APPENDIX 2 Influenza A and B Viruses (Other Than H5N1) Likelihood of Secondary Transmission: • Characteristic of influenza following exposure to Disease Agents: secretions from infected persons • Influenza A and B viruses At-risk Populations: Disease Agent Characteristics: • Elderly individuals (>65 years) • Family: Orthomyxoviridae; Genera: Influenzavirus A • Infants and pregnant women or Influenzavirus B • Those with a variety of chronic medical conditions • Virion morphology and size: Enveloped, helical • During pandemics, much larger segments of the nucleocapsid, spherical to pleomorphic virions, population are immunologically naïve, and suscep- 80-120 nm in diameter tible to infection. • Nucleic acid: Linear, segmented, negative-sense, single-stranded RNA, ~13.6 kb in length for influenza Vector and Reservoir Involved: A and ~14.6 kb in length for influenza B • Influenza A viruses circulate in birds and mammalian • Physicochemical properties: Virions are sensitive to species, especially pigs, where they undergo antigenic treatment with heat, lipid solvents, nonionic deter- drift and shift with eventual transmission to humans. gents, formaldehyde, oxidizing agents; infectivity • Influenza B infection is confined to humans. reduced after exposure to radiation. Blood Phase: Disease Name: • Animal models of influenza A demonstrate viremia • Influenza after experimental infection. Priority Level: • Virus isolation at autopsy from organs outside the respiratory tract (heart, CNS, kidney, spleen, liver, • Scientific/Epidemiologic evidence regarding blood fetus) is indirect evidence of dissemination during safety: Theoretical natural infection that suggests viremia. • Public perception and/or regulatory concern regard- • Viremia and influenza A “RNA-emia” are described in ing blood safety: Very low a small series of symptomatic patients (who would • Public concern regarding disease agent: Moderate have been disqualified as donors because of Background: symptoms). • A single case report describes influenza A H3N2 • Seasonal epidemics are characteristic of influenza A (Hong Kong) viremia in a naturally infected, asymp- and B. These are primarily in the late fall and winter in tomatic patient, which would be most relevant to temperate climates. concerns about transfusion transmission. • When major changes (antigenic shift) occur in influ- • Experimental human infections have been accompa- enza A antigens, pandemics occur with high attack nied by viremia during the incubation period, but the rates and variable morbidity and mortality. relevance of the high-dose intranasal inoculation (as • Influenza B does not undergo shifts but evolves by opposed to the natural droplet route) has been antigenic drift and is not associated with severe pan- questioned. demics. • Influenza B viremia was detected in 4 of 11 pediatric • Depending on vaccine efficacy and other factors asso- patients 2-4 days after symptom onset. ciated with epidemic activity , epidemics occur annu- ally and pandemics every few decades Survival/Persistence in Blood Products: • Influenza A viruses infect avian species, humans, and • Unknown several other mammalian species (especially swine). Influenza B infects only humans. Transmission by Blood Transfusion: Common Human Exposure Routes: • Never documented • Person-to-person spread primarily via contact with Cases/Frequency in Population: droplets expelled during coughing and sneezing • Virions are present in high titers in nasal secretions • The incidence varies from season to season, but starting about 2-3 days after exposure and just before population attack rates during a pandemic first wave symptoms. can approach 40%. During seasonal epidemics, rates • Preschool and school-age children are major con- of up to 18% are seen (higher in children) and up to tributors to transmission of influenza A viruses. 70% in confined or selected populations. 110S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 • Worldwide prevalence: Up to 10% of weekly mortality • Myalgias, commonly occurring in the back, arm, or attributable to influenza during outbreaks legs • In March-April 2009, a new strain of influenza A H1N1 • Headache, chills, dry cough was isolated in Mexico and then rapidly • Retro-orbital pain, conjunctivitis worldwide. The spread of the virus and disease soon • Fatigue, malaise, anorexia qualified as a level 5 of 6 (the highest indicating a • Tracheobronchitis with rhinorrhea; cough can persist pandemic) using the WHO influenza pandemic for 1 or 2 additional weeks after fever and upper res- definitions. Although formally achieving the existing piratory tract symptoms resolve. WHO criteria for level 6, by community spread of the new H1N1 virus in a second region by the end of May, Severity of Clinical Disease: the WHO did not raise the pandemic alert to level 6 • Symptoms can be severe and associated with until June 11, 2009. This is the organization’s first flu increased hospitalizations during epidemics (1/2900 pandemic declaration in more than 40 years. Raising infected for 1- to 44-year-old group and 1/270 the alert to level 6 does not indicate the disease is infected for those older than 65 years). more fatal or riskier than at level 5, but that it has • During the past four influenza seasons, the peak per- spread to an increasing number of countries. As of centage of patient visits for influenza-like illness June 11, 2009: ranged from 4.0 to 7.6%. ᭺ 74 countries reported 28,774 cases including 144 deaths Mortality: ᭺ 94% of global cases are from the Americas with most from Mexico • Influenza is the cause of excess mortality each year, > ᭺ Cases of disease have been milder than expected especially in persons 65 years (1/2200 infected based on initial reports from cases in Mexico increasing to 1 in 300 infected during a pandemic) • Phylogenetic cluster analyses using the new H1N1 • During pandemics mortality is generally highest at strain and its closest relatives support the fact that the the extremes of age; however, during the 1918 pan- 2009 worldwide H1N1 virus derived from one or mul- demic, there was a mortality peak in young adults. tiple reassortments between influenza A viruses cir- Chronic Carriage: culating in swine in Eurasia and in North America (H1N1, H1N2 and H3N2). •No • Receipt of recent (2005-2009) seasonal influenza vac- cines is unlikely to elicit a protective antibody Treatment Available/Efficacious: response to the novel H1N1 virus • Several antiviral drugs (amantadine and rimantadine) ᭺ 2-fold increase in cross-reactive antibody in and neuraminidase inhibitors (zanamivir, oselta- those aged 18-64 (compared to a 12- to 19-fold mivir) are available that have both prophylactic and for the seasonal H1N1 influenza strain) clinical efficacy, although resistance, including trans- Incubation Period: mission of primary resistant strains, is a major concern. • 1-5 days (longer for influenza B virus) Agent-Specific Screening Question(s): Likelihood of Clinical Disease: • No specific question is in use, but symptomatic • Based on experimental infection, most influenza A donors are excluded by current donor criteria (“Are cases are symptomatic, with high fever in 60-90% of you feeling well and healthy today?”). subjects. • No question is feasible for exposure to influenza A or • Asymptomatic influenza A infection does occur and B during a community outbreak. was documented in 4 of 34 infected prisoners. • While some authorities suggest that influenza B is Laboratory Test(s) Available: milder than A, most believe they closely resemble • No FDA-licensed blood donor screening test exists. each other. • Antemortem diagnosis confirmed by viral isolation, Primary Disease Symptoms: experimental nucleic acid testing for virus-specific RNA, and the less sensitive antigen-detection tests • Abrupt onset of fever of 38-40°C but can reach 41°C • All tests have been validated for sputum/pharyngeal when symptoms first develop; usually continuous but secretions but not for blood or blood fractions. Isola- may come and go; may be lower in older adults than tion may be higher from pharyngeal samples (at a in children and younger adults median of 5.5 days). Volume 49, August 2009 Supplement TRANSFUSION 111S APPENDIX 2 • An RT-PCR assay in minipools for the associated Available from: http://www.cdc.gov/flu/weekly/ influenza A H5N1 subtype has been evaluated in weeklyarchives2004-2005/04-05summary.htm 10,272 blood donor samples. All were negative. 2. Centers for Disease Control and Prevention. Influ- enza outbreak—Madagascar, July-August 2002. Morb Currently Recommended Donor Deferral Period: Mortal Wkly Rep MMWR 2002;51:1016-8. 3. Centers for Disease Control and Prevention. Serum • No FDA Guidance or AABB Standard exists. cross-reactive antibody response to a novel influenza • Prudent practice would be to defer donor until signs A (H1N1) vaccination with seasonal influenza and symptoms are gone. vaccine. Morb Mortal Wkly Rep MMWR 2009;58: Impact on Blood Availability: 521-4. 4. Earhart KC, Beadle C, Miller LK, Pruss MW, Gray GC, • Agent-specific screening question(s): Ledbetter EK, Wallace MR. Outbreak of influenza in ᭺ Symptomatic infection is already a cause for highly vaccinated crew of U.S. Navy ship. Emerg deferral. Infect Dis 2001;7:463-5. ᭺ If there is a concern about asymptomatic viremia 5. Eurosurveillance 2009:14(21). [cited 2009 June]. Avail- and a deferral for contact with influenza is con- able from: http://www.eurosurveillance.org/Public/ sidered during a seasonal outbreak or pandemic, Articles.aspx the impact could be major. 6. Fritz RS, Hayden FG, Calfee