Most deaths in the 1918 influenza pandemic were due not to the virus alone but to common bacterial infections that took advantage of victims' weakened immune systems, according to two new studies that could change the nation's strategy against the next pandemic.
"We have to realize that it isn't just antivirals that we need," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases and coauthor of one study. "We need to make sure that we're prepared to treat people with antibiotics," 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In both studies, scientists analyzed a trove of historical documents from around the world, examining firsthand accounts, medical records and autopsy reports.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 deaths were swift, which is what scientists believed characterized a viral pandemic. Instead, they found most deaths occurred a week to two weeks later -- indicating the deaths were the result of opportunistic bacterial infections.
Most of the bacteria recovered from patients, dead or alive, are common colonizers of the noses and throats of healthy people, according to coauthors Dr. John F. Brundage, a medical epidemiologist at the Armed Forces Health Surveillance Center in Silver Spring, Md., and Dr. G. Dennis Shanks, director of the Australian Army Malaria Institute in Queensland.
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 the globe, killing an estimated 50 million people, striking down young, healthy adults even though influenza usually kills the very young, the elderly and the chronically ill.
It has long been recognized that most flu deaths are due to pneumonia caused by secondary bacterial infections.
But to explain the 1918 pandemic's unusual virulence, many scientists had come to believe the virus killed 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 in mice and 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 of them, and scientists fear that it could mutate easily from human to human instead of bird to human.
The two new studies suggest the 1918 virus did induce severe immune reactions, particularly among young adults. But what made the reaction so deadly was that it destroyed the lining of the respiratory system, making it easier for bacteria to infect the lungs.
In most infected populations, Brundage and Shanks found less than 5% of flu deaths occurred within three days of the illness' onset. The median time from the onset of symptoms until death was 7 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 the flu pandemic deaths could have been the result of a polymicrobial infection -- a co-infection by multiple microbes.
"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 stockpiling vast quantities of vaccines and antiviral drugs to combat future pandemic flu strains.
Fauci said scientists also needed to develop new antibiotics as well as vaccines against bacteria, especially against a virulent strain of Staphylococcus aureus that has been linked to seasonal flu deaths and is resistant to many antibiotics.