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Numéro d'archivage 20061208.3468
Date publiée 08-DÉC. -2006
Sujet PRO/AH/EDR> CJD (new var.), blood transfusion risk

CJD (NEW VARIANT), BLOOD TRANSFUSION RISK
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[1]
Date: Fri 8 Dec 2006
From: Pablo Nart <pablo.nart@terra.es>
Source: BBC News online, Fri 8 Dec 2006 [edited]
<http://news.bbc.co.uk/1/hi/health/6217296.stm>


A study of transfusion patients given blood contaminated with the 
human form of mad cow disease has indicated the 24 still alive are at 
"substantial" risk.  Prof John Collinge's assessment follows his 
investigation into the third person infected from the original group of 66.

The patient, the first to be diagnosed with variant Creutzfeldt-Jakob 
disease [abbreviated as CJD (new var.) or vCJD in ProMED-mail] while 
still alive, has since died. Two others died before their illness was 
confirmed. The name of the 3rd patient to be infected has not been 
released, but it is known that he received the blood transfusion at 
the age of 23. He later became ill, and 7.5 years later he was 
referred to the NHS National Prion Clinic at the National Hospital 
for Neurology and Neurosurgery where his symptoms were confirmed to 
be caused by vCJD.  He joined an experimental Medical Research 
Council trial for a treatment called Prion-1 which began in 2004, in 
which patients were given a drug called quinacrine, but he died a 
year later at the age of 32. The diagnosis of vCJD was confirmed 
after his death after his tonsil tissue was examined.

Diseases in humans such as vCJD which are caused by prions, rogue 
proteins, are known to have long incubation periods, and it is 
possible that a person could be silently infected for more than 50 
years before developing symptoms of the disease. During this time 
such a carrier of infection poses a potential risk to others through 
blood transfusion and contamination of surgical and medical 
instruments. The incubation period when prions pass from human to 
human is thought to be much shorter than when they pass from one 
species to another.  So prions that enter the body through a blood 
transfusion rather than through eating meat infected with BSE (bovine 
spongiform encephalopathy) are thought to cause vCJD to develop more quickly.

Experts believe that, based on the cases seen so far, infection from 
a blood transfusion can develop in just 6 or 7 years. Professor John 
Collinge of the MRC Prion Unit said: "That 3 individuals from this 
small group of people that we know to have been exposed through blood 
transfusion have already developed vCJD infection suggests that the 
infection may be efficiently passed by this route. Professor Collinge 
told BBC Radio 4's Today programme: "We know about these particular 
instances because individuals went on to develop vCJD. "But of course 
people who are silently incubating vCJD at the moment may be blood 
donors and there is no way of knowing where that blood is going."

He added: "'A national tonsil tissue screening study being performed 
by the Health Protection Agency may soon give estimates of the number 
of people who are silently infected with prions. He said it was 
possible people at high risk could have their tonsil tissue tested in 
a bid to diagnose if they are infected. Professor Collinge added: 
"Although we do not yet have an effective treatment for any form of 
CJD, a reliable tonsil test could allow people with vCJD to access 
experimental treatments early."

Writing in the Lancet, Kumanan Wilson of Toronto General Hospital and 
Maura Ricketts of the Public Health Agency of Canada said: "This 
third case considerably strengthens the inference that transfusion 
transmission is possible and suggests that the causative prion can be 
efficiently transmitted via this route."

A spokeswoman for the National Blood Service said a large number of 
measures had been put in place to protect people receiving 
transfusions including withdrawing any blood products donated from a 
person who later develops vCJD. She added: "Whilst no medical 
procedure, including blood transfusion, can be 100 percent safe, our 
prime concern is always the safety of patients through the quality of 
blood. To date there have been three cases of vCJD infection where 
blood transfusion is a possible source of infection. However, the 
National Blood Service issues nearly two million units of blood every year."

--
Pablo Nart
<pablo.nart@terra.es>

[ProMED-mail acknowledges receipt of the same report from 
<A-Lan.Banks@thomson.com>. - Mod.CP]

******
[2]
Date: Fri 8 Dec 2006
From: Brent Barrett <salbrent@sbcglobal.net>
Source: Timesonline, Fri 8 Dec 2006 [edited]
<http://www.timesonline.co.uk/article/0,,8122-2493197,00.html>


Infected blood threatens fresh outbreak of vCJD
-----------------------------------------------
Thousands of people are at risk from an outbreak of variant 
Creutzfeld-Jakob disease [abbreviated as CJD (new var.) or vCJD in 
ProMED-mail] spread by contaminated blood or infected surgical 
instruments. An analysis of the death of a 3rd patient after a 
transfusion of infected blood, published yesterday, shows that the 
disease is very easily transmitted by blood. Nobody knows how many 
donors may have given infected blood in the past, or may still be 
giving it today. That it can be transmitted by infected blood means 
that there is a serious risk of a self-sustaining secondary epidemic 
of vCJD. Transmission is much easier than by eating contaminated 
meat, where a species barrier must be overcome. The evidence of the 3 
cases is that vCJD can develop in as little as 6 to 7 years if 
transmitted by blood. The incubation period for vCJD [contracted] 
from infected beef is significantly longer.

The National Blood Service said that it had taken all the 
precautionary measures it could. "The trouble is that there is no 
test we can use," a spokesman said. At greatest risk are a handful of 
people known to have had blood transfusions from healthy donors who 
went on to develop vCJD. There are 24 such recipients still alive, 
and their risk is substantial, Professor John Collinge, Britain's 
leading expert on the disease, said.

The unnamed 3rd patient to [contract] vCJD from contaminated blood 
had a transfusion when he was 23. Seven years later he developed 
symptoms. He opted to join an experimental treatment trial organised 
by the Medical Research Council in which patients are given the drug 
quinacrine. He died a year later, aged 32. He was one of 66 people 
identified by the National Blood Service as having received blood 
from a donor who later developed vCJD. Of these, 34 died of other 
causes within 5 years of the transfusions. Of the remaining 32, 8 
have now died, 3 from vCJD.

Professor Collinge, who reports on the case in The Lancet (see [3] 
below), said: "That 3 individuals from this small group of people 
that we know to have been exposed through blood transfusion have 
already developed vCJD infection suggests that the infection may be 
efficiently passed by this route, so the risk to remaining 
individuals is likely to be substantial."

So far, about 160 people, mostly young, are known to have died of the 
disease by eating contaminated beef. The numbers were relatively low 
because of the species barrier between cows and humans.

Measures taken so far to prevent transmission by blood include 
importing blood plasma from the US, excluding as donors all those who 
have themselves had a transfusion as well as those whose blood has 
gone to recipients who have later developed vCJD, and removing white 
blood cells from all blood components in the belief that they are the 
most likely carriers of the rogue prions that cause the disease.

But without a test it is impossible to screen all blood donations, as 
is done for HIV and other diseases. Nor is it yet known how many 
potentially contaminated donors there are. The incubation period for 
vCJD acquired from beef is so long that there is ample opportunity 
for a blood donor to be carrying the rogue prions for years without 
any knowledge. Experiments in mice show that such subclinical 
infections can still act as a source of full-blown infection if 
transmitted to other mice.

Studies of tonsils removed in routine operations suggest, the 
Spongiform Encephalopathy Advisory Committee (SEAC) says, that there 
could be several thousand subclinical carriers of the disease.

They might infect others in 2 ways: either through blood 
transfusions, if the precautions prove inadequate, or -- more likely 
in SEAC's view -- through contaminated surgical instruments. A big 
potential danger is in dental surgery. "The large number of dental 
procedures coupled with good patient survival implies that any 
significant risk via this route could have a major impact on the 
dynamics of secondary infection," the Committee said. But nobody yet 
knows how infective the mouth and gum tissues of vCJD victims are. 
Dental instruments are sterilised between patients, but routine 
sterilisation is not enough to destroy the prions that cause the disease.

The Lancet paper says that tests on the tonsils of the patient who 
died showed that they were infected with prions. Testing tonsil 
tissue is a way of determining early if there is reason to suspect 
prion disease, Professor Collinge said.

[Byline: Nigel Hawkes]

--
Brent Barrett
Indianapolis, IN, USA
<salbren@sbcglobal.net>

[The Lancet paper entitled "Clinical presentation and pre-mortem 
diagnosis of variant Creutzfeldt-Jakob disease associated with blood 
transfusion: a case report", on which the preceding BBC News and 
Timesonline reports are based is reproduced below. - Mod.CP]

******
[3]
Date: Fri 8 Dec 2006
From: Terry S. Singeltary Sr. <flounder9@verizon.net>
Source: The Lancet 2006; 368:2061-2067, 2996 [edited]
<http://www.thelancet.com/journals/lancet/article/PIIS0140673606698358/abstract>


[Terry Singeltary Sr has provided the abstract of the Lancet paper 
upon which the above BBC and Times-Online reports are based. - Mod.CP]

Clinical presentation and pre-mortem diagnosis of vCJD associated 
with blood transfusion: a case report
--------------------------------------------------
Stephen J Wroe FRCP a b, Suvankar Pal MRCP a b, Durrenajaf Siddique 
MRCP a b, Harpreet Hyare FRCR a b, Rebecca Macfarlane MRCS a b, Susan 
Joiner MSc b, Jacqueline M Linehan BSc b, Sebastian Brandner MRCPath 
b, Jonathan DF Wadsworth PhD b, Patricia Hewitt FRCPath c and Prof 
John Collinge FRS a b


(a. National Prion Clinic, National Hospital for Neurology and 
Neurosurgery, Queen Square, London WC1N 3BG, UK
b. MRC Prion Unit and Department of Neurodegenerative Disease, 
Institute of Neurology, University College London, London, UK
c. National Blood Service, London, UK.)

Background
----------
Concerns have been raised that variant Creutzfeldt-Jakob disease 
(vCJD) might be transmissible by blood transfusion. Two cases of 
prion infection in a group of known recipients of transfusion from 
donors who subsequently developed vCJD were identified post-mortem 
and reported in 2004. Another patient from this at-risk group 
developed neurological signs and was referred to the National Prion Clinic.

Methods
-------
The patient was admitted for investigation and details of blood 
transfusion history were obtained from the National Blood Service and 
Health Protection Agency; after diagnosis of vCJD, the patient was 
enrolled into the MRC PRION-1 trial. When the patient died, brain and 
tonsil tissue were obtained at autopsy and assessed for the presence 
of disease-related PrP by immunoblotting and immunohistochemistry.

Findings
--------
A clinical diagnosis of probable vCJD was made; tonsil biopsy was not 
done. The patient received experimental therapy with quinacrine, but 
deteriorated and died after a clinical course typical of vCJD. 
Autopsy confirmed the diagnosis and showed prion infection of the tonsils.

Interpretation
--------------
This case of transfusion-associated vCJD infection, identified 
ante-mortem, is the 3rd instance from a group of 23 known recipients 
who survived at least 5 years after receiving a transfusion from 
donors who subsequently developed vCJD. The risk to the remaining 
recipients of such tranfusions is probably high, and these patients 
should be offered specialist follow-up and investigation. Tonsil 
biopsy will allow early and pre-symptomatic diagnosis in other 
iatrogenically exposed individuals at high risk, as in those with 
primary infection with bovine spongiform encephalopathy prion

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

[see also:
CJD (new var.) - UK: 3rd transfusion-related case   20060209.0432
CJD (new var.) update 2006   20060111.0101
CJD (new var.) update 2006 (02) 20060206.0386
CJD (new var.) update 2006 (03) 20060306.0728
CJD (new var.) update 2006 (04) 20060404.1005
CJD (new var.) update 2006 (05) 20060508.1332
CJD (new var.) update 2006 (06) 20060605.1566
CJD (new var.) update 2006 (07) 20060703.1831
CJD (new var.) update 2006 (08) 20060807.2207
CJD (new var.) update 2006 (09) 20060904.2519
CJD (new var.) update 2006 (10) 20061002.2820
CJD (new var.) update 2006 (11) 20061106.3190
CJD (new var.) update 2006 (12) 20061205.3431]
............................cp/pg/mpp

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