Eurosurveillance - Volume 10, Issue 2, 01 February 2005

Over the past two decades, a long series of specific and non-specific measures have been introduced into the screening of blood donations in order to reduce the residual risk of transmission of bloodborne viruses. The latest specific measure has been viral nucleic acid testing (NAT), introduced by the European plasma industry in 1995, and subsequently introduced for blood donations in several countries in Europe and elsewhere. NAT was implemented to reinforce the safety of the blood supply; it can detect acute viral infections during the ‘window period’, that were not being detected by the serological screening methods used at that time. To assess the impact of NAT on the safety of the blood supply, it is essential to estimate the residual risk of viral transmission. In this issue, six European countries (France, Germany, Italy, Spain, Switzerland and the United Kingdom) that have recently implemented NAT describe their experiences and the results of the evaluation of the residual risk of viral transmission in their blood supply [1-6].

The use of NAT technology to screen blood donations in Italy became mandatory on 28 June 2002, but had been available experimentally since 2001. During the transition period, an EIA test to detect hepatitis C core antigen (HCVcoreAg) had also been permitted. Considering the large number of blood transfusion centres in Italy, an initial reorganisation of the biological validation of blood units was necessary, with a partial centralisation of NAT testing. The Gruppo Italiano per lo Studio delle Malattie Trasmissibili con la Trasfusione (Italian Group for the Study of Transfusion-Transmissible Diseases) conducted a national survey evaluating NAT testing, based on an annual collection of data through a questionnaire sent to all centres. In the first three years of the investigation, 219 blood transfusion centres returned the questionnaires. In the period between January 2001 and December 2003, 3 894 894 blood donations were investigated for HCV RNA and 2 186 468 for HIV RNA. Of these, 12 were found to be HCV RNA positive and four HIV RNA positive, with an observed NAT versus antibody-based assay yield of 3.1/106 donations for HCV and 1.8/106 donations for HIV, respectively. Five of the 12 HCV RNA positive and anti-HCV negative donors had abnormal ALT values and their donations would have been discarded even in absence of NAT testing. Thus the final NAT yield for HCV is 1.79/106. The residual risk for HCV or HIV transmission by blood transfusion after NAT implementation is currently estimated to be extremely low in Italy.

Monitoring trends in residual risk of transfusion-transmitted viral infections is important to assess improvements in blood safety and to adapt the risk reduction policies. These trends were analysed in France over 4 periods of 3 years (1992-1994, 1995-1997, 1998-2000 and 2001-2003). The 2001-2003 estimates were compared to the results of HIV-1 and HCV NAT implemented on all blood donations in July 2001. Due to improvements in donor recruitment and selection, continuing progress in screening assays, and preventive measures taken in the community to control infections, a significant decrease was observed in residual risks for HIV, HCV and HBV between 1992 and 2003. The residual risk is currently extremely low: for the 2001-2003 period, this risk was estimated at 1 in 3.15 million donations for HIV, at 1 in 10 million for HCV and at 1 in 640 000 for HBV. Of the 6.14 million donations screened with NAT between July 2001 and December 2003 in France, 2 HIV-positive and 3 HCV-positive donations were discarded thanks to NAT, representing a yield of 1 in 3.07 million for HIV and 1 in 2.05 million for HCV. These results show the limited benefit of NAT and suggest that its cost-effectiveness is poor.

Among the well known transfusion-associated risks, the transmission of pathogenic viruses is regarded as one of the most serious. Over the past two decades, a series of overlapping safety procedures have been successively implemented to minimise this risk. It is now generally considered that the risk of transmitting viral infections via blood products is very low in developed countries. The present study analyses the incidence of the key infectious diseases HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) between 1996 and 2003 from 99% of voluntary repeat blood donors visiting the blood transfusion service of the Swiss Red Cross. Furthermore the estimated risk of these viral markers was calculated. From 1996 to 2003 the incidence rate for HCV decreased continuously, whereas no significant decrease in the incidence rate of HIV and HBV was observed. From 2001 to 2003, the last calculated period, the residual risk was estimated to be 1 in 1 900 000 for HIV, 1 in 2 200 0000 for HCV and 1 in 115 000 for HBV, respectively. This agrees with international studies, which have been shown that the estimated residual risk for HBV between 1996 and 2003 is higher than that of HCV and HIV.

Several new tests have been recently introduced by the United Kingdom Blood Services to improve safety. The frequency (or risk) of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infectious donations entering the UK blood supply during 1996-2003 has been estimated. These years span the introduction of nucleic acid testing (NAT) for HCV, HIV combination antigen and antibody test and NAT for HIV. The frequency of an infectious donation entering the blood supply due to i) the window period, ii) assay failures and iii) human and technical errors in testing and processing, was estimated. The window period risk was estimated using the incidence of infection in donors and the length of the window period for tests in use, with an adjustment for atypical inter-donation intervals in seroconverting donors. The estimated frequency of infectious donations entering the blood supply during 1996-2003 was 1.66, 0.80 and 0.14 per million for HBV, HCV and HIV respectively. HCV NAT resulted in an over 95% fall in the risk of HCV. Current usage of HIV combined antibody-antigen tests and of HIV NAT reduced the estimated risk of HIV by 10%. Since 1996, the risk of transfusion-transmitted HBV, HCV and HIV infection in the UK has been lowered by several improvements to donation testing, although the absolute reduction in risk has been small. Vigilance for errors and the affects of donor selection may be as or more important than further reductions to window periods of tests for improving blood safety with respect to HBV, HCV and HIV.

Estimates of the risk of bloodborne viral infections are essential for monitoring the safety of the blood supply and the impact of new screening tests. Incidence rates of seroconversion and the residual risk for HBV, HIV and HCV were calculated among Spanish repeat donors between 1997 and 1999 at 22 blood donation centres, and at 7 centres between 2000 and 2002. The residual risk per million donations was estimated to be 18.67 for HBV, 2.49 for HIV and 10.96 for HCV (between 1997 and 1999). For the 2000-2002 period, the residual risk per million donations was estimated to be 9.78 for HBV, 2.48 for HIV and 3.94 for HCV. Between 1999 and 2003, about 3.4 million donations were tested by NAT, mainly in pools of 44 donations, in 12 of the 22 Spanish blood donation centres participating in the study. Eight anti-HCV negative and HCV-RNA positive donations were found, which represent an approximate yield of 1/420 000, versus a projected yield of 1/240 000 obtained from 1995-1997 data. The residual risks of transfusion-transmitted viral infections in Spain were low, and with the implementation of NAT these risks are even lower.

Blood and plasma donations in Germany are collected by several institutions, namely the German Red Cross, community and hospital-based blood services, private blood centres, commercial plasma donation sites and transfusion services of the army. All blood donation centres are required to report quarterly data on infection markers to the Robert Koch Institute, thus providing current and accurate epidemiological data. The prevalence and incidence of relevant viral infections are low in the blood donor population in Germany, with a decreasing trend for hepatitis C infections in new and repeat donors since 1997. The implementation of mandatory nucleic acid amplification technique (NAT) testing for hepatitis C virus (HCV) in 1999 has markedly improved transfusion safety. HIV-NAT became mandatory in 2004 but was done voluntarily by the majority of the blood donation services before then. The potential benefit of hepatitis B virus (HBV) minipool NAT is not as clear because chronic HBV carriers with very low virus levels might donate unidentified. The residual risk of an infectious window period donation inadvertently entering the blood supply can be estimated using a mathematic model which multiplies the incidence rate by the number of days during which an infection may be present but not detectable, i.e. the length of the window period. The risk of an undetected infection without NAT testing was estimated to be 1 in 2 770 000 for HIV, 1 in 670 000 for HCV and 1 in 230 000 for HBV in 2001/2002. This contrasts with 1 in 5 540 000 for HIV, 1 in 4 400 000 for HCV and 1 in 620 000 for HBV with minipool NAT testing. This demonstrates that NAT testing can further reduce the already very small risk of infectious donations entering the blood supply.