. It could be that there are other cases that get less sophisticated care. And if you really want to identify things in a timely manner, you obviously have to publicize the program and new policies to the neurological community.
DR. SCHONBERGER: Well, let me clarify that the primary group doing the surveillance on this are blood establishments. And if this group wants to recommend that blood establishments, you know, provide blood donors withcards or something that would, you know, speed up any type of reporting, that's possible. The surveillance that CDC is conducting is not designed for that type of rapid turn around or rapid identification in reporting. That's another weakness of the system and relying on this withdrawal system for tremendous protection of the population.
DR. ROOS: Peter?
DR. LURIE: My question/concern is whether or not requiring all nine of these criteria is too restrictive a set of criterion. I guess the data question that I have is: of the 30-odd new variant CJD cases in Britain, how many of them have met all nine of these criteria?
DR. SCOTT: Well, could I also respond to that question?
DR. LURIE: Yes, please do.
DR. SCOTT; I don't know the answer to how many have had all nine of those criteria, but most. However, the CJD surveillance unit has somewhat altered their criteria with time such that the current organization is similar to this but not the same. And most critically, they have gotten rid of the age criteria and added an MRI criteria. But this is not yet published material,and it's very recent. We just got that information on May 31st. And I think the other thing to mention is that we weren't considering only using all nine criteria. But, really, that's the purpose of the third way,if I can say it, which is to have a very low threshold for identifying even potential cases and then to make a rapid decision on a case-by-case basis. But what we're anticipating is probably what you're thinking, that not all of those criteria are going to be met, just due to a lack of information, time hasn't passed, we don't have material to analyze. And so I think whatwe're anticipating is that we would be ?? we would err on the side ofcaution unless investigation showed us that it was most unlikely that this was a new variant case.
snip...page 292
DR. HUESTON: You don't know to what you've been exposed. So it's ?? the second thing is it draws ?? I think it gives a false sense of security and directs, potentially, attention to the wrong products, because the average person thinks of beef as primal cuts of beef. And that's, at this point,the least likely of the sources of exposure, given meat products. The third comment is that I personally am very concerned about the proposed ?? this criteria of possible new variant CJD by FDA. And I have two major reasons for that. The first is that I see the potential for conflict arising between FDA and CDC, where FDA is stepping forward or making a pronouncement of possible new variant CJD, and at the same time CDCsays, "We're still investigating; you know, it's premature." And I think that puts the FDA in a very awkward position, and I think an inappropriate ?? Larry is telling me that they are investigating 25 ??
DR. SCHONBERGER: There's about 25 cases under 55 a year.
DR. HUESTON: So my fear ?? here is my fear based on my experience. Item number 2 says, "Donor has physician's clinical or pathologic diagnosis of CJD."
DR. SCHONBERGER: They're not all donors, by the way. Very few of them are donors. Okay?
DR. HUESTON: Okay. Fair enough. But once you get a terminology like this established, my concern is that it's going to spread further, that people are going to say, "Well, the FDA would have called this a possible case." Number 2 says, "Has a physician's clinical or pathologic diagnosis," it doesn't say anything about the physician. And no offense to my distinguished colleagues, but there are a number of physicians that are simply not in the position to make a clinical diagnosis or a pathologic diagnosis of Creutzfeldt Jakob. That has not precluded some of these same physicians from making a proclamation. Third, I think that the public health and the risk communication implications of this are potentially massive. And having been on the firing?? you know, on the other end of trying to deal with these, you know, the press grabbing hold of a case and blowing it totally out of proportion and creating a great deal of concern, I don't see why you need another term. I think you coordinate with the CDC, you coordinate your investigation when it comes back from a blood collection center that you have a donor less than 55 years of age, where you have some suspicion of Creutzfeldt JakobDisease. You go through the same CDC workup, and you base ?? on a case-by-case basis, you base your decision on that coordination with CDC.
snip...page 296
see full text and all voting results
http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t1.rtf
TSEAC MEETING JUNE 3 1999
http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t2.rtf
PLEASE NOTE IN USA CJD UPDATE AS AT JUNE 2007, please note steady increase in ''TYPE UNKNOWN''. ...TSS
1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17 inconclusive and 9 pending (1 from 2006, 8from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007)
http://www.cjdsurveillance.com/pdf/case-table.pdf
USA NVCJD BLOOD RECALLS ONLY ;
http://www.google.com/search?hl=en&q=CJD+BLOOD+RECALLS+TSS&btnG=Search
vCJD case study highlights blood transfusion risk
http://vcjdblood.blogspot.com/
CREUTZFELDT JAKOB DISEASE MAD COW BASE, CWD, SCRAPIE UPDATE OCT 2007
http://cjdmadcowbaseoct2007.blogspot.com/
NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007
Tuesday, October 9, 2007
NOR-98 SCRAPIE UPDATE AUGUST 31, 2007 RISES TO 5 DOCUMENTED CASES
http://nor-98.blogspot.com/
CREUTZFELDT JAKOB DISEASE MAD COW h-BASE UPDATE USA
http://cjdmadcowbaseoct2007.blogspot.com/
ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007
Date: Mon, 24 Sep 2007 21:31:55 -0500
I suggest that you all read the data out about h-BASE and sporadic CJD, GSS, blood, and some of the other abstracts from the PRION2007. ...
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&F=&S=&P=19744
*** PLEASE READ AND UNDERSTAND THE RAMIFICATIONS OF THIS !!! THE PRICE OF POKER INDEED GOES UP. ...TSSUSA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
From: "Terry S. Singeltary Sr."Subject: CWD UPDATE 88 AUGUST 31, 2007
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450Date:
Wed, 29 Aug 2007 21:13:08 -0500From: "Terry S. Singeltary Sr."Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again)
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=26079
Monitoring the Potential Transmission of Chronic Wasting Disease to HumansUsing a Hunter Registry Database in Wyoming (405 lines)
From: Terry S. Singeltary Sr. <[log in to unmask]>
Date: Thu, 30 Aug 2007 21:23:42 -0500
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654
Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strainDate: August 25, 2007 at 12:42 pm PST
Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strain
Date: August 25, 2007 at 12:42 pm PSTJ Biol Chem. 2007 Aug 20; : 17709374
Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates anew prion strain.
[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , TetsuyukiKitamoto
The genotype (methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform of PrP (PrP(Sc)) are major determinants of the clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that transmission of sCJD prions from a patient with valine homozygosity (129V/V)and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP with methionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate in size between type 1 and type 2. The intermediate type PrP(Sc) was seen in all examined dura mater graft-associated CJD cases with 129M/M and plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility and neuropathology, and the identical type of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or129V/V. These findings suggest that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions.
snip...
In this study, the strain-dependent traits of sCJDMM1 prions were inherited through cross-sequence transmission without any modification. The humanized mice with 129V/V produced type 1 PrPres after inoculation with sCJD-MM1 prions. Becauses CJD-VV1 cases are extremely rare (at most 1-2%of the total number of sCJD cases) and characterized by early onset (mean age at onset: 39.3 years)(5),
####################################
our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals,e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions.
###################################
In conclusion, cross-sequence transmission of sCJD-VV2 prions generates a new prion strain with altered conformational properties and disease phenotypes as p-dCJD prions. Furthermore, the newly generated prions have unique transmissibility including the traceback phenomenon. In the future, if atypical prion strains emerge through cross-sequence transmission, especially from animals, traceback studies will enable us to identify the origin of the prions.
REFERENCES...snip...end
FULL TEXT ;
http://www.jbc.org/cgi/content/abstract/M704597200v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Cross-sequence+transmission+of+sporadic+Creutzfeldt-Jakob+disease+creates+a+new+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIThttp://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267
Re: Colorado Surveillance Program for Chronic Wasting DiseaseTransmission to Humans (TWO SUSPECT CASES)
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165
Subject: MAD COW BASE H-TYPE AND L-TYPEDate: August 23, 2007 at 11:30 am PST
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779Re:
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakobdisease in the United States
Email Terry S. Singeltary:flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue toexpect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs inthe USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, thereshould be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
LANCET INFECTIOUS DISEASE JOURNALVolume 3, Number 8 01 August 2003Newsdesk
http://infection.thelancet.com/journal/journal.isa
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=jamaBRITISH
MEDICAL JOURNALSOMETHING TO CHEW ON BMJ
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
BMJ
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
P04.49
Case Report of Variant Creutzfeldt-Jakob Disease in a Macaque after Blood Transfusion
Lescoutra-Etchegaray, N1; Ruchoux, MM1; Correia, E1; Jolit, A1; Freire, S1;Lasmezas,CI2; Deslys, JP1; Comoy, E1 1CEA/DSV/IMETI/SEPIA, France; 2Scripps Florida,USA
A fourth human case of probable transmission of vCJD through transfusion has now been reported but a number of features affecting transfusion-related infection remain imprecise, including infectious dose, length of incubation period and critical infectious window of blood donors.We report here the first case of experimental transmission of vCJD in primates by blood transfusion. Experimental infection of Cynomolgus macaque has been demonstrated to be a sensitive model for the investigation of human prion diseases,inducing similar distribution of infectivity in peripheral lymphoid tissues and equivalent brain pathology. In our study, transfusion was performed with 40 ml of whole blood drawn from a vCJD-infected macaque at the terminal stage of the disease.Clinical symptoms of vCJD appeared in the recipient animal after five years of incubation. The total amount of infectivity in the transfused blood was approximately 106 fold lower than in the brain (titration still in progress). In several animals infected intravenously with brain homogenate, the presence of PrPres in serial lymph nodes biopsies and in other organs at autopsy was examined and results will be presented.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
P04.51
Atypical Presentation of Variant Creutzfeldt-Jakob Disease in a 73 Year Old Blood Transfusion Recipient
Wroe, S1; Pal, S1; Webb, T1; Alner, K2; Hewitt, P3; Brander, S4; Wadsworth,JD5; Collinge, J1 1National Hospital for Neurology and Neurosurgery,National Prion Clinic,UK; 2National Hospital for Neurology and Neurosurgery, Department ofNeuropsychology, UK;3Health Protection Agency, UK; 4National Hospital for Neurology andNeurosurgery,Department of Neuropathology, UK; 5Institute of Neurology, UCL, UK
We report atypical presentation of variant Creutzfeldt-Jakob Disease (vCJD) identifiedante-mortem in a 73 year-old recipient of blood products. This patient was transfused following orthopaedic surgery in December 1997. Tracing of blood products identified a single unit of non-leucodepleted red cells from an individual who developed neuropathologically confirmed vCJD eleven months after donation. Nine years post transfusion, this individual was referred to the National Prion Clinic for specialist investigation. Six years post transfusion the recipient complained of fluctuating fatigueand impaired concentration. At this time neurological examination and MRI brain(T1/T2 weighted/DWI) were normal. Progressive symptoms emerged six months later with imbalance and deteriorating cognition. Examination two months after onset of neurological symptoms demonstrated cognitive deficits, dyspraxia orvisuospatial dysfunction and normal motor, sensory and gait examination. Six weeks later cognitive impairment was identified alongside tremulousness, impaired manual dexterity and limb ataxia. Serological investigations were normal. MRI (T1/T2weighted/FLAIR/DWI)demonstrated prominent signal change throughout the dorsal thalamus, consistent with vCJD. PRNP genotyping revealed no mutations and homozygosity formethionineat codon 129. The prolonged incubation period of vCJD and possibility of asymptomatic carrier states pose major public health concerns. This case highlightsthe significant risk encountered by recipients of contaminated blood products and the necessity for their specialist monitoring.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
P04.36
Enhanced Surveillance of Persons Identified as at Increased Risk of CJD Due to Blood Transfusion or Healthcare Procedures
Brookes, D1; Chow, Y1; Ward, HJT2; Will, RG2; Hewitt, P3; Gill, ON11HPA, CJD, UK; 2National CJD Surveillance Unit, UK; 3Colindale, NHS Bloodand Tissue, UK
Introduction:Reports of four iatrogenic transmissions of variant-CJD (vCJD) infectionin the UK (all due to transfusion of blood from donors who later developed vCJD), evidence from iatrogenic transmissions of sporadic CJD and experimental work on CJD infectivity in tissues and on healthcare instruments have given rise to concern about the risks of iatrogenic transmission of CJD. This risk warrants a) certain publichealth precautions, and b) follow-up of individuals with identified risks in order to gain evidence about their risks and ensure appropriate management of these risks. Evidence of transmission via iatrogenic routes is important to inform public health measures and so prevent ongoing transmission of CJD.
Methods: The Health Protection Agency and Health Protection Scotland holds details of persons identified as ‘at-risk’ of vCJD due to blood transfusion and of persons identified as ‘at-risk’ of CJD (of any type) from other healthcare procedures. The GPs/clinicians of all persons identified as ‘at-risk’ for public health purposes are provided with: information; risk assessment updates; advice on public health precautions and advice on referral to specialist care. Procedures are being established to obtain enhanced surveillance data on these individuals, including:clinical status updates, date and cause of death, surplus tissue and blood specimens, and postmortem investigations.
Results: Persons ‘at-risk’ of CJD have experienced a range of exposures. Estimated risks are uncertain and overlapping. Some individuals - recipients of vCJD implicated blood components - are considered to be at a clearly higher risk of infection: active follow-up is currently conducted for these individuals. In time, the enhanced surveillance of persons at increased risk of CJD will provide estimates of transmission risks and of the impact of iatrogenic exposures on mortality.
Conclusion: Knowledge about iatrogenic transmission of CJD is being gainedby the follow-up of individuals who have been identified as ‘at-risk’ of CJD in theUK. This enhanced surveillance may need to be sustained for many years.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Prions in Plasma of Patients with Sporadic Creutzfeldt-Jakob Disease
Safar, J.G1,3, Geschwindm M.D2,3, Letessier, F1,Kuo, A1, Pomeroy, K1, Deering, C1, Serban, A1,Groth, D1, Miller, B.L2,3, DeArmond, S.J1,4,Prusiner, S.B1,3,51Institute for Neurodegenerative Diseases,2Memory and Aging Center, Departments of3Neurology, 4Pathology, and 5Biochemistryand Biophysics, University of California,San Francisco, California 94143
http://www.prion2007.com/pdf/Prion%20Friday.pdfhttp://www.prion2007.com/pdf/Prion%20Thursday.pdfhttp://www.prion2007.com/pdf/Prion%20Wednesday.pdf
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
UPDATE 2012
Wednesday, June 27, 2012
First US BSE Case Since 2006 Underscores Need for Vigilance
Neurology Today 21 June 2012
http://transmissiblespongiformencephalopathy.blogspot.com/2012/06/first-us-bse-case-since-2006.html
Tuesday, July 31, 2012
11 patients may have been exposed to fatal disease Creutzfeldt-Jakob Disease CJD Greenville Memorial Hospital
http://creutzfeldt-jakob-disease.blogspot.com/2012/07/11-patients-may-have-been-exposed-to.html
Monday, August 13, 2012
Summary results of the second national survey of abnormal prion prevalence in archived appendix specimens August 2012
http://creutzfeldt-jakob-disease.blogspot.com/2012/08/summary-results-of-second-national.html
1 in 2,000 is huge. considering this study was only looking at the appendix, was only using immunohistochemistry, this study tells little, and may even be giving false hope. in my opinion, everyone in the U.K., back in the worse days of the mad cow epidemic, that consumed beef, would have had to have been exposed to BSE, how many there from that are sub-clinical, that is another question, one this study does not answer in full.
Thursday, August 16, 2012
Blood products, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease ( vCJD) USA JUNE, JULY, AUGUST 2012
http://vcjdtransfusion.blogspot.com/2012/08/blood-products-collected-from-donor-who.html
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Proposal ID: 29403
http://betaamyloidcjd.blogspot.com/2012/05/alzheimers-disease-and-transmissible.html
TSS
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