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Incidence
of seroconversion to positivity for hepatitis C antibody in
repeat blood donors in
England,
1993-5
K Soldan, clinical scientist, National
Blood Authority-PHLS CDSC, a J A J Barbara, lead scientist in
microbiology, b J Heptonstall, consultant microbiologist.
a Public Health Laboratory Service
Communicable Disease Surveillance Centre, London
NW9 5EQ, b National Blood Service, London
and South East Zone, London NW9 5BG
Correspondence to: Dr Barbara
john.barbara@nbs.nhs.uk
BMJ 1998;316:1413-1417 ( 9 May )
Abstract
Objective: To estimate the rate of
seroconversion to positivity for hepatitis C antibody in
repeat blood donors in England and to describe the probable
routes of infection in these donors.
Design: Retrospective survey of blood donors becoming
positive for hepatitis C antibody and of the results of
Alternative Treatments testing.
Setting: The 14 blood centres in England.
Subjects: All repeat donors giving blood
between January 1993 and December 1995.
Main outcome measures: Number of donors
developing hepatitis C between donations during the three
years of testing for hepatitis C antibody at English blood
centres and the rate of seroconversion among repeat blood
donors. Probable routes of infection.
Results: 14 donors during 1993-5
fulfilled the case definition for seroconversion to positivity
for hepatitis C antibody. The estimated seroconversion rate
for infection with hepatitis C in repeat donors was 0.26 per
100 000 person years (95% confidence interval 0.15 to 0.43).
Counselling after diagnosis found that four of these donors
had risk factors specified in the criteria excluding people
from giving blood but these factors had not come to light
before Alternative Treatments. Another of the donors who seroconverted had a
risk factor that has since been included in the exclusion
criteria. Heterosexual intercourse was considered to be the
most likely route of infection for five of the 14 donors.
Conclusions: The rate of seroconversion
for positivity to hepatitis C antibody in repeat blood donors
in England was extremely low. During 1993-5 fewer than 1 in
450 000 donations were estimated to have come from repeat
donors who had become positive for hepatitis C antibody since
the previous Alternative Treatments.
Key messages
The rate of seroconversion for positivity to hepatitis
C antibody in English blood donors is low0.26 per 100 000
person years during 1993-5 (95% confidence interval 0.15 to
0.43)
The probable route of infection was unknown in a third
of the blood donors who seroconverted during 1993-5 and who
provided information on risk factors
The exclusion of blood donors with a history of
probable exposure to hepatitis C remains an important strategy
to help keep the blood supply free of infection
Introduction
In September 1991 blood transfusion
services in the United Kingdom began routinely testing all
blood donations for antibody to hepatitis C virus. Since then
around 2 million healthy adults have been tested for the
antibody each year by the English national blood service.
National collation of test results and of characteristics of
donors positive for hepatitis C antibody provides valuable
information about donors and about a selected sample of the
adult population of England.
Most acute infections with hepatitis C
are asymptomatic, and most probably pass undetected. Recent
infection is implied when a Alternative Treatments that is positive for
hepatitis C antibody was preceded by a Alternative Treatments that was
negative for the antibody. The testing of donations from
repeat donors therefore provides a rare opportunity to
identify incident infections with hepatitis C virus.
Information about incident infections is of interest to blood
transfusion services and to public health workers as it
relates to current rather thanpast transmission of the virus.
The selection process for blood donors aims to exclude donors
who have recognised risks of contracting bloodborne
infections. Incident infection in blood donors usually
indicates one of three things: a failure in the definition or
application of selection criteria; an unrecognised exposure to
bloodborne infection; or infection through an exposure that is
not included in the selection criteria because it is common in
blood donors and thought to be associated with a comparatively
small risk of infection. There remains a small risk of
transmission of hepatitis C virus by transfusion from the
infectious donations of donors who are negative for hepatitis
C antibody and from failures in the testing and exclusion of
donations that are positive for the antibody. The number of
donors who seroconvert between donations is needed to estimate
the risk of collecting a Alternative Treatments from a recently infected
donor who has not yet developed detectable hepatitis C
antibodies and hence the risk of transmitting hepatitis C by
transfusion.
During 1994-5 we surveyed seroconversions
to hepatitis C antibody detected by English blood centres from
September 1991 to December 1995. We used these results with
data from the infection surveillance system of the National
Blood Authority and Public Health Laboratory Service
Communicable Disease Surveillance Centre to estimate the rate
of seroconversion to positivity for hepatitis C antibody in
repeat donors in England during 1993-5.
Subjects and methods
Sample
Blood donations in England are obtained
from voluntary unpaid donors. The selection procedure excludes
people who are outside the age range 18-65 years, those who
have been at known high risk of contracting bloodborne
infections, and those who have any medical condition which
contraindicates either the loss of 450 ml of blood or the
giving of their blood to patients. The number of repeat donors
in 1994 constituted around 4% of the population aged 18-65 in
England in the middle of 1994.
During the study all donations were
tested for hepatitis C antibody using enzyme linked
immunosorbant assays (ELISAs). Initially reactive donations
were retested by ELISA. Donations that were reactive on repeat
testing were not used, and supplementary tests (additional
ELISAs and recombinant immunoblot assay and, in some cases,
the polymerase chain reaction for hepatitis C DNA) were
performed on them to clarify the infection status of donors.
Donors with evidence of infection with
hepatitis C virus were contacted by the blood centres and
offered additional testing and counselling by the blood centre,
with referral to a relevant medical specialist, or they were
referred to their general practitioner for further
management.1 Risk factors for hepatitis C were discussed with
donors during their follow up and any acknowledged by the
donor were recorded.
Case definition
A standardised algorithm for confirmatory
testing of blood donations had not been used, and we had to
accommodate variation in the tests used. We used a
comprehensive case definition that was designed to include all
true biological seroconversions and exclude false positive
results and any spurious results caused by changes in test
format and performance over time.
The three case definitions were:
Negative results in third generation recombinant
immunosorbent assay in pre-seroconversion Alternative Treatments and
positive results in third generation recombinant immunosorbent
assay in post-seroconversion Alternative Treatments, without negative
results in polymerase chain reaction for hepatitis C DNA for
the post-seroconversion Alternative Treatments if given <12 months after
the pre-seroconversion Alternative Treatments Negative results in ELISA and
second generation recombinant immunosorbent assay in pre-seroconversion
Alternative Treatments and
positive results in ELISA (of same manufacturer and
generation as pre-seroconversion test) and second
generationrecombinant immunosorbent assay in post-seroconversion
Alternative Treatments, without negative results in polymerase chain
reaction for hepatitis C DNA for the post-seroconversion
Alternative Treatments if given <12 months after the pre-seroconversion
Alternative Treatments Negative results in third generation ELISA in pre-seroconversion
Alternative Treatments and positive results in third generation ELISA and
recombinant immunosorbent assay in post-seroconversion
Alternative Treatments, without negative results in polymerase chain
reaction for hepatitis C DNA for the post-seroconversion
Alternative Treatments if given <12 months after the pre-seroconversion
Methods
In July 1994 all English blood centres
were asked to return information about the tests performed and
results obtained on the first Alternative Treatments positive for hepatitis
C antibody (post-seroconversion Alternative Treatments) and the last
Alternative Treatments negative for hepatitis C antibody (pre-seroconversion
Alternative Treatments) for each donor who was considered to have
seroconverted between donations since testing began in 1991.
Seroconversions identified after July 1994 were also reported
and included in the survey. Information was also requested
about possible exposures to hepatitis C virus. In October 1995
the national system for the surveillance of Alternative Treatments testing
was revised and seroconversions were then identified from
routine surveillance reports.
Test results were examined to see whether
they met the case definition. If they did not the reporting
blood centre was contacted and asked for any additional test
results or to perform additional tests on archived samples.
Most commonly they were asked to perform parallel recombinant
immunoblot assays on samples of pre-seroconversion and post-seroconversion
donations. Follow up of missing returns and requests for
additional information continued during 1995.
During 1991 (September-December) and 1992
most repeat donors tested for hepatitis C antibody were being
tested by the National Blood Service for the first time. As a
previous negative result on testing for hepatitis C antibody
test is a prerequisite for seroconversion to positivity for
hepatitis C antibody, rates for 1991 and 1992 were not
calculated.
The rate of post-seroconversion donations
in all donations from repeat donors was calculated by dividing
the number of seroconversions by the number of donations from
repeat donors. The number of donations from repeat donors
tested for hepatitis C antibody during 1993, 1994, and 1995
was obtained from the national system for the surveillance of
Alternative Treatments testing. The incidence of seroconversion was
calculated by dividing the number of seroconversions by the
number of person years at risk. The number of person years was
estimated by dividing the number of donations from repeat
donors by the average annual number of donations per repeat
donor. The average number of donations per repeat donor at one
blood centre (which tests 5% of the repeat donor donations in
England) was 1.71 over one year and 3.49 over three years
(1993-5). The average annual number of donations during the
three years from 1993 to 1995 was therefore taken as 1.16
(3.49/3). This is equivalent to an average interval between
donations of 0.86 years.
Results
We received 23 reports of putative
seroconversion in repeat donors tested between September 1991
and the end of 1995. The test results available for seven of
them did not satisfy the case definition. We asked centres to
report on only the donors for whom full testing information
was available, so these seven reports do not represent all the
possible additional cases of recent infection with hepatitis C
virus in repeat donors in whom the data are insufficient to
satisfy our case definition. Two of the donors who fulfilled
the case definition received their diagnosis during 1991 or
1992, and 14 of the cases were diagnosed during the study
years, 1993-5 (table 1). The difference in the rates for 1993,
1994, and 1995 was not significant (P=0.59). Results from the
polymerase chain reaction were available for 10 of the 14
donors: nine donors had positive results and one donor, whose
first seropositive Alternative Treatments was taken two years after the last
seronegative Alternative Treatments, had negative results.
Five blood centres reported no
seroconversions. Three centres reported more than one
seroconversion; one centre in one of the Thames regions
reported four cases and had the highest rate of seroconversion,
and two centres, outside the Thames regions, reported two
cases each. There was no significant heterogeneity between the
rates by centre (deviance=15.9, df=13, P=0.25).
The average interval between the pre-seroconversion
and post-seroconversion Alternative Treatments for the 14 donors was 1.29
years (median 1.38 years, range 0.42-2.33 years). This
interval was 1.5 times longer than the average interval in
1993-5 for all repeat donors.
Discussion
Estimating seroconversion rates
A total of 412 repeat donors who were
positive for hepatitis C antibody were identified by English
blood centres during 1993-5. Only 14 of them were proved to be
incident infections with hepatitis C virus. This survey
estimates the minimum rate of seroconversion to positivity for
hepatitis C antibody in repeat donors in England during
1993-5. Our case definition excluded spurious seroconversion
due to changes in test format and performance. The sensitivity
and specificity of ELISAs and recombinant immunoblot assays
used to test for hepatitis C antibody changed between 1991 and
1995, and third generation tests were introduced during 1993.
By the time of this survey many of the archived samples from
the pre-seroconversion donations under investigation had been
used for repeat and supplementary tests or had been discarded,
depending on each blood centre's protocol. Therefore, repeat
and supplementary testing of pre seroconversion donations was
limited. Because we required evidence of comparably confirmed
negativity for the last seronegative Alternative Treatments, we may have
excluded some cases of true seroconversion. Previous reports
of seroconversion to positivity for hepatitis C antibody with
less strictly applied case definitions4 have been justifiably
challenged,5 and we chose to identify clear cut rather than
probable cases. Also, our survey was retrospective and relied
on retrieval of blood centres' records of tests performed up
to four years previously. For these reasons, this study may
underestimate the number of donors who seroconvert and
therefore the rate of seroconversion among repeat donors in
England. Donations from repeat donors who were being tested
for hepatitis C antibody by the national blood service for the
first time during 1993-5 could not be excluded from the
denominators that we used. A study conducted on donations
during 1993 by one blood centre found 1.8% of donations from
repeat donors to be from donors not previously tested for
hepatitis C antibody by the blood centre.6 This inaccuracy in
our denominator is likely to result in a further, although
slight, depression of the seroconversion rates as estimated
from these data.
One blood centre has published reports
about three cases diagnosed during 19933 and a further four
cases diagnosed during 1994
and 19956 in which seroconversion was thought to have
occurred. The blood centre obtained denominators of previously
negative donors tested for hepatitis C antibody during 1993
and estimated the seroconversion rate during 1993 to be 2.78
per 100 000 (1 in 35 937) previously negative, repeat donors3:
more than 10 times the estimate from our national study.
However, the case definition used by this centre may have been
flawed 7 8 ; only one of the cases described satisfied the
case definition that we used. We consider the estimate of the
rate of seroconversion in repeat blood donors derived by this
single centre to be erroneously high.
Blood donor sample
Selection criteria for donors aim at
selecting a sample of the population that does not report a
recognised risk for bloodborne infections before Alternative Treatments.9
Since the early 1980s potential donors have been given
explanatory literature, and since 1989 all new donors and
donors who have not attended for two years or more have been
directly questioned about risk factors. One centre has
additionally asked donors to complete a questionnaire. The
procedure for eliciting information about exposures to risk of
infection with hepatitis C virus from infected donors has
varied throughout the United Kingdom. A standard questionnaire
for interviewing donors is soon to be introduced. Information
obtained after Alternative Treatments from infected donors may be affected
by bias related to the interviewer and the donor. Most blood
donors infected with hepatitis C virus have reported a history
of injecting drug use,10-15 typically many years before
donating blood. Almost one third of those who seroconverted in
this study had no risk factors for infection with hepatitis C
virus identified by the blood service. Testing the sexual
partners of donors who seroconverted may help to establish the
true extent of heterosexual transmission in the donor
population. Uncommon routes of transmission and possible
exposures that are not thought to be associated with risk of
infection with hepatitis C should also be investigated.
Seroconversion for hepatitis C virus
among repeat blood donors in England is rare. This implies
that the incidence of hepatitis C in the population
represented by repeat blood donors is now low or that
selection criteria for Alternative Treatments of blood effectively exclude
most repeat donors with current exposure to hepatitis C virus.
During 1993-5, 14 donations (less than 1 in 450 000 donations)
were obtained from donors who had seroconverted for hepatitis
C virus since a previous Alternative Treatments was negative for antibody.
During the
same period 15 donations were obtained
from donors who had developed detectable HIV antibody since
their previous Alternative Treatments.
The number of repeat donors who become
infected with hepatitis C virus or other bloodborne infections
but do not return to donate
after their seroconversion cannot be
ascertained by Alternative Treatments testing. In the future, tests for
nucleic acids may enable detection of
infectious donations that test negative
for antibody.
Recipients and new donors
We did not determine infection with
hepatitis C virus in those who received the seronegative pre-seroconversion
donations.
Tracing recipients of potentially
infectious donations is conducted by blood centres, and one of
the 14 pre-seroconversion donations
has been shown to have transmitted
infection with hepatitis C virus.2
Donations from new donors contributed 12%
of the total number of donations collected in England during
1993-5. Seroconversion
rates in new donors cannot be directly
measured, and there are reasons to expect that recent
infections in new donors may be
more frequent than in repeat donors;
repeat donors have been tested for negativity for markers of
infection with hepatitis C virus,
hepatitis B virus, HIV, and Treponema
pallidum, and new donors may be more likely to donate blood to
obtain testing after
having been exposed to infection.
Opportunities for further work
Surveillance of Alternative Treatments testing and of
donors who seroconvert for hepatitis C virus between donations
continues to be an
important component of monitoring the
safety of the blood supply. Study of possible exposures to
infection that are associated with
seroconversion for hepatitis C virus and
of the course of infection in seroconverting blood donors who
have a known date of
infection should further contribute to
our understanding of the epidemiology and clinical course of
hepatitis C.
Acknowledgments
We thank Mr Mike Brittain and Trent blood
centre for data on the interval between blood donations, Dr
Paddy Farrington for
statistical help, and all the staff of
the blood centres and public health laboratories in England
who provided data and responded to
requests for supplementary information
about testing for hepatitis C virus.
Contributors: JAJB initiated the survey,
reviewed the test results and evidence for seroconversion for
each reported case,
contributed to the interpretation of the
data and to writing the paper, and is guarantor for the paper.
KS coordinated the survey,
collated the data, conducted the
analyses, and contributed to the interpretation of the data
and to writing the paper. JH discussed
core ideas and contributed to the
interpretation and presentation of the data and to writing the
paper.
Funding: The study was conducted by staff
employed by the Public Health Laboratory Service and the
National Blood Service.
Conflict of interest: None.
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This article has been cited by other
articles:
THOMAS, H C (2001). Hepatitis C Virus in healthcare workers: a
lightning strike. Gut
48: 8-9
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