The 2009 H1N1 influenza outbreak in its historical context.

Of the 16 known serotypes of influenza A haemagglutinin, 6 have been isolated from humans at the molecular level (H1, H2, H3, H5, H7, H9). 3 of these have been involved in past pandemics (H1, H2, H3). Traditional pandemic surveillance has focussed on monitoring antigenic shift, meaning the re-assortment of novel haemagglutinins into seasonal human influenza A viruses during rare events of double infection with seasonal and zoonotic strains. H5, from avian H5N1 influenza, has been the major cause for concern in recent years. However, the 2009 H1N1 zoonotic event demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. The protein sequence divergence of the 2009 zoonotic H1 from human seasonal influenza H1 is around 20-24%. A similar level of divergence is found between the 2009 H1 and European swine flu. By contrast, its divergence from North American swine flu strains is around 1-9%. Given that the divergence between H1 and its nearest serotype neighbour H2 is around 40-46%, the 2009 H1 may be broadly considered as halfway towards a new serotype. The current situation is one of antigenic pseudo-shift.