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Dengue and Chikungunya viruses in blood donations: risks to the blood supply?

A rbovirus epidemics are raging in tropical areas. Dengue virus (DENV), dengue shock syndrome (DSS), and dengue hemorrhagic fever (DHF) affect millions of individuals every year and cause significant mortality in Latin America, Africa, and Asia. Chikungunya virus (CHIKV) has caused recurrent epidemics in the Indian subcontinent and recent epidemics in Reunion and other islands in the Indian Ocean, with recent detection in areas of Europe. This issue of TRANFUSION includes two articles on the detection of DENV RNA in blood donors from epidemic areas, one article on the clearance of spiked DENV in the course of the manufacture of plasma derivatives, and one article on statistical modeling of transfusion risk during an epidemic of mosquito-borne CHIKV. The surprising seriousness of recurring epidemics of West Nile virus (WNV) in North America has heightened concerns about the potential for introduction and similar epidemic spread of other arbovirus infections in the United States. Dengue has received particular attention since cases have been recognized in the United States at the border between Texas and Mexico. The mosquito species that transmit DENV, Aedes egypti and Aedes albopictus, are present in the Southern and Southeastern parts of the United States, raising the specter of significant spread within the United States if the virus is introduced and efficiently spreads. Does dengue represent a risk to the safety of the US blood supply? Transmission by transfusion (TT) is often difficult to evaluate in the midst of an epidemic because the infection could have been acquired through a mosquito bite, through a transfusion, or even through a needle stick. Doubts about TT of WNV were eliminated when the virus was transmitted to multiple recipients of organs and, subsequently, multiple recipients of blood components obtained from the blood donors determined to be viremic. Despite the recognition of millions of cases of DENV infection and disease every year, there are very few published reports of transfusion transmission. One report was submitted to the public health agency of Hong Kong and, although accessible online, has not been published in a peer-reviewed journal. The other report describes a recent cluster of TT-DENV in Singapore, which is currently in press (P.A. Tambyah, National University of Singapore, personal communication, 2008). There are also reports of transmission by needle sticks and one case associated with a marrow transplant in Puerto Rico (references are included in the articles being published). Considering the available information, should precautionary measures be considered to prevent TT-DENV in the United States or even more important in countries in which DENV epidemics are occurring at expanding rates? What are the data required for decisions to implement measures that mitigate this potential risk? The articles published in the current issue of TRANSFUSION contribute data that will be needed for policy decisions that may be required in the not so distant future. Linnen and coworkers used a transcriptionmediated amplification (TMA) assay for detection of DENV RNA to screen 13,372 specimens collected from blood donors in Honduras, Brazil, and Australia, countries with ongoing seasonal dengue epidemics. They identified 9 donors in Honduras who were repeat reactive for DENV RNA by TMA. Eight were confirmed by a polymerase chain reaction (PCR) assay that identified three different DENV serotypes, DENV-1, -2, and -4. Infectious virus could be recovered from four of these donors. Three samples from Brazil were repeatedly reactive on TMA. One was typed as DENV-1 and the other as DENV-3. None of the Australian specimens was repeatedly reactive. Samples were also tested by enzyme-linked immunosorbent assay for immunoglobulin M and immunoglobulin G antibodies to DENV and by plaque reduction neutralization assay to determine the existence and serotype of prior DENV infections in the viremic donors. Five of the donors in Honduras and one of the donors in Brazil appeared to have secondary DENV infections. The authors discuss the implications of reinfection with heterotypic subtypes because of the increased risk of DHF in these individuals. The study thus documented the presence of asymptomatic viremic donors in Honduras and Brazil who could theoretically transmit the virus to blood recipients. Mohammed and colleagues screened specimens from 16,521 blood donations made during an 11-week period to the American Red Cross in Puerto Rico, starting 2 weeks after the peak of dengue activity at the end of 2005. Twelve were DENV RNA repeatedly reactive using the same TMA assay used by Linnen and coworkers; 5 of the 12 were reactive in a pool of 16 (the operational pool size for WNV using TMA), and 4 of the 5 were positive on PCR. The four PCR-positive samples had viral loads TRANSFUSION 2008;48:1279-1281.