The 1918 Spanish Flu pandemic may be ancient history to most of us but medical researchers are still learning valuable lessons from it.

Why? Because whether it is SARS or Bird Flu or another culprit, the odds are that some day soon, we will be faced with another pandemic caused by a virus similar to the one that killed millions across the globe in 1918.

One of the great mysteries of the 1918 pandemic is why it was so much more deadly in some places than in others. For example, why was St. Louis spared the fate of hard-hit cities like Philadelphia, when both implemented similar public health measures?

What made the difference, according to two new studies, was not only how but how fast different cities responded.

Cities where public health officials imposed strict containment measures such as quarantine, crowd-control and mask-wearing within a few days after the first local cases, had peak weekly death rates less than half of those in cities that waited just a few weeks to respond. Overall mortality was also lower in cities that took early action.

These conclusions — the results of systematic analyses of historical data — are described in two articles published online in the April 2007 Proceedings of the National Academy of Sciences.

"These important papers suggest that a primary lesson of the 1918 influenza pandemic is that it is critical to intervene early," says Anthony S. Fauci, M.D., director of NIH's National Institute of Allergy and Infectious Diseases (NIAID), which funded one of the studies. "While researchers are working very hard to develop pandemic influenza vaccines and increase the speed with which they can be made, nonpharmaceutical interventions may buy valuable time at the beginning of a pandemic while a targeted vaccine is being produced."

The historical analyses are part of an ongoing effort called the Models of Infectious Disease Agent Study (MIDAS), which is supported by NIH. Through MIDAS, researchers have developed computer models to examine how a future pandemic influenza virus might spread and what interventions could minimize the impact.

The ideal way to contain a potential influenza pandemic would be to vaccinate large numbers of people before they were exposed to an influenza virus strain that is easily transmitted from person to person. Developing such a vaccine in advance, however, is difficult because an influenza virus mutates as it replicates, and over time these mutations can change the virus enough so that older vaccines are no longer effective. With current technologies, it would take months to develop a new vaccine after the first cases of pandemic influenza appear.

Nonpharmaceutical measures helped limit the spread of the virus by restricting social gatherings where person-to-person transmission can occur. Schools, theaters, churches and dance halls in cities across the country were closed. Kansas City banned weddings and funerals if more than 20 people were to be in attendance. New York mandated staggered shifts at factories to reduce rush hour commuter traffic. Seattle's mayor ordered his constituents to wear face masks. Both studies showed that while these interventions effectively held down the transmission of influenza virus in 1918, the critical factor was how soon the measures were put in place.

Officials in St. Louis introduced a broad series of public health measures to contain the flu within two days of the first reported cases. Philadelphia, New Orleans and Boston all used similar interventions but took longer to implement them. As a result, peak mortality rates were higher. In the most extreme diffrence, the peak mortality rate in St. Louis was only one-eighth that of Philadelphia, the worst-hit city in the survey. In contrast to St. Louis, Philadelphia imposed bans on public gatherings more than two weeks after the first infections were reported. City officials even allowed a city-wide parade to take place prior to imposing their bans.

The fact that the early, nonpharmaceutical interventions were effective at the height of the pandemic can help pandemic planners today, the authors of both studies say. In particular, the two studies lend weight to guidance that the Centers for Disease Control and Prevention recently released on the use of nonpharmaceutical interventions during a pandemic (, which recommends precisely such a rapid early response.