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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 × 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., (© 2015 AABB.)

Background: Dengue is endemic in Puerto Rico and causes periodic outbreaks involving thousands of persons. Seroprevalence studies among blood donors can provide useful data on the immune status of the adult population. The objective of this study was to determine the prevalence of anti-dengue immunoglobulin (Ig)G antibodies in a random sample of blood donors to the American Red Cross (ARC) in Puerto Rico., Study Design and Methods: Three-hundred randomly selected blood donations collected by the ARC from February 1 to March 31, 2006, were tested using an anti-dengue IgG enzyme-linked immunosorbent assay. One-third of the positive specimens were randomly selected and tested by a microneutralization test (MNT) to determine the serotypes of previous dengue infections., Results: Most (84%) blood donors were male, and the mean age was 44.6 years (range, 18-80 years). The prevalence (95% confidence interval) of anti-dengue IgG antibodies was 92% (89%-95%). Of the 92 specimens tested by the MNT, reactivity to all four dengue serotypes was observed and 96% were secondary infections. The predominant serotype with the highest neutralization titers, as identified by at least a fourfold higher titer compared to any other serotype tested, was identified in 32 specimens; the most common predominant serotypes identified by the MNT were DENV-3 and DENV-2 (63%). Recent infection with DENV-1 was detected but, in 2005, routine surveillance did not detect any cases of this serotype., Conclusion: Supplementary serologic testing of donated blood can potentially provide information on the silent circulation or introduction of dengue serotypes., (© 2012 American Association of Blood Banks.)

Background: Dengue virus (DENV) nucleic acid amplification testing of blood donations during epidemics in endemic locations, including Puerto Rico, has suggested possible sizable transfusion transmission risk. Estimates of the long-term prevalence of DENV viremic donations will help evaluate the potential magnitude of this risk in Puerto Rico., Study Design and Methods: Estimates of the prevalence of DENV viremia in the Puerto Rican population at large from 1995 through 2010 were derived from dengue case reports and their onset dates obtained from islandwide surveillance, estimates of case underreporting, and extant data on the duration of DENV viremia and the unapparent-to-apparent dengue infection ratio. Under the assumptions that viremia prevalence in blood donors was similar to that of the population at large and that symptomatic persons do not donate, statistical resampling methods were used to estimate the prevalence of dengue viremia in blood donations., Results: Over the 16-year period, the maximum and mean daily prevalences of dengue viremia (per 10,000) in blood donations in Puerto Rico were estimated at 45.0 (95% confidence interval [CI], 36.5-55.4) and 7.0 (95% CI, 3.9-10.1), respectively. Prevalence varied considerably by season and year., Conclusion: These data suggest a substantial prevalence of DENV viremia in Puerto Rican blood donations, particularly during outbreaks., (© 2012 American Association of Blood Banks.)

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 10(5) to 10(9) 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 10(8) 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., (© 2012 American Association of Blood Banks.)