If the 1918 flu pandemic broke out today, it would likely kill at least 62 million people, or slightly more than the number that die in a single year from all other causes combined. The estimate stems from a new tally of flu deaths from 1918 to 1920 in different countries, which varied widely. Based on their findings, authors of the study say that 96 percent of the victims of a present-day pandemic would be in the developing world.

The report comes on the heels of fears that the H5N1 flu virus currently circulating among birds in Southeast Asia and Africa may be the precursor to a deadly global outbreak or pandemic. To gauge the potential threat, researchers reviewed the toll of the most severe previous case, which occurred in 1918 when a flu swept the world, claiming at least 20 million lives. "It's the benchmark against which we worry about future flu pandemics," says population health researcher Christopher Murray of the Harvard Initiative for Global Health.

To determine the number of deaths from the 1918 flu, Murray and his colleagues reviewed the death registries from countries that kept good records between 1915 and 1923. They calculated the number of deaths from the flu in each country by subtracting the average death rate during the pandemic years from those of the years before and after. Most prior estimates relied on less credible figures, including eyewitness accounts, Murray says.

The number of dead in a modern pandemic could range from 50 million to 80 million, the group reports in a paper published online by The Lancet. To estimate the death toll if a pandemic struck today, they applied each country's 1918 death rate to its 2004 population. Their figure sets a plausible upper limit on deaths from a similar virus, Murray says. Researchers do not know, however, if the virus that causes the next pandemic will be more or less deadly than the one in 1918. As of late November the H5N1 virus had killed 154 people out of 258 confirmed cases, suggesting to researchers that it may be particularly deadly.

A country's income was the biggest predictor of its death toll, the group found. The fraction of additional deaths per year varied widely between locations, from 0.2 percent in Denmark to 7.8 percent in central India, "That's almost 40-fold variation across countries," Murray says. "A very surprising fraction of the amount of variation in the death rate is explained by one single variable--namely, income per capita."

Current strategies for pandemic flu preparedness include vaccination, antiviral drugs and antibiotics to treat pneumonia, which can set in after flu. "Most of those things aren't really going to reach the lowest income countries or even the poor in middle income countries," Murray says. Accelerating the introduction of new pneumonia vaccines to the developing world might help, he says. England's Institute of Medicine is studying whether simpler steps such as school closures and travel restrictions might also cut deaths.

Worried? You should be. If anything, the new estimate may be optimistic, writes epidemiologist Neil Ferguson of Imperial College London in an accompanying editorial. High incomes may not protect rich countries as much as Murray's group predicts, he cautions. The researchers estimate that the death rate in wealthier nations such as the U.S. would be three times less than in 1918 (when more than 500,000 died from the flu in the U.S.). And in poor countries, he writes, the prevalence of diseases such as HIV/AIDS and malaria might make them even more susceptible to flu than before.