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In 2009, Transfusion published a supplement in which the Transfusion-Transmitted Diseases (TTD) committee presented informative fact sheets for 68 emerging infectious disease (EID) agents judged to be of potential significance to transfusion medicine including a section on pathogen reduction systems and their potential for the mitigation of EID agents.1, 2 Updates and new fact sheets were included ad hoc in subsequent years. In addition to the printed supplement, all fact sheets were made freely available online (i.e., without a subscription).3 The selected agents were those thought to offer some risk of transfusion transmission but for which no testing or alternative mitigation interventions were in place. They represented the universe of recognized human prion, viral, bacterial, fungal, protozoan, and helminth agents. While the primary focus was the US, the information was generally applicable. The intent was to provide fact sheets for responses to inquiries from transfusion services or clinicians and to assist observant clinicians in the potential identification and investigation of agents suspected to be responsible for transfusion-transmitted infections. In addition, the fact sheets were intended to educate the reader about potential transfusion-associated risks of emerging infections. When epidemiologic signals suggest that a pathogen may be emerging as a threat to transfusion safety, careful horizon scanning by the public health, clinical, and transfusion medicine communities is required to monitor changes in a pathogen's epidemiology and bring those threats and their relationship to blood donors into focus. The 2009 Transfusion supplement included an extended review of emerging infections, their risks to blood safety, and an estimate of risk levels. Four years following the publication of the supplement, an article was published in Transfusion that reviewed and updated the background assumptions used in the supplement.4 It added commentary on agents of increasing concern at that time, compared patterns of attributes seen in EID versus other “conventional” transfusion-transmitted agents, and provided a toolkit outline for recognizing, assessing, and managing EID agents posing a risk of transfusion transmission and disease. While development of a toolkit was not pursued further, the framework is still of use and covers the relevant points that lead to the evaluation and implementation of an intervention. Revisions following the initial publication of the supplement included six new factsheets: (1) Middle East Respiratory Syndrome (MERS) Coronavirus, (2) Human Parvovirus 4, (3) Measles, (4) miscellaneous Arboviruses, (5) XMRV and related murine leukemia agents (now archived), and (6) Yellow Fever virus and Yellow Fever vaccine.5 More recently, interim fact sheets discussing Marburg and Mpox (formerly Monkeypox) viruses have been made available in near real time.6 However, it became apparent that, after 15 years, it was appropriate to look at the complete set of fact sheets for their utility moving forward. What is known about an agent may change, our understanding of its threat (or lack thereof) to transfusion recipients will evolve and new agents may become relevant. As the COVID-19 pandemic exploded, the AABB TTD committee was beginning a comprehensive review process with the revised fact sheets being made available in this supplement to the journal. They are being made freely available on line. The approach to the process and its focus was largely unchanged from those used for the original supplement. Individual TTD members were assigned one or more fact sheets and asked to review the literature for relevant changes relating to the agents/agent group including specific reference to transfusion medicine. Draft revisions were submitted to a small working group, new references critically reviewed, and extensive further editing was undertaken in an iterative process to finalize the updated versions. Some of the original fact sheets have been archived, based on the working group's confidence that effective measures have been implemented for their control (e.g., babesiosis) or that they do not constitute a realistic threat (e.g., Porcine Parvovirus). The 73 fact sheets (table) continue to adhere to a common structure including an agent description, disease associations, and a subjective assessment of their priority to several audiences. Each includes a set of epidemiological and clinical sketches, describes the state of knowledge of the agent's presence in blood, and evidence for transmission by transfusion and chronicity. The availability and feasibility of agent-specific screening questions and laboratory assays for donors, donor deferral considerations, what is known about pathogen reduction effectiveness, and other prevention measures are addressed. Lastly, a suggested reading list is provided for each fact sheet addressing transfusion transmissibility, but also general pathogen attributes. In the original supplement, we attempted to prioritize the risk posed by each agent with color-coded rankings. In retrospect, we found this not to have ongoing value. Accordingly, such estimates are not included with these revisions. In fact, the three “red” agents of highest priority are now of less, if any, concern, or mitigations have been implemented. Variant CJD incidence has been so effectively reduced that nearly all countries worldwide have removed most previously implemented blood donor deferral measures.7 Transfusion-transmitted babesiosis has essentially disappeared as a threat with testing required in endemic areas.8, 9 While dengue continues its global reemergence, there is no consensus that a donor intervention is needed at this time.10 However, each fact sheet provides semiquantitative estimates of the levels of scientific, epidemiological, public, and regulatory concern about blood safety. The table lists the 73 agents/agent groups considered as relevant and included as revised fact sheets. Moving forward, the working group will continue real-time review of available sources ranging from publicly available reporting systems (e.g., ProMED, CDC, and WHO) to new peer-reviewed literature that may suggest the need for timely revisions or new fact sheets. This will begin by assigning a subset of fact sheets annually in the near future to members of TTD to make the updating process self-sustaining. A fundamental consideration for the future, beyond individual agents, is how to identify them early during emergence, and respond quickly to new threats. During the last 20 years, largely due to continued expansion of human activity into new ecological niches, global climate change, and enhanced pathogen recognition, there has been an escalating expansion of EID agents in the United States and elsewhere.11 This has been particularly true for arboviruses as driven by expansion of their vectors and human incursions into their habitats. After managing West Nile virus in 2003 by nationwide donation screening (albeit with several breakthrough infections12), dengue, Zika, and chikungunya viruses have drawn our attention; however, there are others that have been considered as noted in a miscellaneous arbovirus fact sheet (with emphasis on agents in Australia). Three coronaviruses (SARS, MERS, and SARS-CoV-2) have required consideration as transfusion-transmitted threats, despite an absence of evidence of transfusion transmission associated with respiratory infection. Nevertheless, COVID-19 in particular had severe impacts upon perceived donor and staff safety at donation sites and, thus, the availability of donors as well as on collection facility supply chains.13 This required substantial reconfiguration of donor rooms to augment their safety and adaptation of operations. The range of babesiosis in the United States is expanding, although now with an effective intervention, and autochthonous malaria has been reported in the United States for the first time in 20 years.14 Emerging infections and research addressing the need for interventions were discussed as areas of focus at the 2022 NHLBI-sponsored State of the Science in Transfusion Medicine Symposium that were broader in scope than examined in our fact sheets.15 In that meeting, several priorities were recognized. Studies of donor populations (epidemiological, laboratory, pathogenesis) alongside traditional clinical and epidemiological surveillance systems were highlighted. Moving these far enough into the field to provide early warning is critical. Expanding the role of pathogen reduction as an “agent agnostic” intervention was a self-evident priority. Beyond new agents, new antimicrobial interventions to prevent or treat established infections must be considered for their possible impacts on transfusion safety. Most critical currently are understanding the ongoing robustness of HIV donation screening technologies in the face of expanding use of pre- and postexposure prophylaxis for HIV,16 the use of direct acting antivirals to cure HCV, and the deployment of new live virus vaccines. In summary, over the past 70 years, the microbial safety of the blood supply has been improved by at least five orders of magnitude.4, 17 This has resulted in success to the point that there can be serious discussion about removing some historic safety measures (e.g., HBsAg and anti-HTLV screening) in lieu of more broad-reaching technologies (e.g., universal pathogen reduction, highly multiplexed nucleic acid assays, metagenomic methods). At the same time, it must be remembered that throughout that interval, more than 10 transfusion-transmissible agents have been recognized and managed. In some cases, the period between recognition of risk and implementation of interventions can be many years which can magnify their impact on recipient populations.18 The tools and interventions now available allow for effective and rapid response to threats, but to a large extent, the recognition of transfusion transmissibility still depends upon astute clinical observations of adverse events following blood administration and then to consideration of their potential relation to transfusion, sometimes long after blood has been given. It is hoped that these updated and new fact sheets (and those in the future) will contribute to the understanding of what is known today and consideration of how we will manage future threats.