The specific aims of this continuation application are to prospectively study pediatric recipients of allogeneic blood transfusion to (1) determine the residual risk of transmitting known infections agents for which there are current donor screening assays and (2) assess the potential risk of known and emergent agents for which there is no or limited testing. When such agents infect blood recipients, the clinical and pathological implications may be unrecognized and approaches to intervention are either poorly established or have questionable cost-benefit. An additional specific aim is to prospectively study the prevalence and persistence of transfusion-associated microchimerism (TA-MC) in a highly transfused pediatric population. Further, we will establish an """"""""early warning"""""""" repository of linked donor and recipient samples so that when an infectious agent emerges in the future, systematic testing can rapidly establish whether or not that agent(s) presents a threat to the blood supply. The current pediatric application will be undertaken collaboratively with an identically designed study in adults being conducted at the NIH Clinical Center. In both studies, recipients are enrolled prior to transfusion and followed for at least 6 months post-transfusion;samples are collected pre- and 2-4, 8,12-16 and 24 weeks post-transfusion. Consented donors provide repository specimens that permit linkage with recipients. Both serologic and molecular assays for a wide spectrum of agents will be performed. These include several unique molecular assays: microarray technology using a pathogen chip to monitor babesia, malaria species, trypanosoma, borrelia and other agents, as well as viral blast discovery, using sequence independent single primer amplification. Further, TA-MC will be analyzed using both HLA- DR and insertion/deletion polymorphism panels. The combined NIH and CNMC study expands the analytic capabilities and power of the data to permit determination of infectious and selected non-infectious risks, allow for a comparison of these risks between adult and pediatric patients and comparison of viral persistence and clinical outcome according to age. This application provides a unique plasma and cell repository available to other NHLBI investigators that will allow for future determination of the transfusion transmissibility of emerging agents, the risk to transfusion recipients and the implications of TA-MC. Relevance to public health: This application is relevant to the missions of the IOM, FDA and NHLBI to ensure that blood collected for transfusion is safe. This application focuses on infants and children, a vulnerable and heretofore poorly studied recipient group.
