Introduction
Successes in preventing transmission of viral infections during the last
10 to 20 years have led to very low incidence rates and estimated residual
risk for transfusion-transmitted viral infections [1]. This reduction
was primary achieved by a careful medical selection of the donors improved
sensitivity of serological tests and the introduction of NAT in minipools
for HCV and HIV [2-4]. This study presents data on the incidence rate
and the estimated residual risk for the key infectious disease HIV, HBV
and HCV between 1996 and 2003, among non-remunerated voluntary repeat
donors in the blood transfusion service of the Swiss Red Cross.
Methods
Clinical and laboratory data collected between 1996 and 2003 at 13 regional
blood transfusion services (RBTS) of the blood transfusion service
of the Swiss Red Cross (BTS SRC), were analysed. Data were available
on 99% of the blood donations given by the voluntary non-remunerated
blood donors in Switzerland. All donations were tested according to
the recognised screening test algorithms for hepatitis B surface antigen(HbsAg),
anti-HCV, anti-HIV1/2, syphilis and alanine aminotransferase (ALAT).
I) Samples repeatedly reactive or indeterminate for HBsAg were further
analysed with a second independent HBsAg EIA, and if further reactive,
tested by a neutralisation assay. In addition, anti-HBc and anti-HBs
tests, were performed;
II) Samples repeatedly reactive or indeterminate for anti-HCV were confirmed
with an additional independent anti-HCV EIA and with a HCV-RIBA assay;
III) Samples repeatedly reactive or indeterminate for HIV were confirmed
with a second independent anti-HIV1/2 test, a p24 Ag assay and a HIV
western blot.
HCV-NAT has been mandatory in Switzerland since July 1999, whereas HIV-1-NAT
was not introduced until March 2002, nearly 3 years later. NAT analysis
for HCV and HIV-1 were performed at seven independent laboratories with
minipools ranging from 16 up to 49 donations per minipool. All donations
were tested with the HCV and HIV-1 Cobas Ampliscreen assays (Roche Diagnostics,
Rotkreuz, Switzerland).
Repeat donors were defined in Switzerland as donors who had been tested
previously at a given regional blood transfusion service. Incident
cases were confirmed positive blood donors whose previous donation
had been negative.
Incidence was calculated using the following formula: Incident cases/number
of repeat donations x mean number of donations per year and donor.
Due to the lack of data on the interdonation interval, we assessed
the average number of donations per year and donor from the data calculated
in the RBTS Berne, which accounted for approximately 35 % of all donations
in Switzerland. For HBV, the incidence data was adjusted by a factor
2.38 according to the model of Korelitz et al [5].
The estimated risk was determined using the following formula: Incidence
x window period in days/ 365 [6]. The serological window period used
for HIV, HCV and HBV were 22, 66 and 59 days respectively and the NAT
window period for HIV and HCV were 11 and 11 days, respectively [7,8].
The same window periods were used for each of the six 3 year periods.
Residual risk for HCV and HIV were calculated taking in account NAT windows,
for 1999 to 2003 for HCV and 2002 to 2003 for HIV.
Results
A total of 3 759 671 blood donations were tested during the study period
from 1996 to 2003. As shown in Table 1, the number of blood donations
has decreased by an average of 3.5 % per year. The percentage of repeat
and first time donors varied from 90.4% to 95.4 % and from 4.6% to
9.6%, respectively.
The number of confirmed positive donations for all 3 viruses HIV, HCV
and HBV [TABLE 1] is detailed below:
I) In 1996 thirteen confirmed HIV positive donations have been identified,
but since 1997 no trend in the number of confirmed HIV positive donations
from repeat and first time donors was observed (between 2 and 7 cases
per year)
II) Conversely, the number of confirmed HCV positive donations decreased
between 1996 and 2002 from 119 to 17 (repeat and first time donors),
but increased again in 2003 (36 repeat and first time donors).
III) The number of confirmed HBV positive donations decreased up to 1998
then remained stable up to 2002 with approximately 40 (range: 38 – 41
repeat and first time donors) positive HBV donations per year, however
it increased again in 2003 from 39 to 48.
From 1996 to 2003, 18, 283 and 349 confirmed positive results were
reported in first time donors for HIV, HCV and HBV respectively, whereas
27, 107 and 66 positive results were reported for repeat donors [TABLE
1].
The incidence rates for HIV, HCV and HBV for the study period 1996 to
2003 are presented in Table 2. The incidence rate for HCV has decreased
for the period 1996/98 in comparison to the period 2001/03 by a factor
of five, whereas the incidence rates for HIV and HBV have not markedly
decreased.
The estimated residual risks for all 3 viral markers HIV, HCV and HBV
from 1996 to 2003 are shown in Figure 1. The estimated residual risk
for HIV was relatively stable over the period 1996 to 2003. For HCV
the estimated residual risk decreased significantly for a factor of
30 over the same period, whereas for HBV no decrease was observed.
In the 3 year period 2001 to 2003 the theoretical calculated residual
risk for HIV, HCV and HBV is 1: 1.9 million donations (95% CI: 0.97 – 4.0
mill.), 1: 2.2 million donations (95% CI: 1.2 – 4.6 mill.) and
1: 115 000 donations (95% CI: 69 900 – 206 000), respectively.
These figures were calculated for the whole of Switzerland, based on
the number of incident cases and the number of donations, donated yearly
by repeat donors. Due to the lack of data on the interdonation interval,
we assessed the average number of donations per year and donor from
the data calculated at the RBTS Berne, which accounted for approximately
35 % of all donations in Switzerland. NAT was included in the risk
calculation for HCV since 1999, and for HIV since 2002.
Discussion
Recent studies performed in other countries have shown that the estimated
risk for transfusion-transmitted HIV and HCV infections and to a lesser
extent also HBV infections via blood products is very low [1,9-12].
Glynn et al reported that since the introduction of NAT in the screening
procedure of blood donations, the estimated risk of HCV and HIV infection
has decreased two-fold for HIV and by a factor of almost 10 for HCV
[13].
In Switzerland, the theoretical estimated risk for HIV is now considered
as very low. However, a comparison of the calculated residual risk between
1996 to 2003 does not indicate a clear trend of a reduction. Even after
the introduction of HIV NAT in 2002 no clear-cut decrease was observed.
We believe the main reason lies in the fact that HIV positive donations
are extremely rare in Switzerland and the relatively low number of total
donations (400 000 to 450 000 per year) prevents statistically significant
calculations. In 2002 and 2003, approximately 750 000 donations were
tested for HIV RNA but no HIV RNA positive but anti-HIV negative unit
has been detected.
For HCV the picture is clearer. A 30-fold reduction in the calculated
estimated risk was observed between the periods 1996-1998 compared
with 2001-2003. The reduction probably arose from the introduction
of a more stringent donor selection policy. The donor population is
composed of 90.4% to 95.5% repeat donors, who are well aware of the
importance of having safe blood products. Repeat donors appear more
attentive to the different information provided by the medical questionnaire
and as a consequence, a selection is introduced before the blood is
donated. In addition, the introduction of NAT in 1999 also played a
role in reducing the risk. From 1999 to 2003, approximately 2 000 000
donations from repeat donors were tested for HCV RNA. One single HCV
RNA positive, anti-HCV negative unit from a donor who donated regularly
since 1999 has been identified.
The estimated residual risk for HBV between 1996 and 2003 is different
to that observed for HIV and HCV. After an initial slight decrease in
the estimated residual risk up to 1997 the number for HBV has remained
quite stable between 8 and 12 estimated cases per million donations.
The estimated residual risk for HBV is significantly higher than those
of HCV and HIV during the 3 years period 2001 to 2003. Despite the complicated
serological course of HBV infection, which leads to difficulties in performing
the residual risk calculations, the estimated risk of HBV transfusion-transmitted
infections presented here agrees with those reported in other international
studies [13-15].
In conclusion, the risk of transfusion-transmitted HIV, HCV and HBV infections
is very low in Switzerland. The data obtained using incidence and window
period models follow similar trends to results of similar studies performed
in other developed countries. However the estimated residual risk for
HBV remains higher and we are presently evaluating the possibility of
introducing additional HBV tests to our screening algorithm as it has
been recently discussed in international meetings.
Acknowledgements
We thank Dr. Peter Gowland for critical reading of the manuscript.
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