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From: TSS ()
Subject: sporadic CJD and TSE in USA ...the facts...TSS
Date: May 11, 2005 at 9:29 am PST

-------- Original Message --------
Subject: [CJDVoice] sporadic CJD and TSE in USA ...the facts...TSS
Date: Tue, 10 May 2005 21:31:43 -0500
From: "Terry S. Singeltary Sr."
Reply-To: cjdvoice@YAHOOGROUPS.COM
To: CJDVOICE


Gerald Wells: Report of the Visit to USA, April-May 1989

snip...

The general opinion of those present was that BSE, as an
overt disease phenomenon, _could exist in the USA, but if it did,
it was very rare. The need for improved and specific surveillance
methods to detect it as recognised...

snip...

It is clear that USDA have little information and _no_ regulatory
responsibility for rendering plants in the US...

snip...

3. Prof. A. Robertson gave a brief account of BSE. The US approach
was to accord it a _very low profile indeed_. Dr. A Thiermann showed
the picture in the ''Independent'' with cattle being incinerated and thought
this was a fanatical incident to be _avoided_ in the US _at all costs_...

snip...

http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

To be published in the Proceedings of the
Fourth International Scientific Congress in
Fur Animal Production. Toronto, Canada,
August 21-28, 1988

Evidence That Transmissible Mink Encephalopathy
Results from Feeding Infected Cattle

R.F. Marsh* and G.R. Hartsough

"Department of Veterinary Science, University of Wisconsin-Madison, Madison,
Wisconsin 53706; and ^Emba/Creat Lakes Ranch Service, Thiensville,
Wisconsin 53092

ABSTRACT
Epidemiologic investigation of a new incidence of
transmissible mink encephalopathy (TME) in Stetsonville, Wisconsin
suggests that the disease may have resulted from feeding infected
cattle to mink. This observation is supported by the transmission of
a TME-like disease to experimentally inoculated cattle, and by the
recent report of a new bovine spongiform encephalopathy in
England.

INTRODUCTION

Transmissible mink encephalopathy (TME) was first reported in 1965 by
Hartsough
and Burger who demonstrated that the disease was transmissible with a
long incubation
period, and that affected mink had a spongiform encephalopathy similar
to that found in
scrapie-affecied sheep (Hartsough and Burger, 1965; Burger and
Hartsough, 1965).
Because of the similarity between TME and scrapie, and the subsequent
finding that the
two transmissible agents were indistinguishable (Marsh and Hanson,
1969), it was
concluded that TME most likely resulted from feeding mink
scrapie-infecied sheep.
The experimental transmission of sheep scrapie to mink (Hanson et al., 1971)
confirmed the close association of TME and scrapie, but at the same time
provided
evidence that they may be different. Epidemiologic studies on previous
incidences of
TME indicated that the incubation periods in field cases were between
six months and
one year in length (Harxsough and Burger, 1965). Experimentally, scrapie
could not be
transmitted to mink in less than one year.
To investigate the possibility that TME may be caused by a (particular
strain of
scrapie which might be highly pathogenic for mink, 21 different strains
of the scrapie
agent, including their sheep or goat sources, were inoculated into a
total of 61 mink.
Only one mink developed a progressive neurologic disease after an
incubation period of
22 mon..s (Marsh and Hanson, 1979). These results indicated that TME was
either caused
by a strain of sheep scrapie not yet tested, or was due to exposure to a
scrapie-like agent
from an unidentified source.

OBSERVATIONS AND RESULTS

A New Incidence of TME. In April of 1985, a mink rancher in
Stetsonville, Wisconsin
reported that many of his mink were "acting funny", and some had died.
At this time, we
visited the farm and found that approximately 10% of all adult mink were
showing
typical signs of TME: insidious onset characterized by subtle behavioral
changes, loss of
normal habits of cleanliness, deposition of droppings throughout the pen
rather than in a
single area, hyperexcitability, difficulty in chewing and swallowing,
and tails arched over
their _backs like squirrels. These signs were followed by progressive
deterioration of
neurologic function beginning with locomoior incoordination, long
periods of somnolence
in which the affected mink would stand motionless with its head in the
corner of the
cage, complete debilitation, and death. Over the next 8-10 weeks,
approximately 40% of
all the adult mink on the farm died from TME.
Since previous incidences of TME were associated with common or shared
feeding
practices, we obtained a careful history of feed ingredients used over
the past 12-18
months. The rancher was a "dead stock" feeder using mostly (>95%) downer
or dead dairy
cattle and a few horses. Sheep had never been fed.

Experimental Transmission. The clinical diagnosis of TME was confirmed by
histopaihologic examination and by experimental transmission to mink
after incubation
periods of four months. To investigate the possible involvement of
cattle in this disease
cycle, two six-week old castrated Holstein bull calves were inoculated
intracerebrally
with a brain suspension from affected mink. Each developed a fatal
spongiform
encephalopathy after incubation periods of 18 and 19 months.

DISCUSSION
These findings suggest that TME may result from feeding mink infected
cattle and
we have alerted bovine practitioners that there may exist an as yet
unrecognized
scrapie-like disease of cattle in the United States (Marsh and
Hartsough, 1986). A new
bovine spongiform encephalopathy has recently been reported in England
(Wells et al.,
1987), and investigators are presently studying its transmissibility and
possible
relationship to scrapie. Because this new bovine disease in England is
characterized by
behavioral changes, hyperexcitability, and agressiveness, it is very
likely it would be
confused with rabies in the United Stales and not be diagnosed.
Presently, brains from
cattle in the United States which are suspected of rabies infection are
only tested with
anti-rabies virus antibody and are not examined histopathologically for
lesions of
spongiform encephalopathy.
We are presently pursuing additional studies to further examine the possible
involvement of cattle in the epidemiology of TME. One of these is the
backpassage of
our experimental bovine encephalopathy to mink. Because (here are as yet
no agent-
specific proteins or nucleic acids identified for these transmissible
neuropathogens, one
means of distinguishing them is by animal passage and selection of the
biotype which
grows best in a particular host. This procedure has been used to
separate hamster-
adapted and mink-udapted TME agents (Marsh and Hanson, 1979). The
intracerebral
backpassage of the experimental bovine agent resulted in incubations of
only four months
indicating no de-adaptation of the Stetsonville agent for mink after
bovine passage.
Mink fed infected bovine brain remain normal after six months. It will
be essential to
demonstrate oral transmission fiom bovine to mink it this proposed
epidemiologic
association is to be confirmed.

ACKNOWLEDGEMENTS
These studies were supported by the College of Agricultural and Life
Sciences,
University of Wisconsin-Madison and by a grant (85-CRCR-1-1812) from the
United
States Department of Agriculture. The authors also wish to acknowledge
the help and
encouragement of Robert Hanson who died during the course of these
investigations.

REFERENCES
Burger, D. and Hartsough, G.R. 1965. Encephalopathy of mink. II.
Experimental and
natural transmission. J. Infec. Dis. 115:393-399.
Hanson, R.P., Eckroade, R.3., Marsh, R.F., ZuRhein, C.M., Kanitz, C.L.
and Gustatson,
D.P. 1971. Susceptibility of mink to sheep scrapie. Science 172:859-861.
Hansough, G.R. and Burger, D. 1965. Encephalopathy of mink. I.
Epizoociologic and
clinical observations. 3. Infec. Dis. 115:387-392.
Marsh, R.F. and Hanson, R.P. 1969. Physical and chemical properties of the
transmissible mink encephalopathy agent. 3. ViroL 3:176-180.
Marsh, R.F. and Hanson, R.P. 1979. On the origin of transmissible mink
encephalopathy. In Hadlow, W.J. and Prusiner, S.P. (eds.) Slow transmissible
diseases of the nervous system. Vol. 1, Academic Press, New York, pp
451-460.
Marsh, R.F. and Hartsough, G.R. 1986. Is there a scrapie-like disease in
cattle?
Proceedings of the Seventh Annual Western Conference for Food Animal
Veterinary
Medicine. University of Arizona, pp 20.
Wells, G.A.H., Scott, A.C., Johnson, C.T., Cunning, R.F., Hancock, R.D.,
Jeffrey, M.,
Dawson, M. and Bradley, R. 1987. A novel progressive spongiform
encephalopathy
in cattle. Vet. Rec. 121:419-420.

MARSH

http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf


CJD YOUNG PEOPLE

in the USA, a 16 year old in 1978;


ALSO IN USA;

(20 year old died from sCJD in USA in 1980 and a 16 year
old in 1981. see second url below)

in France, a 19 year old in 1982;

in Canada, a 14 year old of UK origin in 1988;

in Poland, cases in people aged 19, 23, and 27 were identified in
a retrospective study (published 1991), having been originally
misdiagnosed with a viral encephalitis;


Creutzfeldt's first patient in 1923 was aged 23.


ALSO;


http://www.bseinquiry.gov.uk/files/yb/1995/10/27013001.pdf


20 year old died from sCJD in USA in 1980 and a 16 year
old in 1981. A 19 year old died from sCJD in
France in 1985. There is no evidence of an iatrogenic
cause for those cases....


http://www.bseinquiry.gov.uk/files/yb/1995/10/20006001.pdf


CJD FARMERS WIFE 1989

http://www.bseinquiry.gov.uk/files/yb/1989/10/13007001.pdf

http://www.bseinquiry.gov.uk/files/yb/1989/10/13003001.pdf

20 year old died from sCJD in USA in 1980 and a 16 year
old in 1981. A 19 year old died from sCJD in
France in 1985. There is no evidence of an iatrogenic
cause for those cases....

http://www.bseinquiry.gov.uk/files/yb/1995/10/04004001.pdf

cover-up of 4th farm worker ???

http://www.bseinquiry.gov.uk/files/yb/1995/10/23006001.pdf

http://www.bseinquiry.gov.uk/files/yb/1995/10/20006001.pdf

CONFIRMATION OF CJD IN FOURTH FARMER

http://www.bseinquiry.gov.uk/files/yb/1995/11/03008001.pdf

now story changes from;

SEAC concluded that, if the fourth case were confirmed, it would be
worrying, especially as all four farmers with CJD would have had BSE
cases on their farms.

to;

This is not unexpected...

was another farmer expected?

http://www.bseinquiry.gov.uk/files/yb/1995/11/13010001.pdf

4th farmer, and 1st teenager

http://www.bseinquiry.gov.uk/files/yb/1996/02/27003001.pdf

2. snip...
Over a 5 year period, which is the time period on which the advice
from Professor Smith and Dr. Gore was based, and assuming a
population of 120,000 dairy farm workers, and an annual incidence
of 1 per million cases of CJD in the general population, a
DAIRY FARM WORKER IS 5 TIMES MORE LIKELY THAN
an individual in the general population to develop CJD. Using the
actual current annual incidence of CJD in the UK of 0.7 per
million, this figure becomes 7.5 TIMES.

3. You will recall that the advice provided by Professor Smith in
1993 and by Dr. Gore this month used the sub-population of dairy
farm workers who had had a case of BSE on their farms -
63,000, which is approximately half the number of dairy farm
workers - as a denominator. If the above sums are repeated using
this denominator population, taking an annual incidence in the general
population of 1 per million the observed rate in this sub-population
is 10 TIMES, and taking an annual incidence of 0.7 per million,
IT IS 15 TIMES (THE ''WORST CASE'' SCENARIO) than
that in the general population...

http://www.bseinquiry.gov.uk/files/yb/1995/01/31004001.pdf


It was, however, performed in the USA in 1979, when it was shown that
cattle inoculated with the scrapie agent endemic in the flock of Suffolk
sheep at the United States Department of Agriculture in Mission, Texas,
developed a TSE quite unlike BSE. 32 <

http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820543

The findings of the initial transmission, though not of the clinical or
neurohistological examination, were communicated in October 1988 to Dr
Watson, Director of the CVL, following a visit by Dr Wrathall, one of
the project leaders in the Pathology Department of the CVL, to the
United States Department of Agriculture. 33


http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820546


The results were not published at this point, since the attempted
transmission to mice from the experimental cow brain had been
inconclusive. The results of the clinical and histological differences
between scrapie-affected sheep and cattle were published in 1995.
Similar studies in which cattle were inoculated intracerebrally with
scrapie inocula derived from a number of scrapie-affected sheep of
different breeds and from different States, were carried out at the US
National Animal Disease Centre. 34


http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820549


The results, published in 1994, showed that this source of scrapie
agent, though pathogenic for cattle, did not produce the same clinical
signs of brain lesions characteristic of BSE.


http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm


Visit to USA ... info on BSE and Scrapie


http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf


HOUND STUDY

AS implied in the Inset 25 we must not _ASSUME_ that
transmission of BSE to other species will invariably
present pathology typical of a scrapie-like disease.

snip...

http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf


In Confidence - Perceptions of unconventional slow virus diseases
of animals in the USA - APRIL-MAY 1989 - G A H Wells


http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

WHY is USA insisting _now_ not to use WB, when on the 1st _confirmed_
case Dec. 23, 2003
USA mad cow, WB was used ???

maybe this is the reason ;

JAPAN BSE # 8 & 9 cow

8. 6/10/2003 Holstein Steer 13/10/2001 23 mths
No clinical signs WB+, IHC-, HP-


9. 4/11/2003 Holstein Steer 13/1/2002
21 mths No clinical signs WB+, IHC-, HP-

===========

More information on the first 11 Japanese BSE-cases can be found on the
website of the Japanese Embassy in the US:

http://www.us.emb-japan.go.jp/english/html/fafacts/bse/bse.htm


BASE in cattle in Italy of Identification of a second bovine amyloidotic
spongiform encephalopathy: Molecular similarities with sporadic
Creutzfeldt-Jakob disease

http://www.pnas.org/cgi/content/abstract/0305777101v1

Adaptation of the bovine spongiform encephalopathy agent to primates and
comparison with Creutzfeldt- Jakob disease: Implications for human
health THE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy
Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François
Lamoury*, Nicolas Kopp [Dagger ] , Jean-Jacques Hauw§, James Ironside¶,
Moira Bruce [||] , Dominique Dormont*, and Jean-Philippe Deslys* et al,
that The agent responsible for French iatrogenic growth hormone-linked
CJD taken as a control is very different from vCJD but is similar to
that found in one case of sporadic CJD and one sheep scrapie isolate;

http://www.pnas.org/cgi/content/full/041490898v1

Characterization of two distinct prion strains derived from bovine
spongiform encephalopathy transmissions to inbred mice

http://vir.sgmjournals.org/cgi/content/abstract/85/8/2471


May 2003 A bizarre misshapen protein The story of the mysterious,
devastating prion in a new book from Springer In the space of 12 months,
Stephen Churchill lost his focus, his memory, most of his speech, then
even the ability to dress, feed, and clean himself. He developed an
excessive fear of water and sharp objects and refused to bathe or shave.
And before long, with his unsteady gait and his tendency to fall, he
spent his days slumped in a wheelchair or confined to a bed. To the
staff of the nursing home where Stephen lived, the relentless decline
was depressingly familiar-it had the earmarks of Alzheimer's disease.
But something in the picture did not fit. The patient, when he died, was
only 19 years old. Doctors later discovered that Stephen had succumbed
to a new kind of killer, the prion, now known to be the cause of mad cow
disease in cattle, chronic wasting disease in American deer and elk,
Creutzfeldt-Jakob disease and fatal insomnia in humans, among other
exotic ailments. Doctors and researchers have been aware of some of
these diseases for a century and more, but only in the last two decades
have scientists even begun to understand just how the pathological
protein spreads to new species and kills its victims. In The
Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion
Diseases, Philip Yam describes the history of the scientific effort to
track down and understand the prion, and the medical effort, still
underway, to devise treatments for those who suffer from its ravages.
Philip Yam has been writing and editing for Scientific American since
1989 and is currently the magazine's news editor. This is his first
book. Detailed information and order possibility: Philip Yam The
Pathological Protein Mad Cow, Chronic Wasting, and Other Deadly Prion
Diseases 2003. Hardcover, 285 pp. Euro 29.95 (net price); ã21.00;
$27.50; sFr 51.50 ISBN 0-387-95508-9 Contact and review copies: Joan
Robinson Springer-Verlag Press and Public Relations Tel.: +49- (0)
6221-487-8130, Fax: +49- (0) 6221-487-8141, E-mail: robinson@springer.de
http://www.springer.de/press/newbooks/protein.html The Pathological
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http://www.target.com/gp/detail.html/sr=1-1/qid=1054420048/ref=sr_1_1/602-9780634-9614260?asin=0387955089


snip...

CHAPTER 14 Laying Odds Are prion diseases more prevalent than we
thought? Researchers and government officials badly underestimated the
threat that mad cow disease posed when it first appeared in Britain.
They didn't think bovine spongifbrm encephalopathy was a zoonosisan
animal disease that can sicken people. The 1996 news that BSE could
infect humans with a new form of Creutzfeldt-Jakob disease stunned the
world. It also got some biomedical researchers wondering whether
sporadic CJD may really be a manifestation of a zoonotic sickness. Might
it be caused by the ingestion of prions, as variant CJD is? Revisiting
Sporadic CJD It's not hard to get Terry Singeltary going. "I have my
conspiracy theo- ries," admitted the 49-year-old Texan.1 Singeltary is
probably the nation's most relentless consumer advocate when it comes to
issues in prion diseases. He has helped families learn about the
sickness and coordinated efforts with support groups such as CJD Voice
and the CJD Foundation. He has also connected with others who are
critical of the American way of handling the threat of prion diseases.
Such critics include Consumers Union's Michael Hansen, journalist John
Stauber, and Thomas Pringle, who used to run the voluminous www.mad-
cow.orgWeb site. These three lend their expertise to newspaper and
magazine stories about prion diseases, and they usually argue that 223
224 CHAPTER 14 prions represent more of a threat than people realize,
and that the gov- ernment has responded poorly to the dangers because it
is more con- cerned about protecting the beef industry than people's
health. Singeltary has similar inclinations, but unlike these men, he
doesn't have the professional credentials behind him. He is an 11-grade
dropout, a machinist who retired because of a neck injury sustained at
work. But you might not know that from the vast stores of information in
his mind and on his hard drive. Over the years, he has provided unac-
knowledged help to reporters around the globe, passing on files to such
big-time players as The New Tork Times, Newsweek, and USA Today. His
networking with journalists, activists, and concerned citizens has
helped medical authorities make contact with suspected CJD victims. He
has kept scientists informed with his almost daily posting of news items
and research abstracts on electronic newsgroups, including the bulletin
board on www.vegsource.com and the BSE-listserv run out of the
University of Karlsruhe, Germany. His combative, blunt, opinion- ated
style sometimes borders on obsessive ranting that earns praise from some
officials and researchers but infuriates othersespecially when he
repeats his conviction that "the government has lied to us, the feed
industry has lied to usall over a buck." As evidence, Singeltary cites
the USDA's testing approach, which targets downer cows and examined
19,900 of them in 2002. To him, the USDA should test 1 mil- lion cattle,
because the incidence of BSE may be as low as one in a mil- lion, as it
was in some European countries. That the U.S. does not, he thinks, is a
sign that the government is really not interested in finding mad cows
because of fears of an economic disaster. Singeltary got into the field
of transmissible spongiform encepha- lopathy in 1997, just after his
mother died of sporadic CJD. She had an especially aggressive
versionthe Heidenhain variantthat first causes the patient to go blind
and then to deteriorate rapidly She died just ten weeks after her
symptoms began. Singeltary, who said he had watched his grandparents die
of cancer, considered her death by CJD to be much, much worse: "It's
something you never forget." Her uncon- trollable muscle twitching
became so bad "that it took three of us to hold her one time,"
Singeltary recalled. "She did everything but levitate in bed and spin
her head." Doctors originally diagnosed Alzheimer's disease, but a
postmortem neuropathological exam demanded by Singeltary revealed the
true nature other death. Laying Odds 225 Classifying a disease as
"sporadic" is another way for doctors to say they don't know the cause.
Normal prion proteins just turn rogue in the brain for no apparent
reason. The term "sporadic" is often particularly hard for the victims'
families to accept, especially when the patient was previously in robust
health. Maybe it was something in the water, they wonder, or in the air,
or something they atethe same questions CJD researchers tried to answer
decades ago. The names "sporadic CJD" and "variant CJD" also confuse the
public and raise suspicions that U.S. authorities are hiding something
when they say there have been no native variant CJD cases in the
country. Singeltary suspected an environmental cause in his mother's
demise  a feeling reinforced a year later when a neighbor died of spo-
radic CJD. For years, the neighbor had been taking nutritional supple-
ments that contained cow brain extracts. Researchers from the National
Institutes of Health collected samples of the supplement, Singeltary
recounted, and inoculated suspensions into mice. The mice remained
healthywhich only means that those supplement samples tested were
prion-free. Scientists have made several attempts during the past few
decades to find a connection between sporadic CJD and the environment.
Often, these studies take the form of asking family members about CJD
vic- timstheir diet, occupation, medical history, hobbies, pets, and
so forthand comparing them with non-CJD subjects. Such case-control CJD
studies have produced some intriguingand sometimes contra-
dictoryresults. In 1985, Carleton Gajdusek and his NIH colleagues
reported a correlation between CJD and eating a lot of roast pork, ham,
hot dogs, and lamb, as well as rare meats and raw oysters.2 Yet they
also recognized that the findings were preliminary and that more studies
were needed. Following up, Robert Will of the U.K. National CJD
Surveillance Unit and others pooled this data with those from two other
case-con- trol studies on CJD (one from Japan and one from the U.K.). In
particu- lar, they figured the so-called odds ratiocalculated by
dividing the fre- quency of a possible factor in the patient group by
the frequency of the factor in the control group. An odds ratio greater
than I means that the factor may be significant. In their study, Will
and his collaborators found an increase of CJD in people who have worked
as health profes- sionals (odds ratio of 1.5) and people who have had
contact with cows 226 CHAPTER 14 (1.7) and sheep (1.6). Unfortunately,
those connections were not statisti- cally significant: The numbers of
pooled patients (117) and control sub- jects (333) were so small that
the researchers felt the odds ratios needed to reach 2.5 to 8 (depending
on the assumptions) before they could be deemed statistically
significant. The only statistically significant corre- lations they
found were between CJD and a family history of either CJD (19.1) or
other psychotic disease (9.9), although the latter might simply be
correlated because psychotic disease may be an early symp- tom of
undiagnosed CJD.3 In contrast with earlier findings, the team concluded
that there was no association between sporadic CJD and the consumption
of organ meats, including brains (0.6). Although these case-control
studies shed a certain amount of light on potential risk factors for
CJD, it's impossible to draw firm conclu- sions. Obtaining data that
produces statistically meaningful results can be difficult because of
the rarity of CJD and hence the shortage of sub- jects. Human memory is
quite fragile, too, so patients' families may not accurately recall the
lifestyle and dietary habits of their loved ones over the course of a
decade or more. Consequently, researchers must cope with data that
probably contain significant biases. In a review paper on CJD, Joe Gibbs
of the NIH and Richard T.Johnson of Johns Hopkins University concluded
that "the absence of geographic differences in incidence is more
convincing evidence against major dietary factors, since large
populations eschew pork and some consume no meat or meat products."A CJD
study of lifelong vegetarians, they proposed, could produce some
interesting data.4 The inconclusive results of case-control studies do
not completely rule out the environment as a possible cause of CJD. "Dr.
Prusiner's theory does fit much of the data of spontaneous generation of
[mal- formed] PrP somewhere in the brain," Will remarkedthat is, the
idea that sporadic CJD just happens by itself falls within the realm of
the prion theory. Still, "it's very odd, if you look at all the forms of
human prion diseases there are, all of them are transmissible in the
laboratory and could be due to some sort of infectious agent."5 One of
the great difficulties, he explained, is that "given that this is a
disease of an extraordinarily long incubation period, are we really
confident that we can exclude childhood exposure that is transmitted
from person to person, as people move around? It's difficult to be sure
about that." There might a "carrier state" that leaves people healthy
yet still able to Laying Odds 227 infect others. If so, "you would never
be able to identify what's causing the spread of the disease," concluded
Will, who hasn't stopped looking for a possible environmental link. He
has some preliminary data based on studies that trace CJD victims' lives
well before the time symptoms beganup to 70 years; they suggest some
degree of geographic cluster- ing, but no obvious candidates for a
source of infection. A Case for Undercounting The difficulty in
establishing causal links in sporadic prion diseasesif there are any in
the first placeunderlines the importance of thorough surveillance. The
U.K. has an active program, and when a victim of CJD is reported, one of
Robert Will's colleagues visits and questions the victim's family. "No
one has looked for CJD systematically in the U.S.," the NIH's Paul Brown
noted. "Ever."6 The U.S., through the Centers for Disease Control and
Prevention, has generally maintained a more passive system, collecting
information from death certificates from the National Center for Health
Statistics. Because CJD is invariably fatal, mortality data is
considered to be an effective means of tabulating cases. The CDC
assessed the accuracy of such data by comparing the numbers with figures
garnered through an active search in 1996: Teams covering five regions
of the U.S. contacted the specialists involved and reviewed medical
records for CJD cases between 1991 and 1995. Comparing the actively
garnered data with the death certificate infor- mation showed that "we
miss about 14 percent," said CDC epidemiolo- gist Lawrence Schonberger.
"That's improving. Doctors are becoming more knowledgeable," thanks to
increased scientific and media atten- tion given to prion diseases.7 The
active surveillance study of 1996, however, only looked at cases in
which physicians attributed the deaths to CJD. Misdiagnosed patients or
patients who never saw a neurologist were not tabulated thus CJD may be
grossly underreported. Many neurological ailments share symptoms,
especially early on. According to various studies, autopsies have found
that CJD is misdiagnosed as other ills, such as dementia or Alzheimer's
disease, 5 to 13 percent of the time. The CDC finds that around 50,000
Americans die from Alzheimer's each year 228 CHAPTER 14 (about 4 million
have the disease, according to the Alzheimer's Association). Therefore,
one could argue that thousands of CJD cases are being missed. (On the
flip side, CJD could be mistakenly diagnosed as Alzheimer's disease or
dementia, but the number of CJD patients is so small that they wouldn't
dramatically skew the statistics for other neurological ills.) In part
to address the issue of misdiagnosis, CJD families have asked the CDC to
place the disease on the national list of officially notifiable
illnesses, which tends to include more contagious conditions such as
AIDS, tuberculosis, hepatitis, and viral forms of encephalitis.
Currently, only some states impose this requirement. CDC officials have
discounted the utility of such an approach, arguing that it would
duplicate the mortality data, which is more accurate than early diag-
noses of CJD, anyway. Moreover, mandatory reporting of CJD cases does
not necessarily guarantee the end to missed cases.8 One clue suggests
that the passive system is undercounting CJD in the U.S.: racial
difference. The number of black CJD victims is about 38 percent that of
white victims. Rather than sporadic CJD being a one- in-a-million
lottery, it's more like one-in-2.5-million for African- Americans.
Access to medical care might be one reason. Schonberger recounted that
the CDC had asked other countries with substantial black populations to
submit CJD figures for comparison but found that the surveillance in
those countries was inadequate. "We haven't been able to find any
comparable literature on this issue, so it's still up in the air,"
Schonberger said. On the other hand, Alzheimer's disease is more common
among black people than whites, with an estimated higher prevalence
ranging from 14 percent to almost 100 percent, according to a February
2002 report by the Alzheimer's Association. Are some black CJD cases
being misdiagnosed as Alzheimer's? Answering critics like Terry
Singeltary, who feels that the U.S. under- counts CJD, Schonberger
conceded that the current surveillance system has errors but stated that
most of the errors will be confined to the older population. As
Schonberger pointed out, no doctor would misdiagnose a 30-year-old CJD
patient as having Alzheimer's. The average age of the first 100 variant
CJD victims was 29; should the epidemiology of vCJD changeif older
people start coming down with itthen there would be problems. "The
adequacy of our overall CJD surveillance would be Laying Odds 229
greatly reduced should the proportion of older individuals affected by
variant CJD substantially increase," Schonberger explained.9 To date,
only brain autopsies can confirm CJD. To encourage the necessary
neuropathological studies, in 1997 the CDC helped establish the National
Prion Disease Pathology Surveillance Center at Case Western Reserve
University, under the directorship of Pierluigi Gambetti. But the number
of brains examined has fallen far short of the number of CJD cases in
the U.S.: Gambetti's lab, which receives brains based on referrals from
local physicians and families, looked at only 99 sporadic CJD cases in
2000 and 138 in 2001, when about 300 each year are expected. "I'm very
unhappy with the numbers," Gambetti lamented. "European countries see
100 or 90 percent of all the cases suspected. We see 30 to 40
percent."10 Most families don't think about having an autopsy done
(which can cost upward of $1,500 if the hospitals don't pick up the
tab), and mem- bers of the support group CJD Voice have said they were
too distraught to think of shipping a loved one's brain by Federal
Express to Gambetti's lab. (For accurate analyses of brain tissue, the
autopsy must be performed within 72 hours of death, assuming the body
has been kept refrigerated.) Moreover, physicians often do not suggest
an autopsy, perhaps because of liability fears should the postmortem
reveal that the original diagnosis was wrong. Gambetti has been work-
ing on establishing a network that would enable postmortems to be done
near where the deceased person lived and without cost to the family. He
is also working on advertising the existence of his surveil- lance
center, via meetings and letters to neurologists, pathologists, and
other specialists. Gambetti is also attempting to combat what he termed
"hysteria" over the potential for infection that has pathologists
irrationally shunning CJD cases while they willingly conduct arguably
riskier AIDS autopsies. "In order to make people aware, you have to keep
informing them over and over and over," he said. Money is the main
reason why the U.S. lags behind Europe in terms of surveillance. To
adequately survey the 290 U.S. million residents, "you need a lot of
money," Robert Will explained. "There was a CJD meeting of families in
America in which poor old Larry {Schonberger] got attacked fairly
vigorously because there wasn't proper surveillance. You could only do
proper surveillance if you have adequate resources. 230 CHAPTER 14
That's the bottom line. We're very fortunate in the U.K.; we have very
generous resources for CJD surveillance." Moreover, the U.K. makes
feline spongifbrm encephalopathy an offi- cially notifiable disease.
Domestic cats proved to be good sentinel ani- mals because they dine on
the meat not fit for human consumption the parts more likely to harbor
prion infectivity. In the U.S., FSE isn't federally notifiable. And
while the USDA says it has sent educational material to private
veterinarians and works with vet schools,21 it's not clear just how many
vets can spot FSE, which has never been reported in the U.S. Certainly,
not many cat postmortems are done. The only active portion of the U.S.
CJD surveillance system are the follow-up investigations conducted for
victims of CJD under 55 years of age. It began in 1996, when young
people in the U.K. started succumb- ing to variant CJD. Victims under 30
years of age especially arouse interest, because such cases could
indicate an infection from the envi- ronment. Except for the variant CJD
case in Florida, the CDC has clas- sified all of these more youthful
cases of CJD as having either sporadic or familial origins. One such age
cluster involved the three venison eaters that the CDC tried
unsuccessfully to link to the deer-and-elk borne chronic wasting
disease. A second grouping occurred in 2002 in a pair of Michigan men.
The twoone 26 years old, the other 28 did not know each other but
lived in neighboring counties in Michigan and went to the same hospi-
tal for diagnosis.12 The CDC's investigation turned up nothing that
suggested a new form of CJD had emerged. But the increased frequency of
young CJD cases is disturbing. In the 18-year period between 1979 and
1996, the U.S. had 12 cases in patients under 30, and only one of them
had the sporadic form of CJD. (The other cases resulted from heredity or
from transmission via contami- nated growth hormone or dura mater
grafts.13) Between 1997 and 2001, five people under 30 died of sporadic
CJD: the three venison eaters and the two Michigan patients. That
represents a substantial blip of five young cases in five years, as
opposed to only one case in 18 years. Physicians at the University of
Michigan Health System who examined the two Michigan men concluded: As a
result of our findings, we feel that sporadic CJD may be more common
than previously thought, that it may occur in younger indi- Laying Odds
231 viduals than currently perceived, and that some cases may go undiag-
nosed due to insufficient testing. . . . We recommend that physicians
everywhere begin to consider CJD in rapidly progressive neurological
decline of unknown causes in people under 30 years of age, and that
brain biopsy and autopsy with genetic and prion analysis be performed in
all such cases.14 Pathologically, the recent bout of young casualties in
the U.S. appears to be no different from CJD already seen in America.
Yet theoretically it may have come from a new source of infection, based
on an unex- pected result announced in late November 2002. John Collinge
of the British Medical Research Council's Prion Unit found that not all
trans- genic mice infected with BSE prions developed the
neuropathological and molecular characteristics of variant CJD; some of
the mice instead generated the molecular features of sporadic CJD.
Therefore, some CJD cases classified as sporadic may have actually been
caused by BSE prions, Collinge hypothesized.15 So far, the epidemiology
of CJD in the U.K. does not bear out that suppositionthere has been no
substantial uptick in sporadic CJD as would be expected if BSE could
paint more than one pathological picture. But the preliminary study,
taken at face value, could be seen as evidence that something infectious
is happening in the cases of young, sporadic CJD victims in the U.S.
Another mouse study, reported in March 2002, fueled concern that prion
infections may be more common than previously thought.16 Stanley
Prusiner's lab found that mice infected with mouse prions accu- mulated
PrPSc in their skeletal muscles, mostly in those in the hind limbs. In
some mice, each gram of muscle contained some 10 million infectious
doseson par with that in the brain in other experiments involving
intracerebral inoculation. To some CJD researchers, this find- ing
suggested that muscle meat from cows might not be safe, after all, and
that the measures taken in Europe to protect the food supply banning
high-risk cow partsmay not be enough. Although this study may seem
alarming, its implications are not as sweeping as they may appear. Only
a minority of results in mouse stud- ies end up having a direct analog
in humans. The skeletal muscle discov- ery warrants further examination,
but it would be premature to alter food policies. Prions are different
for each species, and accumulation of prions varies from species to
species and from disease to disease. Furthermore, BSE cattle muscle has
failed to sicken mice in bioassay 232 CHAPTER 14 work, suggesting that
little or no infectious prions lurk there. What such findings truly
reveal is that prion diseases are complicated and still mysterious, and
trying to quantify the risks for human health is fraught with
uncertainties...snip...284 pages.. The Pathological Protein: Mad Cow,
Chronic Wasting, and Other Deadly Prion Diseases, Philip Yam Philip Yam
News Editor Scientific American www.sciam.com
http://www.thepathologicalprotein.com/

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


Terry S. Singeltary Sr.






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