Transfusion Infections Pediatric Prospective Study (TRIPPS)
Condition: Blood Donors; Blood Transfusion; Cytomegalovirus Infections; Hepatitis, Viral, Human; HIV Infections
MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections; Hepatitis, Viral, Human
Study type: Observational

Summary: 
      To conduct a prospective study of pediatric transfusion recipients to determine the risk of
      transmitting various infectious agents by blood transfusion.
    

Detailed description: 
      BACKGROUND:

      Despite a marked reduction in the risk of transfusion-transmitted disease, lessons learned
      from the delayed recognition of HIV transmission by transfusion, underscore the necessity for
      continued vigilance for blood safety. The study will correct a significant lack of
      prospective studies of transfusion transmitted disease in infants and children in this
      country. A critical material outcome of the study will be the establishment of a large serum
      and cell repository of linked patient recipient samples. Such a repository, representing
      prospective studies in a pediatric population, will be unique. It will provide a means for
      ongoing surveillance to identify more rapidly emerging infectious agents and to aid in
      determining whether they present a significant risk to the blood supply. Because of a close
      collaboration and parallel structure with two related adult transfusion studies, age related
      comparisons of viral clearance and clinical outcomes should likewise be derived from this
      work.

      DESIGN NARRATIVE:

      The prospective study of pediatric transfusion recipients will determine the residual risk of
      transmitting known infectious agents such as hepatitis viruses, human immunodeficiency virus
      (HIV) and human T-cell leukemia virus (HTLV), for which there are current donor screening
      assays, and the potential risk of known agents that are not routinely screened during blood
      donation, but might, nonetheless, infect blood recipients with diseases such as
      cytomegalovirus, parvovirus B-19, human herpes virus-8 (HHV-8) and newly proposed hepatitis
      viruses, TTV and the SEN virus (SEN-V). An additional primary goal of the study is to
      establish a repository of linked donor and recipient samples so that if a new infectious
      agent emerges in the future, testing of the repository will rapidly establish whether or not
      that agent presents a threat to the blood supply.

      To insure larger numbers of samples and greater statistical power, samples from this study
      will be merged into a large repository to be generated in the NHLBI-sponsored RADAR (REDS
      Allogeneic Donor and Recipient) study. The current study will be the only pediatric arm of
      the RADAR multi-center study. Further, the current pediatric study will be undertaken
      collaboratively with a similarly designed study in adults being conducted at the NIH Clinical
      Center. In both studies recipients will be enrolled prior to transfusion and then followed
      for at least 6 months post-transfusion. Blood samples will be obtained before and at 2, 4, 8,
      12, 16 and 24 weeks after transfusion. Molecular and serologic testing will be routinely
      performed for the agents cited above with particular emphasis on molecular assays for human
      retroviruses (HRV), hepatitis C virus (HCV). HIV, SEN-V, cytomegalovirus (CMV), parvovirus
      B-i 9 and human herpesvirus-8 (HHV-8). Aliquots will be retained in frozen storage. In
      addition, pre and post-transfusion and donor whole blood samples will be frozen to allow for
      recovery of recipient DNA and identification of microchimerism. Such microchimerism may
      result in transfusion-associated graft versus host disease and immunosuppression and have
      long term consequences for the development of immune mediated diseases in the recipient. In
      summary, the primary pediatric study and the proposed collaborations will allow for
      determinations of the transfusion risk of a variety of blood-screened and unscreened
      infectious agents, and will allow for comparisons of transfusion risk between pediatric and
      adult patients, as well as comparisons of viral persistence and clinical outcome according to
      age. In addition, by contributing pre and post-transfusion samples from blood recipients and
      their linked donor samples, this study will help establish a large serum and cell repository
      that will allow for the future determination of whether virtually any infectious agent is
      transfusion-transmitted and a potential risk to blood recipients.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pediatric recipients of allogeneic blood transfusion and linked blood donors
      
Biospecimen description: 
      Whole blood and plasma samples