Influenza viremia and the potential for blood‐borne transmission

Abstract

I nfluenza is a major cause of morbidity and mortality in the United States and worldwide. The threat of pandemic influenza recently has gained prominent attention because of widespread infection of poultry with highly pathogenic avian influenza A (H5N1) and the potential for the virus to mutate into one capable of efficient human-to-human transmission. As of March 8, 2007, 277 human cases of H5N1 infection had been reported to WHO from Asia, Eastern Europe, and Africa, mostly as a result of close contact between humans and infected birds, although rare, unsustained human-to-human transmission has been documented. If a change in viral characteristics were to allow efficient human-to-human transmission, rapid spread and a worldwide pandemic could result. The global spread of H5N1, continuing outbreaks in birds, and sporadic infections in humans have increased concern that a pandemic virus may emerge and cause an influenza pandemic. The possibility of an influenza pandemic has focused attention on the epidemiology and pathophysiology of influenza, including its potential for transmission through the blood supply. An infectious agent which has a blood-borne phase and can be clinically asymptomatic has the potential to be transmitted by blood transfusion. Planning to ensure an adequate and safe national blood supply during a pandemic prompted consideration of the potential for transfusion-transmitted influenza. Notably, no cases of transfusion transmission of influenza have been documented to date. The risk of transfusion transmission has been assumed to be negligible based on the premise that viremia rarely occurs and does not occur without symptoms, allowing for deferral of potentially infectious blood donors. If these assumptions are incorrect, however, and influenza infection commonly involves a viremic phase, especially before the onset of symptoms, and if influenzainfected blood resulted in clinical illness, it would have implications for blood safety. To further examine this possibility, we surveyed the literature underlying these assumptions and propose methods of redressing gaps in our knowledge. If influenza were transmissible by transfusion, blood product recipients, who include a high proportion of immunocompromised patients, might suffer increased morbidity and mortality. In bone marrow transplant populations influenza infection appears to be associated with approximately 25 percent mortality. If influenza were deemed to represent a transfusion transmission risk, possible screening methods would likely rely on epidemiologic query or laboratory screening. With any screening there is a risk of impacting supply. Testing of the blood supply would also become particularly important if a pandemic were to be caused by a virus similar to the highly pathogenic influenza A (H5N1). Infection in humans has thus far resulted in approximately 60 percent case fatality ratio where the virus has been isolated outside of the respiratory tract, a factor not typically seen with seasonal influenza infections. Detection of influenza in the blood of H5N1 infected humans and in animal studies has occurred predominantly during symptomatic periods and at high viral titers. A positive test might result in discarding ABBREVIATION: CSF = cerebrospinal fluid.