Influenza Epidemics

Abstract Influenza viruses can cause epidemics or pandemics (worldwide epidemics), during which acute febrile respiratory disease spreads rapidly among all age groups, accompanied by excess hospitalisation and death. Here, we describe the recorded influenza virus pandemics, including the most recent pandemic that was caused in 2009 by a novel virus of the H1N1 subtype. Influenza virus replication and adaptation to new hosts account for much of the evolutionary success of these viruses. We review the viral proteins that are known to affect host range and pathogenicity (i.e. the haemagglutinin protein HA, the neuraminidase protein NA, the polymerase protein PB2, the nonstructural protein NS1 and the PB1‐F2 protein). We also discuss the clinical features of influenza virus infections, influenza virus immunology and influenza virus control, including antiviral treatment and vaccination. Key Concepts Influenza A viruses cause annual epidemics that result from point mutations in the surface glycoprotein(s) HA (and NA) (antigenic drift). At random intervals, influenza pandemics are caused by viruses that introduce HA proteins into the human population against which most humans lack immunity. Influenza A viruses evolve through reassortment and point mutations. Aquatic birds are the natural reservoir of influenza A viruses. Influenza A viruses can be transmitted among species, despite host range restriction factors. The HA protein is the major protective antigen and an important determinant of host range and pathogenicity. The PB2, NS1 and PB1‐F2 proteins are also important determinants of pathogenicity. Avian H5N1 and H7N9 viruses sporadically infect humans and cause severe respiratory infections with high case fatality rates; currently, these viruses do not transmit efficiently among humans. For human influenza viruses, inactivated and live attenuated vaccines are available. Three classes of antiviral compounds (ion channel, neuraminidase and polymerase inhibitors) exist: resistance to ion channel inhibitors is now widespread among circulating H1N1 and H3N2 influenza viruses; most human influenza viruses, as well as most avian H5N1 and H7N9 viruses, are sensitive to neuraminidase inhibitors, although viruses with resistance to neuraminidase inhibitors have been reported. Resistance to the recently approved polymerase inhibitor has not been reported yet.