Risks of major TT viruses, progressive blood safety interventions and consequent costs, and EIDs that have been investigated for impact on blood safety over the past 4 decades. (A) Per unit infectious risk for HBV, HCV, and HIV from 1980 to 2018. (B) Temporal relationship of progressive interventions to reduce risks of TTIs to median service fee for acquisition of RBC components from blood-collection organizations in the United States (provided by Louis Katz, America’s Blood Centers [these service fee costs do not reflect increases in the Consumer Price Index for medical care services, which increased fivefold to sevenfold from 1980 to 2018]). (C) Potential TT-emerging infection agents that were investigated over the past 25 years. Red indicates agents proven to be blood-safety threats for which interventions were implemented; blue, agents established to be legitimate infectious agents but not TT or associated with diseases; and green, alleged threats determined to not cause human infections or those due to artifacts. *No interventions in the United States, but interventions implemented in some countries where HEV incidence is higher. HGV, hepatitis G virus; ICL, idiopathic CD4⁺ T-lymphocytopenia; MERS-Cov, Middle Eastern respiratory syndrome coronovirus; PARV-4, parvovirus type 4; PTLV, primate T-cell lymphotrophic viruses; SARS, severe acute respiratory syndrome; SFTSV, severe fever with thrombocytopenia virus; SFV, simian foamy virus. Modified from Perkins and Busch⁴  with permission.