Although we cannot claim that the mutations we describe are the only ones that will switch receptor binding preference of H5 HA, extensive investigation of pandemic evolution [45] coupled with the cumulative research of several groups [18], [20] suggest they are the most likely candidates.
Firm evidence indicates that the fifth and sixth cholera pandemics were caused by the classical biotype whereas the most extensive and ongoing seventh pandemic is caused by the El Tor biotype.
That led the authors to conclude that the virus might require "extensive evolution" to become pandemic.
Through an extensive review of influenza pandemic literature, we have provided support for our assumptions.
These results highlight the fact that, depending on the virulence and transmissibility of an emerging influenza pandemic virus, extensive transmission may occur in a closed setting and thus by implication in the community over and above the observed clinical disease.
The current plan to control influenza advocated by the World Health Organization promotes vaccine use and, in case of emergence of a pandemic virus, extensive use of antiviral drugs and vaccine, assuming that the vaccine could be produced in a timely fashion (41 ).
From an economic viewpoint, mitigating a pandemic could prevent extensive indirect economic losses.
The extensive divergence between the sixth pandemic and other toxigenic isolates studied indicates a long period since divergence from the common ancestor, which presumably occurred well before the sixth pandemic (1899 1923).
The identification of relevant measures within these categories was based on an extensive review of historical seasonal and pandemic influenza literature, including published articles and reports of surveillance data collected from the 1918 pandemic forward.
