U.S. cities slowed the spread of the 1918 pandemic flu by measures such as closing schools and churches and banning mass gatherings, thereby reducing the severity of outbreaks in certain locations, according to a pair of new studies. A few cities appear to have reduced flu transmission so well that they lifted the control measures too early and allowed the virus to spread rapidly again. Researchers say that such practices could, in principle, limit the death toll of a future pandemic, but authorities would have to implement them early and long enough.

Researchers fear that H5N1, the bird flu virus that has so far sickened 288 people and killed 170, may eventually begin jumping from person to person, sparking a catastrophic global flu pandemic. Their best guide to what the worst-case scenario might look like is the 1918 pandemic, which killed an estimated 500,000 to 675,000 people in the U.S. and spurred cities such as New York, Chicago and San Francisco to impose public health measures (nonpharmaceutical interventions) to keep people from transmitting the flu virus to one another.

"The conventional wisdom about 1918 was that nonpharmaceutical interventions had not worked," says Richard Hatchett, an associate director for emergency preparedness at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. But Hatchett and his colleagues compared 17 cities that instituted a variety of measures, including closing schools, churches and theaters, isolating the sick, staggering business hours and allowing only private funerals, typically for two to eight weeks.

They found that timing was critical. Cities such as St. Louis that had intervened within a few days of the first reported cases had a peak weekly death rate about half that of cities like Philadelphia, which had waited a week or more, the group reports. A lower peak death rate implies that the epidemic in those cities was less intense, and therefore placed less of a strain on their medical and other resources, Hatchett says. The early responders also had 20 percent fewer deaths overall than other cities.

Closures of schools and other public places were the most effective types of intervention, the group reports in this week's Proceedings of the National Academy of Sciences USA. The results are consistent with a second study appearing in the same issue, by mathematical epidemiologists Neil Ferguson of Imperial College London and Martin Bootsma of Utrecht University in the Netherlands, who found a similar pattern in 23 cities.

Using a mathematical model of flu transmission, Ferguson and Bootsma estimate that 16 of these cities—the ones with the best surviving records of when their interventions began and ended—saw 10 to 30 percent fewer deaths than they would have, had the virus spread unhindered. The cities that slowed transmission most effectively, they found, were San Francisco, St. Louis, Milwaukee and Kansas City, Mo.—all of which showed a second peak in their weekly death rates, apparently because they had lifted their controls too soon, allowing the virus to spread again.

"Largely they were just delaying the inevitable," Ferguson says. A flu epidemic has to sicken about 50 percent of a population before the group as a whole is resistant enough to the virus to stop its spread, he says, "so when you lift the interventions you get transmission again." But interventions can prevent the virus from spreading like wildfire and causing extra deaths, he says.

Hatchett notes that cities today would have to enforce their interventions for longer than two to eight weeks against a 1918-level outbreak. Guidelines published by the Centers for Disease Control and Prevention in February recommend closing schools for up to 12 weeks in the case of a severe pandemic.

The experts are split on whether countries such as the U.S. and U.K. would be able to intervene successfully, should H5N1 or another flu virus make the jump to pandemic. Modern economies are more interconnected and reliant on "just in time" stocking, Ferguson says. "It's much less clear we could cope for the same amount of time," he says, while waiting for a vaccine.

Hatchett is more upbeat. "It wasn't easy for these cities either," he says. "They were in the middle of a world war…. I would be optimistic that we could do at least as well as cities did in 1918, and possibly quite a bit better."