Scientists who analyzed mortality records from the 1918 influenza pandemic estimate that a similarly severe pandemic today would kill about 62 million people worldwide, the vast majority of them in the developing world.

The authors, led by Christopher Murray, D Phil, MD, from the Harvard Initiative for Global Health, used data from areas that have reasonably complete statistics for the period from 1915 to 1923. They compared influenza mortality with per capita income and latitude in 27 countries, 24 US sates, and 9 Indian provinces.

The researchers used the data to estimate excess mortality for a hypothetical pandemic in 2004, the most recent year for which per capita gross domestic product data are available. The report appears in the Dec 23 issue of The Lancet.

For the 1918 pandemic, the researchers found a 31-fold difference between areas that had the lowest and highest excess mortality rates. Wisconsin´s excess mortality was 0.25%, while India´s Central provinces and Berar had a rate of 7.8% (7.8 extra deaths per 100 people).

The authors concluded that per capita income explained about half of the variance in pandemic mortality in the 1918 event. They determined that a 10% increase in income was associated with a 9% to 10% decrease in mortality. Latitude did not significantly affect mortality rates, so they did not use it to estimate 2004 mortality. Their examination of mortality rates by age and sex confirmed that flu deaths during the 1918 pandemic were concentrated in young adults, rather than elderly people.

The study yielded estimates for a 2004 event ranging from 51 million to 81 million deaths worldwide, with a median of 62 million. Ninety-six percent of the deaths were in developing countries. Southeast Asia accounted for 30%; Sub-Saharan Africa, 29%; East Asia, 19%, and the Middle East, 10%. Latin America, Eastern Europe/Central Asia, and the remaining developed countries each accounted for 4%.

The study´s median estimate for US deaths is 297,000—well below the 1.9 million that the Department of Health and Human Services has estimated would die in a 1918-like pandemic today.

"Most of the strong relation that we observed between per-head income and pandemic mortality must be mediated through factors such as nutritional status, comorbidity, community characteristics associated with poverty, and the effect of supportive care," the authors write.

Acknowledging the difficulty and uncertainty in estimating mortality, the authors say that though many experts use the 1918 pandemic for their upper limit, the next event could be even more severe. On the other hand, they write that a severe pandemic today might be blunted by improvements in medical care among people in high- and middle-income groups.

"Our results indicate that, irrespective of the lethality of the virus, the burden of the next influenza pandemic will be overwhelmingly focused on the developing world, as has been suggested for the 1918-20 pandemic," the article states.

A prudent approach would be to develop practical and affordable strategies for low-income countries, it says.

The conclusion that a severe pandemic would take a heavy toll only in developing countries was disputed by Michael T. Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site.

Osterholm asserted that a pandemic that disrupted industrial production and international transportation would acutely affect developed countries, because their economies depend on just-in-time supply shipments, their healthcare systems have almost no excess capacity, and about 80% of pharmaceutical products are produced offshore.

"We´ll be lucky to have 1918 medical care during a moderate-to-severe pandemic," he said. "There´s no basis that we would be better off."

Crisis management requires more than just money, and people in developing countries might be more resilient than those in rich countries in some ways, Osterholm said. For example, they might be more adept at coping with food shortages in a pandemic because they are likely to be skilled at subsistence farming.

Osterholm also noted that the estimate of 62 million deaths today is lower than some estimates of the death toll in the 1918 pandemic, when the world population was less than a third of what it is today. A 2002 study in the Bulletin of the History of Medicine estimated the 1918 toll at 50 million to 100 million.

In a Lancet editorial that accompanies the Murray study, Neil Ferguson, D Phil, of the Department of Infectious Disease Epidemiology at Imperial College in London, says the study´s projections may be optimistic.

Experts don´t know what effect an influenza pandemic would have on the 35 million people in the world who are infected with HIV, a virus that didn´t exist in 1918, Ferguson writes. In addition, he says, the relation between mortality and income that Murray and colleagues assume leads to a prediction of threefold lower mortality in the developed world than that seen in 1918, "perhaps a rather optimistic conclusion."

Ferguson writes that nonpharmaceutical public health measures such as school closures and mask-wearing might offer the best hope during a pandemic for countries lacking access to medical interventions.

Murray CJL, Lopez AD, Chin B, et al. Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918-20 pandemic: a quantitative analysis. Lancet 2006;368:2211-8

Ferguson N. Poverty, death, and a future influenza pandemic. (Commentary) Lancet 2006;368:2187-8