In the century since the discovery of the ABO blood groups, numerous associations between ABO groups and disease have been noted. However, the selection pressures defining the ABO distributions remain uncertain. We review published information on Plasmodium falciparum infection and ABO blood groups. DNA sequence information dates the emergence and development of the group O allele to a period of evolution before human migration out of Africa, concomitant with P falciparum's activity. The current geographic distribution of group O is also consistent with a selection pressure by P falciparum in favor of group O individuals in malaria-endemic regions. We critically review clinical reports of ABO and P falciparum infection, documenting a correlation between disease severity and ABO group. Finally, we review published data on the pathogenesis of P falciparum infection, and propose a biologic model to summarize the role of ABO blood groups in cytoadherence biology. Such ABO-related mechanisms also point to a new hypothesis to account for selection of the Le(a؊b؊) phenotype. Taken together, a broad range of available evidence suggests that the origin, distribution, and relative proportion of ABO blood groups in humans may have been directly influenced by selective genetic pressure from P falciparum infection. IntroductionThe ABO blood group system is arguably the best known, and yet the most functionally mysterious, genetic polymorphism in humans. In clinical practice, ABO is the most important system for blood group compatibility. In the century since their discovery, ABO antigen associations with infections and other diseases have been the subject of hundreds of publications. 1,2 Some reports found unexpected associations, such as the susceptibility of group A individuals to salivary or gastric cancers. 3 However, associations with diseases affecting humans after reproduction are not expected to exert any genetic selection. Thus, despite a large body of literature, the evolutionary basis for the origin and diversity of ABO blood group antigens remains uncertain. Much new information has emerged since a relationship between ABO and malaria was first suggested more than 40 years ago. 4 We review literature in support of the hypothesis that Plasmodium falciparum malaria has shaped the distribution of ABO blood groups in humans. 5 We offer 4 arguments in support of this hypothesis. First, we review evidence that P falciparum was present at the time when ABO polymorphisms arose. Second, we note that the current worldwide distribution of ABO groups is consistent with an effect from P falciparum. Third, we critically review studies examining clinical outcomes during P falciparum infection. Fourth, we offer proposed biologic mechanisms relating host ABO group to the pathophysiology and lethality of P falciparum malaria. P falciparum: the strongest force in the recent history of the human genome P falciparum has been called "the strongest known force for evolutionary selection in the recent history of the human genome." 6 Th...

Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria. Pathogen inactivation (PI) technologies potentially provide an additional way to protect the blood supply from emerging agents and also provide additional protection against both known and as-yet-unidentified agents. However, the impact of PI on product quality and recipient safety remains to be determined. The purpose of this consensus conference was to bring together international experts in an effort to consider the following issues with respect to PI: implementation criteria; licensing requirements; blood service and clinical issues; risk management issues; cost-benefit impact; and research requirements. These proceedings are provided to make available to the transfusion medicine community the considerable amount of important information presented at this consensus conference.

Several case reports have suggested an association between infections and thrombotic thrombocytopenic purpura (TTP). In Case 1, a 37-year-old female presented with TTP 6 times over 7 years, requiring 242 therapeutic plasma exchanges (TPE), for a per-course range of 4-57 TPE (median 48), and treatment durations of 4-241 days (median 71 days), largely on account of multiple exacerbations (range 0-3, median 3). Twelve of 17 (71%) of her presentations or exacerbations were associated with suspected infections, with confirmation in 9 episodes. These included pulmonary TB, CMV pneumonitis, mucocutaneous HSV, ventilator-associated or urinary tract-associated gram-negative sepsis, central line-associated staphylococcal bacteremia, and cellulitis. Except for TB, all infections occurred after splenectomy, which had been performed on day 33 of presentation 1. In Case 2, a 24-year-old female presented with TTP 3 times over 15 months. Her courses were managed with brief courses of TPE (5-11 treatments per course, median 5). Suppressed ADAMTS13 levels due to inhibitors were confirmed twice. Presentation 1 was antedated by atypical community acquired pneumonia. Presentation 3 (and possibly 2) followed prolonged, progressive, antibiotic-refractory periodontal infections ultimately requiring exodontic surgery. Our cases add to a literature that suggests that infection may be associated with exacerbations or relapses of TTP in some patients. Our patients demonstrated repeated TTP exacerbations in association with different infectious agents. A better understanding of the possible relationship between infection and clinical expression of TTP might lead to improved treatment decisions for patients with this complex illness.