Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain

J. Virol. doi:10.1128/JVI.02561-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain

Qingzhong Kong*, Mengjie Zheng, Cristina Casalone, Liuting Qing, Shenghai Huang, Bikram Chakraborty, Ping Wang, Fusong Chen, Ignazio Cali, Cristiano Corona, Francesca Martucci, Barbara Iulini, Pierluigi Acutis, Lan Wang, Jingjing Liang, Meiling Wang, Xinyi Li, Salvatore Monaco, Gianluigi Zanusso, Wen-Quan Zou, Maria Caramelli, and Pierluigi Gambetti*
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; CEA, Istituto Zooprofilattico Sperimentale, 10154 Torino, Italy; Department of Neurological and Visual Sciences, University of Verona, 37134 Verona, Italy



* To whom correspondence should be addressed. Email: qxk2@case.edu. pxg13@case.edu.


Abstract


Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to have only one strain (BSE-C). BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, BASE (or BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE-affected cattle. Sixty percent of the inoculated Tg mice became infected after 20-22 months incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE-infected Tg mice, but none of the Tg mice infected with a sporadic human prion disease, showed presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE-infected humanized Tg mouse brains are different from those of the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation time are observed in the BASE-infected Tg mice. These results suggest that, in humans, BASE is a more virulent BSE strain and likely lymphotropic.


http://jvi.asm.org/cgi/content/abstract/JVI.02561-07v1?papetoc


Thursday, January 31, 2008

SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 99th
meeting held on 14th December 2007


snip...


snip...


ITEM 8 – PUBLIC QUESTION AND ANSWER SESSION


40. The Chair explained that the purpose of the question and answer
session was to give members of the public an opportunity to ask
questions related to the work of SEAC. Mr Terry Singeltary
(Texas, USA) had submitted a question prior to the meeting,
asking: “With the Nor-98 now documented in five different states so
far in the USA in 2007, and with the two atypical BSE H-base


13
© SEAC 2007


cases in Texas and Alabama, with both scrapie and chronic
wasting disease (CWD) running rampant in the USA, is there any
concern from SEAC with the rise of sporadic CJD in the USA from
''unknown phenotype'', and what concerns if any, in relations to
blood donations, surgery, optical, and dental treatment, do you
have with these unknown atypical phenotypes in both humans and
animals in the USA? Does it concern SEAC, or is it of no concern
to SEAC? Should it concern USA animal and human health
officials?”


41. A member considered that this question ............


snip... please see full text, sources, and comments here ;


http://seac992007.blogspot.com/2008/01/spongiform-encephalopathy-advisory.html


APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15,
2006


http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8


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


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



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


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



Attachment to Singletary comment

January 28, 2007


Greetings APHIS,


I would kindly like to submit the following to ;


BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES
[Docket No. APHIS-2006-0041] RIN 0579-AC01



[Federal Register: January 9, 2007 (Volume 72, Number 5)]
[Proposed Rules]
[Page 1101-1129]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09ja07-21]



http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152



BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS
DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01
Date: January 9, 2007 at 9:08 am PST


http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412



Diagnosis and Reporting of Creutzfeldt-Jakob Disease

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


Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.


To the Editor:

In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr
Bacliff, Tex



1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT


http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT



PDF]Freas, William TSS SUBMISSION
File 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 ...

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf


Asante/Collinge et al, 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;

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm


DER SPIEGEL (9/2001) - 24.02.2001 (9397 Zeichen)USA: Loch in der MauerDie BSE-Angst erreicht Amerika: Trotz strikter Auflagen gelangte in Texas verbotenes Tiermehl ins Rinderfutter - die Kontrollen der Aufsichtsbehördensind lax.Link auf diesen Artikel im Archiv:http://service.spiegel.de/digas/find?DID=18578755


"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...


http://service.spiegel.de/digas/servlet/find/DID=18578755


2 January 2000

British Medical Journal

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

http://www.bmj.com/cgi/eletters/320/7226/8/b#6117


15 November 1999

British Medical Journal

vCJD in the USA * BSE in U.S.


http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406


please notice Texas 2006 ;

† Confirmed in United Kingdom and reported to Texas Department of State
Health Services
through Centers for Disease Control and Prevention.


Only 1 case of variant
CJD has ever been diagnosed in Texas.
The patient was a former resident of the
United Kingdom, where the exposure
was likely to have occurred. Texas has a
population of 23 million, and since the
national rate of sporadic CJD is about 1
per million, it is expected that
approximately 23 cases of CJD would
occur each year in the state. Therefore,
it is believed that CJD is currently underreported
in Texas. ...END...TSS


also see ;


http://www.dshs.state.tx.us/idcu/disease/creutzfeldt-jakob/data/


Creutzfeldt-Jakob Disease in Northeast Texas,

J.A. Rawlings,*1 K.A.
Hendricks1, O.M. Nuno1, D.A. Brown1, D.A. Evans2, Texas Department of
Health, 1Austin and 2Tyler, Texas


Creutzfeldt-Jacob Disease (CJD), a transmissible spongiform
encephalopathy, is caused by prions composed of proteinaceous material
devoid of nucleic acid. CJD occurs sporadically (generally 1
case/1,000,000 population per year) in older patients (average age of
65) and is characterized by rapidly progressive dementia, accompanied by
severe muscle spasms and incoordination. Death usually occurs within 3
to 12 months (average 7 months). CJD activity in Texas, which has a
population of nearly 19 million, appeared to be typical. The statewide
death rate for 1995 and 1996 was just under 1/1,000,000. In April of
1997, the Texas Department of Health became aware of an increased number
of possible CJD cases in a 23-county area of NE Texas with a population
of just over one million. After review of medical and pathology records,
four patients were identified with definite classic CJD and three were
identified with probable CJD. Dates of death for the eight patients were
from April, 1996 through mid-July 1997. The patients were from 46
through 65 years of age; four were male and three were female. A
case-control study to identify risks for CJD in NE Texas has been initiated.


http://www.jifsan.umd.edu/tse/Rawlings.htm


Division of Neuropathology
Pierluigi Gambetti, M.D.,
Director

-----------------------------------

CASE WESTERN RESERVE UNIVERSITY

March 30, 1998

Dr. Gerald A, Campbell

The University of Texas
Medical Branch at Galveston
Division of Neuropathology
Department of Pathology
Galveston, Texas

Dear Dr Campbell,

We performed Western immunoblot analysis on the frozen tissue from your case
#AU97-435 (our #098-28). The Immunoblot reveals the presence of
protease-resistant prion protein (PrPres) confirming the diagnosis of prion
disease. The immunoblot pattern of PrPres is consistent with the diagnosis
of Creutzfeldt-Jakob disease.

Thank you for referring to us this interesting case.


Sincerely,

Piero Parchi, M.D.

Pierluigi Gambetti, M.D.

PP:sbDivision of Neuropathology

Pierluigi Gambetti, M.D.,

Director

Case Western Reserve University

snip...end


see full text ;


http://cjdtexas.blogspot.com/


Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in
the United States

http://cjdusa.blogspot.com/


Creutzfeldt Jakob Disease

http://creutzfeldt-jakob-disease.blogspot.com/


Creutzfeldt-Jakob Disease, Prion Protein Gene Codon 129VV, and a Novel PrPSc Type in a Young British Woman


http://creutzfeldt-jakob-disease.blogspot.com/2008/01/creutzfeldt-jakob-disease-prion-protein.html


CJD QUESTIONNAIRE

http://cjdquestionnaire.blogspot.com/


ANIMAL HEALTH REPORT 2006 (BSE h-BASE EVENT IN ALABAMA, Scrapie, and CWD)

http://animalhealthreport2006.blogspot.com/


CREUTZFELDT JAKOB DISEASE MAD COW BASE UPDATE USA

http://cjdmadcowbaseoct2007.blogspot.com/


Friday, January 11, 2008

CJD HUMAN TSE REPORT UK, USA, CANADA, and Mexico JANUARY 2008


http://cjdmadcowbaseoct2007.blogspot.com/2008/01/cjd-human-tse-report-uk-usa-canada-and.html


Friday, January 25, 2008
January 2008 Update on Feed Enforcement Activities to Limit the Spread of BSE

http://madcowspontaneousnot.blogspot.com/2008/01/january-2008-update-on-feed-enforcement.html

http://madcowspontaneousnot.blogspot.com/


BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA

http://madcowtesting.blogspot.com/


NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007

http://nor-98.blogspot.com/

http://scrapie-usa.blogspot.com/


Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518