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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL067229-09
Application #
7907716
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Welniak, Lisbeth A
Project Start
2001-04-10
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
9
Fiscal Year
2010
Total Cost
$332,000
Indirect Cost
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010
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Xu, Chenyu; Wang, Richard Y; Schechterly, Cathy A et al. (2013) An assessment of hepatitis E virus (HEV) in US blood donors and recipients: no detectable HEV RNA in 1939 donors tested and no evidence for HEV transmission to 362 prospectively followed recipients. Transfusion 53:2505-11
Luban, Naomi L C; McBride, Eileen; Ford, Jason C et al. (2012) Transfusion medicine problems and solutions for the pediatric hematologist/oncologist. Pediatr Blood Cancer 58:1106-11
Sanchez, Rosa; Lee, Tzong-Hae; Wen, Li et al. (2012) Absence of transfusion-associated microchimerism in pediatric and adult recipients of leukoreduced and gamma-irradiated blood components. Transfusion 52:936-45
Yu, Mei-Ying W; Alter, Harvey J; Virata-Theimer, Maria Luisa A et al. (2010) Parvovirus B19 infection transmitted by transfusion of red blood cells confirmed by molecular analysis of linked donor and recipient samples. Transfusion 50:1712-21
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Luban, Naomi L C (2002) Neonatal red blood cell transfusions. Curr Opin Hematol 9:533-6