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 the flu is notoriously unpredictable, but several recent analyses, including one released late Monday, indicate that 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 that people may become 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, an epidemiology professor 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 Monday by the journal PLoS Medicine.
The analysis, based on data collected in New York City and Milwaukee, indicates that the virus may directly cause 6,000 to 45,000 deaths by the end of the winter, with the final toll probably falling between 10,000 and 15,000, Lipsitch said. In the worst-case scenario, the swine flu pandemic would kill no more than about 60,000 people, his new analysis concluded.
'Hundreds of deaths among children'
Several experts noted that even if the overall death toll does end up being relatively low, the pandemic already has taken an unusually high number of 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 that the 2009 H1N1 virus could kill 30,000 to 90,000 in this country.
"Those were the best estimates we could make at the time based on the data available at the time," he 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 a much smaller proportion, perhaps 15 percent, Lipsitch said.
The new analysis also indicates that the pandemic's "symptomatic case-fatality ratio" — the percentage of those who become ill and die — has been far 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 M. Longini Jr., 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.
"From what we know now, it would appear this is the mildest, both compared to 1968 and 1957 and certainly 1918," said Neal M. Ferguson, an epidemiologist at Imperial College in London who advises the World Health Organization and the Health and Human Services Department. The pattern appears to be consistent in other developed countries, such as Britain, he noted.
Deadly late-winter wave?
Others, however, cautioned that previous pandemics have produced deadly late-winter waves, which could occur in this case. More older people could also become infected, which could also increase the toll.
"I would hold my horses until we are through the winter," said Lone Simonsen, a research professor at George Washington University.
To encourage Americans to continue to get vaccinated, Health and Human Services Secretary Kathleen Sebelius announced a new multimedia advertising campaign Monday 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," she said. Lipsitch
While agreeing that people should continue to be inoculated, Lipsitch and others said they doubt that a major increase in deaths would occur in a third wave without some significant shift in the virus.
"There's a faint possibility," Ferguson said. "But I don't think there will be a major change."
Elderly largely unaffected
One major reason for the relatively low death toll is that the elderly have largely been unaffected, apparently because many have some immunity against the disease. The 36,000 deaths blamed on a typical flu season include many that are caused by heart attacks, strokes and other complications associated with the flu among seniors and people with other health problems. About 9,000 deaths are directly caused by the influenza virus during a typical flu season.
"Sometimes Mother Nature throws us a break," said Howard Markel, director of the Center for the History of Medicine at the University of Michigan.
But other factors may also be playing a role, including the virus being less likely to cause 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," Markel 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."
Nonetheless, Lipsitch and others stressed that the multibillion-dollar vaccination campaign and other intense responses were appropriate, given the uncertainty of what the nation and world was facing.
"We got lucky," Lipsitch said. "But if we didn't have a plan in place and we had 60,000 or 70,000 deaths, people would have been justifiably outraged."