Is another influenza pandemic coming soon?

Researchers investigate Spanish influenza sample found in WWI soldier's lungs.

[Mode of transmission] [Government planning for the big one]

May 1997

--- Of the 57,000 Americans who died in WWI, 43,000 died as a result of Spanish influenza.

WASHINGTON, D.C. — It was the fourth year of WWI, and Europe had been turned into a war-scarred landscape from the English Channel to the Crimea.

In that same year another threat began that would rival the war as the greatest killer in human history — Spanish influenza.

Recently, Defense Department scientists discovered a sample of lung tissue from the body of an American serviceman who died of the flu in 1918. Their hope is that the sample unlocks what made the virus so deadly and then helps in the prediction of future pandemics.

"If you look at the natural history of influenza epidemics, they do occur regularly,'' said Jeffery K. Taubenberger, MD, PhD, of the Armed Forces Institute of Pathology here and one of the authors of a new report in Science studying the 1918 pandemic. "If the records are any indication, yes there is another pandemic coming — the question is when?''

The 1918 pandemic found its way from the farmlands of the Midwest, where pigs had spread it to farm families — to every nation on earth, leaving 500,000 Americans and 21 million others dead. At one point, more than 10% of America's workforce was bedridden.

"This was an unusual type of virus,'' said Taubenberger. "The hallmark of the Spanish flu was its ability to selectively kill healthy young adults quickly.''

The virus swept the world in three waves during a two-year period, becoming more infectious with each new assault. In New York City alone, more than 20,000 people died during the fall of 1918. The virus spread so quickly that scientists later learned of entire Inuit villages in remote parts of Alaska completely wiped out by the virus. Even Western Samoa, an island in the South Pacific, was overwhelmed by the pandemic, losing 20% of its population in a short time. The only country on earth not affected greatly was Australia, which had strict quarantine regulations.

"You would have to go back to the Black Death to parallel this type of mortality,'' said Taubenberger.

Scientists of the period were at a loss to explain the pandemic and unable to provide sound medical advice for the world's population. But researchers looking at the virus now hope the dead soldier's lung tissue will provide the answers that so baffled their turn-of-the-century counterparts.

Taubenberger said a key in understanding the lethality of the virus is in its genetic coding.

"The virus carries its genes in eight pieces of RNA that are packed together in a protein coat — so far we have only looked at four of the pieces,'' he said. "It's a tedious process.''

Mode of transmission

One speculation was that the Spanish flu virus passed from birds to pigs and then onto humans, a mode of transmission thought to produce the most dangerous strains of influenza. It was not until recently, however, that Taubenberger's genetic analysis concretely supported the antibody evidence that the virus had in fact come from pigs.

Another hypothesis tested by Taubenberger was based on the chicken influenza virus that quickly annihilated chicken populations in the mid-1980's. The virus was peculiar because one of its proteins had three basic amino acids at a location where the host's enzymes had to break a protein for the virus to infect a cell. At that particular spot there should have been only one amino acid, said Taubenberger. So, the scientists pursued the notion that these three basic amino acids were clues to the virus's lethality and the possibility they were a feature in the 1918 pandemic. But the chicken flu also proved to be a dead end for researchers.

Taubenberger and his colleagues have spent nearly two years looking at the flu's viral RNA, assembling and sequencing it like a biological jigsaw puzzle, trying to determine what made it so lethal. The scientists reported on the sequences of eight fragments of the virus, including pieces of its major genes. So far, though, Taubenberger has analyzed only about 10% of the virus, but he is confident of eventually sequencing and diagramming the other 90% in the next two months.

According to military medical records, the epidemic seems to have swept America by the late spring of 1918, when doctors reported outbreaks in military training camps where young doughboys were drilling before heading overseas to fight in France.

"American soldiers brought the virus to Europe,'' Taubenberger said. "Many of the troopships were crammed with thousands of soldiers, many of whom were already sick when they embarked. The military's primary objective was to rush as many troops to France as quickly as possible. These ships became floating death traps.''

The rush to get American troops to Europe had a devastating impact on the fighting capabilities of the Army. Of the 57,000 Americans who died in WWI, 43,000 died as a result of Spanish influenza — 85% of all service-related deaths.

In his research, Taubenberger wanted lung tissue from someone who had died quickly, within a week of becoming ill, so particles of the virus might still be lurking. The scientists studied 35 cases, but only the dead soldier's tissue sample had enough of the virus left in it to be helpful. The sample belonged to a 21-year-old private who had no previous medical history. He died within five days of becoming infected. His lungs were autopsied by Army doctors and the tissue sent to Washington where it sat, untouched, for nearly 80 years.

Robert Webster, MD of St. Jude's Children's Hospital in Memphis, Tenn., another scientist hinting at a pandemic recurrence, concluded in a study he conducted that all the genes of the influenza viruses of the world are being maintained in the aquatic bird population, in gulls and ducks, and that periodically they are transmitted to other species, including pigs and humans.

"There's an enormous amount of influenza carried by birds," said Webster. "The pigs act as 're-assorters,' where the influenza viruses from humans and birds rearrange their genes and are then let loose upon the world again." The Asian and Hong Kong flu's were the result of this type of reassembling.

Some scientists argue that swine strains, appearing in 100 year cycles, forecast a repeat of the pandemic for sometime around the turn of the century. In the opinion of many experts, another pandemic will occur soon.

Government planning for the big one

Currently, there is an informal, 14-member government roundtable in Washington charged with planning for the next great pandemic. These representatives come from the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration, the DoD, Veteran's Administration and the National Institutes of Health. Although formed in 1993, the group's origins date back to the 1976 Swine flu "epidemic.'' Though the Swine flu did not take on the proportions of the Spanish flu, government officials became concerned because there was no plan to handle another pandemic on the scale of the one in 1918. This panel has yet to release a final plan for dealing with another outbreak, however. Its most recent effort is a 20-page conceptual plan put out in January of last year.

"This type of plan should be considered an evolutionary plan because its impossible to finalize something like this due to updates and changes from committee members and officials,'' said Peter A. Patriarca, MD, deputy director of the Division of Viral Products at the Food and Drug Administration.

Despite the seriousness of a potential pandemic, the group has been working without a formal budget; the panel members calling their efforts at predicting the next pandemic a "hobby.'' CDC researchers said this informal arrangement should continue for the next few years since their funding has been budgeted through fiscal 1998. The CDC has helped the committee with $200,000.

The panel has been working with local and state health officials on such issues as who gets vaccinated first and the nature of communication when the pandemic strikes. Other issues include whether to allow businesses and schools to open; how to provide care for house-bound victims; and whether masks should be worn to prevent transmission of bacteria, which health officials say may cause secondary infections.

"If the pandemic were to appear tomorrow, we would be ready to cope with it,'' Patriarca said.

For more information:

• Taubenberger J, Reid A, Krafft A, et al. Initial genetic characterization of the 1918 "Spanish" influenza virus. Science.1997;275:1793-6.

[Infectious Disease News Homepage]
[Current Issue] [Back Issues] [Breaking News]
[Online Seminar] [Specialty Forums] [Shopping Mall]
[Search]

Copyright 1997, SLACK Incorporated. Revised 2 June 1997.