CHANCE TO APPROVE THE FINAL MS. WE WILL PROVIDE SUCH APPROVAL AS SOON AS POSSIBLE.

We have estimated that the basic reproduction number (R0) – the mean number of secondary infections created by a single case in a fully susceptible population – for pandemic influenza in US cities in 1918 was in the approximate range 2-3-- less than previous estimates, less than that of many other respiratory infections, and less than or equal to that of SARS in 2003. We discuss the main findings of this study here. Even with such a modest value of R0, containment of pandemic influenza would be extremely challenging, since the methods successful in controlling SARS, which depended heavily on identification and isolation of cases, would be much less effective against pandemic influenza, in which transmission occurs more rapidly after infection and before or just at the onset of symptoms. Moreover, biological and probabilistic considerations suggest that, if an influenza pandemic is likely in a given period of time, multiple introductions of strains capable of pandemic spread must also be anticipated. Hence, preparation for a pandemic must proceed on the assumption that multiple introductions are possible. Because vaccines are the only major transmission-blocking measure that is effective against repeated introductions, we argue that the capacity to produce vaccines rapidly and in sufficient quantities to immunize a large majority of the population is the most urgent priority in pandemic preparedness. The modest values of R0 estimated for pandemic influenza, furthermore, make it likely that such an effort could make it possible to block transmission in a population immunized with achievable levels of coverage