An influenza pandemic of the type that ravaged the globe in 1918 and 1919 would kill about 62 million people today, with 96 percent of the deaths occurring in developing countries.
That is the conclusion of a study published yesterday in the Lancet medical journal, which uses mortality records kept by governments during the time of "Spanish flu" to predict the effect of a similarly virulent outbreak in the contemporary world.
The analysis, the first of its kind, found a nearly 40-fold difference in death rates between central India, the place with the highest recorded mortality, and Denmark, the country with the lowest. The reason for the huge variation is not known, but it may reflect differences in nutrition and crowding.
If a modern Spanish flu killed all its victims in one year, it would more than double global mortality. About 59 million people now die each year.
"It is a huge, huge number," said Christopher J.L. Murray, a physician and biostatistician at the Harvard School of Public Health who headed the study. "This really took us by surprise."
One of the World Health Organization's key influenza experts, however, called the main public health implication of the study "no surprise."
"The countries most likely to be adversely affected are the ones with the least resources. This happened then, and is what is likely to happen now," said Keiji Fukuda. "WHO, as it always has done, pays a disproportionate amount of its attention and efforts toward such countries."
Historical accounts suggest that what became known as Spanish flu emerged at an Army camp in Kansas in early March 1918. It was carried to Europe by American troops, where it circulated before undergoing a change early the next fall that made it unusually lethal. It spread around the world and was brought back to the United States, where it killed hundreds of thousands of Americans in October and November 1919. It circulated until early 1920, with virtually everyone on Earth eventually exposed to the virus.
The global death toll from the pandemic is unknown. In the 1920s, it was estimated to be about 20 million. A more complete analysis in 1991 raised that to 30 million. One in 2002 said mortality "may fall in the range of 50 to 100 million."
The new study doesn't make a new estimate. Instead, it calculated the death rate in places that had good birth and death records in 1918 and 1919 in order to estimate what would happen in a larger, older and relatively more affluent world population nearly a century later.
The places with good records included most European nations, the United States, Canada, Australia, Japan and several Latin American countries. The keys to the project, however, were accurate death registries in India, Sri Lanka, Taiwan and the Philippines. They allowed Murray and his colleagues to estimate what happened among the world's non-European poor, where eyewitness accounts describe huge mortality, but few reliable statistics existed.
By far the most informative data came from India.
"The British colonial administration -- they were very good record-keepers," said Murray, who noted that India's contemporary death registries are less complete than ones from 1918.
The researchers compared the death rates during the 1918-1920 period with those in the three years before and after the pandemic. This gave an estimate of "excess mortality" during the flu years, which was assumed to be caused directly or indirectly by the virus. (Because men in countries fighting in World War I had elevated mortality in 1918, they were excluded from the calculation.) The extra deaths ranged from 0.2 percent of the population in Denmark to 7.8 percent in the Central Provinces and Berar region of India -- a 39-fold difference.
In the United States, they ranged from a low of 0.25 percent in Wisconsin to 1 percent in Colorado. (The best-known work of fiction about the pandemic, "Pale Horse, Pale Rider," is Katherine Anne Porter's account of her near-death experience during the Colorado outbreak.) Flu death rates varied greatly over short distances. Virginia's excess mortality, 0.47 percent, was well below Maryland's, 0.72 percent. Sweden's (0.66 percent) was three times Denmark's (0.2 percent).
Murray and his colleagues analyzed the death patterns and deduced that about half the variation from region to region was explained by differences in per capita income. For every 10 percent increase in income, a person's risk of dying during the pandemic fell 10 percent.
Why the poor were so vulnerable is unknown. It could have been that many were already ill with parasites or other illnesses or lacked micronutrients such as Vitamin A and zinc that are essential to immunity.
To estimate the effects of a modern Spanish flu, the researchers applied the 1918-1920 death rates to the current world population broken down by income, sex and age. They came up with a range of 51 million to 81 million deaths, with a median of 62 million.
Even though the world's population is three times what it was during the Spanish flu pandemic, the estimated mortality of a modern Spanish flu isn't three times what it was in 1918. That is mainly because per capita income is higher now -- and the higher the income, the lower the risk of dying of influenza.
The illness caused by the 1918 virus was largely untreatable. There were no antiviral drugs, no mechanical ventilators to help people breathe and no antibiotics to treat bacterial pneumonias that often set in after the viral infection. All are available now and would reduce the death toll, though some interventions would be in sort supply during a pandemic.