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##################### Bovine Spongiform Encephalopathy #####################
Hospital tests man
for brain illness
Therese Smith Cox
Daily Mail staff
Wednesday March 02, 2005
Physicians at Charleston Area Medical Center recently treated a patient
who initially tested positive for a rare, fatal disorder that is the
human equivalent of mad cow disease.
Creutzfeldt-Jakob disease (CJD) prompts rapid, progressive dementia and
death.
But health officials said this elderly man's illness has not been linked
to eating tainted beef or deer. Privacy laws prohibit naming the man.
"This is a different form with a different cause," said Dr. Julie
Sinclair, the Epidemic Intelligence Officer assigned to the state Bureau
of Public Health by the Centers for Disease Control and Prevention.
"There is an undetermined cause in this guy. They are doing further
investigation."
Dr. John Schmidt, who performed a brain biopsy and another procedure on
the patient, said this would be his first CJD case in 25 years of doing
neurosurgery.
"This is a big deal," Schmidt said. "You have a diagnosis of CJD. It's
really weird -- not from a virus, not a bacterium and uniformly fatal.
It takes a long time to develop."
Hospital safety officers had to take special precautions for the
surgery, from removing all extraneous equipment from the operating room
to quarantining the surgical instruments. If specialized lab work
confirms a definitive diagnosis of CJD, then the instruments would have
to be destroyed, Schmidt said.
And all medical waste collected had to be immediately incinerated, said
CAMC spokesman Dale Witte.
Though no cases of iatrogenic (caused by medical treatment) CJD have
been reported since current sterilization procedures were adopted in
1976, transmission of CJD occurred in at least 250 patients worldwide,
according to the CDC. These were linked to contaminated human growth
hormone, corneal grafts or surgical equipment.
Schmidt said he knows of one case of a brain surgeon infected with CJD
after he operated on a patient with it.
Still, CJD is extremely rare, happening in only one in a million people,
Sinclair said. Most cases are confirmed through a post-mortem exam.
Since 1979, 31 deaths have been attributed to CJD in West Virginia,
Sinclair said. All the victims were older than 40 and most were over 60.
Most cases occur sporadically. That means no recognizable pattern of
transmission exists.
Meanwhile, the Centers for Disease Control is quietly reviewing several
mysterious deaths of young Americans from CJD to discern if they may
have eaten cows with the disease. Deaths have occurred over the last
five years in several states, including New Jersey, Texas, Michigan and
Wisconsin, according to the Associated Press.
A small percentage of patients develop CJD because they inherited
mutations of a protein gene called a prion.
Hospital tests man
for brain illness
Therese Smith Cox
Daily Mail staff
Wednesday March 02, 2005
(Page 2 of 2)
But whatever the cause, people with the disease usually die within a
year from what is classified as transmissible spongiform encephalopathy.
Medical officials declined to comment on the prognosis of the man
treated at CAMC.
While the disease is limited among animals, it is not uncommon, said
state Agriculture Commissioner Gus Douglass.
"Mad cow disease, scrapie in sheep and chronic wasting in deer are all
from the same family," he said. "We know these are transmittable to
humans. Others, medical science has not proven they are transmittable.
I'm not surprised we might find CJD in West Virginia."
However, the state has never had a case of mad cow disease, Douglass said.
Indeed, it has never been determined that a mad cow case has originated
in the United States, he said.
Sinclair said the bureau received the report of the CJD case from a
physician treating the elderly patient.
"This is a very good physician, on the ball," Sinclair said, noting that
because the condition is so rare, it would be difficult to diagnose.
Sinclair also said it has not been shown that CJD could be transmitted
casually from person to person.
"Family members don't have to be concerned," Sinclair said.
Contact Therese Smith Cox at 348-4874.
http://www.dailymail.com/news/News/2005030214/
http://www.dailymail.com/news/News/2005030214/?pt=15
> But health officials said this elderly man's illness has not been
> linked to eating tainted beef or deer. Privacy laws prohibit naming
> the man.
>
RIGHT, famous last words. no proof what so ever, they refuse to
acknowledge recent science of the new TSE in cattle that is very
very similar to sporadic CJD not the nvCJD that BSE causes.
this new TSE in cattle called BASE, most media is ignorant of...TSS
> "This is a different form with a different cause," said Dr. Julie
> Sinclair, the Epidemic Intelligence Officer assigned to the state
> Bureau of Public Health by the Centers for Disease Control and
> Prevention. "There is an undetermined cause in this guy. They are
> doing further investigation."
>
Medical Sciences
Identification of a second bovine amyloidotic spongiform
encephalopathy: Molecular similarities with sporadic
Creutzfeldt-Jakob disease
Cristina Casalone *{dagger} , Gianluigi Zanusso {dagger} {ddagger} ,
Pierluigi Acutis *, Sergio Ferrari {ddagger} , Lorenzo Capucci § ,
Fabrizio Tagliavini ¶, Salvatore Monaco {ddagger} ||, and Maria Caramelli *
*Centro di Referenza Nazionale per le Encefalopatie Animali, Istituto
Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via
Bologna, 148, 10195 Turin, Italy; {ddagger} Department of Neurological
and Visual Science, Section of Clinical Neurology, Policlinico G.B.
Rossi, Piazzale L.A. Scuro, 10, 37134 Verona, Italy; § Istituto
Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Via
Bianchi, 9, 25124 Brescia, Italy; and ¶Istituto Nazionale Neurologico
"Carlo Besta," Via Celoria 11, 20133 Milan, Italy
Edited by Stanley B. Prusiner, University of California, San Francisco,
CA, and approved December 23, 2003 (received for review September 9, 2003)
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are
mammalian neurodegenerative disorders characterized by a
posttranslational conversion and brain accumulation of an insoluble,
protease-resistant isoform (PrPSc) of the host-encoded cellular prion
protein (PrPC). Human and animal TSE agents exist as different
phenotypes that can be biochemically differentiated on the basis of the
molecular mass of the protease-resistant PrPSc fragments and the degree
of glycosylation. Epidemiological, molecular, and transmission studies
strongly suggest that the single strain of agent responsible for bovine
spongiform encephalopathy (BSE) has infected humans, causing variant
Creutzfeldt-Jakob disease. The unprecedented biological properties of
the BSE agent, which circumvents the so-called "species barrier" between
cattle and humans and adapts to different mammalian species, has raised
considerable concern for human health. To date, it is unknown whether
more than one strain might be responsible for cattle TSE or whether the
BSE agent undergoes phenotypic variation after natural transmission.
Here we provide evidence of a second cattle TSE. The disorder was
pathologically characterized by the presence of PrP-immunopositive
amyloid plaques, as opposed to the lack of amyloid deposition in typical
BSE cases, and by a different pattern of regional distribution and
topology of brain PrPSc accumulation. In addition, Western blot analysis
showed a PrPSc type with predominance of the low molecular mass
glycoform and a protease-resistant fragment of lower molecular mass than
BSE-PrPSc. Strikingly, the molecular signature of this previously
undescribed bovine PrPSc was similar to that encountered in a distinct
subtype of sporadic Creutzfeldt-Jakob disease.
------------------------------------------------------------------------
{dagger} C.C. and G.Z. contributed equally to this work.
||To whom correspondence should be addressed.
E-mail: salvatore.monaco@mail.univr.it
.
www.pnas.org/cgi/doi/10.1073/pnas.0305777101
http://www.pnas.org/cgi/content/abstract/0305777101v1
Characterization of two distinct prion strains derived from bovine
spongiform encephalopathy transmissions to inbred mice
Sarah E. Lloyd, Jacqueline M. Linehan, Melanie Desbruslais, Susan
Joiner, Jennifer Buckell, Sebastian Brandner, Jonathan D. F. Wadsworth
and John Collinge
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of
Neurology, University College, London WC1N 3BG, UK
Correspondence
John Collinge
j.collinge@prion.ucl.ac.uk
Distinct prion strains can be distinguished by differences in incubation
period, neuropathology and biochemical properties of disease-associated
prion protein (PrPSc) in inoculated mice. Reliable comparisons of mouse
prion strain properties can only be achieved after passage in
genetically identical mice, as host prion protein sequence and genetic
background are known to modulate prion disease phenotypes. While
multiple prion strains have been identified in sheep scrapie and
Creutzfeldt–Jakob disease, bovine spongiform encephalopathy (BSE) is
thought to be caused by a single prion strain. Primary passage of BSE
prions to different lines of inbred mice resulted in the propagation of
two distinct PrPSc types, suggesting that two prion strains may have
been isolated. To investigate this further, these isolates were
subpassaged in a single line of inbred mice (SJL) and it was confirmed
that two distinct prion strains had been identified. MRC1 was
characterized by a short incubation time (110±3 days), a
mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern
of PrP-immunoreactive deposits, while MRC2 displayed a much longer
incubation time (155±1 days), a di-glycosylated-dominant PrPSc type and
a distinct pattern of PrP-immunoreactive deposits and neuronal loss.
These data indicate a crucial involvement of the host genome in
modulating prion strain selection and propagation in mice. It is
possible that multiple disease phenotypes may also be possible in BSE
prion infection in humans and other animals.
http://vir.sgmjournals.org/cgi/content/abstract/85/8/2471
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 KoppDagger , 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.
snip...
Conclusions
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
Conclusions
References
From BSE and vCJD transmissions in nonhuman primates, a number of
conclusions can be drawn that are of major importance for human health:
(i) human-adapted BSE appears to be a variant of the BSE agent that is
more virulent for humans than cattle BSE and is efficiently transmitted
by the peripheral route; (ii) the detection of vCJD in unusually young
patients is probably not because of a lack of diagnosis of cases in
older patients, thus raising the question of the source of human
contamination with BSE early in life; and (iii) iatrogenic transmissions
from patients with vCJD would be readily recognized by using the same
diagnostic criteria as those applied to vCJD [clinical and pathological
criteria (27 )
comprising neuronal loss and gliosis in the thalamus correlated with
high MRI signal (28
, 29
)], whether such
contaminations had occurred by the central or i.v. route. Primary and
iatrogenic cases of vCJD could be distinguished on the basis of the
patient's clinical history.
The risk assessment of biological products of human origin, notably
those derived from blood, has been deeply modified by the appearance of
vCJD. We confirm that the BSE agent has contaminated humans not only in
the U.K. and the Republic of Ireland but also in France, and we show
that its pathogenic properties for primates are being enhanced by a
primary passage in humans. Considering the flow of potentially
contaminated bovine-derived products between 1980 and 1996, it is
obvious that further vCJD cases may occur outside the U.K. Thus, and in
the light of the present study, it is necessary to sustain worldwide CJD
surveillance regardless of national BSE incidence and to take all
precautionary measures to avoid iatrogenic transmissions from vCJD.
snip...
full text;
http://www.pnas.org/cgi/content/full/041490898v1
Ref: MRC/62/04
Under strict embargo until 19.00 British Time Thursday 11 November 2004
GENETIC MAKE-UP MAY DETERMINE WHAT TYPE OF CJD OCCURS WHEN HUMANS ARE
INFECTED WITH BSE
New research published today (19.00 hours Thursday 11th November) by a
team from the Medical Research Council (MRC) Prion Unit offers an
explanation about why only people with a particular genetic make-up have
so far developed vCJD. It also provides evidence that other types of
BSE-derived prion infection with a different pattern of symptoms might
occur in humans. The findings are published in the journal Science.
Variant CJD (vCJD) is the human disease thought to be caused by eating
food contaminated with the infectious agent, known as a prion,
responsible for the epidemic of BSE or mad cow disease in cattle. So
far, everyone known to have developed vCJD has been of a particular
genetic type known as MM. Until now it has been a mystery why everyone
that has developed vCJD is of the MM type and one possibility is that
they are simply the first to develop the disease when infected with BSE,
and that people with the other genetic types1 (known as VV and MV)
infected with BSE prions will also develop vCJD, but some years later.
In a series of experiments spanning more than ten years, the MRC team
has been studying mice genetically modified so that they make human
prion proteins which are used to model human susceptibility to BSE.
The team has now shown that mice with the human VV genetic type do
become infected when given BSE or vCJD prions, but manifest a different
form of the disease which looks quite different to vCJD and has a novel
prion strain type.
Remarkably, when these novel prions were used to infect mice of the MM
genetic type, the mice either developed a disease very like vCJD, or
else a pattern of disease that looks like so-called sporadic CJD the
classical form of CJD. This form has been known about for many years,
is seen all over the world and has not hitherto been associated with
BSE. However, the new strain identified in the mice, being called type
5, has not been seen yet in people and we do not know what pattern of
disease it would cause. It could look like one of the forms of classical
or sporadic CJD or perhaps be yet another different variant form.
The work from the MRC team suggests that type 4 prions, the type
associated with vCJD, can only propagate themselves in people that make
the M form of the protein. It seems the V form of the protein just
cannot adopt the particular molecular shape that characterises type 4.
The studies in mice also suggest that if these prions were to pass from
person to person (for example by blood transfusion) then, depending on
the genetic type of the person becoming infected, at least three
different patterns of disease might result: type 2 (which is seen in
sporadic CJD); type 4 (which causes vCJD) or type 5 (which may cause a
new pattern of disease).
Professor John Collinge, Director of the MRC Prion Unit, which is based
at University College London, said: These mouse studies give us vital
clues about the behaviour of prions and how they appear to modify and
adapt depending on the genetic makeup of the individual they are infecting.
We always have to be cautious about making direct comparison to the
human condition, but our work strongly suggests that we can not assume
only those with one genetic profile are vulnerable to BSE infection.
At this stage it is not possible to say how this should alter estimates
of those likely to become ill, but our findings do suggest we should be
taking steps to draw up a more sophisticated system of categorizing the
disease so that we dont mistake BSE related infection for a version of
sporadic CJD.
ENDS
For more information call the MRC press office on 020 7 637 6011
Notes to Editors
1The human prion protein comes in two common forms, known as M and V.
Because everyone has two copies of this gene, there are three possible
genetic types: MM, MV and VV.
Paper - Human Prion protein v129 prevent expression of vCJD phenotype
Science On line 11.11.04
Prions are rogue forms of one of the bodys own proteins known as the
prion protein which are misshapen. There are several different rogue
or misshapen forms that can infect humans, and these different types of
prions are known as strains . This is analogous to different strains of
other germs such flu virus causing influenza or strains of salmonella
causing different forms of food poisoning for example.
The strain of prion causing vCJD is known as type 4, types 1-3 cause the
different forms of sporadic or classical CJD. Each strain causes a
different pattern or type of disease. It is known that prion strains can
change or mutate when they pass between different animals.
The Medical Research Council (MRC) is a national organisation funded by
the UK tax-payer. Its business is medical research aimed at improving
human health; everyone stands to benefit from the outputs. The research
it supports and the scientists it trains meet the needs of the health
services, the pharmaceutical and other health-related industries and the
academic world. MRC has funded work which has led to some of the most
significant discoveries and achievements in medicine in the UK. About
half of the MRCs expenditure of £430 million is invested in its 40
Institutes, Units and Centres. The remaining half goes in the form of
grant support and training awards to individuals and teams in
universities and medical schools. Web site at: http://www.mrc.ac.uk
.
Send Post-Publication Peer Review to journal:
Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease 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 to
expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in
the 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, there
should 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
TSS
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