Future Directions for Research and Recommendations Related to Influenza Vaccine

Although available influenza vaccines are effective and safe, additional research is needed to improve prevention efforts. Most mortality from influenza occurs among person aged >65 years (6), and more immunogenic influenza vaccines are needed for this age group and other risk groups at high risk for mortality. Additional research is also needed to understand potential biases in estimating the benefits of vaccination among older adults in reducing hospitalizations and deaths (101,193,377). Additional studies of the relative cost-effectiveness and cost utility of influenza vaccination among children and adults, especially those aged <65 years, are needed and should be designed to account for year-to-year variations in influenza attack rates, illness severity, hospitalization costs and rates, and vaccine effectiveness when evaluating the long-term costs and benefits of annual vaccination (378). Additional data on indirect effects of vaccination are also needed to quantify the benefits of influenza vaccination of HCP in protecting their patients (294) and the benefits of vaccinating children to reduce influenza complications among those at risk. Because of expansions in ACIP recommendations for vaccination will lead to more persons being vaccinated, much larger research networks are needed that can identify and assess the causality of very rare events that occur after vaccination, including GBS. These research networks could also provide a platform for effectiveness and safety studies in the event of a pandemic. Research on potential biologic or genetic risk factors for GBS also is needed. In addition, a better understanding of how to motivate persons at risk to seek annual influenza vaccination is needed.

ACIP continues to review new vaccination strategies to protect against influenza, including the possibility of expanding routine influenza vaccination recommendations toward universal vaccination or other approaches that will help reduce or prevent the transmission of influenza and reduce the burden of severe disease (379384). The expansion of annual vaccination recommendations to include all children aged 6 months18 years will require a substantial increase in resources for epidemiologic research to develop long term studies capable of assessing the possible effects on community-level transmission. Additional planning to improve surveillance systems capable of monitoring effectiveness, safety and vaccine coverage, and further development of implementation strategies will also be necessary. In addition, as noted by the National Vaccine Advisory Committee, strengthening the U.S. influenza vaccination system will require improving vaccine financing and demand and implementing systems to help better understand the burden of influenza in the United States (385). Vaccination programs capable of delivering annual influenza vaccination to a broad range of the population could potentially serve as a resilient and sustainable platform for delivering vaccines and monitoring outcomes for other urgently required public health interventions (e.g., vaccines for pandemic influenza or medications to prevent or treat illnesses caused by acts of terrorism).

Seasonal Influenza Vaccine and Avian or Swine Influenza

Human infection with novel or nonhuman influenza A virus strains, including influenza A viruses of animal origin, is a nationally notifiable disease (386). Human infections with nonhuman or novel human influenza A virus should be identified quickly and investigated to determine possible sources of exposure, identify additional cases, and evaluate the possibility of human-to-human transmission because transmission patterns could change over time with variations in these influenza A viruses.

Sporadic severe and fatal human cases of infection with highly pathogenic avian influenza A(H5N1) viruses have been identified in Asia, Africa, Europe and the Middle East, primarily among persons who have had direct or close unprotected contact with sick or dead birds associated with the ongoing H5N1 panzootic among birds (387392). Limited, nonsustained human-to-human transmission of H5N1 viruses has likely occurred in some case clusters (393,394). To date, no evidence exists of genetic reassortment between human influenza A and H5N1 viruses. However, influenza viruses derived from strains circulating among poultry (e.g., the H5N1 viruses that have caused outbreaks of avian influenza and occasionally have infected humans) have the potential to recombine with human influenza A viruses (395,396). To date, highly pathogenic H5N1 viruses have not been identified in wild or domestic birds or in humans in the United States.

Human illness from infection with different avian influenza A subtype viruses also have been documented, including infections with low pathogenic and highly pathogenic viruses. A range of clinical illness has been reported for human infection with low pathogenic avian influenza viruses, including conjunctivitis with influenza A(H7N7) virus in the U.K., lower respiratory tract disease and conjunctivitis with influenza A(H7N2) virus in the U.K., and uncomplicated influenza-like illness with influenza A(H9N2) virus in Hong Kong and China (397402). Two human cases of infection with low pathogenic influenza A(H7N2) were reported in the United States (400). Although human infections with highly pathogenic A(H7N7) virus infections typically have influenza-like illness or conjunctivitis, severe infections, including one fatal case in the Netherlands, have been reported (403,404). Conjunctivitis has also been reported because of human infection with highly pathogenic influenza A(H7N3) virus in Canada and low pathogenic A(H7N3) in the U.K (397,404). In contrast, sporadic infections with highly pathogenic avian influenza A(H5N1) viruses have caused severe illness in many countries, with an overall case-fatality ratio of >60% (394,405).

Swine influenza A(H1N1), A(H1N2), and A(H3N2) viruses are endemic among pig populations in the United States (406), including reassortant viruses. Two clusters of influenza A(H2N3) virus infections among pigs have been recently reported (407). Outbreaks among pigs normally occur in colder weather months (late fall and winter) and sometimes with the introduction of new pigs into susceptible herds. An estimated 30% of the pig population in the United States has serologic evidence of having had swine influenza A(H1N1) virus infection. Sporadic human infections with swine influenza A viruses occur in the United States, but the frequency of these human infections is unknown. Persons infected with swine influenza A viruses typically report direct contact with ill pigs or places where pigs have been present (e.g., agricultural fairs or farms), and have symptoms that are clinically indistinguishable from infection with other respiratory viruses (408). Clinicians should consider swine influenza A virus infection in the differential diagnosis of patients with ILI who have had recent contact with pigs. The sporadic cases identified in recent years have not resulted in sustained human-to-human transmission of swine influenza A viruses or community outbreaks. Although immunity to swine influenza A viruses appears to be low in the overall human population (<2%), 10%20% of persons occupationally exposed to pigs (e.g., pig farmers or pig veterinarians) have been documented in certain studies to have antibody evidence of prior swine influenza A(H1N1) virus infection (409,410).

Current seasonal influenza vaccines are not expected to provide protection against human infection with avian influenza A viruses, including H5N1 viruses, or to provide protection against currently circulating swine influenza A viruses. However, reducing seasonal influenza risk through influenza vaccination of persons who might be exposed to nonhuman influenza viruses (e.g., H5N1 viruses) might reduce the theoretical risk for recombination of influenza A viruses of animal origin and human influenza A viruses by preventing seasonal influenza A virus infection within a human host.

CDC has recommended that persons who are charged with responding to avian influenza outbreaks among poultry receive seasonal influenza vaccination (411). As part of preparedness activities, the Occupational Safety and Health Administration (OSHA) has issued an advisory notice regarding poultry worker safety that is intended for implementation in the event of a suspected or confirmed avian influenza outbreak at a poultry facility in the United States. OSHA guidelines recommend that poultry workers in an involved facility receive vaccination against seasonal influenza; OSHA also has recommended that HCP involved in the care of patients with documented or suspected avian influenza should be vaccinated with the most recent seasonal human influenza vaccine to reduce the risk for co-infection with human influenza A viruses (412).



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