Sensitive Detection Assays for Influenza RNA Do Not Reveal Viremia in US Blood Donors

The 2009 H1N1 influenza outbreak illustrates that the virus remains a global threat with serious sequellae in some affected individuals. Circulating seasonal strains can spread easily from human to human, rapidly covering the globe during the initial phase of a pandemic. In addition to seasonal influenza and the recently introduced triple reassortant 2009 H1N1 strain, highly pathogenic avian influenza (H5N1) circulates in Asian bird populations, and humans have been infected in multiple countries [1, 2]. Fortunately, sustained human-to-human transmission of H5N1 influenza virus has not been seen [3, 4], as mortality can reach 50% [5, 6]. The recent introduction of the novel H1N1 reassortant influenza virus, and the potential for high mortality after infection with highly pathogenic avian influenza virus, have focused attention on the epidemiology and pathophysiology of influenza infection. During the 2009 H1N1 influenza outbreak, the prime concern of most institutions was to maintain operational capability in the face of heightened employee absenteeism due to illness of the worker or family member, as well as the obvious concern regarding an absence of blood donors. In addition to these concerns, blood collectors also had to consider whether blood collected during the outbreak might contain infectious influenza virus. Transfusion transmission of influenza would not likely play a major role in spreading a virus that is primarily transmitted by aerosolization/droplet infection. However, transfusion recipients are likely at increased risk of serious sequellae of influenza infection. Immune compromised subjects are susceptible to severe disease, and influenza virus-infected bone marrow transplant patients have shown ∼25% mortality after infection [7, 8]. In the recent 2009 H1N1 outbreak it was also noted that pregnant women were at risk for more severe disease and death than the general population [9]. Although influenza viremia has infrequently been observed [10–17] (reviewed in [18]), the potential remains that influenza viremia can occur during presymptomatic or asymptomatic infection [19]. After introduction of an antigenically novel influenza virus, attack rates can be extraordinarily high, reaching 15%–30% in some areas [20], with baseline infection rates fluctuating between 5% and 10% [21]. To study whether donated blood contained influenza virus, we capitalized on historical knowledge of influenza incidence and the collection of repository samples from blood donors linked to location and time of donation. In a second phase of testing, we prospectively surveyed blood from donors who reported symptoms consistent with influenza-like illness (ILI) within 3 days of blood donation, with the hypothesis that these donors would be most likely to harbor viremia at the earliest stage of infection. Here we present an analysis of commercially available and research-phase influenza RNA detection assays and the results of screening repository and prospectively collected samples for influenza RNA.