Sunday, September 16, 2018

Mother to Offspring Transmission of TSE PRION DISEASE and risk factors there from

WEDNESDAY, SEPTEMBER 05, 2018 

*** Edmonton woman one of the youngest diagnosed with CJD at 35 years old and pregnant



August 27, 1992 

N Engl J Med 1992; 327:649 DOI: 10.1056/NEJM199208273270918

Demonstration of the Transmissible Agent in Tissue from a Pregnant Woman with Creutzfeldt–Jakob Disease

TO THE EDITOR

Only one case of Creutzfeldt—Jakob disease in pregnancy has been reported so far.1 We report our finding of the transmissible agent in samples from a pregnant patient with Creutzfeldt—Jakob disease.

A 38-year-old woman had visual disturbance in the 20th week of pregnancy. Speech and gait disturbances progressed rapidly until she reached a state of akinetic mutism. A cesarean section was performed in the 30th week. The newborn boy did well, but he was not breast-fed. He is developing normally at the age of six years. The patient died after a three-year course. At autopsy her brain weighed only 800 g. Neuropathological examination revealed a severe loss of nerve cells, a spongy state, and demyelination in both the cerebrum and the cerebellum. On the basis of the history, this case was considered to represent a spontaneous type of Creutzfeldt—Jakob disease. Analysis of prion proteins in the patient's tissues is in progress.

Specimens of the patient's blood, placenta, amniotic fluid, and umbilical-cord blood were obtained at delivery, and a sample of the patient's milk (colostrum) was collected on the fourth day after delivery. The materials from the patient were injected intracerebrally into BALB/c mice, as described previously.2 The tissue from the patient's brain was found to be infective, proving that the case was of a transmissible type (Table 1). Both the placenta and cord leukocytes were infective.

Maternal erythrocytes can be transferred to the fetus.3 That fact plus our demonstration of the transmissible agent in placenta and cord-blood samples mean that it is possible that the fetus was exposed to the transmissible agent of Creutzfeldt—Jakob disease. The mother's colostrum was also found to be infective. Histologic changes in the brains of the mice inoculated with the patient's colostrum included spongiform changes of various degrees in the cortex and white matter in both the cerebrum and the cerebellum, with reactive astrogliosis. However, no signs developed in control mice inoculated with healthy mother's milk. Neither epidemiologic studies4 5 6 nor experimental studies7 , 8 have demonstrated the vertical transmission of this disease to date. However, our findings indicate that we must be concerned about the risk of prenatal and postnatal transmission of the disease, and that follow-up studies are needed of the children at risk.

Yoichi Tamai, M.D. Hisako Kojima, Ph.D. Rie Kitajima, B.S. Fumiaki Taguchi, Ph.D. Yoshio Ohtani, M.D. Takeshi Kawaguchi, M.D. Sadanori Miura, M.D. Masaki Sato, M.D. Kitasato University School of Medicine, Kanagawa 228, Japan

Yoshihiro Ishihara, M.D. Tokyo Metropolitan Institute for Neurosciences, Tokyo 183, Japan 



THE year, 2000...tss

New Thread
(fwd) PRO/AH> New variant CJD, human infant? (05)

(fwd) PRO/AH> New variant CJD, human infant? (05)

J Ralph Blanchfield <jralphb@easynet.co.uk>

Fri, 31 Mar 2000 06:44:30 +0100
228 lines

(fwd) PRO/AH> New variant CJD, human infant? (05)

J Ralph Blanchfield <jralphb@easynet.co.uk>

Fri, 31 Mar 2000 06:51:03 +0100
223 lines

New Thread
(v?)CJD in baby
(v?)CJD in baby

Marc Barbier <barbier@grenoble.inra.fr>

Fri, 10 Mar 2000 16:29:05 +0100
51 lines

 Re: (v?)CJD in baby

Terry S. Singeltary Sr. <flounder@wt.net>

Fri, 10 Mar 2000 18:41:03 -0800
106 lines

Re: (v?)CJD in baby

Roland Heynkes <roland@heynkes.de>

Sat, 11 Mar 2000 08:45:03 +0100
52 lines

 Re: (v?)CJD in baby

Terry S. Singeltary Sr. <flounder@wt.net>

Sat, 11 Mar 2000 09:34:15 -0800
78 lines

New Thread

15 new nv CJD cases announced

Subject:
(fwd) PRO/AH> New variant CJD, human infant? (05)

From: J Ralph Blanchfield <jralphb@easynet.co.uk>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Fri, 31 Mar 2000 06:44:30 +0100

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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Hello Everyone,

I am forwarding this message, posted on ProMED yesterday,  from Rod Stonebow,
Director of Public Health for North Warwickshire, UK.  There has been extensive
discussion on BSE-L based on media reports of this case. For those who do not
also subscribe to ProMED, it will be useful to have his account of events, the
reasons he gives for decisions, and their outcomes to date.

Best wishes
Ralph

******************************************************************

J Ralph Blanchfield MBE
Food Science, Food Technology & Food Law Consultant
Chair, IFST External Affairs
Web Editor, Institute of Food Science & Technology
IFST Web address <www.ifst.org>
e-mail: <jralphb@easynet.co.uk>       ICQ# 6254687. 
ICQ Web page <wwp.mirabilis.com/6254687>

******************************************************************

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

On Thu, 30 Mar 2000 23:16:19 -0500 (EST), ProMED-mail
<promed@promed.isid.harvard.edu> wrote:


CJD (NEW VARIANT), HUMAN INFANT? (05)

*************************************

A ProMED-mail post
<http://www.promedmail.org>

[see also:
New variant CJD, human infant?                         20000304171716
New variant CJD, human infant (02)                     20000309102031
New variant CJD, human infant? (03)                    20000312222951
New variant CJD, human infant? (04)                    20000314205622]

Date: Tue, 21 Mar 2000 07:19:45 +0000
From: Rod Griffiths <Rod@stonebow.demon.co.uk>


I thought it might be helpful if I responded to the previous postings on
this subject and corrected the rather garbled version of events that is
portrayed by your previous postings.

A mother gave birth by caesarian section on 26 Oct 1999 at George Elliot
Hospital which is in North Warwickshire.  At the time she had been noticed
to have some depression and mood swings but was otherwise normal.  On 29
Jan 2000 she was admitted to another hospital in the region with a
deteriorating neurological condition which was suspicious of Variant CJD
(nvCJD).  George Elliot hospital were notified and they immediately began
an investigation.  

George Elliot hospital has a bar coding system on all their theatre
instruments and so were able to identify the actual kit used on this
patient and immediately take it out of use.  National experts from the CJD
surveillance unit were contacted for advice.  George Elliot hospital were
also able to ascertain  7 other women had had caesarian sections using this
theatre kit in the intervening period between 26 Oct 1999 and 29 Jan 2000.

The child of this mother was also admitted to the second hospital because
it was failing to thrive and appeared to have neurological signs.  This
obviously led to speculation as to whether it could be CJD.Various experts
are still thinking about this but at the moment most appear to agree that
the illness does not resemble CJD.  Obviously there is a problem here in
that we have never seen a case of vertical transmission so have no absolute
pattern to compare with. 

Shortly after this the family obtained a court injunction which prohibited
anyone from publishing the name of mother or child or the name of any
hospital at which they were treated in newspapers on cable TV or on what
was called a public computer network.  

There was considerable debate at the hospital as to whether the 7 patients
should be traced and informed.  Expert views were sought from a number of
sources and were still being trawled when the Sunday Times decided to run a
feature on CJD and speculated that this was a case of vertical
transmission.  As they could not name the hospital because of the
injunction taken out by the family they created a worry for every woman in
the region who had recently given birth.

At this point I as the Director of Public Health for the region became
involved.  We had a choice, we could find the 7 women and tell them their
exposure and put out an announcement saying no-one else need worry because
the 7 women had been told.  In effect we inflict the problem on these 7 in
order to save everyone else.  

Advice that we were able to obtain in the short period before we had to
respond to the media suggested we could cause these women significant harm,
both through the anxiety and possible other harm, like reaction of family
members, loss of insurability etc.  We had some bad experiences with the
early days of HIV where sufferers whose status was accidently discovered
and communicated to them without warning were done real harm and some
committed suicide.  The possibility of one of these women killing
themselves because we had forced this information about possible exposure
to nvCJD on them seemed worth avoiding if we could.  

I referred to the ethical principle, 'first do no harm'.  We therefore went
for a different option, aiming to make the information available to anyone
who wished to know but giving patients the choice of knowing their
particular status.  We set up a phone line with the following advice
algorithm.  If caller not from George Elliot tell not to worry.  If from
George Elliot and not in the  relevant period, tell them not to worry.  If
in this period and hospital then issue special number for George Elliot
which connects to counsellors and a team who will visit to discuss risk .

We also discussed the terms of the injunction with the judge and other
legal advisors.  Later in the week the injunction was modified to permit
naming George Elliot Hospital, hence I can name it here but not name the
second hospital which made the vCJD diagnosis.  During the week there have
been over 500 calls to the 2 lines and 6 out of the 7 women have eventually
decided that they want to know their status.  There was an enormous amount
of press coverage, much of it rubbish but we were able to get some sensible
debate on the TV and radio in which our handling of the issues was
accepted.  Feedback from samples of women who came forward for advice was
they appreciated the method we had used and supported the approach.

I think the case raises a number of difficult issues, which were made more
complex by the family taking out their injunction.  The terms of the
injunction prevented me from e-mailing the name of the hospital to all our
General Practitioners because in the British system GPs contract
independently with the NHS and are therefore technically members of the
public.  Although the words 'public computer network' were intended to
catch the internet they actually got in the way of normal public health
work.  If this has been a case in which a rapidly transmissible disease was
the issue I would have ignored the injunction and told the GPs anyway, but
in doing so I would have been in contempt of court and could in theory have
been jailed.

I would be happy to discuss the various technical and ethical issues with
anyone interested . I hope that this sets out enough of what we faced and
how we determined our action to make constructive debate possible. I
appreciate that some of the first report to your journal was so garbled
that it was difficult to see what was happening and it did not bear much
relation to things I actually  and what we did.  

Finally I find it unfortunate that Charles Calisher should immediately
resort to wild flaming of me and those who had to handle this.  It is
insulting to assume that we had sought to cover this up through legal
mechanisms nor do I agree that it is appropriate to drag unsuspecting women
into a potentially life threatening nightmare order to somehow show up
insurance companies or the British Government.

-- 
Rod Griffiths
e-mail: Rod@stonebow.demon.co.uk

[I appreciate Rod giving us a more in depth and clear idea of the actual
happenings. - Mod.TG]

[It is not the intention of ProMED-mail to engage in unwarranted criticism.
We regret this result of our reliance on inadequate media reports. - Jack
Woodall, Chair, ProMED-mail Policy Committee]
......................................jw/es
--
Visit ProMED-mail's web site at <http://www.promedmail.org>.
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Subject: (fwd) PRO/AH> New variant CJD, human infant? (05)

From: J Ralph Blanchfield <jralphb@easynet.co.uk>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Fri, 31 Mar 2000 06:51:03 +0100

Content-Type:
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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Hello Everyone,

Sorry for misnaming the Director of Public Health for North Warwickshire in my
previous posting, as a result of misreading the header of his ProMED posting.
He is Rod Griffiths

Best wishes
Ralph

******************************************************************

J Ralph Blanchfield MBE
Food Science, Food Technology & Food Law Consultant
Chair, IFST External Affairs
Web Editor, Institute of Food Science & Technology
IFST Web address <www.ifst.org>
e-mail: <jralphb@easynet.co.uk>       ICQ# 6254687. 
ICQ Web page <wwp.mirabilis.com/6254687>

******************************************************************
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

On Thu, 30 Mar 2000 23:16:19 -0500 (EST), ProMED-mail
<promed@promed.isid.harvard.edu> wrote the following message from Rod Griffiths:

CJD (NEW VARIANT), HUMAN INFANT? (05)

*************************************


Subject:
(v?)CJD in baby

From: Marc Barbier <barbier@grenoble.inra.fr>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>
Date:
Fri, 10 Mar 2000 16:29:05 +0100
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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

1. Just few questions after this tragedy of the death of this baby .

Is there any research or evidence about the fact that invasion of PrPres
could be modified during the embryogenesis of neural tissue (we know that
the structuration of the neural system is even still going on after the
birth) ? The embryogenetic process could  thus accelerate the incubation
period, which could explain that comparing incubation periode between adult
and babies would be non sense. Have BSE-calves cases been observed for
after a caesarean on BSE-cows ? 

Moreover, we know that collostrum (first milk) contains lymphatic cells
from the mother in the first days after giving birth. Is this a possible
route for infection ?

2. A comment 

Am I wrong if I said that the sterilisation methods against  prions
molecules are just those that common autoclave allows and not based on a
scientific evidence, since it appears that some strains of prions are not
eliminated by the common 133°; 3 bars (+1 atmosp) 20 mn (see Taylor D.M.
June 1995).


MARC BARBIER
INRA-ESR


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Subject: Re: (v?)CJD in baby

From: "Terry S. Singeltary Sr." <flounder@wt.net>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Fri, 10 Mar 2000 18:41:03 -0800

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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Hello Marc,

maybe this will help, don't know if this is the most recent data.
the latest from the USDA/APHIS redbook states;

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

1.8.4 Agent survival

Most information on the survivability of the BSE agent comes from
extrapolation of knowledge concerning scrapie. The scrapie agent is
extremely resistant to heat, ionizing and ultraviolet radiation, and
chemical disinfectants.

The following are known methods which decrease the levels of
infectivity, many times to non detectable levels (if any):

*Autoclaving at 134 to 138 %C (273.2 to 280.4 %F), 30lb/in_ for 18
minutes for porous- load autoclaving, or 132 %C (272.2 %oF) for 1 hour
for gravity-displacement autoclaving

*Treatment with 1N sodium hydroxide solution for 1 hour at 20 %C (68 %F) 

*Treatment with sodium hypochlorite solution containing at least 2
percent available chlorine for 1 hour at 20 %C (68 %F).

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

this disturbs me (decrease), if they don't know what the titre of
infectivity levels that are lethal to humans, then the below findings
didn't help a lot. I believe i just read, where they believe that 1
infected cow, could be 8,000 lethal doses, but i would have to go back
and re-read to be sure, it was in a PDF file???  

>>The following are known methods which decrease the levels of infectivity, >>many times to nondetectable levels (if any):

kind regards, 

Terry S. Singeltary Sr., Bacliff, Texas USA 

__________________________________________


Subject: Re: (v?)CJD in baby

From: Roland Heynkes <roland@heynkes.de>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Sat, 11 Mar 2000 08:45:03 +0100

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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Dear Terry,

> maybe this will help, don't know if this is the most recent
> data. the latest from the USDA/APHIS redbook states;
> -------------------------
> 1.8.4 Agent survival
> The following are known methods which decrease the levels of
> infectivity, many times to non detectable levels (if any):
> *Autoclaving at 134 to 138 %C (273.2 to 280.4 %F), 30lb/in_
> for 18 minutes for porous- load autoclaving, or 132 %C
> (272.2 %oF) for 1 hour for gravity-displacement autoclaving
> *Treatment with 1N sodium hydroxide solution for 1 hour at
> 20 %C (68 %F)
> *Treatment with sodium hypochlorite solution containing at least 2
> percent available chlorine for 1 hour at 20 %C (68 %F).
> --------------------------------
>

It has been shown that the first two of this three methods do
not reduce scrapie infectivity to non detectable levels whereas
the third destroys many instruments by oxydation. Please see
what Tom answered to Marc's questions.

best regards

Roland

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Subject: Re: (v?)CJD in baby

From: "Terry S. Singeltary Sr." <flounder@wt.net>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Sat, 11 Mar 2000 09:34:15 -0800

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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Hello Roland,

yes i saw Toms post, exactly the reason of posting the USDA/APHIS article. It would seem, the information in this document (which states; 'This publication supersedes all copies and versions of USDA Bovine Spongiform Encephalopathy Response Plan issued before October 1998.'). If this is the latest information, then i would suggest, inserting the most recent data on the proper autoclaving procedures, something to 'supersede the supersede' so to speak. To be passing information that is not accurate, could further spread this disease...

kind regards,
Terry S. Singeltary Sr., Bacliff, Texas USA

Roland Heynkes wrote:

>
> #########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Subject:
Baby with CJD????

From: "Leake, Jonathan" <jonathan.leake@SUNDAY-TIMES.CO.UK>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Tue, 11 Apr 2000 12:30:49 +0100

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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Just to be clear: There is still NO confirmation that the baby in question
has CJD. She has had two MRI scans and a variety of blood tests and these
are said to have shown strong indications of the disease but cannot be
considered definitive.

I am told by her family that John Collinge, the Medical Research Council's
professor of prion research who is involved in treating her, still believes
she is likely to have CJD. He has, however, been unable to confirm or deny
this because, as one would expect, he is unable to discuss individual
patients.

There is a possibility that a tonsil or other biopsy - to which the family
has agreed - will tell them one way or the other but I am told the child is
currently too ill for this to be done safely. Additionally, her mother has
deteriorated and the next few weeks and months could be the last they will
have together. For both these reasons, I am told, the operation has been put
back indefinitely

In the midst of the speculation it is important to remember that there are
also many reasons why the baby may not have CJD. Among them is the fact that
- so far as I know - no other prion disease of animals or humans is known to
affect the young without an incubation period. Just this one fact alone
would make it astonishing if this child really has been born with
fully-fledged CJD. But maybe someone out there knows differently?

Hope this helps.

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Subject: Re: Baby with CJD????

From: tom <tom@cyber-dyne.com>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Tue, 11 Apr 2000 10:20:08 -0800

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######### Bovine Spongiform Encephalopathy ######### 

>There is still NO confirmation that the baby in question 
>has CJD. She has had two MRI scans and a variety of blood tests and these 
>are said to have shown strong indications of the disease but cannot be 
>considered definitive. John Collinge, the Medical Research Council's
 >professor of prion research who is involved in treating her, still believes
 >she is likely to have CJD. He has, however, been unable to confirm or deny 
> tonsil or other biopsy - child is 
>currently too ill for this to be done safely. there are 
>also many reasons why the baby may not have CJD. Among them is the fact that 
>- so far as I know - no other prion disease of animals or humans is known to 
>affect the young without an incubation period. Just this one fact alone 
>would make it astonishing if this child really has been born with 
>fully-fledged CJD. But maybe someone out there knows differently?
 > I don't know differently but...

Geneva The number of babies born each year in the UK with undiagnosable neurological disease to healthy young mothers is very small, perhaps one in 5,000. Advanced prion disease in the mother might very well cause a loss of normal prion function or secondary brain or placental dysfunction that could adversely affect the baby without transmitted prion disease being responsible. The baby could survive the initial problem only to succumb to nvCJD at a later date. But these distinctions between direct and indirect disease are in many ways moot to the families involved. Medline has 8 articles on 'prion and placenta'. This tissue has one of the highest levels of expression. 

1 : Race R, Jenny A, Sutton D. Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. J Infect Dis. 1998 Oct;178(4):949-53. 

2 : Wrathall AE. Risks of transmitting scrapie and bovine spongiform encephalopathy by semen and embryos. Rev Sci Tech. 1997 Apr;16(1):240-64. Review. 

3 : Saeki K, Matsumoto Y, Hirota Y, Matsumoto Y, Onodera T. Three-exon structure of the gene encoding the rat prion protein and its expression in tissues. Virus Genes. 1996;12(1):15-20. 

4 : Tanji K, Saeki K, Matsumoto Y, Takeda M, Hirasawa K, Doi K, Matsumoto Y, Onodera T. Analysis of PrPc mRNA by in situ hybridization in brain, placenta, uterus and testis of rats. Intervirology. 1995;38(6):309-15. 

5 : Billette de Villemeur T, Pradel A. [Iatrogenic Creutzfeldt-Jakob disease. Lessons from cases secondary to extracted growth hormone in France]. Transfus Clin Biol. 1994;1(5):333-7. French. 

6 : Onodera T, Ikeda T, Muramatsu Y, Shinagawa M. Isolation of scrapie agent from the placenta of sheep with natural scrapie in Japan. Microbiol Immunol. 1993;37(4):311-6. 

7 : Bradley R. The research programme on transmissible spongiform encephalopathies in Britain with special reference to bovine spongiform encephalopathy. Dev Biol Stand. 1993;80:157-70. Review. 

8 : Manson J, West JD, Thomson V, McBride P, Kaufman MH, Hope J. The prion protein gene: a role in mouse embryogenesis? Development. 1992 May;115(1):117-22. 

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Subject:
A woman who became ill with variant CJD while pregnant has died...

From: "Terry S. Singeltary Sr." <flounder@wt.net>

Reply-To:
Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Wed, 7 Jun 2000 09:58:43 -0700

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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Jonathan Leake
Science Editor

A woman who became ill with variant CJD while pregnant has died -
leaving behind the mystery of whether she has passed the disease to her
child. The 24-year-old Midlands woman died last week. She had contracted
pneumonia after becoming bedridden with her illness.

This weekend the dead woman's family were gathering at the family home
near Nottingham in preparation for the funeral early this week. The
child, now eight months old, is being cared for by her grandparents.
Neither she nor her family can be identified for legal reasons.

The dead woman's mother - grandmother to the child - spoke yesterday of
her anger at her daughter's death which she blamed on the "greed of the
agricultural industry and the incompetence of officials and ministers in
the last Conservative government. She has already started a compensation
claim against the government on behalf of the child.

She said: "This disease would never have happened but for the disgusting
practice of turning cows into cannibals and it would never have spread
among humans if the agriculture ministry had heeded its own scientists'
warnings when the disease first appeared in cows."

Doctors have spent the last few days conducting tests on tissues taken
from the dead woman in the hope of finding a link to her child's
illness. All that can be said with certainty is that the youngster is
suffering from a degenerative brain condition whose symptoms have many
similarities to those found in variant CJD.

Magnetic resonance images taken of the youngster's brain have shown
strong resemblances to those found of adult victims of variant CJD.
There have also been similarities in various other diagnostic features.
Doctors have not, however, been able to find any sign of the infective
prion particles which are widely believed to be the cause of variant
CJD. This is despite carrying out a whole battery of tests on the child,
including microscopic examination of potentially infective tissue
Doctors treating the mother and child have told the family that they
believe the youngster's condition was, at the very least, caused by her
mother's illness..

The implications of the investigation are huge. Almost everyone in
Britain is thought to have eaten bovine material infected with the prion
agent believed to cause CJD. About 750,000 infected animals entered the
human food chain before 1996 when new rules came in.

The potential size of a human epidemic remains, however, very  uncertain
because there is still no reliable test of who is incubating the
disease. Professor John Collinge of Imperial College London, head of the
Medical Research Council's prion unit, believes that "it is logical to
conclude that many more cases must result from the dietary exposure."
If Collinge, who is also leading the investigation into the baby's
condition, finds she was infected by her mother, it would open a whole
new infective pathway and mean that generations of children as yet
unborn could be at risk. There is some evidence that prion disease can
transmit from mother to offspring in sheep and cattle, possibly during
pregnancy, birth or through suckling.

Frances Hall, a spokesman for the BSE foundation which represents
victims and their families, said her thoughts were with the woman's
family. "It is terrible enough for a family to have one victim of this
disease but for two to be damaged is beyond belief. We are all still
waiting for the final results of the tests to see if it could have
passed to the child. If so it will be very worrying."

One of the complicating factors is that all the 70-odd definite or
probable victims share a particular genetic make-up, having two
molecules called methionine at a particular position on the gene
responsible for making prions. About 38% of Britons have similar genes.
The baby, however, is understood to have a different genetic make-up,
with a molecule called valine in place of one of the methionines. This
configuration is found in about half the British population.

Doctors at the Medical Research Council's prion research unit at Queen
may Hospital in London have speculated that the illness could show very
different symptoms in such people and may only be confirmed by a
post-mortem.

Other experts have, however, suggested that the child's illness is not
related to her mother's and that she is simply one of a small number of
children born every year with terrible and inexplicable handicaps.
CJD and its animal equivalents such as BSE in cattle and scrapie in
sheep are thought to be caused when naturally occurring proteins known
as prions undergo a change in shape that alters their behaviour and
makes them attack brain  tissue.

In BSE and variant CJD the change in shape is initiated simply by
contact with abnormal prions which can enter the body via contaminated
food. Humans are thought to have acquired variant CJD be eating one of
the 750,000 cows infected with BSE that entered the human British food
chain before 1996.

In cows and sheep, however, scientists have found that infection may
also pass down the generations - possibly from mothers to their
offspring. It is not known whether this happens during pregnancy, birth,
suckling or by some other means.

In Britain only one other woman has been known to give birth to a child
while ill with variant CJD and that youngster, a boy now aged five,
remains completely healthy.


Jonathan Leake
Science & Environment Editor
The Sunday Times
1 Pennington Street
Wapping London E1 9XW
Email: jonathan.leake@sunday-times.co.uk
Tel 020 7782 5333                    (Outside UK .. 44 20 7782 5333)
Fax 020 7782 5731 or 5542
Mbl 07957 420334                     (Outside UK .. 44 7957 420334)

http://www.sunday-times.co.uk/news/pages/changing-times.html?999

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Subject: Re: A woman who became ill with variant CJD while pregnanthas died...

From: Roland Heynkes <roland@heynkes.de>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>

Date: Thu, 8 Jun 2000 23:07:48 +0200

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#########  Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>  #########

Hello Terry,

> i started not to reply to your rude outburst, but thought
> i should defend the reporters (most), that are just
> reporting what information they get from the doctors and
> scientist. i for one, and i am sure others as well, are
> very interested in reading Mr Leake's reports of the Mother
> whom died from vCJD and her Baby. Because if we don't
> hear from him about it, then we don't hear about it at all.
> May i suggest using your DELETE button, if the TSE news
> coming from reporters upset you so much.
>

I am of course interested in the final diagnosis of the baby
and I have absolutely no problem with news coming from
reporters - if they are correct. But the article does not
tell us something new about what the baby is suffering from
and instead misinforms non-experts. The latter is the problem
and it does not help when I use my DELETE button. I don't
want this list to spread misleading wrong information and
therefore I have to correct mistakes. It is no problem for
me to discuss the correct interpretation of existing data
as with Rachel, but it is really frustrating to correct the
same simple mistakes every two weeks. For this reason I asked
you not to forward complete articles with all mistakes. You
are experienced enough to forward only the valuable information
without all the misleading things.

> Roland, i respect your views as a scientist, with the utmost
> respect, but you missed the boat on this one. (just my view).
>

I respect your view, but a stupid mistake is a stupid mistake
and my aim was to make Mr Leake somewhat more careful with
what he publishes. I tried to explain friendly during the
last months, why and how journalists should try to avoid
to publish obvious and misleading mistakes, but now I thought
I should speak a bit more more plainly.


>>> Doctors have spent the last few days conducting tests on
>>> tissues taken from the dead woman in the hope of finding
>>> a link to her child's illness.
>
>> I am sure that they indeed hope to reach a different diagnosis.
>
> i suppose we all are hoping for that, but i think it is very
> possible to pass the prion through birth, by some means or
> another...
>

I agree with you, but read what Mr Leake wrote.

>> There is no evidence that prion disease can transmit from
>> mother to offspring in cattle. Journalists who write things
>> like this, should be able to give the evidence.
>

> once again, absent of evidence is not evidence of absent, and
> with what is known (BSE still spreading, since the SRM have
> been put into place???) something is causing it. plus, you
> speak of showing evidence by journalists, what about all
> the hypothesis that the doctors/scientist put forth, without
> evidence???
>

You are right - the lack of evidence does not mean that there
is no maternal transmission. But as long as there is no
evidence, nobody should write there is.

The second point is somewhat more complicated. Is BSE still
spreading? Until now we do not really now, as we don't have
BSE cases born after the final improvement of the measurements.
Personally I think that there will be such cases, but this
again will not mean that maternal transmission is the only
possible explanation for suchcases. It is only more comfortable
to explain such cases with maternal transmission instead of
mites, fly larvae, or just contaminated pastures. I am sure
you see the difference.

I agree with you that unfortunately scientists sometimes
mix facts and speculation and of course it is not always
easy for journalists to correct the scientists. But they
should know that and they are naiv if they believe everything
that they become told by scientists or what they read in
peer reviewed journals. They have to live with the fact that
things are not so easy and that they have to check very
scrupulous what they have been told. This is what thousands
of journalists in other fields like politics or finances
do every day and therefore it is - in my opinion - not too
much to ask science writers to do the same.

>>> One of the complicating factors is that all the 70-odd
>>> definite or probable victims share a particular genetic
>>> make-up, having two molecules called methionine at a
>>> particular position on the gene responsible for making
>>> prions.

>
>> It is terrible that so called Science Editors write such
>> unbelievable nonsense. Nobody should finish the high school
>> without knowing that methionin is no component of DNA and
>> nobody should write about TSE without knowing what
>> 129 met/met means.
>

> i am sure mr. Leake has finished high school and knows
> what 129 met/met means.
>

But Terry - he wrote that there are two methionins at a
particular position on one gene. This is no didactic reduction
in order to make it more understandable - this is simply a
total nonsense that confuses readers. We know that in all
patients with nvCJD both, the maternal and the paternal
gene for the normal cellular prion protein code for methionin
instead of valin at position 129 of the prion protein. This
explanation is not much longer and not too difficult to
understand - and it has the advantage that it is correct.


>>> CJD and its animal equivalents such as BSE in cattle and
>>> scrapie in sheep are thought to be caused when naturally
>>> occurring proteins known as prions undergo a change in
>>> shape that alters their behaviour and makes them attack
>>> brain  tissue.

>

>> Terry, you know that prions are no naturally occurring
>> proteins.

>

> yes sir, i do, thanks, but this is just more B.S.e., that the
> scientist are passing, not reporters, they are just reporting
> the B.S.e. that the scientist are telling them. when you have
> scientist that continue to try to push the issue of naturally
> occurring prions, to try and push the obvious 85%+ sporadic
> CJD numbers down with this nonsense, you are going to have
> reporters, report it. it should be the scientist you slam,
> for passing such B.S.e...

>

Indeed even some scientists sometimes do not use this term
correctly and you are right to call this B.S.e. But it is
really easy to find the definition of prions and other
journalists do not spread every nonsense as facts that
politicians may tell them. It makes me sad that scientists
use technical terms incorrectly, but normally this is no
problem because they do it among professional colleagues.
When journalists use wrong terms this is a problem, because
they confuse their readers. Imagine people read in such
articles that everybody naturally has prions and a couple
of days later they learn that prions are deadly infectious.
This may cause panic feelings and indeed I often get telephon
calls by such very concerned people.

I perfectly know that it is not easy to write about prion
diseases, but in my opinion it is very important to use
the terms correctly. When I wrote my first article about
prion diseases, I needed several weeks although I already
studied this diseases for 5 years. But too many journalists
think that they can write about it after speaking with an
expert for half an hour.

> Roland, as i said before, i greatly respect your views as a
> scientist, but give these reporters a chance. i for one have
> learned things from reporters. and i really doubt that you
> could say, you have never learned something from a reporter,
> at some time, but i could be wrong.
>

Intelligent people can learn even from idiots (This does of
course not mean that all journalists are idiots.) and of
course I do not want to give someone no chance. But I want
to motivate journalists to become more careful with what
they write and I am prepared to use even rude words if I feel
that this is necessary to make them waking up.

I definitively have no problem with the fact that some
journalists become very angry about my critics. But I
want them to become very concerned about what I might write
about their next articles when they do not do their best.
I think that this is a chance for journalists to become
better and I think that this is better than giving them
the chance to write their nonsense ad infinitum.

In my opinion not journalists need a chance to write
whatever they want, but their readers should get a chance
to become informed correctly.


> but one must learn to separate the B.S.e. from the
> beneficial news. please try, or just use the delete button.
>


This separation is no problem for me, but there are not only
experts in this list. Therefore I asked you already some
weeks ago to do this separation for the less experienced
members before you forward articles. You wrote that you
understood my point and therefore I was somewhat astonished
that you forwarded this article without any warnings.


I hope that you now at least understand why I do not use
the delete button and instead become somewhat angry when
I find such articles in BSE-L. May be that my comments
on such articles are not very nice when I have to do it
in English, but my postings are available for perhaps
300 people, not for millions as articles in prominent
newspapers.


kind regards,

Roland


p.s.: I do not answer private emails about this matter
      even when they come with "high priority". Everybody
      who thinks that I made a mistake or are too rude,
      can discuss her/his points in BSE-L like Rachel and
      Terry did. I am not at all interested in wasting my
      time with defending my words privately. For me the
      only important point is that wrong statements do
      not stay without comment in BSE-L. Private emails
      become victims of my DELETE button immediately.


############  http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html  ############


the year, 2004


Subject: re-Mother passes on CJD to unborn baby SUNDAY TELEGRAPH Sun, 17 Sep 2000 10:09:01 -0700

From: "Terry S. Singeltary Sr." <flounder@WT.NET>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE>

Date: Sun, 26 Dec 2004 11:32:26 -0600

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#####################  Bovine Spongiform Encephalopathy  #####################

Greetings list members,

> re-Mother passes on CJD to unborn baby SUNDAY TELEGRAPH  Sun, 17 Sep 
> 2000 10:09:01 -0700 

WHY is it we have heard nothing else about this case?

WHAT is the latest about this child that was supposedly to have
been infected with nvCJD via his mother from birth, after which
the mother passed on with confirmed nvCJD ???

thank you,
kind regards,

Terry

Subject: Re: re-Mother passes on CJD to unborn baby SUNDAY TELEGRAPH Sun, 17 Sep 2000 10:09:01 -0700

From: "Terry S. Singeltary Sr." <flounder@WT.NET>

Reply-To: Bovine Spongiform Encephalopathy <BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE>

Date: Tue, 28 Dec 2004 16:01:13 -0600

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#####################  Bovine Spongiform Encephalopathy  #####################

I was wondering if this small statement might be referring to this case ;

> The item was discussed in a reserved business session because it 
> involved consideration of confidential medical information and 
> unpublished data.


MATERNAL TRANSMISSION OF vCJD

DH asked SEAC to consider the potential for maternal transmission of 
vCJD. The item was discussed in a reserved business session because it 
involved consideration of confidential medical information and 
unpublished data.

SEAC concluded that there is no evidence for maternal transmission of 
vCJD, but acknowledged that most of the relevant information is indirect 
rather than direct. Therefore, although it was considered that a 
hypothetical risk of maternal transmission is likely to be low, a risk 
cannot be ruled out.

http://www.seac.gov.uk/summaries/summ_301104.htm


see updated url link for this old seac statement here...2018...tss






Terry S. Singeltary Sr. wrote:


Sunday, 17 September, 2000, 00:54 GMT 01:54 UK

Mother 'passed CJD to baby'

A baby whose mother died of Creutzfeldt-Jakob disease is showing symptoms of the same illness, it has been reported.

The 11-month-old girl has been examined by doctors, according to the Sunday Telegraph, and is said to have brain damage and suffer from fits and convulsions.

If the disease is confirmed, it would be the first proof that vCJD, the human form of mad cow disease, can be transmitted from mother to child.

It would support the theory that the disease is hereditary rather than caught by eating infected meat.

But there are also fears that the illness can be transmitted through blood, in this case to the baby while in the womb.

The doctors who examined the baby are reported as saying they cannot be sure she has the illness but that they did not find any other ailment.

Slow growth

Tests carried out on her appendix apparently proved inconclusive in finding traces of vCJD. The girl is due to undergo further brain scans later this year.

She is said to be growing at half the normal rate for a child her age and suffers from poor sight and abnormally stiff limbs. 

However, only a post mortem examination would give conclusive evidence.

Richard Lacey, a professor of medical microbiology at Leeds University, believes it is "inevitable" that mothers infected with vCJD will pass the illness on to their offspring through the placenta.

"The only thing that is uncertain is the scale on which it is happening," he is quoted as saying in the Sunday Telegraph.

The Ministry of Agriculture said in 1996 that a pregnant cow could pass BSE to its unborn calf.

So far, 67 people are known to have died of vCJD, with their ages ranging from 18 to 40. 


CJD and Baby foods (the great debate 1999)

Subject: Re: Girl, 13, shows CJD symptoms.

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

Date: Wed, 24 Nov 1999 11:35:44 -0600 Content-Type: text/plain Parts/Attachments: text/plain (67 lines)

######### Bovine Spongiform Encephalopathy #########

Heather Paine should be educated on the products she over-sees. These children's health are at risk, and if she does not know what has and has not been going into baby-foods, she does not need to hold that position. The Inquiry was very concerned about baby foods, and at one point said something about; they were no different than the SBO's, in some cases, depending on the ingredients, of that particular kind of baby food. I forget the exact quote and by whom it was said??? I have it somewhere, but my filing system has a lot, _not_ to be desired for..............

Debora MacKenzie wrote:

######### Bovine Spongiform Encephalopathy #########

The mother diagnosed as having CJD gave birth last autumn at a Midlands hospital. Neither the mother nor the hospital can be named for legal reasons. Her daughter is also thought to be suffering from a neurological condition and doctors are awaiting the result of tests to see if she also has CJD.
Asked to quantify the risk to those mothers exposed to the instruments, Dr Griffiths added: "When something has never happened, you don't know whether it's one in a million or one in a thousand." ....

Comment (Rachel Shepherd, New Zealand): "In my opinion the mothers and children who have been exposed should be told. It is their right to know and act appropriately. It is not enough to tell the family doctor, many people to not keep in touch with one doctor and although records can be forwarded to a new doctor they frequently are not forwarded.
What happens when one of these mothers gets pregnant again? What happens if either mother or child need surgery? Are we going to contaminate yet more unsuspecting people and say "it was an accident, it could not have been avoided"?
What happens when the mother or child show symptoms? There is the delay in treatment and the damage to a family in which a loved one is going insane. The only reason I can see for this "paternalistic" attitude is fear of legal action or damage to reputations."

Comment (J Ralph Blanchfield, Institute of Food Science & Technology, UK): "The reported decision not to tell the women is morally wrong, and dangerous if effective. Actually it is almost certainly ineffective, because the CJD victim gave birth in November 1999 and the instruments were used for two months after that; and (as was inevitably going to happen)at least one newspaper has named the hospital. So the women at risk (plus some others not at risk) will already know.
Why did it take two months after the delivery to diagnose in the mother? One can only speculate, but in other cases of vCJD (sorry, Roland, but vCJD is a convenient "shorthand") the early symptoms were assumed to be psychiatric. Assuming that in due course the disease is confirmed in the infant, it suggests an extraordinarily short incubation period, almost certainly beginning while a foetus."

Comment (Roland Heynkes, Germany's TSE expert): " Is it really ok not to tell them, that they can live without this fear? But perhaps there may be many more patients with developing CJD who all contaminate British surgical instruments. Indeed contaminated surgical instruments may be not be a problem for many British women, because they are already infected directly from cattle. What a depressing situation of uncertainity!"



***> see HISTORY great debate here <*** 

BSE, CJD, and Baby foods (the great debate 1999 to 2005)

http://bseinquiry.blogspot.com/2008/05/bse-cjd-and-baby-foods-great-debate.html


SO, WHAT WAS THAT FINAL DIAGNOSIS OF THAT POOR CHILD $$$


i think maybe Jonathan will try and find out...September 2018...tss


Volume 24, Number 7—July 2018

Dispatch

Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification

Daisy BougardComments to Author , Maxime Bélondrade, Charly Mayran, Lilian Bruyère-Ostells, Sylvain Lehmann, Chantal Fournier-Wirth, Richard S. Knight, Robert G. Will, and Alison J.E. Green

Author affiliations: Etablissement Français du Sang, Montpellier, France (D. Bougard, M. Bélondrade, C. Mayran, L. Bruyère-Ostells, C. Fournier-Wirth); University of Montpellier, Montpellier (S. Lehmann); University of Edinburgh, Edinburgh, Scotland, UK (R.S. Knight, R.G. Will, A.J.E. Green)

Abstract

A patient with a heterozygous variant of Creutzfeldt-Jakob disease (CJD) with a methionine/valine genotype at codon 129 of the prion protein gene was recently reported. Using an ultrasensitive and specific protein misfolding cyclic amplification–based assay for detecting variant CJD prions in cerebrospinal fluid, we discriminated this heterozygous case of variant CJD from cases of sporadic CJD.

Variant Creutzfeldt-Jakob disease (vCJD) is a neurodegenerative infectious disease caused by transmission of a cattle prion disease (bovine spongiform encephalopathy) to humans (1). Most vCJD cases have occurred in the United Kingdom, where an estimated 1 in 2,000 persons is potentially asymptomatically infected, although there is some uncertainty about interpretation of detection of abnormal prion protein (PrPTSE) in appendix tissues on which this incidence is based (2) (Public Health England, 

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/546883/hpr2616.pdf

Until recently, all clinical cases of vCJD for which the prion protein gene has been analyzed have been shown to be methionine homozygous at codon 129, a genotype present in almost 40% of Caucasian populations. The report of the first definite heterozygous methionine/valine vCJD patient who died in 2016 (3) underlined previous concern about a possible second wave of vCJD cases (4). The clinical features of this patient were more similar to those of patients with sporadic CJD (sCJD) than to those with vCJD. This patient had met the agreed surveillance diagnostic criteria for probable sCJD (5). However, vCJD was diagnosed during an autopsy; florid plaques were observed by histologic examination of the brain and peripheral detection of PrPTSE in lymphoid tissues. Western blot analysis of brain tissue confirmed a type 2B molecular profile of PrPTSE, which is characteristic for vCJD.

A diagnostic test to identify methionine/valine heterozygous vCJD cases is urgently needed to enable discrimination between heterozygous vCJD and sCJD and in view of the potential reservoir of methionine/valine heterozygous asymptomatic vCJD carriers in the blood donor population. We developed a highly sensitive and specific assay that accurately detects vCJD prions in blood even before the occurrence of clinical signs (6). We adapted this assay, which was based on protein misfolding cyclic amplification (PMCA) (7), for specific detection of vCJD in cerebrospinal fluid (CSF) and confirmed the ability of this assay to differentiate patients with atypical heterozygous vCJD from patients with sCJD.

The Study

We blindly analyzed 98 CSF samples provided by the National CJD Research and Surveillance Unit (Edinburgh, Scotland, UK) and the Centre Hospitalier Universitaire de Montpellier (Montpellier, France) after obtaining appropriate consent. Clinicians distributed CSF samples into blinded panels from the United Kingdom and France; 41 from patients with vCJD; 23 from patients with sCJD; 1 from a patient with genetic CJD; and 33 from patients with non-CJD, including samples from patients with Alzheimer’s disease and patients with nonneurodegenerative diseases.

CSF samples were thawed at room temperature and used directly in PMCA. We performed PMCA amplification by using brains from humanized transgenic mice as substrate for normal prion protein. After successive rounds of 160 cycles of PMCA for 15 min and sonication for 20 s, we detected PrPTSE by using Western blot after digestion with proteinase K (6).

Of the 98 CSF samples analyzed, our assay identified 40 of 41 cases of clinical vCJD, including the methionine/valine heterozygous patient, thus showing a diagnostic sensitivity of 97.6% (95% CI 87.1%–99.9%) (Table). One CSF sample from a probable case of vCJD showed a negative result. After decoding by clinicians, we retested this sample in duplicate; it showed a positive result.

Our assay also showed high analytical specificity; 0 of 57 potentially cross-reacting CSF specimens from patients with sCJD, gCJD, Alzheimer's disease, and other nonneurodegenerative diseases showed a positive result (specificity 100% [95% CI 93.7%–100%]) (Table). The case-patient with methionine/valine heterozygous vCJD was specifically discriminated from the 12 methionine/valine heterozygous neuropathologically confirmed sCJD case-patients tested.

[[AA:F1:PREVIEWHTML]] We then compared by using Western blot the PrPTSE molecular signature obtained for the clinical vCJD amplified samples from classical methionine homozygous cases and the new methionine/valine heterozygous vCJD case with that of the reference brain sample from a patient with vCJD (Figure). As expected, the profile obtained after PMCA amplification of the CSF from the methionine/valine heterozygous vCJD patient was similar to those obtained for methionine homozygous vCJD patients. The characteristic type 2 mobility and clear predominance of the diglycosylated isoform was obtained for all vCJD patients before or after amplification.

Conclusions We report a specific detection method that enables clinical diagnosis of a heterozygous methionine/valine heterozygous vCJD patient. This patient was the first definite heterozygous patient described since the start of the vCJD epidemic in the United Kingdom in 1996 (3). Clinical diagnosis was difficult because clinical signs and symptoms, particularly cerebral appearance by magnetic resonance imaging, were suggestive of sCJD (3). The vCJD blood test (direct detection assay) developed by the Medical Research Council Prion Unit (London, UK) (8) showed a negative result for this case-patient. We found characteristic vCJD prion protein amplification in the CSF, which led to a specific diagnosis of vCJD because sCJD samples did not show positive results by PMCA. This result also demonstrates the possibility of amplifying methionine/valine heterozygous vCJD prion protein by PMCA with a substrate from humanized transgenic mice that overexpress homozygous methionine prion protein (9). However, PMCA analysis should be performed in a Biosafety Level 3 laboratory and requires highly experienced personnel.

Iatrogenic transmission of vCJD by blood transfusion has been documented in 3 recipients of nonleukodepleted erythrocyte concentrates from blood donors during development of disease (10). One additional probable case of vCJD transmission by blood transfusion was identified during an autopsy of a methionine/valine heterozygous patient who died from a nonneurologic disorder and in whom vCJD prion protein was detected in the spleen (11). The presence of infectivity in blood of the definite methionine/valine heterozygous vCJD patient involved in our study is uncertain and requires further investigation.

From a clinical point of view, prion amplification technologies, such as PMCA and real-time quaking-induced conversion (RT-QuIC), have already shown their sensitive detection of disease-related prion protein in biologic fluids (6,12–14). Independent studies have shown that detection of prion protein seeding activity in CSF by RT-QuIC might have a specificity of 99%–100% for diagnosis of sCJD (13,15). Application of RT-QuIC and PMCA for CSF samples might represent a suitable strategy for premortem discrimination between sCJD and vCJD including methionine/valine heterozygous case-patients, particularly for cases with a heterozygous codon 129 genotype in which clinical distinction between sCJD and vCJD is problematic.

 Top

Dr. Bougard is a research scientist in charge of the Prion Group at Etablissement Français du Sang of Montpellier, France. Her primary research interests include development of innovative tools for the prevention of transfusion risk associated with nonconventional agents.

 Top

Acknowledgments

We thank Maria-Teresa Alvarez and Jacques-Damien Arnaud for providing helpful assistance in the L3 facility at the Etablissement Confiné d’Expérimentation–Centre d'Elevage et de Conditionnement Expérimental des Modèles Animaux of the University of Montpellier.

This study was supported by Etablissement Français du Sang and the UK Department of Health Policy Research Programme (grant PRST061400008).

 Top

References

snip...



The vCJD epidemic is in marked decline both in the UK and internationally ( Figure 4). Until recently, all tested cases of definite and probable vCJD had been MM at codon 129 of PRNP, but in 2015 a confirmed case with an MV genotype was identified 12. This raises the possibility of a further outbreak, although it is likely that should this occur the number of cases will be relatively limited and probably lower than those of the primary epidemic in the MM population. The UK population were exposed to a significant level of BSE infectivity in the food chain in the 1980s and early 1990s, and the relatively small scale of the vCJD epidemic may imply a significant barrier to infection between bovines and humans 24.


CORRESPONDENCE

Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129 

18 Citing Articles TO THE EDITOR: Prions cause lethal neurodegenerative diseases in mammals and are composed of multichain assemblies of misfolded host-encoded cellular prion protein (PrP). A common polymorphism at codon 129 of the PrP gene (PRNP), where either methionine (M) or valine (V) is encoded, affects the susceptibility to prion disease, as well as the incubation period1 and clinical phenotype of prion disease. Human infection with the epizootic prion disease bovine spongiform encephalopathy resulted in variant Creutzfeldt–Jakob disease, which provoked a public health crisis in the United Kingdom and other regions. All definite cases of variant Creutzfeldt–Jakob disease to date have occurred in patients with the MM genotype at PRNP codon 129.1

Figure 1.

MRI of the Brain. A 36-year-old man was referred to the United Kingdom National Prion Clinic in August 2015 with personality change. Over a period of 9 months, he had become uncharacteristically irascible and had progressive episodic memory impairment, gait ataxia, and myoclonus. His score on the Mini–Mental State Examination was 25 (with scores ranging from 0 to 30 and higher scores indicating less impairment); clinical examination revealed extraocular eye-movement abnormalities, pyramidal and cerebellar signs, and multifocal myoclonus. Magnetic resonance imaging of the brain (Figure 1) revealed restricted diffusion in the basal ganglia, hypothalami, insular cortexes, and medial thalami but not in the pulvinar nuclei.2 Examination of the cerebrospinal fluid for protein 14-3-3 was negative, as was a real-time quaking-induced conversion assay, although these two tests are known to have low sensitivity for variant Creutzfeldt–Jakob disease.3 His genotype at PRNP codon 129 was MV. During the following 6 months, the patient’s condition declined progressively, and severe dysphagia and agitation occurred shortly before his death in February 2016.

At autopsy, histologic examination of the brain revealed frequent florid and cluster plaques in cerebral and cerebellar cortexes, microvacuolar degeneration in neuropil, and immunostaining for abnormal PrP in a stellate pericellular and perivascular distribution. Minute amounts of protease-resistant PrP (PrPSc) were seen in lymphoid tissue of the spleen. Immunoblotting of brain homogenate revealed type 4 PrPSc (according to the London classification system), which is pathognomonic of variant Creutzfeldt–Jakob disease.4 (For more details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org.)

This patient’s clinical features differed from those of typical variant Creutzfeldt–Jakob disease, and his neuroimaging features suggested a diagnosis of sporadic Creutzfeldt–Jakob disease. He did not meet the epidemiologic diagnostic criteria for probable or possible variant Creutzfeldt–Jakob disease,5 yet the results of the neuropathological examination and molecular strain typing were consistent with variant Creutzfeldt–Jakob disease. It remains uncertain whether this case marks the start of a second wave of variant Creutzfeldt–Jakob disease in persons with the MV genotype at PRNP codon 129 (the most common genotype in the United Kingdom), mirroring the long incubation periods seen in persons with the MV genotype who have other acquired prion diseases, notably kuru.1 This case emphasizes the importance of performing an autopsy and molecular strain typing in cases of prion disease to ascertain the prevalence of human prion disease related to bovine spongiform encephalopathy.

Tzehow Mok, M.R.C.P. University College London Institute of Neurology, London, United Kingdom

Zane Jaunmuktane, F.R.C.Path. University College London Hospitals NHS Foundation Trust, London, United Kingdom

Susan Joiner, M.Sc. Tracy Campbell, B.Sc. University College London Institute of Neurology, London, United Kingdom

Catherine Morgan, M.D. Benjamin Wakerley, M.D. Farhad Golestani, M.D. Gloucestershire Hospitals NHS Foundation Trust, Gloucester, United Kingdom

Peter Rudge, F.R.C.P. Simon Mead, M.D. H. Rolf Jäger, M.D. Jonathan D.F. Wadsworth, Ph.D. Sebastian Brandner, F.R.C.Path. John Collinge, F.R.S. University College London Institute of Neurology, London, United Kingdom jc@prion.ucl.ac.uk

Supported by the National Institute of Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and the Medical Research Council (United Kingdom).

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

5 References 1.2.3.4.5.

Supplementary Material Supplementary Appendix PDF 557KB Disclosure Forms PDF 223KB


Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease

Natalia Fernández-Borges,1 Juan Carlos Espinosa,1 Alba Marín-Moreno, Patricia Aguilar-Calvo, Emmanuel A. Asante, Tetsuyuki Kitamoto, Shirou Mohri, Olivier Andréoletti, Juan María Torres

Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (HuPrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val129 Hu-PrP–positive humans with the emergence of new strain features.

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Discussion

We report a detailed comparison of the transmission properties of BSE and vCJD prions among humanized transgenic mice with different PRNP codon 129 genotypes. Because a high expression level of PrP in transgenic mice directly influences prion disease susceptibility and incubation time, these transgenic mice have an advantage over knock-in mice for evaluating these features in the different human PrP genotypes. In addition, the 3 mouse models used in our study have equivalent PrP expression levels, making them suitable for studying comparative susceptibilities across the different PRNP codon 129 genotypes.

In previous reports, we demonstrated that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent to a higher degree than to cattle BSE and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD (31). In this study, we wanted to extend these results to the other human PRNP genotypes: Met/Val129 and Val/ Val129. We gained a different perspective when several BSE isolates adapted to different species inoculated in TgVal129 mice showed an apparent lack of transmission. In addition, almost all inoculated TgMet/Val129 mice did not transmit BSE; this finding supports the interpretation by Wadsworth et al. that human PrP Val129 severely restricts propagation of the BSE prion strain (27).

An unexpected result of this study was the finding that 1 BSE isolate from a goat (Ca-BSE/Go) was clinically transmitted to 1 of 10 TgMet/Val129 mice and subclinically transmitted to TgVal129 mice. This particular isolate is characterized by a high infectious titer (35) that could explain the potential for this inoculum to overcome the restriction on BSE prions to propagate in TgVal129 mice.

Although cattle BSE did not transmit to TgMet/Val129 mice directly, adaptation of the BSE agent to human PrP Met129 sequence and subsequent inoculation of the resultant vCJD prions to TgMet/Val129 mice produced a 100% attack rate. However, we did not detect clinical prion disease, supporting a slower rate of vCJD conversion compared with that among TgMet129 mice. This slow but potential conversion rate in TgMet/Val129 mice correlates well with the single vCJD case of a human carrying the PrP Met/Val129 genotype (22) and with the description of subclinical secondary transmissions through human vCJD–infected tissues (4–7,47).

TgVal129 mice challenged with Hu-vCJD2 did not produce detectable brain PrPres and clinical signs, in spite of the overexpression of HuPrP-Val129 and the use of the more efficient intracerebral route of infection. However, subclinical infection in these TgVal129 mice was demonstrated in BoPrP-Tg110 mice. These data suggest that PrP Val129 could sustain a very slow and limited vCJD conversion rate that is consistent with the detection of PrPres in tonsils and appendixes of asymptomatic PrP Val129 persons (23–25). Previous studies of other transgenic mice expressing PrP Val129 have also shown a low transmission efficiency of vCJD (2,27,30).

The fluctuating subclinical transmissibility of both vCJD inocula in TgVal129 mice (negative for Hu-vCJD1 and positive for Hu-vCJD2 ) might be caused by differences in prion titer between inocula. This assessment was strengthened after the transmission of both vCJDs to TgMet129 mice, in which a shorter incubation period was observed in animals inoculated with Hu-vCJD2 . A certain variability in subclinical transmissibility and incubation time between different vCJD isolates is not uncommon, as has been previously reported (2,27,30), suggesting that a Val129 transmission barrier can only be overcome with highly infectious vCJD isolates.

The dramatic changes in the susceptibility of TgVal129 mice (Table 3) challenged with vCJD isolates first passaged in TgMet129 mice suggest an apparent increase in titer of both vCJD prion isolates; however, adaptation of the inocula to the new host mouse cannot be disregarded as being partly responsible for this increased susceptibility. We observed a 100% infection rate, but without clinical signs of prion disease. We observed similar transmission features when we passaged vCJD in TgMet/Val129 mice. In addition, the apparent PrPVal129 restricted propagation of cattle BSE and BSE from other species was completely abolished after its adaptation to human PrPMet129.

Although PrP overexpression and the inoculation route can affect transmission efficiency, our results and those previously reported in both overexpressing and knock-in transgenic mice (2,27,30) suggest that the Val129 PrP variant could sustain a very slow and limited vCJD conversion rate, and is unable to completely prevent vCJD transmission. Biochemical and neuropathological features of vCJD transmission to TgVal129 mice showed substantial differences compared to TgMet129 or TgMet/ Val129 mice. Similar to previous reports (2,27,28,48), a type 5 PrPSc associated with very weak and diffuse PrP plaques without a florid morphology was the hallmark among these mice. In addition, our demonstration of previously unreported type 5 PrPSc in brain samples of vCJDchallenged knock-in Ki-Hu129V/V mice (30) establishes that the evolution of type 5 PrPSc associated with the transmission of vCJD prions to the Val129 genotype is not an artifact of PrP overexpression. This finding further reinforces the specific biochemical features of vCJD when transmitted to the human-PrP Val129 sequence.

Extrapolation of results from prion transmission studies based on transgenic mice has to be done with caution, especially when human susceptibility to prions is analyzed. However, our results clearly indicate that PrPVal129 individuals are highly resistant to transmission of cattle BSE or BSE passaged in other species. Also, PrPVal129 individuals might be susceptible to infection with human-passaged BSE (vCJD) prions, and the propagated agents might transmit with molecular and neuropathological properties distinguishable from those of type 4 PrPres. Although the resultant type 5 PrPSc shares the same fragment sizes as those of type 2 PrPSc, the 2 PrPSc types can be distinguished by the predominance of the diglycosylated glycoform associated with type 5 PrPSc. Overall, our results indicate that human Val129-PrP polymorphic variant is a strong molecular protector against BSE zoonotic transmission but fails to prevent human-to-human vCJD transmission. Because potential late-onset vCJD cases could appear in the population (49,50) these findings underline the need for continued investigation of all forms of human prion disease.

Acknowledgments We thank Wilfred Goldmann for providing the goat-BSE material (gBSE-P12); Juan Piquer, Irene Prieto, Patricia Lorenzo, Ana Esteban, and Ana Villa for their technical assistance; and the staff of the Biosafety Level 3 animal facility and the Biosafety Office at the CISA-INIA (Valdeolmos-Madrid) for their excellent animal care and work. This work was funded by the European Union projects CT-2006-36353 (GoatBSE), CT-2009-222887 (Priority), and 219235 ERANET EMIDA (GOAT-TSE-FREE); the UK Food Standards Agency grant M03043; the Alliance BioSecure Foundation grant FABS201403; and the Spanish Plan Nacional de I+D+I RTA2012-00004 and AGL2015-71764-REDT projects. Dr. Fernández-Borges is a research scientist in the Prion Group at Centro de Investigación en Sanidad Animal–Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain. Her research interests include prion strain characterization and evolution and the pathogenesis of prion diseases and their effects on human and animal health. 

References ...snip...end


Iatrogenic and sporadic Creutzfeldt-Jakob disease in 2 sisters without mutation in the prion protein gene

Karl Frontzek1 , Rita Moos1 , Elke Schaper1,2, Lukas Jann3 , Gregor Herfs4 , Dieter R Zimmermann5 , Adriano Aguzzi1 , and Herbert Budka1,* 

1 Institute of Neuropathology; University Hospital of Zurich; Zurich, Switzerland;

2 Vital-IT group; SIB Swiss Institute of Bioinformatics; Lausanne, Switzerland;

3 University Hospital of Psychiatry; Geriatric Psychiatry Clinic; University of Zurich; Zurich, Switzerland;

4 Department of Internal Medicine; University Hospital of Zurich; Zurich, Switzerland;

5 Institute of Clinical Pathology; University Hospital of Zurich; Zurich, Switzerland

ABSTRACT.

 Human genetic prion diseases have invariably been linked to alterations of the prion protein (PrP) gene PRNP. Two sisters died from probable Creutzfeldt-Jakob disease (CJD) in Switzerland within 14 y. At autopsy, both patients had typical spongiform change in their brains accompanied by punctuate deposits of PrP. Biochemical analyses demonstrated proteinase Kresistant PrP. Sequencing of PRNP showed 2 wild-type alleles in both siblings. Retrospectively, clinical data revealed a history of dural transplantation in the initially deceased sister, compatible with a diagnosis of iatrogenic CJD. Clinical and familial histories provided no evidence for potential horizontal transmission. This observation of 2 siblings suffering from CJD without mutations in the PRNP gene suggests potential involvement of non-PRNP genes in prion disease etiology.

KEYWORDS. Prion, prion diseases, Creutzfeldt-Jakob disease, PRNP, gene

ABBREVIATIONS. CJD, Creutzfeldt-Jakob disease; FFI, fatal familial insomnia; gCJD, genetic/ familial Creutzfeldt-Jakob disease; GSS, Gerstmann-Str€aussler-Scheinker disease; iCJD, iatrogenic CJD; PCR, polymerase chain reaction; PRNP, PrP gene; PK, proteinase K; PrP, prion protein; PrPSc, scrapie (disease-associated) prion protein; sCJD, sporadic CJD; TSEs, transmissible spongiform encephalopathies

Transmissible spongiform encephalopathies (TSEs) or prion diseases are inevitably fatal neurodegenerative diseases that result from the seeded propagation of the scrapie prion protein PrPSc onto the cellular prion protein PrPC. 1 Genetic TSEs in humans account for 10–15% of all cases and comprise genetic/familial Creutzfeldt-Jakob disease (hereafter referred to as gCJD), Gerstmann-Str€aussler-Scheinker disease (GSS), and fatal familial insomnia (FFI),2 all of which follow an autosomal dominant pattern of inheritance.3 Only one previous report has shown the co-incidence of CJD in 2 siblings without aberrations in the human PrP coding

gene PRNP.4 To date, however, all reported genetic prion diseases have been exclusively ascribed to mutations in PRNP. 3 We present the case of 2 sisters carrying wild-type PRNP, both of whom were diagnosed at autopsy with CJD.

Patient 1 was a 52-year-old woman who was admitted to the hospital because of progressive abnormal behavior, intermittent vision disorders and fatigue for over 6 months. In addition, she had developed anorexia and listlessness accompanied by obliviousness and occasional confusion during the last 2 weeks. At admission, she complained about dizziness, prefrontal headaches and expressed paranoid ideas. Furthermore, she was unable to stand and to walk safely. Focal lesions were excluded by magnetic resonance imaging. Empiric therapy with ceftriaxone and acyclovir was immediately initiated after sampling for virological and microbiological testing. All analyses of blood and cerebrospinal fluid were negative, except for a positive PCR for varicella zoster virus. In addition to the latter, cerebrospinal fluid samples tested repeatedly positive for the 14-3-3 protein. A brain biopsy was performed, and Western blot analysis of the biopsy was in line with CJD. During the course of disease the patient had to be intubated because of worsening neurology. A follow-up magnetic resonance imaging indicated new occipito-temporo-basal brain lesions on the right side. She developed paracentral bilateral pulmonary embolism in spite of thromboprophylactic treatment. Because of the diagnosis and poor prognosis, therapy was discontinued and the patient was extubated. She died in palliative care around 7 months after her first symptoms had occurred. Patient 2 was a 73 y old female patient who presented at admission with fluctuating memory deficits, paranoid delusions, visual hallucinations and unattended personal hygiene.

According to her relatives, cognitive dysfunction and social isolation had worsened rapidly over the last 3 months, when she still was able to manage book keeping at home. Moreover, the patient showed pronounced amnestic aphasia as well as severe apraxia such as not knowing how to sit down on a chair. Within two weeks after admission, she exhibited increasing swallowing difficulties, painful myoclonia on the forearms, tactile sensory dysfunction of the lower extremities, positive pyramidal signs including Babinski, gait and static ataxia, as well as emotional lability. The patient developed a formal thought disorder as indicated by incoherent speech, became increasingly bedbound and exhibited behavioral symptoms, characterized by mood-incongruent euphoria and partly mutistic states. Sixteen days after admission she was transferred to a palliative care ward where she finally died 14 y after the death of her sister, with a disease duration of approximately 5 months.

Both patients came from a family of 4 sisters, with patient 1 being the youngest and patient 2 the oldest sibling, respectively. Patient 1 was married and had one healthy son. Their father died from chronic myeloid leukaemia, their mother was mildly demented at age 98 or 99. Patient 1 had a dura mater graft at an operation for prolactinoma in 1978, 22 y before death. Unfortunately no detail on the source of the graft is now available. There was neither a history of blood transfusions nor organ donations or other possible horizontal cross-contamination between the 2 sisters. The two sisters lived 30.5 km apart from each other in linear distance, and the relationship between both was described as close and harmonic. Until the death of her sister, patient 2 spent the night at her apartment at least once a week, accompanied by a shared lunch and dinner. For around 12 years, both sisters had regularly spent their holidays in Greece together.

At autopsy, neuropathology was very similar in both patients, showing typical spongiform degeneration in all areas of the cortex with small- to medium-sized, predominantly nonconfluent vacuoles accompanied by neuronal cell loss and subsequent thinning of the cortical layer (Fig. 1A, upper panel). A marked gliosis was observed in both white and gray matter. Spongiform change was observed to a lesser extent also in the basal ganglia. The cerebellum showed signs of spongiform degeneration with small vacuoles in the molecular and granular cerebellar layers and accompanying neuronal cell loss, with relative sparing of Purkinje cells.

Immunohistochemical examination showed a diffuse and fine granular synaptic pattern of PrPSc deposition in the gray matter of the cortex and the molecular and granular layers of the cerebellum (Fig. 1A, lower panel). Western blots of proteinase K-digested brain homogenates from the frontal cortex of both patients with mouse anti-human monoclonal anti-PrP-antibodies POM1 and POM2 showed 3 bands,5 with the lowest band corresponding to unglycosylated PrP at 21 kDa, consistent with proteinase K-resistant PrP Type I according to Parchi and Gambetti (Fig. 1B).6

In both patients, PCR followed by Sanger sequencing of PRNP from DNA isolated from blood leukocytes showed no mutations in the entire coding sequence, with homozygosity for methionine codon at position 129. Hence histological, immunohistochemical, biochemical and genetic analyses are well in accordance with an MM/MV 1 histotype based on the consensus classification of sporadic CJD (sCJD) histotypes.7

After a previous description of CJD in 2 siblings without mutations in PRNP, 4 this second report of such a situation raises several questions and considerations. The first case in this report can be classified as iatrogenic CJD (iCJD) after a dural transplant; globally, more than 200 cases are on record after dural grafting.8 However, the second case cannot be classified other than sCJD, as no medical exposure risk or known genetic aberration was identified.

The chance co-occurrence of 2 rare conditions in siblings is a distinct possibility. Based on data from the Swiss CJD surveillance system, the probability of at least one of the 4 Swiss iCJD patients to have at least one sibling suffering from any kind of CJD is in the order of 103 (see derivations in Appendix). This is a small, but not vanishingly small, probability.

As CJD co-occurrence in sisters without PRNP aberrations has been now observed more than once, alternative explanations should be considered. Theoretically, both cases could have been exposed to a common prion source, as clinical, pathological and biochemical features were strikingly similar in these sisters, suggesting a similar or identical prion strain in both. Equally a remote but more intriguing possibility is consideration of potential horizontal transmission. Horizontal transmission of prion disease from one patient to another individual has been reported only for invasive medical procedures including blood transfusion or, historically, for cannibalistic Kuru.

Only very few tissues, and instruments contaminated with these, are considered to have high prion infectivity titers, and have been implicated in iCJD.8,9 However, nothing was found in our cases suggesting a conceivable way of exposure. A similar situation has been reported previously in a husband and wife where either human-to-human transmission or chance co-occurrence of sporadic CJD were discussed.10

Finally, the possibility of gCJD caused by aberrations in gene(s) other than PRNP might be considered. Most neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases as well as amyotrophic lateral sclerosis, can be caused by mutations in many different genes resulting in converging pathological phenotypes. Genetic prion diseases are exceptional in that they have only been linked to PRNP. However, it is very likely that additional factors (possibly including chaperones, heat-shock proteins, and disaggregases) may contribute to prion pathogenesis, and one would expect polymorphisms in these factors to affect genetic prion disease. A possible example for that is the description of apparently sporadic fatal insomnia in a fatal familial insomnia pedigree.11 The occurrence of families such as the one reported here may help identify such non-PRNP genes, thereby broadening our understanding of prion pathogenesis and, ideally, delivering additional therapeutic targets.

DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

None of the authors has any conflict of interest or financial interest to disclose in relation with this work.

*Correspondence to: Herbert Budka; Email: Herbert.budka@usz.ch Received September 11, 2015; Revised November 10, 2015; Accepted November 11, 2015. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/kprn 


Creutzfeldt-Jakob disease and blood transfusion safety 

C. R. Seed,1 P. E. Hewitt,2 R. Y. Dodd,3 F. Houston4 & L. Cervenakova5 1 Australian Red Cross Blood Service, Perth, WA, Australia 2 NHS Blood and Transplant, London, UK 3 American Red Cross Scientific Affairs, Gaithersburg, MD, USA 4 The Roslin Institute, University of Edinburgh, Midlothian, Scotland 5 The Plasma Protein Therapeutics Association (PPTA), Annapolis, MD, USA

Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, ‘mad cow disease’). Currently, 230 vCJD cases have been reported in 12 countries, the majority in the UK (178) and France (27). Animal studies demonstrated highly efficient transmission of natural scrapie and experimental BSE by blood transfusion and fuelled concern that sCJD was potentially transfusion transmissible. No such case has been recorded and case–control evaluations and lookback studies indicate that, if transfusion transmission occurs at all, it is very rare. In contrast, four cases of apparent transfusion transmission of vCJD infectivity have been identified in the UK. Risk minimization strategies in response to the threat of vCJD include leucodepletion, geographically based donor deferrals and deferral of transfusion recipients. A sensitive and specific, high-throughput screening test would provide a potential path to mitigation but despite substantial effort no such test has yet appeared. The initial outbreak of vCJD appears to be over, but concern remains about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and there will be at least a perception of some continuing risk to blood safety. Accordingly, at least some precautionary measures will remain in place and continued surveillance is necessary.

Key words: blood safety, epidemiology, prions, transfusion - transmissible infections.

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The first case of vCJD in such an individual was reported from the UK in 2016 and was in a 129MV PRNP heterozygote [7, 68]. Does this represent the start of a second wave, or a random event? Epidemiological studies of kuru, a disease in aboriginal tribes of Papua New Guinea practicing cannibalistic rituals, and acquired CJD have indicated that persons with any 129MM, 129VV, 129 MV PRNP genotype have been infected [69, 70], although the incubation periods were more prolonged in 129MV individuals [71, 72].

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It thus appears, at present, that a second wave cannot be discounted, but is most likely to be due to past infection through diet becoming manifest after a prolonged incubation period in non-129MM PRNP genotype individuals, rather than person-to-person transmission. Only time and surveillance will answer this question.

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Second wave probability

Although the peak of vCJD cases occurred in the UK in 2000, there remains uncertainty about the possibility or probability of a second wave of infection. There are two possible sources of a second wave. First, the development of clinical disease in those infected through diet in the past, perhaps due to an extended incubation period in individuals of a non-129MM PRNP genotype. The first case of vCJD in such an individual was reported from the UK in 2016 and was in a 129MV PRNP heterozygote [7, 68]. Does this represent the start of a second wave, or a random event? Epidemiological studies of kuru, a disease in aboriginal tribes of Papua New Guinea practicing cannibalistic rituals, and acquired CJD have indicated that persons with any 129MM, 129VV, 129 MV PRNP genotype have been infected [69, 70], although the incubation periods were more prolonged in 129MV individuals [71, 72].

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One further recipient (129 MV heterozygous) who received transfusion from a third donor died five years later without any clinical signs of vCJD, but abnormal prion protein was found at post-mortem in the spleen and one lymph node but not in the brain [76]. Other deceased recipients have either had no post-mortem, or negative findings. Fourteen of 68 identified recipients remain alive and symptom-free, and all have now passed the tenth anniversary since the transfusion in question.

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Unanswered questions and future directions Future management of the risk of transfusion-transmitted vCJD and CJD is unclear. Current evidence suggests that the transmission of vCJD from the food-chain has been effectively eliminated, at least in the UK and, in the USA, regulators have established that donors are considered at risk only if their exposure in the UK was between 1980 and 1996. It is to be presumed that such cut-off dates will also be implemented as other countries eliminate food-borne risk. Nevertheless, a taxing question is the extent to which those exposed before 1996 may be incubating infection; incubation periods beyond 40 years have been noted for kuru. One concern is that all but one of the clinically apparent vCJD cases have occurred among those with the 129MM PRNP genotype and this raises the question that the 129MV or 129VV genotypes may have a much longer incubation period. As noted, the latest UK case of vCJD was in a 129MV individual [7], which may indicate the beginning of a second wave of the epidemic.

In the UK, individuals born after 1996, and in theory not exposed to BSE in the food chain, might form a ‘lower risk’ cohort for vCJD. Their donations could then be preferentially used for recipients who also belong to the ‘lower risk’ cohort having been born after the precautionary measures for food were enacted. It was suggested, for example, that FFP from this donor cohort could be ear-marked ‘lower risk’ and could replace the supplies of FFP being imported from outside the UK. The results of the Appendix III study have naturally led to more uncertainty about when exposure to BSE through diet in the UK can be said to have ceased also leading to a lack of confidence that a date can be defined for any cohort of ‘lower risk’ donors. It also raises a question about the definition of a ‘lower risk’ group of recipients and continued use of imported FFP for this group. 

The current outbreak of vCJD appears to be over for PRNP codon 129 MM homozygotes, although there is some degree of concern about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and as long as the cohort that was exposed to BSE survives, there will be at least a perception of some (albeit small) risk to blood safety. Accordingly, some precautionary measures will remain in place. Whether feasible testing methods for potential infectivity will be available or, if available, will be used, is an open question. Certainly cost-benefit assessments have not favoured the adoption of prion filters, especially in view of existing evidence that their efficacy appears to be less than optimal. It is possible that the apparent resolution of the BSE and vCJD epidemics will result in a reduction of public, political and financial interest in this field, which will be unfortunate, because there is much yet to be learned about TSE diseases and their management. It is also reasonable to consider that there may be lessons for the future. Is it possible that there could be further outbreaks of novel TSE diseases of zoonotic origin? CWD of cervids is extraordinarily infectious in nature, and there have been some studies indicating the possibility of limited cross-species infection. As is true for other agents that may impact blood safety, continued alertness and surveillance is necessary.



 One concern is that all but one of the clinically apparent vCJD cases have occurred among those with the 129MM PRNP genotype and this raises the question that the 129MV or 129VV genotypes may have a much longer incubation period. As noted, the latest UK case of vCJD was in a 129MV individual [7], which may indicate the beginning of a second wave of the epidemic.



2018

WEDNESDAY, SEPTEMBER 05, 2018 

*** Edmonton woman one of the youngest diagnosed with CJD at 35 years old and pregnant



PRION 2017 CONFERENCE ABSTRACT 

P61 vCJD strain properties in a Spanish mother and son replicate as those of a young UK case 

Dr Abigail Diack1, Mrs Aileen Boyle, Dr Diane Ritchie2, Jesus de Pedro-Cuesta3, Alberto Rabano4, Prof Robert WiLL2, Prof Jean Manson1 1The Roslin Institute, Easter Bush, United Kingdom, 2National CJD Research & Surveillance Centre, Edinburgh, United Kingdom, 3National Center of Epidemiology and CIBERNED, Madrid, Spain, 4CIEN Tissue Bank, ClEN Foundation, and ClBERNED, Madrid, Spain 

Aims 

Since the first report in 1996, there have been 228 cases of vCJD worldwide. Comparative studies of vCJD cases have demonstrated similar clinical symptoms, patterns of neuropathology and biochemical phenotype between cases originating from different countries. Here we have investigated transmission characteristics of the first cases of vCJD in first-degree relatives, a mother and son who resided in Spain. Both individuals are in the older age range of reported vCJD cases and had relatively atypical early clinical symptoms when compared to UK cases. 

Methods 

A strain typing panel of wild-type mice was inoculated with brain homogenate prepared from both the Spanish mother (aged 64) and son (aged 41) and compared with a UK case of vCJD. Mice were assessed for clinical signs, neuropathology and PrPres glycoform profile. 

Results 

All three vCJD brain isolates transmitted successfully to the wild-type mouse panel with the appearance of clinical and pathological signs associated with TSE transmission to mice. Inocula from the Spanish mother and son showed the same temporal order of clinical endpoint in each mouse strain when compared with the UK case. The distribution of TSE vacuolation was consistent for each vCJD inocula however variability in the intensity of vacuolation distribution was apparent. This was most evident in the VM mice challenged with the Spanish mother and may be indicative of low titre. PrP deposition patterns were similar between inocula with variability in the intensity of PrP accumulation between mice observed both within and between groups. PrPres was detected in the brains of RIII and VM mice challenged with all three isolates with no differences detected. 

Conclusions 

This study of two first degree relatives with vCJD confirms that the same infectious TSE agent was responsible for both cases and is consistent with that of a UK case of vCJD and historical vCJD transmission data. This is the first strain characterisation study of an older individual with vCJD and highlights the need for awareness of vCJD in older age groups particularly in those presenting with atypical dementias. These findings add additional supporting evidence to the hypothesis that a single strain of TSE agent is responsible for vCJD cases regardless of geographical origin or age at infection and indirectly support the hypothesis of a dietary origin for primary cases of vCJD. 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS 

SEAC 102nd Meeting on Wednesday 4 March 2009 (SEE DH risk assessment on sourcing and pooling plasma) SEACAgenda 102nd Meeting on Wednesday 4 March 2009 Room 808, Nobel House, 17 Smith Square, Defra, London SW1P 3JR10.05 Approval of draft minutes from SEAC 101

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ITEM 3 - CURRENT ISSUES 8. SEAC was informed about the following issues: . A mother and son in Spain had died of variant Creutzfeldt-Jakob Disease (vCJD). This is the first recorded instance of more than one case of vCJD within one family. As both the mother and son lived in a region of Spain with a history of BSE, had frequently shared meals of cattle brain, and as no other risk factor has been identified, it seems most likely that both infections were acquired from dietary exposure. Furthermore, the similar times of onset of disease of the cases did not suggest transmission had occurred from one to the other.

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Thursday, February 26, 2009 

SEAC 102nd Meeting on Wednesday 4 March 2009 (SEE DH risk assessment on sourcing and pooling plasma) 


snip...see full text;



 >>> Here, in an experimental model of CWD, we have demonstrated the transmission of infectious prions from clinical and subclinical mothers to full-term viable, nonviable and in utero harvested offspring, revealing that the transmission of TSEs from mother to offspring can occur and may be underestimated for all prion diseases. <<<


Sunday, August 25, 2013

Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission




IMPORTANCE The facile dissemination of chronic wasting disease within captive and free-range cervid populations has led to questions regarding the transmission dynamics of this disease. Direct contact with infected animals and indirect contact with infectious prions in bodily fluids and contaminated environments are suspected to explain the majority of this transmission. A third mode of transmission, from mother to offspring, may be underappreciated. The presence of pregnancyrelated prion infectivity within the uterus, amniotic fluid, and the placental structure reveals that the developing fetus is exposed to a source of prions long before exposure to the infectious agent during and after the birthing process or via contact with contaminated environments. These findings have impact on our current concept of CWD disease transmission.


Review How do PrPSc Prions Spread between Host Species, and within Hosts? 

Neil A. Mabbott ID The Roslin Institute & Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK; neil.mabbott@roslin.ed.ac.uk; Tel.: +44-131-651-9100 Received: 2 November 2017; Accepted: 21 November 2017; Published: 24 November 2017

snip...

The possibility that human prion diseases may be maternally transmitted has obviously raised concern, especially as a number of children have been born to CJD-affected parents. However, current analyses have found no evidence that human prion diseases are maternally transmitted. For example, one study in 2011 analyzed 125 children born to parents who were diagnosed with vCJD [92]. None of these children developed vCJD during the study period or were classified as suffering from a progressive neurodegenerative disorder. The mothers of nine of these children were symptomatic at conception, birth or within a year of clinical onset, and one child was known to have been breast fed. A study in primates also found no evidence of maternal transmission of kuru, sCJD or scrapie [93], consistent with the absence of prion disease-specific PrPSc in the uterus and gestational tissues, including the placenta and amniotic fluid, of a pregnant woman with sCJD [94]. Of course, obvious caveats to these studies are the small numbers of cases analyzed, and the potentially long duration of the preclinical phase of the disease in the children. However, despite these concerns, the available data do not support the conclusion that human prion diseases can be maternally transmitted.

Pathogens 2017, 6, 60 7 of 41 Milk and Colostrum The presence of PrPSc within the mammary glands of scrapie-affected sheep has been reported [95], and the abundance may be enhanced in tissues with chronic inflammation or mastitis [96–98]. Colostrum and milk from scrapie-affected ewes have similarly been shown to contain infectious prions [99,100], which may also be enhanced in milk derived from animals with scrapie and mastitis [97]. These studies demonstrate the potential risk of prion spread between sheep and other species through the consumption of sheep milk or milk products. These studies raised important concerns that prions BSE may also be transmitted to humans through consumption of cattle milk or milk products. However, the risk is considered to be extremely low as abnormal PrP was undetectable in the milk from BSE-infected cattle [101]. As mentioned above, no evidence to support a role for vCJD transmission from an infected mother to child in humans has been reported [92].


Tuesday, April 30, 2013

Transmission of classical scrapie via goat milk

Veterinary Record2013;172:455 doi:10.1136/vr.f2613

Friday, May 10, 2013

Evidence of effective scrapie transmission via colostrum and milk in sheep

Thursday, April 26, 2012

Maternal Transmission of the BSE and Birth Cohorts



This is the first report of prion infectivity within the cervid pregnancy microenvironment, revealing a source of fetal CWD exposure prior to the birthing process, maternal grooming, or encounter with contaminated environments.




Experimental details were presented illustrating how easily CWD spreads from animal to animal including by contact with ordinary body secretions, environmental contamination and with evidence of maternal transmission (from mother to unborn offspring). 



PRION 2018 CONFERENCE


WA1 An overview— Chronic Wasting Disease mother to offspring transmission studies conducted at Colorado State University 



Nalls AV1‡, McNulty EE1‡, Hoover C1, Hoover EA1, Wild M2, Powers J2, Selariu A1, Mathiason CK1

1Colorado State University, Fort Collins, CO USA, 2 National Park Services, Fort Collins, CO USA.


Chronic wasting disease (CWD) demonstrates remarkable transmission efficiency among captive and free-ranging cervid populations. Intrigued by this facile transmission, we designed a series of studies to determine the potential for CWD transmission from mother to offspring. Viable offspring born to early or late-stage CWD-infected Reeves‘ muntjac dams demonstrated lymphoid biopsy positivity as early as 40 days post birth and developed clinical disease in 2-5 years. Prion infectivity was validated in the milk and colostrum collected from these dams via oral infection studies in naïve fawns, providing a potential mechanism for maternal transmission. High nonviability (~60%) was noted in full-term offspring born to this cohort of CWD-infected muntjac dams. Tissues harvested from the nonviable offspring contained prion seeding activity, suggesting that CWD had been trafficked from mother-to- offspring during gestation. Gestational timing of CWD transfer was assessed by analysis of in utero harvested tissues from a second cohort of preclinical and clinical CWD-infected muntjac dams, and it was found that transmission can occur as early as the first trimester of pregnancy. The next series of studies were initiated to determine if this was a phenomenon of experimental infection, or whether it also occurs in naturally-infected cervids. In collaboration with the National Park Service we evaluated in utero derived tissues from healthy free-ranging elk dams whose habitat is a known CWD endemic region. Prion seeding activity was detected in fetal tissues harvested from several preclinical CWD positive naturally-infected dams in this population. To begin to unravel the biological relevance of these findings we initiated mouse bioassay to assess the infectivity of the pregnancy microenvironment of muntjac dams. Uterus, placenta, ovary and amniotic fluid contained prion infectivity. Ongoing mouse bioassay will further define infectivity in fetal and reproductive tissues harvested from free-ranging naturally-exposed elk dams. 

This work has led to a better understanding of the transmission dynamics of CWD, demonstrating that: 

(i) fetuses of preclinicalinfected cervid dams are exposed to CWD long before exposure to maternal saliva or contaminated environments, 

(ii) CWD mother-to- offspring transmission occurs in free-ranging naturally-exposed cervid populations, and 

(iii) the Reeves‘ muntjac deer can be used to further explore mechanisms of in utero prion trafficking and the potential for multigenerational CWD transmission. 

PRION 2018 CONFERENCE


P74 High Prevalence of CWD prions in male reproductive samples 


Carlos Kramm (1,2), Ruben Gomez-Gutierrez (1,3), Tracy Nichols (4), Claudio Soto (1) and Rodrigo Morales (1) 
(1) Mitchell Center for Alzheimer´s disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA (2) Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile (3) Universidad de Málaga, Málaga, Spain (4) National Wildlife Research Center, United States Department of Agriculture, Fort Collins, CO 80521, USA. 

Chronic wasting disease (CWD) is a highly infectious and fatal illness affecting captive and freeranging cervids. Mother-to-offspring prion transmission has been described in some animal prion diseases, including CWD. However, few studies have been performed to analyze the prevalence of CWD prions in reproductive male tissues and fluids. Here, we optimized the Protein Misfolding Cyclic Amplification (PMCA) assay for the efficient detection of CWD prions in these samples. This study was done in collaboration with United States Department of Agriculture (USDA) scientists who provided blindly field-collected testes, epididymis and seminal fluid samples from 21 white-tailed deer that were analyzed for prion infection by post-mortem histological studies in brain stem and lymphoid tissues. The results showed positive CWD prion detection in testes, epididymis and seminal fluid samples. A high prevalence of CWD-PrPSc was found in samples collected at the late-presymptomatic stage of the disease. Our results showed a correlation between the presence of CWD-PrPSc in male reproductive organs and blood. These findings demonstrate a high efficiency of CWD prion detection by PMCA in testes, epididymis and seminal fluid, and offer a possibility for a routine screening of semen samples to be commercially distributed for artificial insemination. Our results may uncover new opportunities to understand the mechanisms of CWD spreading and decrease putative interindividual transmission associated to insemination using CWD contaminated specimens. 
END...TSS

https://prion2018.org/

POSITION STATEMENT MATERNAL TRANSMISSION OF vCJD SEAC January 2005


-------- Original Message -------- 

Subject: POSITION STATEMENT MATERNAL TRANSMISSION OF vCJD SEAC 

Date: Fri, 04 Feb 2005 09:54:58 -0600 

From: "Terry S. Singeltary Sr." 

To: Bovine Spongiform Encephalopathy 


1

POSITION STATEMENT MATERNAL TRANSMISSION OF vCJD Issue

1. The Chief Medical Officer for England asked SEAC to consider current evidence and comment on the potential transmission of vCJD from mother to child via human breast milk. In utero transmission was also considered. The committee also commented on the scientific basis of a risk reduction measure for possible transmission of vCJD via banked breast milk.

Background

2. No diagnostic test is currently available for the detection of abnormal PrP in milk. Research is under way to develop tests to screen for the possible presence of abnormal prion protein (PrP) in milk samples from cattle experimentally infected with BSE1. These modified tests may also be applicable to human milk. However, it is not yet clear when/if a reliable test will be available.

3. A small number of breast milk banks in the UK supply highly vulnerable premature babies for whom no milk may be available from the mother. A model developed by the Department of Health to assess the effect of pooling breast milk from multiple donors on the possible risks of transmission of vCJD via breast milk banks was considered.

4. There is some, albeit limited, published epidemiological and experimental research on maternal transmission of prion diseases. There are also unpublished surveillance data of children born to vCJD cases from the National CJD Surveillance Unit and UK surveillance of neurological illness in children which might inform on potential risks of maternal transmission. 

1 A joint FSA/SEAC milk working group is monitoring and providing advice on this research carried out at the Veterinary Laboratories Agency. 

2 Breast milk banks

5. There is no evidence that vCJD infectivity has ever been transmitted through breast milk. However, a theoretical risk exists. Modelling studies clearly show that the practice of pooling breast milk increases the number of donors to which a recipient is exposed and thereby increases the potential risk of an infant receiving milk contaminated with vCJD infectivity. The theoretical risk of infection can be minimised by not pooling the milk, by the use of individual hand operated breast milk pumps for single donors, and by the use of single-use sterilised bottles for collection. In addition, available evidence suggests that infection/inflammation of the breast results in increased lymphocytes in milk and therefore increased risk of infectivity. This risk would be minimised if milk from donors showing signs of infection is not used.

6. The committee suggested that, if practicable, milk could be stored for an appropriate period of time to allow the health status of donors to be monitored, before it is released. However, information was not available to the committee on whether long-term storage of human milk is detrimental to its nutritional quality. Maternal transmission

7. There is evidence from animal studies for low level maternal transmission of prions in cattle and sheep. This transmission may occur in utero, via milk and/or perinatally. However, the possibility that this putative maternal transmission might have been due to another mode of transmission, for example through a contaminated environment or feed, cannot be ruled out.

8. In contrast, in humans there is no evidence for maternal transmission in cases of familial prion disease, other than the transfer of a mutant form of the PrP gene, and there is no evidence of maternal transmission of Kuru. However, compared with other human prion diseases vCJD may pose a greater risk because of the greater involvement of the lymphoreticular system in vCJD pathogenesis. Although, breast tissue (and placenta) from a single vCJD case tested negative for PrPvCJD, transfer of infectivity to breast milk may depend on the physiological status of the mammary gland. Similar tests or infectivity bioassays have not been conducted on breast tissue from lactating patients with vCJD. 3

9. A published study suggesting transmission of sCJD in colostrum2 was considered unreliable because tissues not normally associated with high levels of infectivity (blood and placenta) showed equivalent infectivity to that of the brain in this study.

10. Analysis of prospective surveillance data of UK children born to mothers with, or that had subsequently developed clinical vCJD, provide no evidence for maternal transmission of vCJD. However, the number of cases is very small and the incubation period of vCJD, if transmitted from mother to child, is unknown and so the children may yet be too young to have developed symptoms.

11. The phenotype of BSE infection in humans expressing PrP genotypes other than M/M at codon 129 is not known. Given recently published studies in mice expressing the human PrP gene3, which suggest that the human PrP genotype may affect disease phenotype, the committee considered it very important that undiagnosed neurological diseases be carefully monitored. In this respect, amongst others, it is recommended that the careful monitoring of neurological illnesses through the PIND surveillance of children4 continue.

Conclusions

12. In summary, there is currently no epidemiological evidence for maternal transmission of vCJD, including transmission via breast milk. However, there is a hypothetical risk. Although available evidence is limited and mostly indirect rather than direct, this risk, if any, appears to be low. As a risk cannot be excluded, a watching brief should be maintained.

SEAC

January 2005

2 Tamai Y et al. Demonstration of the transmissible agent in tissue from a pregnant woman with CJD. New Eng J Med 1992 327, 649. 3 Wadsworth et al. Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science. 2004 306, 1793-1796. 4 Devereux G et al. Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND). Arch Dis Child. 2004 89, 8-12.


-------- Original Message -------- 

Subject: re-Mother passes on CJD to unborn baby 

SUNDAY TELEGRAPH Sun, 17 Sep 2000 10:09:01 -0700 

Date: Sun, 26 Dec 2004 11:32:26 -0600 

From: "Terry S. Singeltary Sr." 

Reply-To: BSE-L 

Greetings list members,

> re-Mother passes on CJD to unborn baby SUNDAY TELEGRAPH Sun, 17 Sep > 2000 10:09:01 -0700

WHY is it we have heard nothing else about this case?

WHAT is the latest about this child that was supposedly to have been infected with nvCJD via his mother from birth, after which the mother passed on with confirmed nvCJD ???

thank you, kind regards,

Terry 

Date: Sun, 17 Sep 2000 10:09:01 -0700 Reply-To: BSE-L

Sender: BSE-L

From: "Terry S. Singeltary Sr." 

Subject: Mother passes on CJD to unborn baby 

SUNDAY TELEGRAPH

Bovine Spongiform Encephalopathy

ISSUE 1941 Sunday 17 September 2000 

Mother passes on CJD to unborn baby 

By Rajeev Syal, Jenny Booth and Chris Hastings 

Scientists shocked as disease reveals new deadly traits Tragic inheritance of baby 'born with CJD' BSE report DOCTORS believe that a baby girl has been born with new variant Creutzfeldt-Jakob disease, the human form of mad cow disease. Her mother died of the illness earlier this year. Four specialists who have examined the 11-month-old girl believe that she is exhibiting the symptoms of vCJD and that she contracted the condition in the womb. The Telegraph knows the identity of the child, but cannot name her for legal reasons. The specialists have passed on their findings to the child's grandmother after tests failed to detect any other ailment in the girl. Only a post-mortem examination, however, can offer conclusive proof of vCJD. If confirmed, this would be the first known example of vCJD being transmitted from mother to child, and will heighten fears that the disease can be transmitted through blood. One leading microbiologist believes that some of the 67 people who have already died of vCJD may have inherited it from their mothers, rather than contracting it from eating infected meat. The baby's 50-year-old grandmother, who is now her legal guardian, said the doctors suspected that prions - the infectious agents believed to cause the disease - had been passed on to the baby in the womb and had given her brain damage. She said: "They don't know if it's gone into incubation. If so, it could be years before we can finally confirm the disease." The health of the child has been the subject of speculation since her mother died of vCJD in May, seven months after giving birth. The girl was found to have brain damage and has been suffering from fits and convulsions. Doctors have said that she is growing at half the normal rate for a child of her age and suffers from poor sight and abnormally stiff limbs. Her appendix has been examined by doctors looking for signs of vCJD, but the tests proved inconclusive. She will undergo further brain scans later this year. On Friday, The Lancet reported research by scientists at the Institute for Animal Health confirming for the first time that BSE can be transmitted in sheep by infected blood transfusions. The finding increases the likelihood that a vCJD-infected mother could pass on the disease to her baby. Richard Lacey, the emeritus professor of medical microbiology at Leeds University, said that it was "inevitable" that infected mothers would pass on vCJD through the placenta. He said: "The only thing that is uncertain is the scale on which it is happening." New variant CJD, a fatal disease of the brain and nervous system, is believed to have been transmitted to humans through eating beef infected with bovine spongiform encephalopathy. The Ministry of Agriculture admitted in 1996 that a pregnant cow could pass BSE to its unborn calf. Maternal transmission also occurs in sheep, rats and mice. Scientists have observed that offspring often develop the disease more virulently than the parent and after a much shorter incubation period. Until now, researchers have been baffled at the youth of the 67 people known to have died of vCJD. Their average age is 27. Most victims were aged 18 to 40. Dr Rob Will, of the National CJD Surveillance Unit in Edinburgh, has suggested that the victims caught the disease through eating cheap mechanically recovered meat used in school meals or even baby food. Dr Lacey however suspects that some may have contracted the illness from their mothers. The Telegraph has also learnt that the Department of Health is now considering the use of disposable surgical instruments throughout the NHS because of growing concern that blood and tissue from vCJD carriers could remain infectious even after sterilisation. As this newspaper revealed four years ago, tissue from such patients is capable of passing ordinary CJD to healthy patients, yet current standards for sterilising equipment are not adequate to destroy the prions.


SSUE 1941 Sunday 17 September 2000 

Tragic inheritance of baby 'born with CJD' 

By Rajeev Syal, Chris Hastings and Jenny Booth 

Mother passes on CJD to unborn baby THE dark-haired baby attracts admiring glances wherever she goes. She has her mother's striking blue eyes, says her adoring grandmother. Medical experts believe, however, that she is the first child to inherit the disease which killed her mother, variant Creutzfeldt-Jakob disease, while still in the womb. The child's 50-year-old grandmother, who has to feed the 11-month-old girl through a tube, said: "Every time I look at her, I see the agony that my daughter endured in her last days. Seeing my own child die in agony nearly killed me and now I am terrified that I will also see my grandchild die in the same way." For months she suspected that her granddaughter was suffering from the symptoms of vCJD. Over recent weeks, her worst fears have been confirmed by doctors from the leading London hospital that is treating her grandchild. The tragedy began in July 1998, when the woman's 22-year-old daughter - who ran her own catering business - became moody, tired and constantly tearful. Her daughter's frequent outbursts of temper were untypical; the two normally lived harmoniously together in a semi-detatched home in a Warwickshire village. By February last year, the young woman had become pregnant. She developed severe back trouble and, five months into her pregnancy, had to give up work. She could hardly move her arms and legs and had to be helped around the house. Other symptoms included pins and needles in her legs and swollen and sore lips. Doctors were mystified as to the cause of the illness. In October, to try to protect mother and child, the baby girl was delivered by Caesarean section weighing 6lb 4oz. Immediately, however, the doctors were aware that the little girl had difficulties swallowing and she was placed in a special baby care unit. The family was told by doctors two days after the birth that the baby probably had brain damage. The specialists decided to conduct a series of tests on the child. The family had begun to guess the truth. The dead woman's mother recalled: "I had spoken to someone who told me that their relative had died of CJD, and I had seen the news reports on television about cows. Then it dawned on me; my daughter's moods and the jerky movements she had begun to suffer were similar. It was an awful moment." By January, vCJD was confirmed in the mother by a biopsy on her tonsils - a procedure that is 98 per cent accurate.After this she was warned that her baby may also have contracted the disease.The young woman was virtually confined to a wheelchair and her memory was so bad that she sometimes failed to recognise her mother and her child. The baby's father had moved away from the area. Doctors tried to discover if her baby also had vCJD, but because the case was unique, and hampered by the poor health of the child, they were not sure how to reach a diagnosis. In May, the child's mother died after months of suffering. In the same month, doctors removed the little girl's appendix and took samples of her lymph tissue in the hope that an analysis would show whether she was carrying the prions - aberrant proteins - that caused the disease that killed her mother. According to the baby's grandmother, the tests carried out by the doctors were necessarily inconclusive because vCJD infection can only be finally confirmed after death through a post-mortem. They nevertheless believe that her granddaughter has been suffering from the effects of vCJD from the time of her conception. Caring for her dead daughter's child has now become the focus of the woman's life, and it is proving to be a daunting task. Her granddaughter's eyesight has been affected, and it is impossible to know how much she can see. Her limbs are stiff and she needs physiotherapy. She sleeps a lot of the time, as her mother did when she was ill. Last week she was suffering fits and convulsions, and doctors have said that she is growing at half the normal rate. She is to undergo further examinations by vCJD specialists later this year. Her grandmother said: "The appalling thing is that I am watching my granddaughter die while the Government fails to warn others that they may be passing the disease on. I want this baby's case highlighted because no other family should go through what we have been through,"


ISSUE 1941 Sunday 17 September 2000 

Scientists shocked as disease reveals new deadly traits 

By Robert Matthews 

THE growing concern over the health of the baby born to a mother with variant CJD and the new evidence, announced last week, that the disease may have spread through blood transfusions, highlight the disturbing ability of vCJD to surprise the experts. A conclusive diagnosis of vCJD in the 11-month-old child would imply a far shorter incubation period than many scientists thought possible. It would also mean that the disease can be passed down the generations, not merely acquired through contact with infected tissue. Scientists have yet to pin down the likely size of the vCJD epidemic, with estimates for Britain ranging from about 100 cases to more than 100,000; so far there have been only 82 probable or confirmed cases. The case of the baby girl means that scientists are now admitting that many predictions may have to be rethought. According to Dr Neil Ferguson of the University of Oxford, a leading expert on the mathematics of epidemics, so-called vertical transmission down the generations has, at least until now, been thought to be relatively unimportant. Dr Ferguson said: "It very much depends on the probability of it taking place. If a woman has to be very sick and symptomatic in order to give it to her baby, then the number of cases it creates are going to be very small, because she is unlikely to get pregnant." The mother of the baby at the centre of the current concern is, however, understood to have been showing only minor symptoms of the disease at the time of conception; only later in her pregnancy did she develop the classic symptoms of vCJD from which she died in May this year. Richard Lacey, an emeritus professor of medical microbiology at Leeds University, said that the Telegraph story had wider implications than its obvious medical significance. Prof Lacey said: "The only thing that is certain is the scale on which it is happening. That will take decades to find out. I am aware of other cases where maternal transmission could be an issue; this isn't the only one. "This poses difficult ethical problems: to what extent should individuals be told of the risk? Should such a person be told not to give blood when he or she is old enough to do so? What effect will this knowledge have on that person's way of life, on their emotions? There needs to be some sort of discussion about how we cope with it, but at the moment there is nothing." Epidemiologists are puzzled by the fact that vCJD is predominantly affecting young people, while classic CJD is a disease of the old. Prof Lacey suggested that one possible explanation is that the teenagers and young people who have died from vCJD may have contracted the disease from their mothers while in the womb. He added that it is a recognised clinical syndrome that infectivity accumulates when it is passed on from one generation to the next. Dr Stephen Dealler, an expert on BSE and vCJD at Burnley Hospital, said that it had been believed that mother-to-offspring infection could take place in cows, but only with a considerable incubation period. "The thinking is that it may take place in cows, but the incubation period is still three to five years," he said. "This would lead us to expect an incubation period of around seven years in humans. If the baby does have vCJD, that's a very fast incubation period." Last week's revelation resulting from animal experiments that the disease may be transferred through blood transfusions from infected people with no symptoms was being played down by government scientists, who said that all British blood is screened to remove cells that may harbour vCJD. The Telegraph has learnt, however, that the Department of Health is seriously considering the use of disposable surgical instruments throughout the National Health Service. This follows growing concern that blood and tissue from asymptomatic carriers of the disease could remain infectious even after sterilisations.




Subject: vicky rimmer THEY BEGGED ME TO HUSH IT UP – GRAN’S AGONY



***> 2018 Florida Mad Cow BSE confirmed <***


USA DETECTS AND CONFIRMS MAD COW DISEASE BSE IN FLORIDA, AND THEY ARE ONLY TESTING 20k CATTLE A YEAR FOR MAD COW DISEASE, A NUMBER BY THEY KNOW WILL NOT FIND BSE TSE PRION. OIE SAYS 40K A YEAR, AND THAT IS NOT ENOUGH, BUT IF YOUR NOT WANTING TO FIND, WORKS MOST OF THE TIME...not this time...terry


FRIDAY, AUGUST 31, 2018 

South Korea Plans to Strengthen Inspection of U.S. Beef After BSE Case


TUESDAY, AUGUST 28, 2018 

USDA finds BSE infection in Florida cow 08/28/18 6:43 PM


WEDNESDAY, AUGUST 29, 2018 

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT


WEDNESDAY, AUGUST 29, 2018 

Transmissible Spongiform Encephalopathy TSE Prion Atypical BSE Confirmed Florida Update USA August 28, 2018


WEDNESDAY, AUGUST 29, 2018 

OIE Bovine spongiform encephalopathy, United States of America Information received on 29/08/2018 from Dr John Clifford, Official Delegate, Chief Trade Advisor, APHIS USDA

''The event is resolved. No more reports will be submitted.''

well, so much for those herd mates exposed to this atypical BSE cow, and all those trace in and trace outs.

The OIE, USDA, and the BSE MRR policy is a joke, a sad, very sad joke...


THURSDAY, AUGUST 30, 2018 

Florida Department of Agriculture and Consumer Services announced it is working closely with U.S. Department of Agriculture regarding an atypical case of Bovine Spongiform Encephalopathy BSE


THURSDAY, AUGUST 30, 2018 

TRACKING HERD MATES USDA MAD COW DISEASE, TRACE FORWARD, TRACE BACK RECORDS, WHO CARES, NOT THE OIE


USDA ONLY TESTING 20k HEAD OF CATTLE A YEAR FOR MAD COW DISEASE ...LOL!

WEDNESDAY, AUGUST 29, 2018 

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT





WEDNESDAY, AUGUST 29, 2018 

***> USDA DROPS MAD COW TESTING FROM 40K A YEAR TO JUST 20K A YEAR, IMPOSSIBLE TO FIND BSE, BUT THEY DID, IN FLORIDA!



''Atypical BSE is different, and it generally occurs in older cattle, usually 8 years of age or greater. It seems to arise rarely and spontaneously in all cattle populations.''

FALSE!

''The primary source of infection for classical BSE is feed contaminated with the infectious prion agent, such as meat-and-bone meal containing protein derived from rendered infected cattle.  Regulations from the Food and Drug Administration (FDA) have prohibited the inclusion of mammalian protein in feed for cattle and other ruminants since 1997 and have also prohibited high risk tissue materials in all animal feed since 2009.''

FALSE!

LET'S REVIEW RECENT AND PAST SCIENCE THAT SHOWS THE ABOVE TWO STATEMENTS ARE FAR FROM TRUE;

PRION 2018 CONFERENCE

P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge 

Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) 

(1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States. 

In 2006, a case of H-type bovine spongiform encephalopathy (BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). 

The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. 

Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. 

The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure. 

Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with either H-type BSE from the 2004 US Htype BSE case (n=3) or from the 2006 US H-type case associated with the E211K polymorphism (n=4) using 10% w/v brain homogenates. 

Cattle were observed daily throughout the course of the experiment for the development of clinical signs. 

At approximately 50 months post-inoculation, one steer (EK211 inoculated with E211K associated H-BSE) developed clinical signs including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and was euthanized. 

Enzyme immunoassay confirmed that abundant misfolded protein was present in the brainstem, and immunohistochemistry demonstrated PrPSc throughout the brain. 

Western blot analysis of brain tissue from the clinically affected steer was consistent with the E211K H-type BSE inoculum. 

With the experiment currently at 55 months post-inoculation, no other cattle in this study have developed clinical signs suggestive of prion disease. 

This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. 

These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains. 

=====

O10 Zoonotic potential of atypical BSE prions: a systematic evaluation 

Marín-Moreno A (1), Espinosa JC (1), Douet JY (2), Aguilar-Calvo P (1), Píquer J (1), Lorenzo P (1), Lacroux C (2), Huor A (2), Lugan S (2), Tillier C (2), Andreoletti O (2) and Juan María Torres (1) 

(1) Centro de Investigación en Sanidad Animal, CISA-INIA, Carretera Algete-El Casar s/n, Valdeolmos, 28130 Madrid, Spain.(2) UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, France. 

Bovine Spongiform Encephalopathy (BSE) is the only zoonotic prion recognized to date. The transmission of BSE to humans caused the emergence of variant Creutzfeldt-Jakob disease (vCJD). In 2004 two new atypical prion agents were identified in cattle: H- and L- BSE prion strains. 

The zoonotic potential of atypical BSE prions was assessed by inoculating three different isolates of cattle H- and L-BSE in transgenic mouse lines that overexpress the human PrP covering the three different genotypes of the aminoacid 129 (TgMet129, TgMet/Val129 and TgVal129). This polymorphism is known to be a key element involved in human resistance/susceptibility to BSE. In addition, TgMet129 and TgVal129 were challenged with one H- and L-BSE isolates adapted to sheep PrP expressing hosts to assess if intermediate passage in sheep could modify the capacity of these prions to cross the human species barrier. 

Our results confirm that L-BSE transmits to TgMet129 even better than epidemic BSE. However, atypical L-BSE agent was unable to infect TgVal129 or TgMet/Val129 mice, even after passage in TgMet129. No transmission was observed with H-BSE in any mice model inoculated, irrespectively of the 129 polymorphism. After passage in sheep PrP expressing host, the properties of both H and LBSE including their capacity to cross the human species barrier were dramatically affected, emerging prion strains features that resemble those of sporadic Creutzfeldt-Jakob disease (sCJD). 

To date, this is the more extensive and complete analysis of the zoonotic potential of atypical BSE prions. These results advise not to ignore the zoonotic potential of these agents.

=====

P77 In vitro approach to estimate the human transmission risk of prions 

Iwamaru Y (1) Imamura M (2) Matsuura Y (1) Kohtaro Miyazawa (1) Takashi Yokoyama (3) 

(1 ) National Institute of Animal Health, Prion Disease Unit, Ibaraki, Japan (2) University of Miyazaki, Division of Microbiology, Miyazaki, Japan (3) National Institute of Animal Health, Department of Planning and General Administration, Ibaraki, Japan. 

Prion diseases are fatal neurodegenerative disorders in humans and animals. The key event in the pathogenesis of these disease is the conversion of host-encoded normal cellular prion protein (PrPC) into its pathogenic isoform (PrPSc) and its accumulation in the central nervous system. One of the characteristics of prion is the species barrier that limits the transmission between different species. Currently, bioassays using transgenic mice (Tg) overexpressing PrP of different species have become valuable tools for assessing cross species transmissibility of prions. 

The recent reports describing the emergence of novel bovine spongiform encephalopathy (BSE) from H-BSE and the transmission of chronic wasting disease to swine have generated concerns of human infections of newly identified prions. Although Tg expressing human PrP have been used to model human susceptibility to animal prions, these experiments are costly and time-consuming. In addition, the results of bioassays are influenced by the lines of transgenic mice used and the lifespan of the challenged animals. These factors are needed to be taken into account when assessing the human risk of prions. 

In attempt to develop the more time- and cost-saving method for assessment of the human transmission risk of prions, we performed experiments using protein misfolding cyclic amplification (PMCA) technique to investigate whether PMCA can be compatible with bioassay. Using brain homogenates of Tg expressing bovine PrP as the PrP substrate, we optimized the versatile PMCA condition that could amplify PrPSc from cattle affected with C-, H- or L-BSE. We measured the 50% PMCA seeding activity dose and the 50% lethal dose in 1 g equivalent of C-, H- or L-BSE cattle brain tissue by using PMCA or bioassay, respectively, and assessed the correlations between these doses. 

===== 

 P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge 


Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States. 

reading up on this study from Prion 2018 Conference, very important findings ;

***> This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. 

***> These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.


PRION 2018 CONFERENCE ABSTRACT



WEDNESDAY, AUGUST 15, 2018 

The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge



Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

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

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. ...

”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.

*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.



***>2018<***


TUESDAY, AUGUST 7, 2018 

Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?



TUESDAY, AUGUST 07, 2018 

Passage of scrapie to deer results in a new phenotype upon return passage to sheep



WEDNESDAY, AUGUST 29, 2018 

OIE Bovine spongiform encephalopathy, United States of America Information received on 29/08/2018 from Dr John Clifford, Official Delegate, Chief Trade Advisor, APHIS USDA

''The event is resolved. No more reports will be submitted.''

well, so much for those herd mates exposed to this atypical BSE cow, and all those trace in and trace outs.

The OIE, USDA, and the BSE MRR policy is a joke, a sad, very sad joke...



THURSDAY, AUGUST 30, 2018 

Florida Department of Agriculture and Consumer Services announced it is working closely with U.S. Department of Agriculture regarding an atypical case of Bovine Spongiform Encephalopathy BSE



THURSDAY, AUGUST 30, 2018 

TRACKING HERD MATES USDA MAD COW DISEASE, TRACE FORWARD, TRACE BACK RECORDS, WHO CARES, NOT THE OIE



USDA ONLY TESTING 20k HEAD OF CATTLE A YEAR FOR MAD COW DISEASE ...LOL!

WEDNESDAY, AUGUST 29, 2018 

USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT






WEDNESDAY, AUGUST 29, 2018 

USDA DROPS MAD COW TESTING FROM 40K A YEAR TO JUST 20K A YEAR, IMPOSSIBLE TO FIND BSE, BUT THEY DID, IN FLORIDA!



CANADA MAD COW DISEASE

BSE Cases Identified in Canadian-born Cattle Recommend on FacebookTweetShare Update: February 12, 2015 a New Case of BSE Detected in Canada The Canadian Food Inspection Agency (CFIA) announced the confirmation of another bovine spongiform encephalopathy (BSE) in a beef cow from Alberta born in March 2009. See the CFIA notice.

As of July 2017, 20 BSE cases in Canadian-born cattle have been identified, 19 in Canada and 1 in the U.S. Of these 20 cases, 14 were known to have been born after the implementation of the 1997 Canadian feed ban; 13 of these 14 were born after March 1, 1999. (See BSE Cases in North America, by Year and Country of Death, 1993-02/2015). This latter date is particularly relevant to the U.S. because since a USDA rule went into effect on November 19, 2007, Canadian cattle born on or after March 1, 1999 have been legally imported into this country for any use.

One of the 20 Canadian-born BSE cases was reported in an animal that was most likely born before or possibly very shortly after implementation of the 1997 feed ban.

Based on the known or most likely year of birth, an average of 1.4 cases of BSE occurred among the group of animals born each year in Canada from 1991 through 2004. The highest reported number of cases by birth year in a single year, 3 BSE cases, occurred in 2000, 2001 and 2002. The most recently reported case extends the period of BSE transmission in Canada through at least the early half of 2009.



MONDAY, FEBRUARY 23, 2015 

20th BSE Case Raises New Concerns about Canada's Feeding Practices and Voluntary Testing Program; Highlights Importance of COOL


MONDAY, MAY 29, 2017 

Canada CCA optimistic over potential for revisions to OIE criteria for BSE negligible risk



JUST HOW DID CANADA GET THAT NEGLIGIBLE BSE RISK FROM THE OIE $$$


Canada BSE TSE Prion ''any self-respecting rancher would have shot, shovelled and shut up''

EDMONTON - Some of former Alberta premier Ralph Klein's most colourful quotes — and the reactions they elicited:

SNIP...

"This all came about through the discovery of a single, isolated case of mad cow disease in one Alberta cow on May 20th. The farmer — I think he was a Louisiana fish farmer who knew nothing about cattle ranching. I guess any self-respecting rancher would have shot, shovelled and shut up, but he didn't do that." — Klein recalls how the mad cow crisis started and rancher Marwyn Peaster's role. The premier was speaking at the Western Governors Association meeting in Big Sky, Mont. September 2004. 

"The premier meant that in an ironic or almost a sarcastic way." — Klein spokesman Gordon Turtle.

---

"You would have to eat 10 billion meals of brains, spinal cords, ganglia, eyeballs and tonsils." — Klein speaking in Montreal in January 2005 on the risk of humans contracting mad cow disease.

---

"I would offer $5 billion to have a Japanese person to come over here and eat nothing but Alberta beef for a year. And if he gets mad cow disease, I would be glad to give him $5 billion — make it $10 billion — Canadian." — Klein speaking after Japan closed its borders to Canadian beef.

---


SUNDAY, NOVEMBER 13, 2016

Canada Transmissible Spongiform Encephalopathy TSE Prion Report Update


KOREA BANS CANADIAN ELK IMPORTS: According to the Calgary Sun, Korea has moved to ban imports of Canadian deer and elk products (antlers and antler velvet) due to the outbreak of Chronic Wasting Disease (CWD) in Saskatchewan elk herds. Late last year, the Canadian Food Inspection Agency (CFIA) ordered the slaughter of 1,700 domesticated elk at six Saskatchewan farms in attempt to stop the spread of CWD (see CA 0206). The disease has not been detected in any other province. Canada's elk population is estimated at 53,000 head and is raised primarily for antler velvet. Canada is the fourth-largest antler velvet producer in the world, behind New Zealand, China and Russia. Most of Canadian antler velvet is exported to Asia where it is sold for medicinal purposes and as an aphrodisiac.

spreading CWD around, or Trucking CWD or shipping CWD i.e. interstate movement of CWD by transportation of cervid or cervid materials

Between 1996 and 2002, chronic wasting disease was diagnosed in 39 herds of farmed elk in Saskatchewan in a single epidemic. All of these herds were depopulated as part of the Canadian Food Inspection Agency’s (CFIA) disease eradication program. Animals, primarily over 12 mo of age, were tested for the presence CWD prions following euthanasia. Twenty-one of the herds were linked through movements of live animals with latent CWD from a single infected source herd in Saskatchewan, 17 through movements of animals from 7 of the secondarily infected herds.

***The source herd is believed to have become infected via importation of animals from a game farm in South Dakota where CWD was subsequently diagnosed (7,4). A wide range in herd prevalence of CWD at the time of herd depopulation of these herds was observed. Within-herd transmission was observed on some farms, while the disease remained confined to the introduced animals on other farms.

Friday, May 13, 2011

Chronic Wasting Disease (CWD) outbreaks and surveillance program in the Republic of Korea

Hyun-Joo Sohn, Yoon-Hee Lee, Min-jeong Kim, Eun-Im Yun, Hyo-Jin Kim, Won-Yong Lee, Dong-Seob Tark, In- Soo Cho, Foreign Animal Disease Research Division, National Veterinary Research and Quarantine Service, Republic of Korea

Chronic wasting disease (CWD) has been recognized as an important prion disease in native North America deer and Rocky mountain elks. The disease is a unique member of the transmissible spongiform encephalopathies (TSEs), which naturally affects only a few species. CWD had been limited to USA and Canada until 2000.

On 28 December 2000, information from the Canadian government showed that a total of 95 elk had been exported from farms with CWD to Korea. These consisted of 23 elk in 1994 originating from the so-called “source farm” in Canada, and 72 elk in 1997, which had been held in pre export quarantine at the “source farm”.Based on export information of CWD suspected elk from Canada to Korea, CWD surveillance program was initiated by the Ministry of Agriculture and Forestry (MAF) in 2001.

All elks imported in 1997 were traced back, however elks imported in 1994 were impossible to identify. CWD control measures included stamping out of all animals in the affected farm, and thorough cleaning and disinfection of the premises. In addition, nationwide clinical surveillance of Korean native cervids, and improved measures to ensure reporting of CWD suspect cases were implemented.

Total of 9 elks were found to be affected. CWD was designated as a notifiable disease under the Act for Prevention of Livestock Epidemics in 2002.

Additional CWD cases - 12 elks and 2 elks - were diagnosed in 2004 and 2005.

Since February of 2005, when slaughtered elks were found to be positive, all slaughtered cervid for human consumption at abattoirs were designated as target of the CWD surveillance program. Currently, CWD laboratory testing is only conducted by National Reference Laboratory on CWD, which is the Foreign Animal Disease Division (FADD) of National Veterinary Research and Quarantine Service (NVRQS).

In July 2010, one out of 3 elks from Farm 1 which were slaughtered for the human consumption was confirmed as positive. Consequently, all cervid – 54 elks, 41 Sika deer and 5 Albino deer – were culled and one elk was found to be positive. Epidemiological investigations were conducted by Veterinary Epidemiology Division (VED) of NVRQS in collaboration with provincial veterinary services.

Epidemiologically related farms were found as 3 farms and all cervid at these farms were culled and subjected to CWD diagnosis. Three elks and 5 crossbreeds (Red deer and Sika deer) were confirmed as positive at farm 2.

All cervids at Farm 3 and Farm 4 – 15 elks and 47 elks – were culled and confirmed as negative.
Further epidemiological investigations showed that these CWD outbreaks were linked to the importation of elks from Canada in 1994 based on circumstantial evidences.

In December 2010, one elk was confirmed as positive at Farm 5. Consequently, all cervid – 3 elks, 11 Manchurian Sika deer and 20 Sika deer – were culled and one Manchurian Sika deer and seven Sika deer were found to be positive. This is the first report of CWD in these sub-species of deer. Epidemiological investigations found that the owner of the Farm 2 in CWD outbreaks in July 2010 had co-owned the Farm 5.

In addition, it was newly revealed that one positive elk was introduced from Farm 6 of Jinju-si Gyeongsang Namdo. All cervid – 19 elks, 15 crossbreed (species unknown) and 64 Sika deer – of Farm 6 were culled, but all confirmed as negative.

FRIDAY, SEPTEMBER 02, 2016

Canada Chronic Wasting Disease CWD Surveillance Update 2016

We have completed testing all heads received to date from the 2015/16 hunting seasons. In total we tested 4929 heads and detected CWD in 116 deer (2.4%). This is an increase in annual overall prevalence from the 2.1% in the 4163 heads tested in the 2014 surveillance program. The 116 cases in 2015 included 105 mule deer, 11 white-tailed deer; 84 males, 31 females, 1 of unknown gender). Majority of these cases (77 of 116; 66%) are mule deer bucks.



Friday, February 20, 2015

A BSE CANADIAN COW MAD COW UPDATE Transcript - Briefing (February 18, 2015)



SATURDAY, FEBRUARY 14, 2015 

Canadian Food Inspection Agency Confirms Bovine Spongiform Encephalopathy (BSE) in Alberta



FRIDAY, JANUARY 10, 2014 

USDA AUDIT ON CANADA'S MEAT INSPECTION DISTURBING (pot calling kettle black again)



Tuesday, May 21, 2013

Canada, USA, Bad feed, mad cows: Why we know three BSE cases had a common origin and why the SSS policy is in full force $$$



Thursday, January 17, 2013

Canada, U.S. agree on animal-disease measures to protect trade, while reducing human and animal health protection.



Sunday, December 2, 2012

CANADA 19 cases of mad cow disease SCENARIO 4: ‘WE HAD OUR CHANCE AND WE BLEW IT’



Tuesday, October 2, 2012

Canadian veterinarian fined after approving banned BSE high risk cattle for export to U.S.A.



Saturday, January 21, 2012

Quick facts about mad cow disease


Friday, March 4, 2011.

Alberta dairy cow found with mad cow disease.



Thursday, February 10, 2011.

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31.



Wednesday, December 22, 2010.

Manitoba veterinarian has been fined $10,000 for falsifying certification documents for U.S. bound cattle and what about mad cow disease?



Thursday, August 19, 2010.

REPORT ON THE INVESTIGATION OF THE SEVENTEENTH CASE OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN CANADA.



Wednesday, August 11, 2010.

REPORT ON THE INVESTIGATION OF THE SIXTEENTH CASE OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN CANADA.



Increased Atypical Scrapie Detections.

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.



SUNDAY, JULY 27, 2008

Docket No. 03-080-1 -- USDA ISSUES PROPOSED RULE TO ALLOW LIVE ANIMAL IMPORTS FROM CANADA 



CANADA MBM LIVE CATTLE BSE TSE PRION TO USA

Date: Sat, 14 Jun 2003 02:23:12 +0200



OIG REPORT ON IMPORTS FROM CANADA



TUESDAY, SEPTEMBER 4, 2018 

USA CJD, BSE, SCRAPIE, CWD, TSE PRION END OF YEAR REPORTS September 4, 2018

prepare for the storm...



TUESDAY, SEPTEMBER 4, 2018 

USA CJD, BSE, SCRAPIE, CWD, TSE PRION END OF YEAR REPORTS September 4, 2018



WEDNESDAY, SEPTEMBER 5, 2018 

APHIS Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0012]



WEDNESDAY, SEPTEMBER 05, 2018 

Edmonton woman one of the youngest diagnosed with CJD at 35 years old and pregnant



TUESDAY, JULY 31, 2018 

USA CJD TSE Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined May 1, 2018

http://prionunitusaupdate.blogspot.com/2018/07/usa-cjd-tse-tables-of-cases-examined.html


remember vickey rimmer, thought it was nvCJD, turned out to be sporadic CJD, just a teen...so damn sad$$$

if these links don't work now, let me know, and i will get them fixed.........terry



This was not simply another farmer but the third farmer.......




suspect case of CJD in a farmer who has had a case of BSE in his beef suckler herd.


cover-up of 4th farm worker ???


CONFIRMATION OF CJD IN FOURTH FARMER

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?

4th farmer, and 1st teenager

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...

CJD FARMERS WIFE 1989

It is premature to start ringing alarm bells but...



BSE11/1 0006 

IN CONFIDENCE 

Dr R G will 

Consultant Neurologist 

Western General Hospital 

Crewe Road 

EDINBURGH 

EH4 2XU 

13 October 1989 

Dear Bob,

An otherwise enjoyable dinner last night as guest of the Association of Clinical Pathology was marred by a conversation with a neuropathologist who was just about to write to CMO with details of a case of CJD he had just seen. When first mentioning the case, he claimed she was only 36, but after a few more glasses of wine he became less certain of that and thought she could have been older. Locally, they made quite an association with BSE, since she was a farmers wife on 'a farm that, atypically for that area of S Yorkshire, had several BSE cases. I was told the clinical and pathological pictures were typical of CJD. The brain is now preserved in Sheffield, but fresh material was sent to Newcastle for animal inoculation. I suggested the NPU might be interested in molecular biology studies at some time so asked them to retain any other material they may still have in the freezer. 

When I hear more, I will pass on the details to you, but you may hear from your own grapevine contacts in any case. Lets hope Dr Timperley got the age wrong by several decades. And lets also hope the media do not hype it up before we have a chance to investigate in adequate detail. 

I presume all, is going well with your plans for the monitoring study and that my lack of news on that at this end only means that you and Dr Dastgir are still sorting it out between you. Still no news of when the "Tyrrell" report will be published. 

with best wishes. Yours sincerely 

Dr Hilary Pickles Principal Medical Officer 

89/10.13/3.1 


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....

THE COVER UP OF MAD COW DISEASE IN FARMERS, FARMERS WIVES, AND VICKY RIMMER, THE DAY MAD COW SCIENCE CHANGED $$$

Monday, May 19, 2008

*** SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS ***

DOES ANYONE BESIDES ME SEE A PATTERN YET ???

Vickey Rimmer, 16, DID NOT DIE FROM nvCJD, she died from a form of sporadic CJD, whatever the hell that is. and there have been 16 year old die from sporadic CJD in the USA as well.

SIMPLY PUT, the ukbsenvcjd only theory was wrong from day one. the elderly are expendable, pets and kids are not.

Science was dictated by 'big buisness' after the Vickey Rimmer case with the ukbsenvcjd only myth.
and there have been 16 year old die from sporadic CJD in the USA as well.

snip...

I have interviewed Mrs Rimmer at my constituency surgery

IF there is nothing to hide, why is there so much SECRECY? WHY is the Government and other Bodies trying to stop any CHANCE OF PEOPLE CONNECTING THE TWO DISEASES. The B.S.E. problem is obvious, but if the correct measures are taken, surely the problem could be contained, however, as it stands the lack of investigation and interest of the possibility of B.S.E.. and C.J.D. being linked is open for speculation and surely someone has to account for peoples lives! WHY is so much trouble being taken to convice people that B.S.E. and C.J.D. are not linked? Guilty Conscience perhaps ? - or cover up?

HOUSE OF COMMONS

FROM BARRY JONES, M.P.

22 FEBRUARY 1994

Alleged Case of Creutzfeld Jakob Disease: Victoria Rimmer.

(now story changes that biopsy shows she does not have CJD....tss)

now story changes to ;

Advice

7. The Parliamentary Secretary is invited to note the recent statements made on __________ and the present position which remains that CJD cannot be confirmed, in this case at this stage.

3. The Medical Director at ___________________ Hospital advised the Department on 6 June that the results of ___________________ brain biopsy had been received and that it showed NO EVIDENCE OF CJD. ______________ Hospital subsequently issued a statement to the press to this effect and this was publicised widely in the press (doc 1). News coverage which followed suggested that the statement made by ________________ Hospital had been misleading (doc 2). Enquires have been made of the Medical Director at _______________ Hospital who has CONFIRMED THAT THE STATEMENT ISSUED BY THE HOSPITAL WAS ISSUED IN ERROR. The facts are that two pathology reports on the same piece of brain tissue were recieved. The first report indicated that CJD was unlikely, The second report indicated that CJD was possible, PERHAPS EVEN LIKELY, but that no definitive diagnosis could be made before a post mortem was undertaken.

MAD COW MEAL DESTROYED MY DAUGHTERS LIFE

A TEENAGE GIRL may have caught the human form of MAD COW DISEASE by eating a contaminated burger it was claimed last night.

VICKY RIMMER, 16, has the killer Creutzfeldt-Jakob disease (CJD).

GIVE ME BACK MY LIFE

THEY BEGGED ME TO HUSH IT UP – GRAN’S AGONY

HUSH UP! GOVERNMENT TOLD GRAN: ''YOU MUST THINK OF THE ECONOMY''

WHY IS MY GIRL DYING ? '' IT WAS LIKE SOMEBODY OLD INSIDE A YOUNG PERSON'S BODY



2018


ZOONOSIS UPDATE ON THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE aka mad cow type disease


 O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf 

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 



http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20



PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20


why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY



https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf



Title: Transmission of scrapie prions to primate after an extended silent incubation period) 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 



http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160



***> Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility. <***


Transmission of scrapie prions to primate after an extended silent incubation period 


Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation

Abstract 

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

SNIP...


Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.

The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.

We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.

Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.

The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.

Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.

Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.

Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.

Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.




Singeltary on Scrapie and human transmission way back, see;



ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

here is the latest;

PRION 2018 CONFERENCE

Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice 
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge). 


To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. 

Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. 

Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.

***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***

READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;

P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States 

Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA. 


SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.

AND ANOTHER STUDY;


P172 Peripheral Neuropathy in Patients with Prion Disease 

Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..


IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017, AND included 104 patients.

SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%), AND THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.

snip...see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below...terry




Prion 2017
Conference Abstracts CWD 2017 PRION CONFERENCE

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 


This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). 

Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. 

Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. 

All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 


PRION 2017 

DECIPHERING NEURODEGENERATIVE DISORDERS 

Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO 

PRION 2017 

CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS 
*** PRION 2017 CONFERENCE VIDEO 



TUESDAY, JUNE 13, 2017 

PRION 2017 CONFERENCE ABSTRACT 

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 

 SATURDAY, JULY 29, 2017 

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 

just out CDC...see;



Research

Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions

Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell) M. A. Barria et al.

ABSTRACT

Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.

Molecular Barriers to Zoonotic Transmission of Prions

Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author 

snip... 

The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine. 

***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype. 

snip... 

However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring. 

***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain. 


ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION 

10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question... 

''In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II)

EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors 

First published: 17 January 2018 
https://doi.org/10.2903/j.efsa.2018.5132 ;

also, see; 

8. Even though human TSE
exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available. 

snip... 

The tissue distribution of infectivity in CWD
infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure. 
https://efsa.onlinelibrary..wiley.com/doi/full/10.2903/j.efsa.2018.5132

zoonosis zoonotic cervid tse prion cwd to humans, preparing for the storm 

***An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE.116*** 


https://www.tandfonline.com/doi/pdf/10.4161/pri.29237

 
To date there is no direct evidence that CWD has been or can be transmitted from animals to humans. 

However, initial findings from a laboratory research project funded by the Alberta Prion Research Institute (APRI) and Alberta Livestock Meat Agency (ALMA), and led by a Canadian Food Inspection Agency (CFIA) scientist indicate that CWD has been transmitted to cynomolgus macaques (the non-human primate species most closely related to humans that may be used in research), through both the intracranial and oral routes of exposure. 

Both infected brain and muscle tissues were found to transmit disease. 

Health Canada’s Health Products and Food Branch (HPFB) was asked to consider the impact of these findings on the Branch’s current position on CWD in health products and foods. 

Summary and Recommendation: 

snip...

Health Portfolio partners were recently made aware of initial findings from a research project led by a CFIA scientist that have demonstrated that cynomolgus macaques can be infected via intracranial exposure and oral gavage with CWD infected muscle. 

These findings suggest that CWD, under specific experimental conditions, has the potential to cross the human species barrier, including by enteral feeding of CWD infected muscle. 


https://www.thetyee.ca/Documents/2017/06/24/Risk-Advisory-Opinion-CWD-2017.pdf


*** WDA 2016 NEW YORK *** 

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. 

In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. 

Student Presentations Session 2 

The species barriers and public health threat of CWD and BSE prions 

Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University 

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. 

These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. 

The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. 

We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. 

We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders


http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf


TUESDAY, SEPTEMBER 12, 2017 

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 


http://chronic-wasting-disease.blogspot.com/2017/09/cdc-now-recommends-strongly-consider.html



SATURDAY, JANUARY 27, 2018 

CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018


http://chronic-wasting-disease.blogspot.com/2018/01/cdc-chronic-wasting-disease-cwd-tse.html


Subject: CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018

CHRONIC WASTING DISEASE CWD TSE PRION IS THE USA AND NORTH AMERICA'S MAD COW DISEASE. 

THE USDA INC ET AL WORKED VERY HARD CONCEALING BSE TSE PRION IN CATTLE. they almost succeeded $$$

BUT CWD TSE PRION IN CERVIDS IS A DIFFERENT BEAST, THE COVER UP THERE, USDA INC COULD NOT CONTAIN.

SPORADIC CJD IS 85%+ OF ALL HUMAN TSE PRION DISEASE.

SPORADIC CJD HAS NOW BEEN LINKED TO TYPICAL AND ATYPICAL BSE, SCRAPIE, AND CWD.

SPORADIC/SPONTANEOUS TSE HAS NEVER BEEN PROVEN.

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***



https://www.nature.com/articles/srep11573 



CDC CWD TSE PRION UPDATE USA JANUARY 2018

As of January 2018, CWD in free-ranging deer, elk and/or moose has been reported in at least 22 states in the continental United States, as well as two provinces in Canada. In addition, CWD has been reported in reindeer and moose in Norway, and a small number of imported cases have been reported in South Korea. The disease has also been found in farmed deer and elk. CWD was first identified in captive deer in the late 1960s in Colorado and in wild deer in 1981. By the 1990s, it had been reported in surrounding areas in northern Colorado and southern Wyoming. Since 2000, the area known to be affected by CWD in free-ranging animals has increased to at least 22 states, including states in the Midwest, Southwest, and limited areas on the East Coast.. It is possible that CWD may also occur in other states without strong animal surveillance systems, but that cases haven’t been detected yet. Once CWD is established in an area, the risk can remain for a long time in the environment. The affected areas are likely to continue to expand. Nationwide, the overall occurrence of CWD in free-ranging deer and elk is relatively low. However, in several locations where the disease is established, infection rates may exceed 10 percent (1 in 10), and localized infection rates of more than 25 percent (1 in 4) have been reported. The infection rates among some captive deer can be much higher, with a rate of 79% (nearly 4 in 5) reported from at least one captive herd. As of January 2018, there were 186 counties in 22 states with reported CWD in free-ranging cervids... 

Chronic Wasting Disease Among Free-Ranging Cervids by County, United States, January 2018 

snip.... 



https://www.cdc.gov/prions/cwd/occurrence.html


*** 2017-2018 CWD TSE Prion UPDATE


https://www.cdc.gov/prions/cwd/occurrence.html


*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies. 


http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf


Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS

resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip...


https://web.archive.org/web/20090506002237/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf



Prion Infectivity in Fat of Deer with Chronic Wasting Disease
 

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.


http://jvi.asm.org/content/83/18/9608.full



Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.


http://science.sciencemag.org/content/311/5764/1117.long


*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.

see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”

From: TSS (216-119-163-189.ipset45.wt.net)

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

-----Original Message-----

From: Sent: Sunday, September 29, 2002 10:15 AM

To: 
rr26k@nih.govrrace@niaid.nih.govebb8@CDC.GOV

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.

snip...

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

snip... full text ;



> However, to date, no CWD infections have been reported in people. 

key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry 

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** 


http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true


https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article


SEE; Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Monday, May 23, 2011

CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

Public release date: 23-May-2011

Contact: Francesca Costanzo 
adajmedia@elsevier.com 215-239-3249 Elsevier Health Sciences

CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association Philadelphia, PA, May 23, 2011 – Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular – bovine spongiform encephalopathy (BSE or “Mad Cow Disease”), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) – were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association.

“While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases,” commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta.”But it’s also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents.”

Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak.

CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York.

Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild.

The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents.

The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWD-endemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses.

According to Abrams, “The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health.”

###

The article is “Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet population survey” by Joseph Y. Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger, MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic Association, Volume 111, Issue 6 (June 2011) published by Elsevier.

In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at 
http://adajournal.org/content/podcast.

http://www.eurekalert.org/pub_releases/2011-05/ehs-cap051811.php


Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH , Lawrence B. Schonberger, MD , Ermias D. Belay, MD

Accepted 15 November 2010. Abstract Full Text PDF References .

Abstract

The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission.


http://www.adajournal.org/article/S0002-8223(11)00278-1/abstract


PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ; 

Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.


http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html


NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;

Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II


http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html


 Transmissible Spongiform Encephalopathies



BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane 

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.


http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf


*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report
 ;


https://web.archive.org/web/20170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf


WEDNESDAY, SEPTEMBER 5, 2018 

APHIS Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0012]



TUESDAY, JULY 31, 2018 


USA CJD TSE Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined May 1, 2018

http://prionunitusaupdate.blogspot.com/2018/07/usa-cjd-tse-tables-of-cases-examined.html



TUESDAY, SEPTEMBER 4, 2018 

USA CJD, BSE, SCRAPIE, CWD, TSE PRION END OF YEAR REPORTS September 4, 2018



HUMAN MAD COW DISEASE nvCJD TEXAS CASE NOT LINKED TO EUROPEAN TRAVEL CDC
Sunday, November 23, 2014

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas

Updated: October 7, 2014

CDC and the Texas Department of State Health Services (DSHS) have completed the investigation of the recently reported fourth vCJD case in the United States. It confirmed that the case was in a US citizen born outside the Americas and indicated that the patient's exposure to the BSE/vCJD agent most likely occurred before he moved to the United States; the patient had resided in Kuwait, Russia and Lebanon. The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia. The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.

https://www.cdc.gov/ncidod/dvrd/vcjd/other/confirmed-case-in-texas.htm

https://vcjd.blogspot.com/2014/11/confirmed-variant-creutzfeldt-jakob.html



DECEMBER 14, 2017, 20 YEARS POST DOD MOM HEIDENHAIN VARIANT CREUTZFELDT JAKOB DISEASE HVCJD DECEMBER 14, 1997, JUST MADE A PROMISE TO MOM, AND YOU DON'T BREAK PROMISES WITH YOUR MOM, NEVER FORGET, AND NEVER LET THEM FORGET...

TERRY S. SINGELTARY SR.


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