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From: TSS ()
Subject: Summary of SEAC’s discussion on the second presumed case of blood transfusion-associated infection with vCJD
Date: February 25, 2005 at 9:27 am PST
© SEAC 2004
1
Summary of SEAC’s discussion on the second presumed case of blood
transfusion-associated infection with vCJD
Background
1. The Department of Health sought advice from the committee on a presumed
second instance of blood transfusion-associated transmission of the variant
Creutzfeldt-Jakob disease (vCJD) agent. The first case of probable blood
transfusion-associated transmission of vCJD1 was considered by SEAC in
February 2004.
2. The National CJD Surveillance Unit (NCJDSU) had investigated this second
patient after death, as the patient was a known recipient of blood from
a donor
incubating vCJD. Patient confidentiality and medico-legal issues surrounding
the patient at the time of reporting required that the issue was
considered in the
reserved session of the meeting.
3. The elderly patient died in 2004, showed no clinical signs of vCJD at
the time of
death, which was from an unrelated cause. The patient had received a single
unit of non-leucodepleted blood in 1999 that had been donated by an
individual
who was confirmed in 2001 as a definite vCJD case. The donor’s disease onset
was in 2000.
4. The NCJDSU had investigated the neuropathology, accumulation of prion
protein and PrPres in autopsied tissues in the case. The PRPN genotype had
also been determined. The following details were reported:
• No evidence of a spongiform encephalopathy in an examination of brain
material.
• Immunohistochemical detection of prion protein accumulation in the
spleen and in a cervical lymph node. PrPres was detected by high
sensitivity western blotting in the spleen.
• No accumulation of prion protein was detected in multiple regions of the
central nervous system, tonsils, appendix, large intestine, skeletal muscle
or thymus.
• Glycotype profile of PrPres in spleen was the same as has been found in
clinical cases of vCJD.
1 Llewelyn CA, Hewitt PE, Knight RS, Amar K, Cousens S, Mackenzie J,
Will RG. Possible transmission
of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet. 2004
Feb 7;363(9407):417-21.
© SEAC 2004
2
• Histological pattern of PrP accumulation in the spleen and the lymph node
is similar to that in two appendixes reported by Hilton et al (2004)2.
• Methionine/valine heterozygosity at codon 129 of PrP gene (PRNP).
5. SEAC was informed that the findings suggested that this might be a
preclinical
or subclinical case of iatrogenic vCJD associated with blood transfusion.
However, UK residency of the patient meant that oral exposure to the BSE
agent
could not be excluded as a possible cause of infection. Statistical analysis
suggested it was extremely unlikely that two cases of infection with the
vCJD
agent would have been detected by chance in recipients of blood from
pre-onset
vCJD cases, even if the prevalence of prion protein accumulation in spleen
tissue in the UK population was substantially larger than suggested by
studies
on appendix and tonsil tissue from persons without clinical vCJD.
6. The Department of Health (DH) asked SEAC to assess the data available
on this
case, and to advise on the implications this finding may have on the risk
associated with blood, and on any additional concerns for public health.
Summary of SEAC’s discussion
7. SEAC agreed that the western blot results and glycotype profile
suggested it
was unlikely that the infection was preclinical sporadic CJD (sCJD). The
committee noted that a single study by Glatzel et al (2003) had reported
PrPres in
the spleen of sCJD clinical cases. However, the levels of PrPres present
in sCJD
cases were low and detected in patients with a lengthy clinical illness from
sporadic CJD.
8. The committee agreed that the statistical analysis suggested that the
presence
of PrPres in the case was attributable to a vCJD infection acquired via
blood
transfusion rather than a primary infection resulting from a food borne
exposure.
9. SEAC agreed that this second patient with apparent vCJD infection
added to the
evidence that the vCJD agent can be transmitted by blood. However the
committee noted that in this instance, although vCJD infection appeared
to have
been transmitted, it was not known if clinical vCJD would have developed
if the
patient had lived longer.
10. SEAC agreed that this case added support to its view on the risk
associated with
blood transfusion. The finding was consistent with there being a
substantial risk
associated with receipt of non-leucodepleted blood from a donor incubating
vCJD. The extent to which leucodepletion reduces that risk is not known.
11. The committee agreed that it should be a public health priority for
all recipients of
blood (leucodepleted or not) from donors incubating vCJD to be subject
to the
kind of careful post-mortem examination that had been possible in this case.
This would help to quantify the nature and magnitude of the risks of
transmission
2 Hilton DA, Ghani AC, Conyers L, Edwards P, McCardle L, Ritchie D,
Penney M, Hegazy D, Ironside
JW. Prevalence of lymphoreticular prion protein accumulation in UK
tissue samples. Journal of
Pathology: 203 (3).733-739. Published Online: 21 May 2004
© SEAC 2004
3
of the vCJD agent through blood [donated by preclinical cases of vCJD]. The
committee re-iterated the continuing importance of the Transfusion Medicine
Epidemiology Review (TMER) to identify vCJD cases who have been donors
and the recipients of such donations.
12. SEAC noted that the detection of PrPres in lymphoreticular tissues
of vCJD cases
and the presence of infection in the spleen of this case was compatible
with the
lymphoreticular system being involved in the early spread of infection
before
entering the CNS. SEAC agreed that the detection of prion protein in the
spleen
but not in the tonsil of the case has implications for the national
anonymous
tonsil archive. The SEAC chair agreed to refer this finding to the DH/MRC
steering group overseeing the archive.
13. SEAC noted that the patient was heterozygous at codon 129 of the
PRNP gene
and that this was the first time infection with the vCJD agent had been
reported
in an individual not methionine homozygous. This indicated that
genotypes other
than the methionine homozygous were susceptible to infection with the vCJD
agent. Uncertainties remain as to the relative susceptibility of
heterozygotes to
food borne (or other) infection or the possible outcomes of infection. The
committee agreed that the similarities between the western blot band
analysis
and PrPres glycoprofile seen in this case and in cases of vCJD who were
methionine homozygous was reassuring with respect to the ability to make the
diagnosis of vCJD in those of genotypes other than methionine homozygous.
14. SEAC stated that, in the interests of public health, this case
demonstrates the
importance of both in life and in death surveillance of recipients of blood
products derived from blood donations from individuals subsequently
found to be
infected with the vCJD agent. The committee also noted that this case
highlighted the importance of obtaining autopsies in such patients and, more
generally, the committee reiterated the concern that it had expressed
previously,
that a mechanism was needed to increase the autopsy rate amongst the UK
population to reduce the possibility that cases of vCJD were being missed.
15. SEAC emphasised the importance of the DH-funded sheep transfusion study
which is designed to investigate the infectivity of different blood
fractions taken
from sheep experimentally infected with BSE by transfusing them into ARQ
homozygous sheep. The committee noted that the two presumed human cases
of blood transfusion-associated vCJD infection indicated the potential
infectivity
of transfused blood. However, current technology is unable to quantify
the levels
of infectivity in blood and a rapid diagnostic test remained a key research
priority.
SEAC
16th July 2004 http://www.seac.gov.uk/papers/transfusion.pdf TSS
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