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From: TSS ()
Subject: MELBOURNE grandmother who died this week from suspected CJD was a blood donor for 25 years
Date: October 21, 2006 at 10:15 am PST

CJD link to Gran's mystery death
Robyn Riley

October 22, 2006 12:00am

A MELBOURNE grandmother who died this week from suspected Creutzfeldt-Jakob disease was a blood donor for 25 years.

Valerie Powell, 68, died on Tuesday. Her husband Ron, 70, said his wife was a regular blood donor until a year ago.
But he said doctors had told him the type of CJD his wife had could not be transmitted by blood or blood products.

The Australian Red Cross said there had never been a reported case of classical CJD being passed from a blood donor anywhere in the world.

CJD expert Prof Colin Masters, head of the Department of Pathology at Melbourne University, said Victorians who may have received blood from Mrs Powell should not be alarmed because there was no evidence classical CJD was passed through the blood.

But he said in the past year there had been three cases, all in Britain, of variant CJD -- more widely known as mad cow's disease -- passed from blood donors.

Mr Powell said his wife went to her GP in July because she was feeling unwell.

"He diagnosed depression and put her on medication," he said. "It didn't help. Valerie's symptoms became worse."

Mrs Powell's family was told a test of her spinal fluid showed she "probably" had sporadic CJD, which makes up 90 per cent of all classical CJD cases.

It was not known how she developed the rare, but fatal, brain disease. Only a biopsy will confirm suspicions that Mrs Powell died from CJD.

Prof Masters said there was no way of screening blood donors. About 20 Australians a year die from classical CJD.

THERE are support groups for families of victims of CJD. Contact Suzanne Solvyns 1800 052 466, Carol Wilson 1800 181 683 or Mandy Newton 1800 884 897.

http://www.news.com.au/sundayheraldsun/story/0,21985,20622280-661,00.html

Infectious Prions in the Saliva and Blood of Deer with Chronic Wasting Disease
Date: October 5, 2006 at 1:45 pm PST
Infectious Prions in the Saliva

and Blood of Deer with Chronic

Wasting Disease


Candace K. Mathiason,1 Jenny G. Powers,3 Sallie J. Dahmes,4 David A. Osborn,5 Karl V. Miller,5

Robert J. Warren,5 Gary L. Mason,1 Sheila A. Hays,1 Jeanette Hayes-Klug,1 Davis M. Seelig,1

Margaret A. Wild,3 Lisa L. Wolfe,6 Terry R. Spraker,1,2 Michael W. Miller,6 Christina J. Sigurdson,1

Glenn C. Telling,7 Edward A. Hoover1*


A critical concern in the transmission of prion diseases, including chronic wasting disease (CWD)

of cervids, is the potential presence of prions in body fluids. To address this issue directly, we

exposed cohorts of CWD-nai¨ve deer to saliva, blood, or urine and feces from CWD-positive deer.

We found infectious prions capable of transmitting CWD in saliva (by the oral route) and in blood

(by transfusion). The results help to explain the facile transmission of CWD among cervids and

prompt caution concerning contact with body fluids in prion infections.


SNIP...


Deer cohorts 1 (blood), 2 (saliva), and 3

(urine and feces) were electively euthanized at

18 months pi to permit whole-body examination

for PrPCWD. The greatest scrutiny was directed

toward those tissues previously established

to have highest frequency of PrPCWD deposition

in infected deer and generally regarded

as the most sensitive indicators of infection—

medulla oblongata and other brainstem regions,

tonsil, and retropharyngeal lymph node. We

found unequivocal evidence of PrPCWD in brain

and lymphoid tissue of all six tonsil biopsy–

positive deer in cohorts 1 (blood) and 2 (saliva),

whereas all deer in cohorts 3 and 5 were negative

for PrPCWD in all tissues (Table 2 and

Figs. 1 and 2).

The transmission of CWD by a single blood

transfusion from two symptomatic and one

asymptomatic CWDþ donor is important in at

least three contexts: (i) It reinforces that no tissue

from CWD-infected cervids can be considered

free of prion infectivity; (ii) it poses the

possibility of hematogenous spread of CWD,

such as through insects; and (iii) it provides a

basis for seeking in vitro assays sufficiently

sensitive to demonstrate PrPCWD or alternate

prion protein conformers in blood—one of the

grails of prion biology and epidemiology.

The identification of blood-borne prion

transmission has been sought before with mixed

results (9–11). Bovine spongiform encephalopathy

and scrapie have been transmitted to naBve

sheep through the transfer of 500 ml of blood

or buffy coat white blood cells from infected

sheep (12, 13). In addition, limited but compelling

evidence argues for the transmission of variant

Creutzfeldt-Jakob disease (vCJD) through blood

from asymptomatic donors (14–16). Even in

sporadic CJD, PrPres has been found in periph-

eral organs of some patients (17). The present

work helps establish that prion diseases can be

transmitted through blood.

The presence of infectious CWD prions in

saliva may explain the facile transmission of

CWD. Cervid-to-cervid interactions (SOM text),

especially in high density and captive situations,

would be expected to facilitate salivary crosscontact

(11, 18, 19). Salivary dissemination of

prions may not be limited to CWD. Proteaseresistant

prion protein has been demonstrated in

the oral mucosa, taste buds, lingual epithelium,

vomeronasal organ, and olfactory mucosa of

hamsters infected with transmissible mink

encephalopathy (19) and ferrets infected with

CWD (20). Although no instance of CWD

transmission to humans has been detected, the

present results emphasize the prudence of using

impervious gloves during contact with saliva or

blood of cervids that may be CWD-infected.

Environmental contamination by excreta

from infected cervids has traditionally seemed

the most plausible explanation for the dissemination

of CWD (21). However, we could not

detect PrPCWD in cohort 3 deer inoculated repeatedly

with urine and feces from CWDþ deer and examined up to 18 months pi (Table 2).

There are several reasons to view this negative

finding cautiously, including small sample size,

elective preclinical termination, and potential

variation in individual susceptibility that may

be associated with the 96 G/S polymorphism in

the PRNP gene (7, 22). Although no genotype

of white-tailed deer is resistant to CWD infection,

PRNP genotypes S/S or G/S at codon 96

appear to have reduced susceptibility manifest

by longer survival (7). Both deer in cohort 3

(urine and feces) were subsequently shown to

be of the PRNP 96 G/S genotype. Thus, it is

possible, although we think unlikely, that these

deer had a prolonged incubation period (918

months pi) before the amplification of PrPCWD

became detectable in tissues. Recent studies

have shown that PrPres is poorly preserved

after incubation with intestinal or fecal content

(23, 24). Further research using cervid and surrogate

cervid PrP transgenic mice (25) are indicated

to continue to address the presence of

infectious CWD prions in excreta of CWDþ deer and to provide a more substantial basis for

reconsideration of the assumption that excreta

are the chief vehicle for CWDdissemination and

transmission.

The results reported here provide a plausible

basis for the efficient transmission of CWD in

nature. We demonstrate that blood and saliva in

particular are able to transmit CWD to naBve deer

and produce incubation periods consistent with

those observed in naturally acquired infections

(3, 26). The time from exposure to first detection

of PrPCWD by tonsil biopsy was variable—as

short as 3 months but as long as 18 months (likely

underestimates due to sampling frequency).

The results also reinforce a cautious view of the

exposure risk presented by body fluids, excreta,

and all tissues from CWDþ cervids. ...

SNIP...END


http://www.sciencemag.org/

Prion infections, blood and transfusions

Adriano Aguzzi* and Markus Glatzel

SUMMARY

Prion infections lead to invariably fatal diseases of the CNS, including

Creutzfeldt–Jakob disease (CJD) in humans, bovine spongiform

encephalopathy (BSE), and scrapie in sheep. There have been hundreds

of instances in which prions have been transmitted iatrogenically among

humans, usually through neurosurgical procedures or administration of

pituitary tissue extracts. Prions have not generally been regarded as bloodborne

infectious agents, and case–control studies have failed to identify

CJD in transfusion recipients. Previous understanding was, however,

questioned by reports of prion infections in three recipients of blood

donated by individuals who subsequently developed variant CJD. On

reflection, hematogenic prion transmission does not come as a surprise, as

involvement of extracerebral compartments such as lymphoid organs and

skeletal muscle is common in most prion infections, and prions have been

recovered from the blood of rodents and sheep. Novel diagnostic strategies,

which might include the use of surrogate markers of prion infection, along

with prion removal strategies, might help to control the risk of iatrogenic

prion spread through blood transfusions.

SNIP...

TRANSMISSION OF PRION DISEASES

IN HUMANS

The cause of most human prion diseases is

unknown. In the case of sCJD, the term ‘sporadic’

is used as a euphemism, meaning that we have

no idea about the origin of this form of CJD. By

contrast, gCJD always segregates within families

with mutations in the gene encoding the prion

protein (PRNP), suggesting that these mutations

are causally involved in disease pathogenesis. As

no families have been described in which gCJD

segregates with mutations in genes other than

PRNP, it has been difficult to use human genetics

to understand the pathogenesis of prion diseases.

The discovery of PRNP mutations in gCJD has

led to the proposal that at least some cases of

sCJD might be due to somatic PRNP mutations

analogous to those found in the germline of

gCJD patients. It is equally possible, however,

that some of the cases of alleged sCJD derive

from hitherto unrecognized infectious causes.

In apparent agreement with the ‘intrinsic’

origin of sCJD, which accounts for more than

90% of all human prion diseases, epidemiological

studies were not able to identify a

conclusive link between this form of CJD and

external risk factors.19 This fact is reflected in

the pathological and biochemical features of

these diseases. Although low levels of PrPSc and

prion infectivity can be demonstrated in peripheral

sites such as lymphoid organs or skeletal

muscle,20,21 the highest levels of PrPSc and prion

infectivity appear to occur in the CNS. These

facts might account, at least in part, for the lack

of evidence of sCJD transmission by labile or

stable blood products.22 Indeed, several retrospective

studies have failed to identify blood

transfusion or exposure to plasma products as

risk factors for the development of sCJD,19 and

prion diseases appear to be exceedingly rare

in hemophiliacs, a group of patients that is at

particularly high risk of contracting emerging

blood-borne infectious diseases. Although these

studies cannot exclude the possibility that transmission

of sCJD might have occurred through

blood transfusions in rare cases, and despite

the fact that the etiology of sCJD is unclear,

it would appear that transmission of sCJD by

trans fusion of blood or blood products does

not play a major role in the pathogenesis of this

disease entity.

In the case of acquired prion diseases, however,

the situation is very different. For vCJD, high

levels of prion infectivity and of PrPSc have

been detected in lymphoid organs such as the

appendix and tonsils (Figure 1).23,24 For this

reason, it has been speculated for almost a decade

that vCJD might be associated with a higher risk

of blood-borne transmission than sCJD. It is

important to be cautious, however, as the differences

in the organ tropism of sCJD and vCJD

might be quantitative rather than qualitative, and

PrPSc has been detected in the lymphoid organs

of both vCJD and sCJD patients.21 Initial studies

have failed to detect PrPSc and prion infectivity

in the blood of patients with vCJD, but these

negative data are likely to be attributable to

the lack of sensitivity of the assays available at

the time.23

The recent identification of three indiv iduals

with probable transmission of vCJD via blood

transfusion has provided tragic evidence that vCJD

prions can indeed be transmitted through blood

(Figure 2). On the basis of the epi demiological

and pathogenetic considerations discussed above,

it can only be a matter of time before further

cases of blood-transfusion-associated cases of

vCJD will ensue (Figure 3). ...snip...END

JUNE 2006 VOL 2 NO 6 AGUZZI AND GLATZEL NATURE NEUROLOGY

=========================================================

SHORT REPORT

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

E A Croes, G Roks, G H Jansen, P C G Nijssen, C M van Duijn ...............................................................

J Neurol Neurosurg Psychiatry 2002;72:792-793

A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.


snip...


An incubation period as long as 38 years had never been reported for iatrogenic CJD. Huillard d'Aignaux et al7 studied the incubation period in 55 patients with hGH related CJD in a cohort of 1361 French hGH recipients. The median incubation period was between 9 and 10 years. Under the most pessimistic model, the upper limit of the 95% confidence interval varied between 17 and 20 years. Although the infecting dose cannot be quantified, it can be speculated that the long incubation period in our patient is partly explained by the administration of a limited amount of hGH. This hypothesis is supported by experimental models, in which higher infecting doses usually produce shorter incubation periods.6 Since our patient was one of the first in the world to receive hGH, this case indicates that still more patients with iatrogenic CJD can be expected in the coming years. Another implication of our study is that CJD can develop even after a low dose of hGH. This case once more testifies that worldwide close monitoring of any form of iatrogenic CJD is mandatory. ...snip...END


Transmission of Creutzfeldt-Jakob Disease from Blood and Urine Into Mice

The Lancet, November 9, 1985

Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) report
transmission to animals of Creutzfeldt-Jakob disease (CJD) from the
buffy coat from two patients. We also transmitted the disease from
whole blood samples of a patient (and of mice) infected with CJD.1
Brain, Cornea, and urine from this patient were also infectious, and
the clinicopathological findings2 are summarised as follows.

A 70-year-old man was noted to have a slowing of speech and writing
and some disorientation, all of which progressed rapidly. Decorticate
rigidity, forced grasping, positive snout reflex, and myoclonus
appeared within 2 months. Electroencephalogram revealed typical
periodic synchronous discharge, and he died of pneumonia and upper
gastrointestinal haemorrhage, about 3 months after onset of the
symptoms. The Brain weighed 1290g and showed severe histological
changes diagnostic of CJD, including spongiform change, loss of
nerve cells, and diffuse proliferation of astrocytes. There were no
inflammatory cells, microglia, neurofibrillary tangles, and
amyloid plaques, although virus-like particles were detected by
electron microscopy.

Results of innoculation in Mice

Inocula NO* Incubation period (days)+
Brain 7/10 (4) 789 (+ or - 112)
Cornea 1/6 (0) 1037
Blood 2/13 (0) 1080 (+ or - 69)
Urine 5/10 (1) 880 (+ or - 55)
CSF 0/10

* Number of mice with CJD change/number examined histologically.
Number with amyloid plaques shown in parentheses.

+ means + or - SD

Samples were taken aseptically at necropsy. 10% crude homogenates
of brain and cornea in saline, whole blood (after crushing a clot),
and untreated CSF and urine were innoculated intracerebrally into
CF1 strain mice (20 ul per animal). Some mice showed emaciation,
bradykinesia, rigidity of the body and tail, and sometimes tremor
after long incubation periods. Tissues obtained after the animal
died (or was killed) were studied histologically (table). Animals
infected by various inocula showed common pathological changes,
consisting of severe spongiform changes, glial proliferation, and
a moderate loss of nerve cells. A few mice inoculated with brain
tissue or urine had the same amyloid plaques found in patients and
animals with CJD.3

In our long-term experiments, inoculating materials taken from
twenty patients with CJD or Gerstmann-Straussler-Scheinker's
disease (GSS) into rodents, positive results were obtained in
seventeen cases, including this patient. Brain tissue transmitted
the disease most frequently within the shortes incubation period,
except for one case where the lymph node was the most infectious.
Transmission through the cornea has been noted in man4 and in
guineapigs.5 Whole blood samples taken from three patients were
inoculated and a positive transmission occured only in the case
recorded here. Mouse-to-mouse transmission through blood
inoculation was successful after a mean incubation period of 365
days.1 Transmission through urine was positive in this patient
only, and negative in one other patient and in many infected animals.
Transmission through the CSF from eight patients was negative, yet
transmission via the CSF of infected rats was positive.1

As viraemia has been proved in guineapigs,6 mice,1,7 and lately
in patients with CJD, blood for transfusion or blood products for
medical use must be tested for unconventional pathogens. For this
purpose, we inoculated blood products inot rodents.8 The CJD
pathogen was not found in the products examined. However, this
approach takes too long to be of practical value. More efficient
methods must be developed to detect pathogens and to eliminate
them from blood. One proposal9 is to apply membrane filtration to
the pruification protocol of human growth hormone suspected of
being contaminated with CJD. Similar methods are needed for blood
contamination.

Department of Neuropathology,
Neurological Institute,
Faculty of Medicine,
Kyushu University,
Fukuoka812, Japan

JUN TATEISHI

1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmission
of human subacute spongiform encephalopathy to small
rodents 1: Clinical and histological observations.
Acta Neuropathol (Berl) 1980; 51: 127.

2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob
disease with demonstration of virus-like particles.
Acta pathol Jpn 1982;32: 695.

3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the
brains of mice with Creutzfeldt-Jakob disease.
Ann Neurol 1984; 15: 278.

4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D.
Possible person-to-person transmission of Creutzfeldt-Jakob disease.
N Engl J Med 1974; 290: 692.

5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L.
Experimental Creutzfeldt-Jakob disease transmitted via the eye
with infected cornea. N Engl J Med 1977; 296: 1334.

6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental
Creutzfeldt-Jakob disease. Science 1978: 200: 1069.

7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC.
Creutzfeldt-Jakob disease in mice. Persistent viremiam and
preferential replication of virus in low-density lymphocytes.
Infect Immun 1983; 41: 154.

8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform
encephalopathis absent in blood products. J Med Virol 1985; 15: 11.

9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease
pathogen in growth hormone preparations is eliminatable.
Lancet (in press).


========================================================


Transmission of prion diseases by blood transfusion


Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2

1 Journal of General Virology (2002), 83, 2897-2905. Printed in Great Britain Published ahead of print (16 July 2000) in JGV Direct as DOI 10.1099/vir.0.18580-0 Transmission of prion diseases by blood transfusion Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2 1 Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK 2 Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK Author for correspondence: Nora Hunter. Fax +44 131 668 3872. e-mail nora.hunter@bbsrc.ac.uk Received 16 May 2002; Accepted 9 July 2002 This article is now available in the November 2002 print issue of JGV (vol. 83, 2897-2905). The complete issue of the journal may be seen in electronic form on JGV Online (http://vir.sgmjournals.org). 0001-8580 © 2002 SGM

Abstract

Attempts to detect infectivity in the blood of humans and animals affected with transmissible spongiform encephalopathies (TSEs or prion diseases) have often been inconclusive because of the limitations of cross-species bioassays and the small volumes of blood that can be injected by the intracerebral route. A model has been developed for the experimental study of TSE transmission by blood transfusion using sheep experimentally infected with bovine spongiform encephalopathy (BSE) or natural scrapie as donors and susceptible scrapie-free sheep as recipients. Donors and recipients of the same species greatly increase the sensitivity of the bioassay and in sheep large volumes of blood can be injected by the intravenous (i.v.) route. Transmission of BSE to a single animal using this approach was reported recently. This study confirms this result with a second transmission of BSE and four new cases of transmission of natural scrapie. Positive transmissions occurred with blood taken2 at pre-clinical and clinical stages of infection. Initial studies indicate that following such infection by the i.v. route, deposition of the abnormal prion protein isoform, PrPSc, in peripheral tissues may be much more limited than is seen following oral infection. These results confirm the risks of TSE infection via blood products and suggest that the measures taken to restrict the use of blood in the UK have been fully justified.

Introduction

Creutzfeldt-Jakob disease (CJD) is one of a group of related diseases known as prion diseases or transmissible spongiform encephalopathies (TSEs), a group that also includes scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle. A new variant of CJD (vCJD) in human beings in the UK (Will et al., 1996) is thought to have been the result of infection with the same agent that causes BSE in cattle (Bruce et al., 1997). The numbers of vCJDinfected people remain unknown, although, to date, over 100 clinical cases have been recordedin the UK. Amongst many sources of concern, one major question relates to the safety of blood transfusions and blood products - especially when inadvertently sourced from individuals during the long pre-clinical phase of vCJD, a time at which these individuals may act as asymptomatic carriers of the infectious agent. There is no epidemiological evidence to indicate that iatrogenic CJD has ever occurred via blood or blood products but vCJD is a new disease with a different pathogenesis and may present different risks.

The TSE disease-associated form of the prion protein (PrPSc) of the neuronal glycoprotein PrPC is often used as a marker for infectivity. Using a sensitive Western blotting technique, no PrPSc was detected in the buffy coat from one vCJD patient (Wadsworth et al., 2001). Although a novel method for detection of PrPSc in scrapie sheep blood has been described (Schmerr et al., 1997), the study was limited by a low number of samples and the technique requires further validation. Other investigators using the more conventional method of immunocytochemistry failed to demonstrate PrPSc in peripheral blood leucocytes of scrapie-infected sheep (Herrmann et al., 2002).

An alternative to PrPSc detection is direct bioassay of infectivity by inoculation of material into hosts of the same or different species. In laboratory rodents experimentally infected with TSE, a number of investigators have demonstrated infectivity in blood and blood components during the pre-clinical and clinical phases of infection (Brown et al., 1998; Diringer, 1984; Manuelidis et al., 1978). However, infectivity has not been isolated, so far, from blood components of natural animal hosts of TSEs (Hadlow et al., 1982; Marsh et al., 1973). Isolated reports of transmission of CJD to laboratory rodents by whole blood or buffy coat from human3 patients have been questioned for a variety of reasons (Brown, 1995).

A large-scale study conducted by the National Institutes of Health failed to demonstrate infectivity in blood from 13 patients with CJD, using either highly susceptible primates or rodents as bioassay hosts (Brownet al., 1994). With vCJD, no infectivity was detected in blood from two patients using mouse bioassays (Bruce et al., 2001). Many of these studies could have failed to reveal low levels of infectivity in blood because of the use of rodents as bioassay hosts, thus limiting the sensitivity by crossing a species barrier. Also, in most cases, the intracerebral (i.c.) route of inoculation was used, because it is the most efficient, but this severely limits the volume of blood that can be assayed.

Thus, where transmission from blood has been successful, infectivity was usually concentrated in some way, for example, by the use of buffy coat fractions. Transmission by the intravenous (i.v.) route has been shown to be up to seven times less efficient than following i.c. infection (Brown et al., 1999), but there have been very few attempts to transmit TSEs by whole blood transfusion. Units of whole blood from three CJD cases were transfused into chimpanzees with negative results (Brown et al., 1994) and pooled blood from three terminally ill TSEinfected mice produced disease in 1 of 20 transfusion recipients (Brown et al., 1999). Sheep infected orally with BSE show widespread deposition of PrPSc in the lymphoreticular system (LRS) (Foster et al., 1996a, 2001b), similar to that seen in human vCJD patients.

In contrast, in cases of sporadic human CJD and cattle BSE, peripheral pathogenesis does not appear to involve the LRS (Hill et al., 1999; Wells et al., 1998). Sheep were chosen as a model in which to study transmission of TSEs by blood transfusion because of the similarity of the pathogenesis with vCJD and because large volumes of blood can be transferred in the absence of a species barrier. We have transfused whole blood and buffy coat from BSE-infected sheep and natural scrapie-infected sheep into susceptible but scrapie-free recipient animals. In the first report on these experiments (Houston et al., 2000), we described a single case of BSE infection via blood transfusion.

The significance of this finding in a single animal has been questioned. However, the present report gives details of further successful transmissions from BSE and natural scrapie cases, the latter being the first conclusive demonstration of infectivity in blood of naturally infected individuals. Although still incomplete, our study indicates a frequency of transmission of TSEs in at least 10 % of the transfusion recipients. We have decided to provide an update of our results because of the potential importance of the study for human health. In addition, in the two BSE transfusion cases examined so far, deposition of PrPSc in peripheral tissues appears rather limited when compared with sheep infected by the oral route. The potential implications of this observation for pre-clinical diagnosis and screening are discussed.

SNIP...

14 Discussion

With this report we have confirmed and extended our initial observation of a single case of BSE following transfusion of blood from a BSE-infected sheep and have provided the first conclusive evidence of significant levels of infectivity in blood in a naturally occurring TSE (scrapie). The experiment may take up to 5 years to complete; however, so far we have clear evidence of disease transmission by the blood transfusion route in 2 of 24 sheep (8 %) with BSE and 4 of 21 sheep (19 %) with scrapie, with two additional animals showing clinical signs in the BSE group. If the clinically suspect BSE-transfused sheep progress as expected, this would bring the transmission rate for BSE up to 17 %, comparable with the scrapie rate.

Positive transmissions have occurred not only with samples taken from sheep at the clinical phase of disease but also with those from apparently healthy donors as early as halfway through the incubation period (Fig. 1, lane 9; no PrPSc detection in the brain of donor J2746). Each TSE is transmitting to its appropriate susceptible genotype (AXQ/AXQ for BSE and VRQ/VRQ for scrapie) and Western blot/glycoform analyses support the conclusion that donors and recipients are infected with the same strains of BSE and scrapie. Our negative controls remain healthy, although still at relatively early stages post-transfusion and our positive controls are developing clinical signs at around, or greater than, 600 days post-challenge, showing incubation periods very similar to the transfusion cases. Whole blood transfusion (400-450 ml) cases are presenting incubation periods of around 600 days, which is very similar to those resulting from i.v. injection of 0.2 g BSE cattle brain homogenate. The transfusions might be expected to be more efficient because they are a sheepto-sheep transmission with no species barrier, which contrasts with the i.v. brain infections, which is a cattle-to-sheep transmission.

A full titration of the inoculum used in the cattle BSE brain i.v. controls is under way in mice but is incomplete at the time of writing. Accurate estimation of the levels of infectivity in blood will require i.v. titration in sheep; however, the results presented here suggest that they are significantly higher than suspected previously. Another important consideration is the distribution of infectivity among different blood components. Perhaps surprisingly, most positive transmissions so far have followed transfusion of whole blood rather than buffy coat, whereas previous studies have tended to find infectivity concentrated in the buffy coat fraction. As we now have a clinical case of scrapie resulting from transfusion of buffy coat, it is clear that, in our model, infectivity is also carried by the cells in this fraction. However, these preliminary results suggest that infectivity is not confined to the buffy coat fraction and that there may also be significant levels of infectivity in the plasma and/or red cell fractions. 15

The presence of infectivity in blood suggests that it should be possible to detect PrPSc or other surrogates of infectivity by alternative methods, with obvious benefits for development of ante-mortem diagnostic tests. Early reports of the use of capillary electrophoresis to detect PrPSc in the blood of scrapie-infected sheep showed some promise (Schmerr et al., 1997); however, a recent study could not detect PrPSc in peripheral blood leucocytes of scrapie-infected sheep using immunocytochemistry (Herrmann et al., 2002). PrPC is known to be expressed only on peripheral blood mononuclear cells in sheep, in contrast to humans where it is also found on platelets and, at low levels, on erythrocytes (Barclay et al., 2002; Herrmann et al., 2001; Holada et al., 1998). Since tissues that express PrPC do not always equate with areas that accumulate PrPSc and infectivity during disease, the distribution of infectivity in blood fractions of different species clearly merits more detailed analysis.

Immunocytochemical detection of PrPSc in peripheral tissues of two of the BSE transfusion cases has shown a greatly reduced involvement of lymphoid tissues, including tonsil, in the peripheral pathogenesis compared with NPU Cheviot sheep orally infected with BSE or natural scrapie (Foster et al., 2001a). A recent report has shown that a proportion of Romney sheep in the late pre-clinical stages of infection with BSE following oral dosing (22 months post-infection) have PrPSc deposits in the CNS in the absence of any detectable involvement of peripheral lymphoid tissues (Jeffrey et al., 2001). This study also noted the relatively late and variable onset of PrPSc accumulation in the lymphoid tissues of BSE-infected sheep.

A more detailed study of BSE and scrapie transfusion cases, and positive controls, will be undertaken to determine whether lack of involvement of the LRS is a consistent feature in animals infected by the i.v. route; the results will be published at a later date. If our preliminary observations are confirmed, there may be implications for human patients with the misfortune to have received blood products from vCJD cases, because a negative tonsil biopsy as a means of reassurance might very well be unreliable. On the other hand, it also may mean that if a human patient became infected with vCJD by the i.v. route, then the peripheral tissues and blood of this secondary case may not themselves be highly infectious. In conclusion, our results so far indicate that, with more than 10 % of transfusions resulting in disease in the recipients, blood transfusion represents an appreciable risk for transmission of TSEs in sheep and, by extension, of vCJD in human beings. The relatively short and consistent incubation periods seen in positive cases suggests that levels of infectivity in the blood may be higher than suspected previously, even in the pre-clinical stages of infection, and/or that transmission by the i.v. route is highly efficient. From these preliminary results, it would appear that measures taken to safeguard the blood supply in the UK are fully justified. 16

However, further work, in particular a thorough investigation of the distribution of infectivity in different blood fractions, is required before a reliable estimate of the risks associated with contaminated blood products can be made.

Acknowledgements The authors are indebted to the UK Department of Health, European Union and DEFRA for their financial contribution to this study.

see full text:

http://www.socgenmicrobiol.org.uk/JGVDirect/18580/18580ft.pdf

Transfusion
Volume 43 Page 1687 - December 2003
doi:10.1046/j.0041-1132.2003.00586.x
Volume 43 Issue 12


Similar levels of infectivity in the blood of mice infected with human-derived vCJD and GSS strains of transmissible spongiform encephalopathy
Larisa Cervenakova, Oksana Yakovleva, Carroll McKenzie, Svetlana Kolchinsky, Lisa McShane, William N. Drohan, and Paul Brown
BACKGROUND:
The possible transmission of variant CJD (vCJD) through blood transfusion or use of plasma-derived products prompted this study comparing infectivity in murine models of vCJD and Gerstmann-Sträussler-Scheinker (GSS) disease, a non-vCJD form of transmissible spongiform encephalopathy (TSE).

STUDY DESIGN AND METHODS:
RIII/Fa/Dk (RIII) or Swiss-Webster (Swiss) mice were inoculated intracerebrally (IC) with mouse-adapted strains of vCJD or GSS (Fukuoka-1) of similar infectivity. Groups of RIII mice were euthanized 17 weeks after inoculation (during the incubation period), and another 23 weeks after inoculation (when symptomatic). Blood was collected, separated into components, and inoculated into groups of healthy mice; brains and spleens from all mice were harvested and tested for the presence of PrPres by Western blot using 6H4 MoAb.

RESULTS:
Levels of 20-30 infectious doses per mL were present in buffy coat and plasma during both the incubation and symptomatic stages of disease; PLT pellet infectivity was lower (10 ID/mL) and RBCs were not infectious. The disease was transmitted more efficiently by IV than IC inoculation of plasma, but there was no difference observed with inoculation of buffy coat. The incubation period was shorter after IC inoculation of GSS- than vCJD-brain inocula. The amount of PrPres in spleens was similar for both TSE agents, but was slightly lower in brains of vCJD than GSS mice.

CONCLUSION:
Infectivity was detected in blood components of mice infected with a human-derived strain of vCJD during both the preclinical and clinical phases of disease in a similarly low range of concentrations as in mice infected with a human-derived nonvariant strain (GSS, Fukuoka-1). Other measures of virulence, including brain infectivity titers, incubation periods, and the accumulation of PrPres in spleens and brains, were also comparable in both experimental models.

http://www.blackwell-synergy.com/doi/abs/10.1046/j.0041-1132.2003.00586.x

USA FDA MAD COW BLOOD HUMANS RECALL (these are dime a dozen)

RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS II
______________________________
PRODUCT
Source Plasma, Recall # B-1708-6
CODE
Units: MI180733, MI180927, MI181625, MI181780, MI182337, MI182519, MI183140,
MI183311, MI183955, MI185006, MI185278, MI185822, MI186081, MI186855,
MI187183, MI187903, MI188273, MI188695, MI189257, MI189553, MI190136,
MI190473, MI191073, MI191395, MI191972, MI192303, MI193473, MI194343,
04MINA0377, 04MINA0801, 05MINA7147, 05MINA7451, 05MINA8094, 05MINA8504,
05MINA9548, 05MINA9883, 05MINB0489, 05MINB0875, 05MINB1469, 05MINB1874,
05MINB3116, 05MINB7192, 05MINB7529, 05MINB8246, 05MINB8612, 05MINB9236,
05MINB9366, 05MINB9475, 05MINB9641, 05MINC0031, 05MINC0237, 05MINC0336,
05MINC0894, 05MINC0964, 05MINC1138, 05MINC1619, 05MINC1750, 05MINC1907,
05MINC1977, 05MINC2375, 05MINC2774, 05MINC3113, 05MINC3484, 05MINC4277,
05MINC4623, 05MINC5623, 05MINC5914, 05MINC7545, 05MINC7870, 05MINC8355,
05MINC8689, 05MINC9437, 05MINC9775, 05MIND0067, 05MIND0393, 05MIND0892,
05MIND0951, 05MIND1836, 05MIND2183 and 05MIND2962
RECALLING FIRM/MANUFACTURER
BioLife Plasma Services L.P., Muncie, IN, by facsimile on November 22, 2005.
Firm initiated recall is complete.
REASON
Blood products, collected from unsuitable donors based on risk factors for
Creutzfeldt-Jakob Disease (CJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
80 units
DISTRIBUTION
CA, NC, and MD

______________________________

PRODUCT
a) Red Blood Cells, Leukocytes Reduced, Recall # B-1714-6;
b) Fresh Frozen Plasma, Recall # B-1715-6;
c) Platelets, Recall # B-1716-6
CODE
a), b), and c) Unit: 2443732
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by letters dated
November 11, 2003 and December 18, 2003. Firm initiated recall is complete.
REASON
Blood products, collected from a donor who was at increased risk for new
variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX and WI

END OF ENFORCEMENT REPORT FOR SEPTEMBER 13, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00969.html

PRODUCT
Fresh Frozen Plasma, Recall # B-1751-6
CODE
Unit: 4936623
RECALLING FIRM/MANUFACTURER
Gulf Coast Regional Blood Center, Houston, TX, by facsimile dated September
16, 2005. Firm initiated recall is complete.
REASON
Blood product, which was collected from an unsuitable donor based on risk
factors for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
TX

END OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html


Mon Aug 7, 2006 10:24
71.248.132.189

PRODUCT
a) Red Blood Cells, Recall # B-1587-6;
b) Cryoprecipitated AHF, Recall # B-1588-6;
c) Recovered Plasma, Recal # B-1589-6
CODE
a), b) and c) Unit: 2016719
RECALLING FIRM/MANUFACTURER
Walter Shepeard Community Blood Center, Inc., Augusta, GA, by facsimile on
March 13, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased
risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
GA and Germany

______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1590-6;
b) Fresh Frozen Plasma, Recall # B-1591-6
CODE
a) and b) Unit: 2443595
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June
30, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased
risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX

______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1592-6;
b) Fresh Frozen Plasma, Recall # B-1593-6
CODE
a) and b) Unit: 2545596
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on
December 14, 2004 and January 3, 2005. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased
risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX

______________________________

http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html



PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1550-6;
b) Fresh Frozen Plasma, Recall # B-1551-6
CODE
a) and b) Unit 2395371
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on August 20, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX
______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1552-6;
b) Platelets, Recall # B-1553-6;
c) Fresh Frozen Plasma, Recall # B-1554-6
CODE
a), b) and c) Unit 2438702
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on May 29, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX

______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1555-6;
b) Fresh Frozen Plasma, Recall # B-1556-6
CODE
a) and b) Unit 2454970
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on July 23 and December 11. 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX

______________________________
PRODUCT
a) Red Blood Cells, Recall # B-1494-6
b) Cryoprecipitated AHF, Recall # B-1495-6
CODE
a) and b) Unit 5013100
RECALLING FIRM/MANUFACTURER
Walter L. Shepeard Community Blood Center, Inc., Augusta, GA, by fax on May 17, 2005. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
GA

______________________________
PRODUCT
Source Plasma, Recall # B-1450-6
CODE
Unit numbers ST0824313 and ST0824764
RECALLING FIRM/MANUFACTURER
Stillwater Plasma Center LLC, Stillwater, OK, by fax on November 21, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor whose suitability pertaining to risk factors for Creutzfeldt-Jakob Disease (vCJD) was not adequately determined, were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
UK

______________________________
PRODUCT
Plasma Frozen, Recall # B-1422-6;
Recovered Plasma, Recall # B-1423-6
CODE
a) Unit 03E42218;
b) Unit 03E38153
RECALLING FIRM/MANUFACTURER
American Red Cross Blood Services, Atlanta, GA, by telephone, e-mail or letter on February 20 or 21, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
GA and Switzerland

______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1374-6;
b) Recovered Plasma, Recall # B-1375-6
CODE
a) and b) unit 2453906
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by fax on October 31 and November 5, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX and Austria

______________________________
PRODUCT
Source Plasma. Recall # B-1295-6
CODE
Units: NG0046551, NG0045950
RECALLING FIRM/MANUFACTURER
DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 20, 2002, Firm initiated recall is complete.
REASON
Blood products, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire appropriately, were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
KY

______________________________
PRODUCT
Source Plasma. Recall # B-1296-6
CODE
Unit: NG 0044520
RECALLING FIRM/MANUFACTURER
DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 12, 2002. Firm initiated recall is complete.
REASON
Blood product, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire, was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
KY

______________________________
PRODUCT
Source Plasma. Recall # B-1297-6
CODE
Units: NG0042874, NG0043139, NG0043312, NG0043618, NG0043797, NG0044020, NG0044209, NG0044507, NG0044718, NG0044977, NG0045161, NG0045412, NG0045555
RECALLING FIRM/MANUFACTURER
DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 20, 2002. Firm initiated recall is complete.
REASON
Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
13 units
DISTRIBUTION
KY

______________________________
PRODUCT
Source Plasma, Recall # B-1298-6
CODE
Units: NG 0046823, NG 0046671, NG 0045205, NG 0044635, NG 0043095, NG 0042525, NG 0042341
RECALLING FIRM/MANUFACTURER
DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 20, 2002. Firm initiated recall is complete.
REASON
Blood products, collected from a donor who answered questions on the variant Creutzfeldt-Jacob disease (vCJD) questionnaire inappropriately, were distributed.
VOLUME OF PRODUCT IN COMMERCE
7 units
DISTRIBUTION
KY

______________________________
PRODUCT
Recovered Plasma, Recall # B-1299-6
CODE
Unit: 4357117
RECALLING FIRM/MANUFACTURER
Department of the Navy, Naval Medical Center, San Diego, CA, by fax and letter on September 25, 2003. Firm initiated recall is complete.
REASON
Blood product, collected from a donor considered to be at risk of exposure to Creutzfeldt-Jacob Disease (CJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
Germany

END OF ENFORCEMENT REPORT FOR July 12, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html


CJD WATCH MESSAGE BOARD
TSS
FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY
Fri Jul 7, 2006 09:37
70.110.83.160


FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY

PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1379-6;
b) Platelets, Recall # B-1380-6;
c) Fresh Frozen Plasma, Recall # 1381-6;
d) Recovered Plasma, Recall # B-1382-6
CODE
a) Unit numbers: 2343106, 2377779, and 2403533;
b) and c) Unit numbers: 2377779;
d) Unit numbers: 2343106 and 2403533
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June 12, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
7 units
DISTRIBUTION
TX and Austria
______________________________


PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1467-6;
b) Recovered Plasma, Recall # B-1468-6
CODE
a) and b) Unit numbers: 2329380
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on May 8, 2003. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX and Switzerland

______________________________

PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1479-6;
b) Cryoprecipitated AHF, Recall # B-1480-6;
c) Recovered Plasma, Recall # B-1481-6
CODE
a), b), and c) Unit numbers: 2383280
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on July 23 and 29, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX and Switzerland

______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1482-6;
b) Fresh Frozen Plasma, Recall # B-1483-6
CODE
a) and b) Unit number: 2501452
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on October 5, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
TX and NY

______________________________
PRODUCT
a) Red Blood Cells Leukocytes Reduced, Recall # B-1484-6;
b) Plasma Cryoprecipitated Reduced, Recall # B-1485-6;
c) Recovered Plasma, Recall # B-1486-6
CODE
a) and c) Unit number: 2554077;
b) Unit number: 2415708
RECALLING FIRM/MANUFACTURER
South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on August 13, 2004. Firm initiated recall is complete.
REASON
Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
TX and Austria

_____________________________________

END OF ENFORCEMENT REPORT FOR July 5, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00959.html

FDA Fines American Red Cross $4.2 Million (BLOOD CJD)
Fri Sep 8, 2006 20:01
71.248.154.242


FDA Statement
FOR IMMEDIATE RELEASE
Statement
September 8, 2006
Media Inquiries:
301-827-6242
Consumer Inquiries:
888-INFO-FDA


FDA Fines American Red Cross $4.2 Million for Failure to Meet Established
Blood Safety Laws

The U.S. Food and Drug Administration (FDA) announced today that the
American Red Cross (ARC) is being fined $4.2 million for failure to comply
with requirements under Federal laws and FDA regulations relating to the
collection of blood products. These fines were assessed under an amended
2003 consent decree that calls for significant financial penalties when ARC
fails to comply with FDA regulations and consent decree provisions designed
to ensure the safety of the nation's blood supply.

The fines stem from a recently completed FDA review of recalls conducted by
ARC between 2003 and 2005 that found these events were preventable by ARC.
The violations include breaches of Good Manufacturing Practice (GMP) such as
a failure to ask appropriate donor screening questions and failure to follow
manufacturer test protocols. We have no evidence that these violations
resulted in serious health consequences.

Because receiving blood products always carries a degree of risk, it is
important that the blood industry complies with the full set of safeguards
in Federal laws and FDA regulations to minimize that risk. However, any
particular breach of the safeguards does not necessarily translate into
unsafe blood products, because the safeguards designed to protect the blood
supply are to some extent overlapping. The FDA continues to advise care
providers and consumers that rigorous protections are in place and that the
blood supply is safe. Patients in need of a transfusion should continue to
follow the advice of their physicians. The risks of receiving a transfusion
are far less than the risk of failing to receive a transfusion when blood
treatment is indicated.

Improvements in donor screening procedures and the use of a variety of new
tests in the last few years have made the national blood supply safer from
infectious diseases and other risks than it has been at any other time.
However, because there is always some degree of risk in receiving blood
products, each individual safeguard is considered critical to minimizing
that risk. Although the failure of an individual safeguard does not
automatically translate into the release of unsafe products, it may increase
the potential for risk. It is the potential risk that FDA insists the Red
Cross Board of Directors prioritize and support its new management's ability
to immediately address and work to improve its approach to quality.

The amended consent decree requires ARC to:

Establish clear lines of managerial control over a newly established
comprehensive quality assurance system in all regions;
To enhance training programs; and
To improve computer systems, records management, and policies for
investigating and reporting problems, including adverse reactions
Since entry of the 2003 consent decree and prior to this action, FDA has
issued the American Red Cross seven similar letters and assessed a total of
$5.7 million in penalties.

While achieving a blood supply with zero risk of transmitting infectious
disease is the ultimate objective, we recognize based on the available
science that this may not be realistic. Therefore, the FDA requires blood
processors to adopt and strictly follow a multi-layered safety program to
protect and enhance the safety of blood products at each stage of their
manufacture. At the blood collection stage, these measures generally
include:

Accurate and complete educational material for donors so that they can
assess their risk and decline to donate if that is appropriate;
Administration of donor screening questions to identify safety risks;
Checking of lists to prevent use of blood from persons known to be
ineligible to donate;
Quality controlled infectious disease testing procedures;
Inventory controls to prevent the release of units that are unsuitable;
Appropriate handling and distribution of blood and blood products for
patient use; and
Investigation and correction of deviations from standards
ARC is responsible for approximately 45% of the nation's blood supply; other
independent community-based blood centers together provide another 45%, and
hospitals collect most of the remaining 10%.

Blood donations are critically needed every day to save lives, and blood
donation is a safe procedure. FDA encourages persons who are in good health
to donate blood and to become regular blood donors.

####

http://www.fda.gov/cber/talkpapers.htm#arc

Red Cross fined $4.2 mln over blood safety

By Lisa Richwine

WASHINGTON (Reuters) - The U.S. government fined the American Red Cross $4.2
million for failing to ask blood donors proper screening questions and
skipping other steps meant to keep the blood supply safe, officials said on
Friday.

The fine, the largest ever levied by the Food and Drug Administration for a
blood safety violation, follows a multiyear battle between the FDA and the
Red Cross, which collects about 45 percent of the blood donated in the
United States each year for transfusions.

The agency said it had no evidence that any blood collected by the Red Cross
harmed people who got transfusions.


But FDA officials said the failure to follow multiple safeguards increased
the risk that patients could receive blood tainted by an infectious disease.

"It is not acceptable that the quality systems failed in this way," Margaret
O'K. Glavin, FDA associate commissioner for regulatory affairs, told
reporters.

The FDA said its investigation found that several Red Cross recalls of blood
between 2003 and 2005 could have been prevented if it had taken a series of
mandatory steps to ensure donations are free of HIV or other infectious
agents.

One way the Red Cross erred was by failing to ask donors about travel
history that could increase the chances of having malaria or the human
version of mad cow disease, FDA officials said.

The problems involved 12,000 units of blood and blood components, FDA
officials said. None of the units was found to be contaminated after they
were recalled.

The latest fine was issued as part of a legally binding consent decree
reached in 2003 in which the Red Cross promised to improve its blood safety
system. Previously, the FDA had fined the organization a total of $5.7
million.

The 2003 deal revised a 1993 agreement that allowed the FDA to fine the Red
Cross for blood collection lapses.

The Red Cross said it would review the FDA's letter outlining its new
concerns and respond within 20 days.

"American Red Cross's senior management takes (the letter) seriously and is
committed to full compliance with the amended consent decree and all
applicable federal regulations," the organization said in a statement.


The FDA said the blood supply remained very safe.

http://today.reuters.co.uk/news/articlenews.aspx?type=healthNews&storyID=2006-09-08T224834Z_01_N08403053_RTRIDST_0_HEALTH-REDCROSS-DC.XML

http://today.reuters.co.uk/news/articlenews.aspx?type=healthNews&storyID=2006-09-08T224834Z_01_N08403053_RTRIDST_0_HEALTH-REDCROSS-DC.XML&pageNumber=1&imageid=&cap=&sz=13&WTModLoc=NewsArt-C1-ArticlePage1

SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2004. SPORADIC CJD CASES TRIPLED, and that is
with a human TSE surveillance system that is terrible
flawed. in 1997 cases of the _reported_ cases of cjd
were at 54, to 163 _reported_ cases in 2004. see stats
here;

p.s. please note the 47 PENDING CASES to Sept. 2005

p.s. please note the 2005 Prion D. total 120(8)
8=includes 51 type pending, 1 TYPE UNKNOWN ???

p.s. please note sporadic CJD 2002(1) 1=3 TYPE UNKNOWN???

p.s. please note 2004 prion disease (6) 6=7 TYPE
UNKNOWN???


http://www.cjdsurveillance.com/resources-casereport.html

HOW MANY WERE BLOOD DONORS ???

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine
Spongiform Encephalopathy (BSE)


http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf

[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle

03-025IFA
03-025IFA-2


http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf

THE SEVEN SCIENTIST REPORT ***


http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf

From: Terry S. Singeltary Sr. [flounder@wt.net]

Date: Monday, January 08,200l 3:03 PM

To: freas@CBS5055530.CBER.FDA.GOV

snip...

CJDIBSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and

Consultants Staff January 2001 Meeting (short version)

I am beginning to think that the endless attempt to track

down and ban, potential victims from known BSE Countries

from giving blood will be futile. You would have to ban

everyone on the Globe eventually? AS well, I think we

MUST ACT SWIFTLY to find blood test for TSE's,

whether it be blood test, urine test, eyelid test,

anything at whatever cost, we need a test FAST.

DO NOT let the incubation time period of these TSEs fool you. ...

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.

http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=dignosing+and+reporting+creutzfeldt+jakob+disease&searchid=1048865596978_1528&stored_search=&FIRSTINDEX=0&journalcode=jama


Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518





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