Search

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. STUDY DESIGN AND 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 × 107 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.

BACKGROUND: In 2007, a total of 10,508 suspected dengue cases were reported in Puerto Rico. Blood donations were tested for dengue virus (DENV) RNA and recipients of RNA-positive donations traced to assess transfusion transmission. STUDY DESIGN AND METHODS: Blood donation samples from 2007 were maintained in a repository and tested individually for DENV RNA by transcription-mediated amplification (TMA); a subset was further tested by an enhanced TMA (eTMA) assay. TMA-reactive samples were considered confirmed if TMA (including eTMA) was repeat reactive (RR). All TMA-RR samples were tested by quantitative, DENV type–specific reverse transcriptase–polymerase chain reaction (RT-PCR) and for anti-DENV immunoglobulin (Ig)M by enzyme-linked immunosorbent assay. Samples positive by RT-PCR were further tested for infectivity in mosquito cell culture. Patients receiving components from TMA-RR donations were followed. RESULTS: Of 15,350 donation samples tested, 29 were TMA-RR for a prevalence of 1 per 529 (0.19%). DENV Types 1, 2, and 3 with viral titers of 105 to 109 copies/mL were detected by RT-PCR in 12 samples of which all were infectious in mosquito culture. Six TMA-RR samples were IgM positive. Three of the 29 recipients receiving TMA-RR donations were tested. One recipient in Puerto Rico transfused with red blood cells containing 108 copies/mL DENV-2 became febrile 3 days posttransfusion and developed dengue hemorrhagic fever. The recipient was DENV-2 RNA positive by RT-PCR; both the donor and the recipient viruses had identical envelope sequences. CONCLUSIONS: High rates of viremia were detected in blood donors in Puerto Rico coupled with the first documented transfusion transmission of severe dengue disease, suggesting that further research on interventions is needed.

BACKGROUND: A single instance of transfusion-transmitted dengue infection has been reported. The high incidence of dengue in endemic countries, the high proportion of asymptomatic infection, and the median 5-day viremia, however, suggest that transfusion-associated dengue transmission may be more widespread than documented. STUDY DESIGN AND METHODS: The prevalence of dengue virus (DENV) RNA was determined in all blood donations to the American Red Cross in Puerto Rico from September 20 to December 4, 2005, using a specific type of nucleic acid amplification test called transcription-mediated amplification (TMA). TMA-positive donations were defined as those having two repeatedly reactive TMA results. TMA-positive donations were tested by enzyme-linked immunosorbent assay for immunoglobulin M (IgM) antibodies, by reverse transcription–polymerase chain reaction (RT-PCR), and by viral culture. RESULTS: Twelve (0.07%) of 16,521 blood donations tested were TMA-positive. Four were positive by RT-PCR (DENV serotypes 2 and 3). Virus was cultured from 3 of 4 RT-PCR–positive donations. One of the 12 TMA-positive donations was IgM-positive. Only 5 donations remained TMA-positive when diluted 1:16, as is done for routine minipool screening for other transfusion-transmissible viral infections (hepatitis C, human immunodeficiency, West Nile viruses [WNVs]). CONCLUSION: Nearly 1 in 1000 blood donations contained DENV RNA, and virus could be cultured from TMA-positive donations, suggesting a transfusion transmission risk similar to that which existed in the United States for WNV before universal donation screening. Similar to WNV, IgM antibody screening is likely to be ineffective, and some potentially infectious donations will be missed by minipool screening. Transfusion transmission should be considered in patients with dengue after blood transfusion.