Influenza Epidemics and Pandemics

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 HA (and NA) proteins (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 PB1, NS1 and PB1‐F2 proteins are also important determinants of pathogenicity. For seasonal and pandemic 2009 H1N1 influenza viruses, inactivated and live attenuated vaccines are available. Two classes of antiviral compounds (ion channel inhibitors and neuraminidase inhibitors) exist: resistance to ion channel inhibitors is now widespread among circulating H1N1 and H3N2 influenza viruses; resistance to neuraminidase inhibitors has been reported for most seasonal H1N1 viruses, some pandemic 2009 H1N1 viruses and some highly pathogenic avian H5N1 influenza viruses.