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Published Date: 2011-02-11 16:00:09
Subject: PRO/AH/EDR> Prion disease update 2011 (02)
Archive Number: 20110211.0473

PRION DISEASE UPDATE 2011 (02)
******************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

[With the continuing decline of the number of cases in the human
population of variant Creutzfeldt-Jakob disease -- abbreviated
previously as vCJD or CJD (new var.) in ProMED-mail -- it has been
decided to broaden the scope of the occasional ProMED-mail updates to
include other prion-related diseases. In addition to vCJD, data on
other forms of CJD: sporadic, iatrogenic, familial, and GSS
(Gerstmann-Straussler-Scheinker disease) are included also since they
may have some relevance to the incidence and etiology of vCJD. -
Mod.CP]

In this update:
[1] UK: National CJD Surveillance Unit - monthly statistics as of Tue
8 Feb 2011 - no new vCJD cases
[2] France: Institut de Veille Sanitaire - monthly statistics as of
Tue 1 Feb 2011 - no new vCJD cases
[3] USA: National Prion Disease Pathology Surveillance Center -
cumulative case numbers for 2010 up to 1 Nov 2010 - no vCJD cases
[4] Airborne transmission (mice)
[5] Milk borne transmission (sheep)
[6] vCJD blood test

******
[1] UK: National CJD Surveillance Unit - monthly statistics as of Tue
8 Feb 2011 - no new vCJD cases
Date: Tue 8 Feb 2011
Source: UK National CJD Surveillance Unit, monthly statistics
[edited]
<http://www.cjd.ed.ac.uk/figures.htm>

The number of deaths due to definite or probable vCJD to the end 2010
was 170. A total of 4 definite/probable patients are still alive so
the total number of definite or probable vCJD cases remains 174.

Although 3 vCJD deaths were recorded in 2010, the overall picture is
still consistent with the view that the vCJD outbreak in the UK is in
decline, albeit now with a pronounced tail. The 1st cases were
observed in 1995, and the peak number of deaths was 28 in the year
2000, followed by 20 in 2001, 17 in 2002, 18 in 2003, 9 in 2004, 5 in
2005, 5 in 2006, 5 in 2007, 1 in 2008, 3 in 2009, 3 in 2010, and none
so far in 2011.

Totals for all types of CJD cases in the UK in the year 2011
------------------------------------------------------------
During 2011 so far [as of 8 Feb 2011], there have been 14 referrals,
8 fatal cases of sporadic CJD, 1 case of GSS, and none of familial
CJD, iatrogenic CJD, or vCJD.

Since records began in 1990 there have been 2745 referrals, 1210
fatal cases of sporadic CJD, 170 cases of vCJD, 64 cases of iatrogenic
CJD, 82 cases of familial CJD and 44 of GSS.

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[2] France: Institut de Veille Sanitaire - monthly statistics as of
Tue 1 Feb 2011 - no new vCJD cases
Date: Tue 1 Feb 2011
Source: IVS - Maladie de Creutzfeldt-Jakob et maladies apparentees
[in French, trans. & summ. Mod.CP, edited]
<http://www.invs.sante.fr/display/?doc=publications/mcj/donnees_mcj.html>

During the 1st month of 2011, there were 115 referrals, 1 confirmed
case of sporadic CJD, and none of familial CJD, iatrogenic CJD, or
vCJD.

A total of 25 cases of confirmed or probable vCJD have been recorded
in France since records began in 1992. There was 1 case in 1996, 1 in
2000, 1 in 2001, 3 in 2002, 2 in 2004, 6 in 2005, 6 in 2006, 3 in
2007, 2 in 2009, and none in 2010.

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******
[3] USA: National Prion Disease Pathology Surveillance Center -
cumulative case numbers for 2010 up to 1 Nov 2010 - no vCJD cases
Date: Mon 1 Nov 2010
Source: US National Prion Disease Pathology Surveillance Center
[edited]
<http://www.cjdsurveillance.com/pdf/case-table.pdf>

Cumulative data 1 Jan 2010 to 31 October 2010
---------------------------------------------
During the 10-month period 1 Jan 2010 to 31 Oct 2010, there were 333
referrals, 213 of whom were classified as prion disease cases,
comprising 158 cases of sporadic CJD, 33 of familial CJD, and none of
iatrogenic CJD or vCJD.

Overall of 3831 referrals examined since screening began in 1996 or
thereabouts, diagnosis is still pending in 18 cases, and another 18
cases have been considered inconclusive. [This is a measure of the
difficulty in achieving unequivocal diagnoses. - Mod.CP]

During the same period a total of 2265 prion disease cases have been
screened, a figure which includes 23 (22 during 2010) cases with type
determination pending, but in which a diagnosis of vCJD has been
excluded. 3 cases of vCJD recorded in the USA during the same period
have been attributed to infection in the United Kingdom in 2 cases,
and in Saudi Arabia in the other.

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******
[4] Airborne transmission (mice)
Date: 14 Jan 2011
Source: Science Daily [edited]
<http://www.sciencedaily.com/releases/2011/01/110113213056.htm>

New findings suggest airborne pathogens can induce mad cow disease
------------------------------------------------------------------
Airborne prions are also infectious and can induce mad cow disease or
Creutzfeldt-Jakob disorder, new findings suggest. This is the
surprising conclusion of researchers at the University of Zurich, the
University Hospital Zurich, and the University of Tuebingen. They
recommend precautionary measures for scientific labs, slaughterhouses,
and animal feed plants. The prion is the infectious agent that caused
the epidemic of mad cow disease, also termed bovine spongiform
encephalopathy (BSE), and claimed the life of over 280 000 cows in the
past decades. Transmission of BSE to humans, such as, by ingesting
food derived from BSE-infected cows, causes variant Creutzfeldt-Jakob
disease, which is characterized by a progressive and invariably lethal
break-down of brain cells.

It is known that prions can be transmitted through contaminated
surgical instruments and, more rarely, through blood transfusions. The
consumption of food products made from BSE-infected cows can also
induce the disease that is responsible for the death of almost 300
people. However, prions are not generally considered to be airborne --
in contrast to many viruses including influenza and chicken pox.

Prof Adriano Aguzzi's team of scientists at the universities of
Zurich and Tuebingen and the University Hospital Zurich have now
challenged the notion that airborne prions are innocuous. In a study,
mice were housed in special inhalation chambers and exposed to
aerosols containing prions. Unexpectedly, it was found that inhalation
of prion-tainted aerosols induced disease with frightening efficiency.
Just a single minute of exposure to the aerosols was sufficient to
infect 100 per cent of the mice, according to Prof Aguzzi who
published the findings in the Open-Access-Journal "PLoS Pathogens."
The longer exposure lasted, the shorter the time of incubation in the
recipient mice and the sooner clinical signs of a prion disease
occurred. Prof Aguzzi says the findings are entirely unexpected and
appear to contradict the widely held view that prions are not
airborne. The prions appear to transfer from the airways and colonize
the brain directly because immune system defects -- known to prevent
the passage of prions from the digestive tract to the brain -- did not
prevent infection.

Precautionary measures against prion infections in scientific
laboratories, slaughterhouses, and animal feed plants do not typically
include stringent protection against aerosols. The new findings
suggest that it may be advisable to reconsider regulations in light of
a possible airborne transmission of prions. Prof Aguzzi recommends
precautionary measures to minimize the risk of a prion infection in
humans and animals. He does, however, emphasize that the findings stem
from the production of aerosols in laboratory conditions and that
Creutzfeldt-Jakob patients do not exhale prions.

Reference
---------
Haybaeck J, Heikenwalder M, Klevenz B, et al: Aerosols Transmit
Prions to Immunocompetent and Immunodeficient Mice. PLoS Pathog. 2011;
7(1): e1001257. DOI:10.1371/journal.ppat.1001257;
<http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001257>

Abstract: Prions, the agents causing transmissible spongiform
encephalopathies, colonize the brain of hosts after oral, parenteral,
intralingual, or even transdermal uptake. However, prions are not
generally considered to be airborne. Here we report that inbred and
crossbred wild type mice, as well as tga20 transgenic mice
overexpressing PrPC, efficiently develop scrapie upon exposure to
aerosolized prions. NSE-PrP transgenic mice, which express PrPC
selectively in neurons, were also susceptible to airborne prions.
Aerogenic infection occurred also in mice lacking B- and
T-lymphocytes, NK-cells, follicular dendritic cells, or complement
components. Brains of diseased mice contained PrPSc and transmitted
scrapie when inoculated into further mice. We conclude that aerogenic
exposure to prions is very efficacious and can lead to direct invasion
of neural pathways without an obligatory replicative phase in lymphoid
organs. This previously unappreciated risk for airborne prion
transmission may warrant re-thinking on prion biosafety guidelines in
research and diagnostic laboratories.

Author summary: Prions, which are the cause of fatal
neurodegenerative disorders termed transmissible spongiform
encephalopathies (TSEs), can be experimentally or naturally
transmitted via prion-contaminated food, blood, milk, saliva, feces,
and urine. Here we demonstrate that prions can be transmitted through
aerosols in mice. This also occurs in the absence of immune cells as
demonstrated by experiments with mice lacking B-, T-, follicular
dendritic cells (FDCs), lymphotoxin signaling, or with
complement-deficient mice. Therefore, a functionally intact immune
system is not strictly needed for aerogenic prion infection. These
results suggest that current biosafety guidelines applied in
diagnostic and scientific laboratories ought to include prion aerosols
as a potential vector for prion infection.

--
communicated by:
Terry S Singeltary Sr
<flounder9@verizon.net>

[Despite the perceived risk revealed by these experiments with
laboratory mice there has been no evidence to date linking prion
disease to employees in slaughterhouses, animal feed plants, or
research laboratories. - Mod.CP]

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[5] Milkborne transmission (sheep)
Date Thu 20 Jan 2011
Source: Science Daily [edited]
<http://www.sciencedaily.com/releases/2011/01/110119191350.htm>

Prion disease spreads in sheep via mother's milk
------------------------------------------------
Transmission of prion brain diseases such as bovine spongiform
encephalopathy (BSE) -- also known as mad cow disease -- and human
variant Creutzfeldt-Jakob disease (vCJD) is generally attributed to
the consumption of the brain or organ meat of infected animals but new
research demonstrates lambs exposed to milk from prion-infected sheep
with inflamed mammary glands can develop prion disease as well. The
research, which is published in the January 2011 issue of the Journal
of Virology, has major implications for human and livestock health.

"Prions cause devastating, ultimately fatal infections in humans,"
says corresponding author Christina Sigurdson of the University of
California, San Diego School of Medicine. "This study is the 1st
demonstration of prions from an inflamed organ being secreted, and
causing clinical symptoms in a natural host for prion disease."

Recent research had suggested that human-to-human transmission of
prions has occurred via blood transfusions, "underscoring the
importance of understanding possible transmission routes," the
researchers write. The misfolded prions that cause vCJD in humans, and
BSE in cattle -- which can be transmitted to humans -- commonly
accumulate in lymphoid tissues before invading the central nervous
system, where they wreak their deadly effects. Inflammation can cause
lymphoid follicles to form in other organs, such as liver and kidney,
which leads prions to invade organs that normally do not harbor
infection. In recent research, this team, led by Ciriaco Ligios of the
Istituto Zooprofilattico Sperimentale in Sardinia, Italy and Adriano
Agguzi at the University of Zurich, Switzerland, reported sheep with
misfolded prions in inflamed mammary glands, also known as mastitis,
raising concerns that prions could be secreted into milk.

In the new research, the team infected sheep with a common retrovirus
that causes mastitis, and misfolded prions. They bred the sheep, in
order to stimulate the females to produce milk, which they then
collected and fed to lambs that had never been exposed to prions. The
lambs developed prion disease after only 2 years, a speed which
surprised the researchers, and "suggested that there was a high level
of prion infectivity in milk," says Sigurdson.

The research raises several disturbing possibilities.
- A common virus in a sheep with prion disease can lead to prion
contamination of the milk pool and may lead to prion infection of
other animals.
- The same virus in a prion-infected sheep could efficiently
propagate prion infection within a flock, through transmission of
prions to the lambs, via milk. This might be particularly likely on
factory farms, where mastitis may be common, and could occur in goats
as well as sheep.
- Humans with variant Creutzfeldt-Jakob disease might accumulate
prions in inflamed organs, and could also secrete prions.

However, "this work cannot be directly extrapolated to cattle," says
Sigurdson. She says that BSE prions do not accumulate to detectible
levels in lymphoid organs, and thus would not be expected to
accumulate with inflammation. "Nonetheless," she says, "it would be
worth testing milk from cattle with mastitis for prions as there may
be other cellular sources for prions entry into milk."

Reference
---------
Ligios C, Cancedda MG, Carta A, et al: Sheep with Scrapie and
Mastitis Transmit Infectious Prions through the Milk. J Virol. 2011
Jan; 85(2):1136-9. Epub 2010 Nov 17. DOI:10.1128/JVI.02022-10;
<http://jvi.asm.org/cgi/content/abstract/85/2/1136>.

Abstract: Prions are misfolded proteins that are infectious and
naturally transmitted, causing a fatal neurological disease in humans
and animals. Prion shedding routes have been shown to be modified by
inflammation in excretory organs, such as the kidney. Here, we show
that sheep with scrapie and lentiviral mastitis secrete prions into
the milk and infect nearly 90 per cent of naive suckling lambs. Thus,
lentiviruses may enhance prion transmission, conceivably sustaining
prion infections in flocks for generations. This study also indicates
a risk of prion spread to sheep and potentially to other animals
through dietary exposure to pooled sheep milk or milk products.

--
communicated by:
Terry S Singeltary Sr
<flounder9@verizon.net>

[These research confirms experimentally previous observations by
others (such as, Lacroux C et al: Prions in Milk from Ewes Incubating
Natural Scrapie. PLoS Pathog 4(12): e1000238.
doi:10.1371/journal.ppat.1000238;
<http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238>).
Despite the potential risk of prion spread to other animals through
dietary exposure to pooled sheep milk or milk products none has been
observed so far.

Perhaps of greater interest is the comment that humans with variant
Creutzfeldt-Jakob disease might accumulate prions in inflamed organs,
and could also secrete prions.- Mod.CP]

******
[6] vCJD blood test
Date: Thu 3 Feb 2011
Source: Nursing in Practice [edited]
<http://www.nursinginpractice.com/article/24301/VCJD_blood_test_developed_in_UK>

vCJD blood test developed in UK
-------------------------------
UK researchers have developed the 1st ever reliable blood test for
the human version of CJD. The diagnosis and screening of the fatal
brain illness could be transformed by the discovery, which also
identifies carriers. Scientists believe it could also give them their
1st real chance of accurately assessing how many Britons are
incubating the disease.

The new blood test is the first of its kind to successfully detect
variant Creutzfeldt-Jakob Disease (vCJD), which is the human
equivalent of cattle disease bovine spongiform encephalopathy (BSE).
vCJD was identified in the 1990s when the disease was linked to the
consumption of contaminated beef products. The disease creates a
number of holes in the brain, leading to mental problems, reduced body
functions, and eventually death. People can harbour the infectious
proteins -- called prions -- for years with no symptoms and pass the
disease on by donating blood or undergoing surgery. There is currently
no cure for the illness.

Until now there has been no way of telling for sure if someone has
the disease other than examining their brain tissue. The prototype
blood test developed by scientists at the Medical Research Council
(MRC) is 100 000 times more sensitive than any studied before.

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The reference and text of the abstract of the publication in Lancet
upon which the report above is based are the following:
Edgeworth JA, Farmer M, Sicilia A, et al: Detection of prion
infection in variant Creutzfeldt-Jakob disease: a blood-based assay
The Lancet 377(9764): 487-93
<http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62308-2/fulltext>.

Summary
-------
Background: Variant Creutzfeldt-Jakob disease (vCJD) is a fatal
neurodegenerative disorder originating from exposure to
bovine-spongiform-encephalopathy-like prions. Prion infections are
associated with long and clinically silent incubations. The number of
asymptomatic individuals with vCJD prion infection is unknown, posing
risk to others via blood transfusion, blood products, organ or tissue
grafts, and contaminated medical instruments. We aimed to establish
the sensitivity and specificity of a blood-based assay for detection
of vCJD prion infection.

Methods: We developed a solid-state binding matrix to capture and
concentrate disease-associated prion proteins and coupled this method
to direct immunodetection of surface-bound material. Quantitative
assay sensitivity was assessed with a serial dilution series of 1 in
10 million to 1 in 10 billion of vCJD prion-infected brain homogenate
into whole human blood, with a baseline control of normal human brain
homogenate in whole blood (1 in 1 million). To establish the
sensitivity and specificity of the assay for detection of endogenous
vCJD, we analysed a masked panel of 190 whole blood samples from 21
patients with vCJD, 27 with sporadic CJD, 42 with other neurological
diseases, and 100 normal controls. Samples were masked and numbered by
individuals independent of the assay and analysis. Each sample was
tested twice in independent assay runs; only samples that were
reactive in both runs were scored as positive overall.

Findings: We were able to distinguish a 1 in 10 billion dilution of
exogenous vCJD prion-infected brain from a 1 in 1 million dilution of
normal brain (mean chemiluminescent signal, 130 000 (standard
deviation 11 000) for vCJD vs 99 000 (SD 4500) for normal brain; p
less than 0.0001) -- an assay sensitivity that was orders of magnitude
higher than any previously reported. 15 samples in the masked panel
were scored as positive. All 15 samples were from patients with vCJD,
showing an assay sensitivity for vCJD of 71.4 per cent (95 per cent
confidence interval 47.8-88.7) and a specificity of 100 per cent (95
per cent CIs between 97.8 per cent and 100 per cent).

Interpretation: These initial studies provide a prototype blood test
for diagnosis of vCJD in symptomatic individuals, which could allow
development of large-scale screening tests for asymptomatic vCJD prion
infection."

Hopefully the authors optimism will prove to be well founded and this
research will prove to become a significant step in the investigation
of neurological disease. - Mod.CP

See Also