Influenza virus
infections remain an important cause of morbidity and mortality. Furthermore, a recurrence of pandemic
influenza remains a real possibility. There are now effective ways to both prevent and treat
influenza. Prevention of
infection is most effectively accomplished by vaccination. Vaccination with the inactivated, intramuscular
influenza vaccine has been clearly demonstrated to reduce serious morbidity and mortality associated with
influenza infection, especially in groups of patients at high risk (e.g. the elderly). However, the inactivated, intramuscular
vaccine does not strongly induce cell-mediated or mucosal immune responses, and protection induced by the
vaccine is highly strain specific. Live, attenuated
influenza vaccines administered intranasally have been studied in clinical trials and shown to elicit stronger mucosal and cell-mediated immune responses. Live,
attenuated vaccines appear to be more effective for inducing protective immunity in children or the elderly than inactivated, intramuscular
vaccines. Additionally, novel
vaccine methodologies employing conserved components of influenza virus or
viral DNA are being developed. Preclinical studies suggest that these approaches may lead to methods of vaccination that could induce immunity against diverse strains or subtypes of
influenza. Because of the limitations of vaccination,
antiviral therapy continues to play an important role in the control of
influenza. Two major classes of
antivirals have demonstrated ability to prevent or treat
influenza in clinical trials: the adamantanes and the
neuraminidase inhibitors. The adamantanes (
amantadine and
rimantadine) have been in use for many years. They inhibit viral uncoating by blocking the
proton channel activity of the
influenza A viral M2
protein. Limitations of the adamantanes include lack of activity against
influenza B, toxicity (especially in the elderly), and the rapid development of resistance. The
neuraminidase inhibitors were designed to interfere with the conserved
sialic acid binding site of the viral
neuraminidase and act against both
influenza A and B with a high degree of specificity when administered by the oral (
oseltamivir) or inhaled (
zanamivir) route. The
neuraminidase inhibitors have relatively low toxicity, and viral resistance to these inhibitors appears to be uncommon. Additional novel
antivirals that target other phases of the life cycle of
influenza are in preclinical development. For example, recombinant
collectins inhibit replication of
influenza by binding to the viral haemagglutinin as well as altering phagocyte responses to the virus. Recombinant techniques have been used for generation of
antiviral proteins (e.g. modified
collectins) or
oligonucleotides. Greater understanding of the biology of influenza viruses has already resulted in significant advances in the management of this important pathogen. Further advances in vaccination and
antiviral therapy of
influenza should remain a high priority.