A residual risk of transfusion-transmitted infection persists despite the adoption of stricter donor selection criteria and continuous improvements in the performance of screening assays. This risk is mainly linked to donations in the window following a recent, undetected infection. The residual risk of transmitting HIV, HCV, or HBV during a blood transfusion was estimated between 2000 and 2010. An incidence/window period model was used to estimate the residual risk. A mathematical model to quantify viral nucleic acid concentrations was developed in the early 2000s, when most developed countries began nucleic acid testing (NAT) for donations . NAT for HIV and HCV in Korea was commenced in February 2005. 10 HIV and 19 HCV NAT yield donations were identified between 2005 and 2010 among 14,246,270 donations. Since the average yield per year was extremely low, the method of Schreiber was used in this study even though it may over-estimate the incidence density.
Residual risk estimates vary among countries, depending on the incidence rates among blood donors and the tests used. Thus, some variations might reflect differences in the incidence and background prevalence, as well as the testing methods used. NAT, which was introduced to industrialized countries in the 1990s and 2000s, dropped the residual risk from 1 in 513,000 to 1 in 3,415,000 for HIV and from 1 in 149,000 to 1 in 1,935,000 for HCV [7, 12–14]. The residual risks of HIV and HCV for several countries have become immeasurably small in recent years (approximately 1 infection per 1 to 2 million units) [15, 16].
The HBV prevalence differs by geography . The residual risk of HBV in countries with low prevalence (<2%), such as the UK, was 1 in 296,736 (3.37 per million donations) in the 1990s, and 1 in 729,927 (1.37 per million donations) in the 2000s . The residual risk of HBV in countries with moderate to high prevalence declined from 1 in 10,700 to 1 in 340,000 during a similar period [19, 20]. Even though the probability of missing a donation infected with HBV has declined over time, the residual risk of HBV is greater than the risks for HIV and HCV.
In this report, we determined the trend of incidence rates and residual risks of infection in donations made to Korean Blood Services through 2000 to 2010. The risk of HCV in 2000/2001 decreased 56-fold by 2008/2009, but those of HIV and HBV have not changed.
The residual risk for HIV did not change significantly. It is due to the fact that the assay for HIV did not change from 2005 to 2010, and the exclusion of donors with high risk behaviors were not done completely. The current risk level of HIV is comparable to developed countries. If the risk of HIV needs to be reduced, other safety measures should be applied to completely exclude the donors with risk behaviors. Blood safety regarding HCV has improved immensely during the last decade due to the implementation of NAT and improved performance of serologic assays. The residual risk has decreased 31% (95% CI, 20~56%) annually (data not shown).
Even though the residual risk for HBV in 2008/2009 has decreased 19.9-fold from that in 1995/1996 , the risk for HBV did not change significantly during the last decade. Even after using a more sensitive CLIA, the residual risk of HBV is still substantial. This can be generally explained by differences in infectivity, viral doubling time, and minimum infectious dose. Practically, the reason of the immaterial reduction of risk through the application of CLIA is due to a comparatively small reduction of window period. The reduction rate of window period was only 23.7% and the reduction of residual risk was 32.3% from 2000/2001 to 2008/2009. The current residual risk for HBV is more than 20-fold higher than that for HIV and HCV, and approximately 5-fold higher than those in other countries with moderate to high prevalence. That is why the introduction of HBV-NAT is urgent in Korea and will commence in July 2012 nationwide. The residual risk of HBV will be efficiently reduced through an individual HBV-NAT like Spain, which has a similar prevalence of HBV . However, HBsAg will remain as one of the mandatory tests for blood screening after the implementation of HBV-NAT, since Korea is an endemic area and dropping a blood screening test is not an easy decision for governmental officials.
Interestingly, the serial trend of residual risk showed that the residual risks of all three viruses increased in 2009/2010 compared to the previous study period (2008/2009). This phenomenon might be attributed to the application of several strong incentive systems for blood donors commenced in 2010 to secure the blood supply. Approximately 80% of Korean blood donors are in their 10s and 20s. The target population of donor recruitment programs is usually young students. The Korean parents are excessively education-oriented, and the students are extremely sensitive to the incentives related to extra credit for school. In this situation, application of donor recruitment related to the school grade might hinder the effective exclusion of donors with high risk behaviors. Therefore, incentives especially for young donors should be applied with discretion. Generally the residual risk depends upon the prevalence and the sensitivity of the test method (window period of the test). However, other factors besides these two traditional typical factors could influence the actual residual risk. Therefore, a continuous monitoring of residual risk is critical in management of blood safety, even though the same test method is continually used and the prevalence of disease does not change. Even though the declining trend of residual risk for HCV has stopped and increased in 2009/2010 and residual risk for HIV in 2009/2010 was higher than that in 2008/2009, the current residual risks for HIV and HCV do not substantially differ from those of developed countries.
The assays have changed several times over the years that data were analyzed. NAT was commenced in 2005 and the same reagents and the same instruments have been used until 2010. Since the assay reagents and instruments were maintained the same for more than 70-80% of blood donations, the change of assays does not seem to affect the estimates significantly.
We adjusted the total residual risk for the incidence of first-time donors. This estimate was based on the fact that donor behavior was not affected during the window period, but donors with an early acute infection with subtle mild symptoms or a history of risky behavior might delay the next donation. Thus, the residual risk might be underestimated due to an inaccurate and smaller number of seroconvertors among blood donors.
The incidence rates of HCV and HBV were higher among first-time donors than repeat donors. The incidence rates of HIV did not differ among first-time and repeat donors. Some repeat donors with high-risk behavior may not have answered the questionnaire honestly. Our HIV findings differed from previous reports [16, 23].
We did not include donors with chronic infection in the risk assessment. Even though the infectivity from donors with a chronic hepatitis C infection is 1,000 times weaker than from donors with an acute hepatitis C infection, the donation from a donor with chronic HCV can be infectious . Likewise, low-level HBV carriers and HBsAg mutant viruses were not considered in our estimate of residual risk.
Our model does not reflect infectivity. A minimum infectious dose might cause infectivity to differ during the window period, but all donations during the window period were assumed to be infectious.
Current data suggest that HIV is considerably less infectious than HCV and HBV. A recent report shows that 100 to 10,000 copies of transmitted HIV RNA falls well in the 0- to 100-percent infectivity range . Literature shows that less than 100 copies of HCV and HBV can cause infection .
Recently, Busch et al introduced a new approach to estimate the duration of infectious window period, based on back-extrapolation of acute viral replication dynamics . The NAT yield data for the last 6-year period seemed to be large enough to apply an alternative method, but the estimated window period of HCV NAT was too long to accept. As Busch et al mentioned about their limitation, the new method was based on the concept that the incidence in donor population does not change significantly, which was not fit in our situation. There are multiple factors that could influence the residual risk other than the prevalence and the sensitivity of screening assay. This phenomenon seems to be attributed to the unique cultural environment in Korea, such as application of excessive pre-cautionary safety measures after the blood scandal in 2005. Using NAT screening data from large numbers of donations by a new approach did not always guarantee an accurate estimation of window period.
We may have overestimated the residual risk by assuming that all window period donations were infectious. The presence of virus in a donation does not imply that the recipient was infected. The viral load may have been too low, the infectivity may have been too weak, or the recipient might have been vaccinated.
Korea has a moderate to high risk of HBV . HBsAg-positive rate reached 4.6% in Korean residents aged 10 and older in 1998, and the prevalence dropped gradually to 2.9% in 2010 . However, the prevalence of HBV is still substantially higher than those in other developed countries. Since introducing the hepatitis B virus vaccine in 1985, the prevalence of immunized residents aged 30 and older has reached 58.0%. One study showed that the positive rate of anti-HBs was approximately 80% in young patients . The universal vaccination of HBV since 1995 will contribute to the reduction of residual risk of HBV in Korea. Thus, the actual transmission of HBV from a transfusion is likely lower than the estimated residual risk.