A basic principle of medical treatment is the Hippocratic oath "primum nihil nocere" (Latin: First, do no harm). This principle can be stifling in situations where harms and benefits must be weighed against one another. As a biological substance from a particularly poorly controlled source, blood has always been an obvious way in which pathogens can easily be transmitted. However, screening methods have become available and have steadily improved blood safety. First, serological assays became available, which assessed the immunological response of the host to an infectious agent, and were later supplemented with NAT tests for the infectious agent itself. Much of the effort to develop more sensitive infectious disease marker (IDM) screening methods was fuelled by the AIDS scandal in the 80s and 90s, when many patients were infected and killed by HIV transmitted through contaminated blood products [
10‐
15]. Germany was among the first to implement NAT for all blood donations for hepatitis B, hepatitis C and HIV-1 [
16,
17]. Similar technology is now in use in one-third of all countries around the world [
18]. A total of 300 million blood donations later, 244, 680 and 1,884 NAT-only positive blood donations with HIV-1, HCV and HBV, respectively, have been identified; each likely stands for an averted infection [
18]. NAT technology has shrunk the diagnostic window between infection and detection to a minimum (< 10 days for HiV and HCV, 30 days for HBV). The residual risk for HCV, HIV-1 and HBV in Germany was recently estimated as 1 per 10.88, 4.3 and 0.36 million transfusions, respectively [
19]. The power of NAT is particularly apparent in places like South Africa with its high prevalence of blood-borne infections, where introduction of NAT managed to control the risk of transfusion-transmitted virus infection that had been expected to rise dramatically after inclusion of donors from high-risk populations [
20]. Nevertheless, NAT is more sensitive to subtle changes of the viruses than serology; mutations within primer and probe binding regions led to three false-negative NAT results in Germany in 2010 alone [
21]. As a consequence, the federal authority (Paul-Ehrlich-Institute) recently recommended dual-targeting, that is, amplification in two conserved genome regions, for HIV-1 [
21]. An alternative or complementary strategy to improve blood safety might be implementation of fourth generation antigen-antibody assays, which are available for HIV-1 with others to follow suit. The diagnostic window period will likely be similar to that of NAT. Emerging pathogens like dengue, Chikungunya and hepatitis E virus or malaria will present future challenges for blood transfusion services.
As an alternative to ever more sensitive test methods and ever broader pathogen spectra, global pathogen inactivation could be implemented. However, the need for different technologies for the different blood components, price, concerns about cell quality, long-term recipient safety, loss of product and other disadvantages have thus far impeded wide-spread use of available and emerging pathogen inactivation technologies.
Because of the sensitive screening methods used today, blood has become a relatively safe drug. Nevertheless, it should be self-intuitive that any relaxation of donor deferral rules which allow populations with an increased risk for certain transmissible diseases to donate blood, will be associated with an increased risk for recipients. It is always possible, as we have seen, to miss infectious agents [
21], and a certain window period, although short, remains. Since relaxation of deferral criteria has not often been employed, (the South African example given above [
20] being a unique exception), and numbers for at-risk individuals wishing to become blood donors are unknown, useful estimates of the risk increase can not be provided.