With the second wave of H1N1 infections having crested in the United States, leading epidemiologists are predicting that the pandemic could end up ranking as the mildest since modern medicine began documenting influenza outbreaks.

Experts warn that influenza is notoriously unpredictable, but several recent analyses, including one released late yesterday, indicate the death toll is likely to be far lower than the number of fatalities caused by past pandemics.

The predictions are being met with a mix of skepticism, relief and trepidation: Public health officials worry people may get complacent about getting vaccinated, which could prove disastrous if a third wave of infections swells later this winter or the virus mutates into a more dangerous form.

"I think it is very likely to be the mildest pandemic on record," said Marc Lipsitch, a professor of epidemiology at the Harvard School of Public Health, who led a federally funded analysis with researchers at the Centers for Disease Control and Prevention and elsewhere published online yesterday by the journal PLoS Medicine.

The analysis, based on data collected in New York City and Milwaukee, indicates that the virus might cause 6,000 to 45,000 deaths by the end of the winter, with the final toll falling somewhere between 10,000 and 15,000, Lipsitch said.

In the worst-case scenario, the swine flu pandemic would claim no more than about 60,000 lives, Lipsitch's new analysis concluded.

Even if the overall death toll does end up being relatively low, several experts noted that the pandemic has already taken an unusually high tally among children and young adults.

"We've had hundreds of deaths among children, which is a tragedy any way you look at it," said Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases.

A typical flu season is associated with an average of 36,000 deaths in the United States, and an estimate released in August by a presidential advisory panel that Lipsitch was involved in predicted the 2009 H1N1 virus could kill between 30,000 and 90,000 Americans.

"Those were the best estimates we could make at the time based on the data available at the time," Lipsitch said. "We now have much better data to make estimates from."

When the presidential council's estimate was made, experts thought the virus could make up to 30 percent of the population sick. So far the virus appears to be causing symptoms in much smaller proportion, perhaps 15 percent, Lipsitch said.

'QUITE MILD'

The new analysis also indicates that the pandemic's "symptomatic case-fatality ratio" — the percentage of those who become ill that die — has been lower than the previous three pandemics.

"If things continue as they've gone so far, this could turn out to be quite mild," said Ira Longini, a professor of biostatistics at the University of Washington in Seattle who has calculated a similarly low case-fatality rate based on CDC data. Several experts praised the new analysis as the most sophisticated, and therefore reliable, to date.

Others, however, cautioned that previous pandemics have produced deadly late-winter waves, which could occur in this case, pushing up the death toll dramatically. More older people could also start to get infected, which could also increase the toll.

To encourage Americans to continue to get vaccinated, Health and Human Services Secretary Kathleen Sebelius yesterday unveiled a new advertising campaign aimed at countering complacency. After a slow start, more than 80 million doses of vaccine are now available, she said.

"We have to seize this opportunity as disease is going down slightly to remind folks how important this is," Sebelius said.

ELDERLY SPARED

One major reason for the relatively low death toll is that the elderly, who tend to be most vulnerable to dying from complications from the flu, have largely been spared so far, apparently because many have some immunity against the disease. The 36,000 deaths blamed on a typical flu season include many that are actually caused by heart attacks, strokes and other complications associated with the flu among the elderly and people with other health problems. Only about 9,000 deaths are directly caused by the flu virus during a typical flu season.

But other factors may also be playing a role, including the virus being less likely to cause illness and severe illness than viruses involved in previous pandemics as well as better medical care available than in previous decades, such as antiviral drugs and more sophisticated intensive care techniques.

"In 1918 it was really prehistoric medical care," Howard Markel, director of the Center for the History of Medicine at the University of Michigan, said. "In 1957, we really didn't have intensive care. In 1968 we were starting to have it but it was nothing like we have today."