Most deaths in the 1918 influenza pandemic were caused not by the virus alone but by common bacterial infections that overwhelmed victims’ weakened immune systems, according to two new studies that could change the strategy against the next pandemic.

“We have to realize that it isn’t just antivirals that we need,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and co-author of one of the studies.

“We need to make sure that we’re prepared to treat people with anti-biotics,” said Fauci, whose study will be released online this month by the Journal of Infectious Diseases.

In both studies, scientists analyzed a trove of historical documents from around the world, examining firsthand accounts, medical records and autopsy reports.

Writing about the 1918 influenza outbreak in the August issue of the journal Emerging Infectious Diseases, researchers reported that few of the deaths were swift.

Instead, they found that most of the deaths occurred a week to two weeks later — indicating opportunistic bacterial infections.

Most of the samples collected from patients, dead or alive, were bacteria common to the noses and throats of healthy people, according to co-authors Dr. John Brundage, a medical epidemiologist at the U.S. Armed Forces Health Surveillance Center in Silver Spring, Md., and Dr. G. Dennis Shanks, director of the Australian Army Malaria Institute in Queensland, Australia.

Both groups of researchers were trying to understand why the 1918 virus — a novel strain of influenza for which few people had natural immunity — was so lethal.

The virus swept around the globe, killing an estimated 50 million people, striking down young, healthy adults even though influenza usually kills infants, the elderly and the chronically ill.

It long has been recognized that most flu deaths are the result of pneumonia caused by secondary bacterial infections.

But to explain the 1918 pandemic’s unusual virulence, many scientists had come to believe that the virus caused death by provoking an overzealous, destroy-the-village-to-save-it immune response, especially in young adults with robust immune systems.

In a previous experiment, scientists reconstructed the 1918 virus — using a genetic blueprint pieced together in 2005 from scraps of frozen DNA — and injected it first into mice and then into monkeys. The animals’ immune systems responded violently, inflaming and flooding their lungs with blood and fluids, essentially drowning them.

A similar overkill response has been seen in deaths from the ongoing avian flu outbreak that began in Asia. Capable of jumping the species barrier, the H5N1 virus has infected 385 people, killing 243, and scientists fear that it could mutate to spread easily from human to human.

The two new studies suggest that the 1918 virus did induce severe immune reactions, particularly among young adults. But what made the reactions so deadly was the destruction of the respiratory system’s lining, which is easier for bacteria to infect the lungs.

In most infected populations, Brundage and Shanks found less than 5 percent of deaths occurred within three days of onset. The median time from onset of flu symptoms until death was seven to 10 days. A significant number died two weeks after their initial symptoms, which is typical of bacterial pneumonia.

Michael Katze, a University of Washington virologist who was a lead scientist in the mice and monkey experiments, said the animals’ violent and rapid immune response made it “almost unreasonable” to expect victims of the 1918 virus to live long enough to develop secondary infections.

But he acknowledged that the pandemic could have been the result of a polymicrobial infection.

“Certainly the idea that resident bacteria flora already present could play a role in developing pneumonia is relatively reasonable,” he said. “If the 1918 flu had any impact that compromised (immune) function, it could render a normal resident bacteria pathological.”

So far, public health officials around the world have focused on producing and stockpiling vast quantities of antiviral drugs to combat future pandemic flu strains.

Fauci said scientists also need to develop new antibiotics and vaccines against bacteria, especially against a virulent strain of Staphylococcus aureus that has been linked to seasonal flu deaths worldwide and is resistant to many antibiotics.