Variant CJD and blood transfusion: are there additional cases?
Vox Sanguinis (2014) 107, 220–225 ORIGINAL PAPER © 2014 International
Society of Blood Transfusion DOI: 10.1111/vox.12161
Variant CJD and blood transfusion: are there additional cases?
L. R. R. Davidson, 1 C. A. Llewelyn, 2 J. M. Mackenzie, 1 P. E. Hewitt 3
& R. G. Will 1 1 National CJD Research & Surveillance Unit, Western
General Hospital, Edinburgh, UK 2 NHS Blood and Transplant, Cambridge Centre,
Cambridge, UK 3 NHS Blood and Transplant, Colindale Centre, London, UK Received:
12 February 2014, revised 29 April 2014, accepted 30 April 2014, published
online 11 June 2014
Background and Objectives In this study, we compare variant
Creutzfeldt-Jakob disease (vCJD) cases definitely linked to blood transfusion,
those with a history of blood transfusion in which no donor has developed vCJD
and primary cases with no history of blood transfusion. The aim is to determine
whether there are any differences in the demographics or clinical phenotype in
these groups that might suggest additional cases of transfusion transmission of
vCJD.
Materials and Methods All cases of vCJD who are old enough to donate blood
(i.e. >17 years old) are notified to the UKBTS at diagnosis, regardless of
whether they are known to have a blood donation history. A search is then made
for donor records and, if found, all components produced and issued to hospitals
are identified and their fate determined. Recipient details are then checked
against the NCJDRSU register to establish whether there is a match between these
individuals and patients who have been diagnosed with vCJD. In the reverse
study, attempts are made to trace the donors to all cases reported to have
received a blood transfusion and donors’ details are checked against the
register to determine if any have developed vCJD.
Results Of the 177 cases of vCJD diagnosed in the UK as of 1 February 2014,
the TMER study identified 15 cases reported to have received a blood
transfusion. Transfusion records were unavailable for 4 of these cases, all
pre-1980, and in one other case there was no transfusion recorded in the medical
notes. Transfu- sion records were found for 10 cases. One case transfused at
symptom onset was excluded from this analysis. The mean age at onset of symptoms
of the remain- ing nine transfusion recipients (four female and five male) was
42Á9 years; 57Á6 years in the three known transfusion-transmitted cases and 35Á5
years in the six not linked cases. In one of these cases, details of components
transfused were unavailable, and the remaining five cases received a total of
116 donor exposures with 112 donors identified, none of whom is known to have
developed clinical vCJD. To date, five of the 112 identified donors have died
and none was certified as dying of vCJD or any other neurological disorder. Two
of the transfu- sion-transmitted cases did not fulfil diagnostic criteria for
probable vCJD during life but were confirmed at post-mortem. Both cases were in
the older age range (68 and 74 years, respectively), and neither had a positive
MRI brain scan. The remaining cases all fulfilled the criteria for the diagnosis
of vCJD in life, but two of these had atypical features and were older than the
expected age at onset for vCJD.
Conclusion In conclusion, it is possible that one or more of the vCJD cases
that received a blood transfusion derived from an individual not known to have
vCJD were infected by the blood transfusion. However, the evidence for this is
weak, and the absence of a past history of transfusion in most cases of vCJD
excludes a large number of unrecognised transfusion-transmitted cases.
Letter Variant CJD and blood transfusion J. P. Wallis* Article first
published online: 6 MAR 2015
DOI: 10.1111/vox.12241
© 2015 International Society of Blood Transfusion
Dear
Editor,
The recently published histological study of surgically
removed appendix tissue raised the possibility of silent carriers of the disease
affecting 1 in 2000 UK donors [1].
Davidson et al. [2]
report on the characteristics of patients with clinical vCJD who had previously
received blood transfusion but where the donors have not themselves gone on to
develop clinical vCJD. On the basis of a higher-than-expected mean age of these
cases, they suggest an association between transfusion and vCJD. However, they
do not adjust for factors affecting the likelihood of prior transfusion. From
our study in 1994 of point incidence of transfusion and subsequent survival, I
have estimated the prevalence of prior transfusion by age (Table 1)
[3].
To allow for the effect of repeated transfusion and the observed 80% 5-year
survival, I have applied a correction factor of 0·5 to the data. My figures are
similar to other surveys of prior transfusion prevalence [4]. I have excluded neonatal transfusion as practice
markedly changed during the previous 2 decades.
|
Table 1. Estimates of
expected prevalence of prior transfusion in patients with clinical
vCJD
| |||
|
Age
group
|
Transfusion prevalence
per 100 in 1994
|
vCJD clinical
cases
|
Estimated cases with
prior transfusion
|
|
10–14
|
0·27
|
0
|
0
|
|
15–19
|
0·94
|
25
|
0·24
|
|
20–24
|
1·79
|
44
|
0·79
|
|
25–29
|
3·00
|
44
|
1·32
|
|
30–34
|
4·04
|
32
|
1·27
|
|
35–39
|
5·18
|
19
|
0·98
|
|
40–44
|
6·59
|
6
|
0·42
|
|
45–49
|
8·59
|
2
|
0·16
|
|
50–54
|
10·88
|
4
|
0·48
|
|
55–60
|
14·67
|
1
|
0·09
|
|
Total
|
|
177
|
5·75
|
The Table 1 shows the estimated prevalence of prior transfusion in
quintiles from 10 to 60 years. This increases because the cumulative likelihood
of having received transfusion increases with time at risk and because
transfusion point incidence rises with age. Using the known age distribution of
the 177 vCJD cases, I have estimated that 5·75 cases would be expected to have
had prior transfusion. Davidson et al. find 14 cases who had definitely
been transfused. Of these, three were from donors who subsequently developed
vCJD and are excluded, one was transfused immediately prior to diagnosis,
leaving 10 cases. One was transfused as a neonate, a period I have excluded
leaving 9. Four were from a period before records of donors were available, and
not knowing their age at transfusion, I cannot know whether they should be
included in an analysis of transfusion after the age of 10 years. A figure of
between 5 and 9 remaining cases having received transfusion in the last
10–20 years prior to diagnosis is close to 5·75 as estimated above. Older
patients with clinical vCJD are more likely to have been transfused, and the
mean age will be higher than the whole cohort. Based on the age-adjusted
transfusion prevalence, the mean age of cases that might have received an
unlinked prior transfusion is 33·4 years. This compares with the observed figure
given by Davidson et al. of 35·5 years. The prevalence of transfusion in
females is almost twice that in males between the ages of 30 and 60. Four of six
vCJD patients with prior transfusion were female.
The observations of Davidson
et al. given the analysis above would suggest no significant excess of
prior transfusion amongst vCJD cases during the recent epidemic, and no
unexpected age or sex distribution in vCJD cases with prior
transfusion.
References
1.
Top of
page
· 1
Gill ON, Spencer Y, Richard-Loendt A, et al.: Prevalent
abnormal prion protein in human appendices after bovine spongiform
encephalopathy epizootic: large scale survey. BMJ 2013;
347:f5675
· 2
Davidson LR, Llewelyn CA, Mackensie JM, et al.: Variant
CJD and blood transfusion: are there additional cases? Vox Sang 2014;
107:220–225
· 3
Wallis JP, Wells AW, Matthews JN, et al.: Long-term
survival after blood transfusion: a population based study in the North of
England. Transfusion 2004; 44:1025–1032
· 4
Kamper-Jørgensen M, Edgren G, Rostgaard K, et al.: Blood
transfusion exposure in Denmark and Sweden. Transfusion 2009;
49:888–894
Friday, February 06, 2015
Evaluation of the protection of primates transfused with variant
Creutzfeldt-Jakob disease–infected blood products filtered with prion removal
devices: a 5-year update
Thursday, January 22, 2015
Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to
disease etiology?
TSE Prion related endoscopy and potential risk factors, see below link
;
Saturday, February 21, 2015
Design of Endoscopic Retrograde Cholangiopancreatography (ERCP)
Duodenoscopes May Impede Effective Cleaning: FDA Safety Communication
Wednesday, September 10, 2014
Creutzfeldt-Jakob disease (CJD) biannual update (August 2014), with updated
guidance on decontamination of gastrointestinal endoscopy equipment
Research and analysis
Tuesday, August 26, 2014
Blood reference materials from macaques infected with variant
Creutzfeldt-Jakob disease agent
EMBARGOED ADVANCE COPY Not to be published in full, or in part, in any form
before 00.01am on Thursday 24 July 2014 HC 327
House of Commons Science and Technology Committee
After the storm?
UK blood safety and the risk of variant Creutzfeldt-Jakob Disease
Second Report of Session 2014–15
EMBARGOED ADVANCE COPY Not to be published in full, or in part, in any form
before 00.01am on Thursday 24 July 2014
Summary
snip...see full text ;
Wednesday, July 23, 2014
After the storm? UK blood safety and the risk of variant Creutzfeldt-Jakob
Disease
Thursday, July 24, 2014
Government must do more to reduce risk of vCJD infection
Sunday, February 08, 2015
FDA SCIENCE BOARD TO THE FOOD AND DRUG ADMINISTRATION BOVINE HEPARIN BSE
CJD TSE PRION Wednesday, June 4, 2014
Tuesday, December 30, 2014
TSEAC USA Reason For Recalls Blood products, collected from a donors
considered to be at increased risk for Creutzfeldt-Jakob Disease (CJD), were
distributed END OF YEAR REPORT 2014
Monday, March 02, 2015
Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease
Using Cerebrospinal Fluid
Wednesday, January 28, 2015
Another new prion disease: relationship with central and peripheral
amyloidoses
here we go again...
Wednesday, November 12, 2014
Molecular Modeling of Prion Transmission to Humans
snip...
Brains from humans or transgenic mice expressing a human PrP with
methionine at codon 129 of PRNP provided the best substrates to amplify vCJD and
BSE PrPsc [6,7], suggesting that PMCA may reproduce faithfully the genotypic
transmission barrier. It was thus proposed as a means to evaluate the zoonotic
risk associated with emerging prion strains (Nor98 in sheep, L-type BSE in
cattle). Indeed, while classical BSE strain has been recognized to be at the
origin of vCJD in humans, L-BSE is considered to be a sporadic form of prion
disease in cattle, differing in many aspects (epidemiology, neuropathology,
biochemical features) from the C-BSE strain.
***Moreover, L-BSE has been transmitted more easily to transgenic mice
overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may
result from an exposure to the L-BSE agent.
***Lending support to this hypothesis, pathological and biochemical
similarities have been observed between L-BSE and an sCJD subtype (MV genotype
at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and
another sCJD subtype (MM genotype) [15].
snip...
Tuesday, November 04, 2014
Towards an Age-Dependent Transmission Model of Acquired and Sporadic
Creutzfeldt-Jakob Disease
Thursday, September 18, 2014
Development of Dose-Response Models of Creutzfeldt-Jakob Disease Infection
in Nonhuman Primates for Assessing the Risk of Transfusion-Transmitted variant
Creutzfeldt-Jakob Disease
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in
June 2014 confirmed as home grown case
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in
Texas
Updated: October 7, 2014
CDC and the Texas Department of State Health Services (DSHS) have completed
the investigation of the recently reported fourth vCJD case in the United
States. It confirmed that the case was in a US citizen born outside the Americas
and indicated that the patient's exposure to the BSE/vCJD agent most likely
occurred before he moved to the United States; the patient had resided in
Kuwait, Russia and Lebanon. The completed investigation did not support the
patient's having had extended travel to European countries, including the United
Kingdom, or travel to Saudi Arabia. The specific overseas country where this
patient’s infection occurred is less clear largely because the investigation did
not definitely link him to a country where other known vCJD cases likely had
been infected.
>>>the patient had resided in Kuwait, Russia and Lebanon.
>>>The completed investigation did not support the patient's
having had extended travel to European countries, including the United Kingdom,
or travel to Saudi Arabia.
Monday, June 02, 2014
Confirmed Variant CJD Case in Texas
Terry S. Singeltary Sr.
Sunday, December 14, 2014
ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD
strains, TSE prion aka Mad Cow Disease United States of America Update December
14, 2014 Report
Sunday, December 7, 2014
Scientific update on the potential for transmissibility of non-prion
protein misfolding diseases PRIONOIDS
Saturday, December 6, 2014
Detection of protein aggregates in brain and cerebrospinal fluid derived
from multiple sclerosis patients
Monday, November 17, 2014
Prion-like transmission and spreading of tau pathology
Greetings again Friends, Neighbors, and Colleagues,
I would kindly like to follow up on ‘vpspr, sgss, sffi, TSE, an iatrogenic
by-product of gss, ffi, familial type prion disease, what it ???’ ran across an
old paper from 1984, that some might find interest in, and I will update the
link with this old science paper from 1984, a 2010 paper from Japan, and some
information on scrapie transmission. The paper from Japan first, then the 1984
paper, and then the scrapie transmission studies.
***The occurrence of contact cases raises the possibility that transmission
in families may be effected by an unusually virulent strain of the agent.
From: Terry S. Singeltary Sr.
Sent: Saturday, November 15, 2014 9:29 PM
To: Terry S. Singeltary Sr.
Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL
1984
THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE
R. G. WILL
1984
snip...
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3,
2014
Singeltary comment ;
>>> Variant CJD and blood transfusion: are there additional cases?
TSE Prion and blood transfusion: will there be additional cases?
this should be the concern. ...TSS
posted by Terry S. Singeltary Sr. | 10:47 AM
|
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