From: TSS (216-119-133-125.ipset13.wt.net)
Subject: BSE MAY CAUSE MORE CJD CASES THAN THOUGHT (NEW SCIENTIST)
Date: November 29, 2002 at 1:02 pm PST
In Reply to: BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein (FULL TEXT) posted by TSS on November 28, 2002 at 9:32 am:
BSE may cause more CJD cases than thought
13:20 28 November 02 NewScientist.com news service
The eating of BSE-infected meat might cause classical CJD in people, as well as variant CJD, a new mouse study suggests.
Classical CJD, also called sporadic CJD (sCJD), is generally believed to develop spontaneously and existed before the BSE epidemic in British cattle, while variant CJD (vCJD) is thought to be the human form of mad cow disease.
There has been a recent rise in cases of sCJD, in the UK in particular, but it was thought this was due to better surveillance and diagnosis. But the surprising new finding adds weight to suggestions that the rise is in fact linked to the BSE epidemic.
The new work involved injecting the BSE infectious agent - a misfolded prion protein - into the brains of mice. The mice had been genetically modified to act as human models of infection and to be susceptible to CJD.
As expected, some of these mice developed symptoms and a molecular subtype of prion protein misfolding associated with vCJD. But others developed a sub-type associated with the most common of three strains of sCJD previously identified in people.
"This finding has important potential implications," the team led by John Collinge at the MRC Prion Unit in London, UK, writes in the EMBO Journal . "It raises the possibility that some humans infected with BSE prions may develop a clinical disease indistinguishable from classical CJD."
Models predicting the future extent of the human epidemic associated with eating BSE-infected meat are based on the observation of vCJD in the population. But if BSE prions can also cause sCJD, these models will underestimate the ultimate human death toll. To date, 117 people have died in the UK from vCJD.
Steady rise
More sCJD deaths are recorded annually than vCJD deaths. In 2001, 53 people in Britain died from sCJD and 20 from vCJD. This compares to 35 from sCJD and three from vCJD in 1995, when the variant form was first identified.
The steady rise in the recorded incidence of sCJD has been put down to better detection. "What we're speculating is that a proportion of that rise, not all of it but a proportion, is due to BSE," Collinge says.
In Switzerland, which had the highest incidence of cattle BSE in continental Europe between 1990 and 2002, there has been a doubling in the number of sCJD cases in that period.
But establishing how many, if any, cases of sCJD in people resulted from BSE infection will be very difficult, Collinge says. The two diseases cause similar symptoms, and the molecular type of sCJD seen in the BSE-injected mice is indistinguishable from the human type identified before the first cases of mad cow disease.
This is not the first study to link eating meat from an animal infected with a prion disease to sCJD. In March 2001, a French team found that one strain of scrapie - a prion disease present in sheep for centuries - can cause the same brain damage in mice as sCJD. This suggested that some cases of sCJD in people might be down to eating scrapie-infected sheep.
Journal reference: The European Molecular Biology Organization Journal (vol 21, p 6358)
Emma Young
http://www.newscientist.com/news/news.jsp?id=ns99993122
i was glad to see the New Scientist article remind everyone
of the French Scrapie strain that was identicle to a strain
of sporadic CJD. the New Scientist article was taken off
the web??? FYI here is full text of that article;
NEW SCIENTIST MAGAZINE 4/02/01
NEW SCIENTIST EDITORIAL PAGE 3
MAD SHEEP DISEASE?
IF THERE is one categorical pronouncement you
can safely make about prion diseases like BSE
or CJD, it is that one should not make
categorical pronouncements. "British beef is
safe" and "there is no BSE in Germany" come
to mind. Now there are two more: "scrapie is
safe", and "people don't catch sporadic CJD".
Scrapie is the most widespread prion
disease, infecting untold numbers of
sheep worldwide. Sporadic CJD is the
old-fashioned pre-BSE kind that is supposed
to happen spontaneously in unlucky people.
But a surprise observation in France suggests
some sCJD cases--though by no means all--may
be linked to scrapie after all (see p 4).
For years, British authorities asserted that
BSE was harmless because it was a form of
scrapie. In fact, the only evidence scrapie
is safe is some broad-brush epidemiology, good
as far as it goes but unable to reveal
occasional risks for some people from some
sheep. Alarm bells should have rung in 1980
when researchers gave monkeys scrapie by
feeding them infected brains. But that
research, like so much other work on
prion diseases, was never followed up.
We still have little idea what BSE does
in pigs and chickens. The Queniborough
vCJD outbreak (see p 5) would be easier
to understand if we knew how much brain
we must eat to be infected. As for scrapie,
it shouldn't take a chance finding to
tell us that there may be dangerous sheep
out there.
Suspect symptoms
What if you can catch old-fashioned CJD by
eating meat from a sheep infected with
scrapie?
Exclusive from New Scientist magazine
Four years ago, Terry Singeltary watched his
mother die horribly from a degenerative brain disease.................
full text url follows
By Debora MacKenzie
Suspect Symptoms
http://www.newscientist.com/hottopics/bse/suspectsymptoms.jsp
if url dead, go here for 'SUSPECT SYMPTOMS'
you can access article here also;
http://www.organicconsumers.org/meat/scrapiecjd.cfm
http://www.vegancowboy.org/TSS-SuspectSymptoms.html
this is what the New Scientist article ref;
Published online before print March 20, 2001
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041490898
Abstract of this Article
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Neurobiology
Adaptation of the bovine spongiform encephalopathy agent to primates and
comparison with Creutzfeldt- Jakob disease: Implications for human health
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*
* Commissariat à l'Energie Atomique, Service de Neurovirologie,
Direction des Sciences du Vivant/Département de Recherche Medicale,
Centre de Recherches du Service de Santé des Armées 60-68, Avenue du
Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; [Dagger
] Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003
Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la
Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶
Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital,
Crewe Road, Edinburgh EH4 2XU, United Kingdom; and [||] Institute for
Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9
3JF, United Kingdom
Edited by D. Carleton Gajdusek, Centre National de la Recherche
Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000
(received for review October 16, 2000)
Abstract
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
Conclusions
References
There is substantial scientific evidence to support the notion that
bovine spongiform encephalopathy (BSE) has contaminated human beings,
causing variant Creutzfeldt-Jakob disease (vCJD). This disease has
raised concerns about the possibility of an iatrogenic secondary
transmission to humans, because the biological properties of the
primate-adapted BSE agent are unknown. We show that (i) BSE can be
transmitted from primate to primate by intravenous route in 25 months,
and (ii) an iatrogenic transmission of vCJD to humans could be readily
recognized pathologically, whether it occurs by the central or
peripheral route. Strain typing in mice demonstrates that the BSE agent
adapts to macaques in the same way as it does to humans and confirms
that the BSE agent is responsible for vCJD not only in the United
Kingdom but also in France. 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. These data will be key in identifying the origin of
human cases of prion disease, including accidental vCJD transmission,
and could provide bases for vCJD risk assessment.
Introduction
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
Conclusions
References
The recognition of a variant of the human transmissible spongiform
encephalopathy (TSE) Creutzfeldt-Jakob Disease (vCJD) in the U.K. in
1996 raised the major concern that it would correspond to human
infection with the agent responsible for bovine spongiform
encephalopathy (BSE; ref. 1). Transmission of BSE to macaques provided
the first experimental evidence as it produced a disease close to vCJD
in humans (2). Strain typing in inbred mice (consisting of measuring the
incubation period and establishing lesion profiles corresponding to the
strain-specific distribution of brain vacuolation) allows reliable
identification of TSE strains (3). This method, together with
biochemical methods, has revealed a single phenotype for the agents of
BSE and the British cases of vCJD (4-6). Mice expressing only the bovine
prion protein (PrP) were highly susceptible to vCJD and BSE, which
induced the same disease (7). Thus, it is now well established that BSE
has caused vCJD, probably by alimentary contamination. In this respect,
the finding of abnormal PrP labeling in the gastrointestinal tract and
lymphatic tissues of orally BSE-contaminated lemurs shows that the BSE
agent can infect primates by the oral route (8). About 1 million
contaminated cattle may have entered the human food chain, and the
future number of vCJD cases could range from 63 to 136,000 depending on
the incubation period of BSE in humans (9). Unlike sporadic CJD (sCJD)
and iatrogenic CJD (iCJD) linked to the administration of contaminated
growth hormone extracted from human hypophyses, in vCJD, the infectious
agent seems to be widely distributed in lymphoid organs, as pathological
PrP (PrPres) can be detected in tonsils, lymph nodes, spleen, and
appendix even in the preclinical phase of the disease (10, 11). This
raises a public health issue with regard to the risk of iatrogenic
transmission of vCJD through surgical instruments, grafts, blood
transfusion, or parenteral administration of biological products of
human origin. However, this risk is difficult to assess, because it
largely depends on factors such as the virulence of the BSE agent
adapted to primates and the efficiency of secondary transmission to
humans by a peripheral route such as the i.v. one. A further issue is
whether vCJD accidentally acquired from humans would be recognized. The
latter poses the question of a phenotypic variation of the BSE agent
after successive transmissions in humans: does it retain its strain
characteristics, and does it induce a pathology similar to that observed
in the previous host? A 9-year history of transmission of BSE to
primates and mice enables us today to clarify a number of these
important points.
Although BSE has mainly affected the U.K., two definite cases and one
probable case of vCJD have now been reported in France in people who
have never resided in the U.K. (12, 13). We strain-typed the first of
these cases to establish its origin. Strain typing in C57BL/6 mice of
BSE, French, and British vCJD was compared with that of BSE passaged in
nonhuman primates, thus allowing us to study the effect of serial
passages in primates. Comparisons were also made with French cases of
sCJD and iCJD and two strains of scrapie (one of French and one of U.S.
origin). Our findings provide experimental demonstration that the same
agent, namely that responsible for the cattle disease BSE, has caused
vCJD both in France and in the U.K., in line with biochemical data and
with the fact that, until 1996, about 10% of the beef consumed in France
was imported from the U.K. We found that the BSE agent in nonhuman
primates is similar to that causing vCJD in humans and tends to evolve
rapidly toward a primate-adapted variant. Furthermore, we showed that
the strain responsible for iCJD is closely related to that of one
patient with sCJD, and, more unexpectedly, that these agents were
similar to the French scrapie strain studied (but different from the
U.S. scrapie strain). This finding requires a cautious interpretation
for several reasons, not least because of the inevitably limited number
of TSE strains that can be studied by such a cumbersome method as strain
typing. Nonetheless, it also prompts reconsideration of the possibility
that, in some instances, sheep and human TSEs can share a common origin.
snip...
http://www.pnas.org/cgi/content/full/041490898v1
TSS
