title: Probable and possible transfusion-transmitted dengue associated with NS1 antigen-negative but RNA confirmed-positive red blood cells.
abstract: BACKGROUND
  In the absence of active blood donation screening, dengue viruses (DENV) have been implicated in only a limited number of transfusion transmissions worldwide. This study attempted to identify if blood from donors testing negative by an NS1-antigen (Ag) enzyme-linked immunosorbent assay (ELISA) but confirmed positive for DENV RNA caused DENV-related disease in recipients during the epidemic years of 2010 to 2012 in Puerto Rico.
  
  
  METHODS
  Donation aliquots testing negative by an investigational NS1-Ag ELISA were stored frozen and retested retrospectively using a research transcription-mediated amplification assay (TMA) detecting DENV RNA. All RNA-reactive donations were subject to confirmatory RNA and antibody testing. Recipient tracing was conducted for all components manufactured from TMA-reactive components. Medical chart review, recipient interview, and follow-up sampling occurred for 42 recipients transfused with TMA-reactive components.
  
  
  RESULTS
  Six of 42 recipients developed new-onset fever in the 2 weeks posttransfusion; three (50%) received RNA confirmed-positive, NS1-Ag-negative red blood cell (RBC) units. One recipient of a high-titer unit (7 × 10(7) DENV-4 RNA copies/mL) developed severe dengue, and a second recipient had only fever recorded but had a negative sepsis work-up. New fever attributable to DENV infection in a third recipient was confounded by fever potentially attributable to posttransfusion sepsis.
  
  
  CONCLUSIONS
  In our retrospective study, NS1-Ag detected 20% of all RNA confirmed-positive donations demonstrating limitations of NS1-Ag ELISA for blood donation screening. We identified one recipient with a clinical syndrome compatible with severe dengue who had received an NS1-Ag-negative but RNA confirmed-positive RBC unit. This investigation illustrates the difficulty in confirming transfusion transmission in dengue-endemic areas among severely ill transfusion recipients.
authors.affiliation: American Red Cross Blood Services Region and.
authors.forename: Desiree
authors.initials: D
authors.lastname: Matos
authors.affiliation: Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico.
authors.forename: Kay M
authors.initials: KM
authors.lastname: Tomashek
authors.affiliation: Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico.
authors.forename: Janice
authors.initials: J
authors.lastname: Perez-Padilla
authors.affiliation: Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Muñoz-Jordán
authors.affiliation: Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hunsperger
authors.affiliation: Division of Vector-Borne Disease Information Technology Support, Centers for Disease Control and Prevention, Fort Collins, Colorado.
authors.forename: Kalanthe
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico.
authors.forename: David
authors.initials: D
authors.lastname: Noyd
authors.affiliation: American Red Cross Scientific Support Office, Gaithersburg, Maryland.
authors.forename: Colleen
authors.initials: C
authors.lastname: Winton
authors.affiliation: American Red Cross Scientific Support Office, Gaithersburg, Maryland.
authors.forename: Gregory
authors.initials: G
authors.lastname: Foster
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Marion
authors.initials: M
authors.lastname: Lanteri
authors.affiliation: Hologic, San Diego, California.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Linnen
authors.affiliation: American Red Cross Scientific Support Office, Gaithersburg, Maryland.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Stramer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D058731:Blood Safety; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000635:transmission*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood*; D012189:Retrospective Studies; D065227:Transfusion Reaction; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015415:Biomarkers; D012367:RNA, Viral