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Mystery of 1918 flu pandemic solved

Scientists identify key factor in switch from birds to humans

Tim Radford, science editor
Friday February 6, 2004
The Guardian

British scientists have solved a secret of an avian flu virus which killed up to 40 million people worldwide 86 years ago. They now know more about how a disease of birds switched to humans to trigger the most lethal outbreak in history.

A team from the National Institute for Medical Research at Mill Hill, north London, used pathological samples taken from victims of the Spanish influenza pandemic of 1918 to recreate the structure of a haemagglutinin protein vital in the leap between species.
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Flu kills thousands of Britons every year but those most at risk are the elderly, the very young or those suffering from some other illness.

But the 1918 strain was different: it hit the young, healthy and well nourished of neutral countries as fiercely as it ravaged the refugee camps in wartorn Europe.

It first appeared in March 1918 in a military camp in Kansas, in the US, and 522 soldiers were ill within two days. In the end it killed about 700,000 people in the US and about 230,000 in Britain. The French called it la grippe, the Russians, "the Spanish lady". Mortality rates were huge: in some communities up to 70% died. The virus disappeared within 18 months as mysteriously as it came, leaving 20-40 million dead.
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As their lungs filled … the patients became short of breath and increasingly cyanotic. After gasping for several hours they became delirious and incontinent, and many died struggling to clear their airways of a blood-tinged froth that sometimes gushed from their nose and mouth. It was a dreadful business.

--Isaac Starr, 3rd year medical student, University of Pennsylvania, 1918.

By the fall of 1918 a strain of influenza seemingly no different from that of previous years suddenly turned so deadly, and engendered such a state of panic and chaos in communities across the globe, that many people believed the world was coming to an end. It struck with amazing speed, often killing its victims within just hours of the first signs of infection. So fast did the 1918 strain overwhelm the body's natural defenses, that the usual cause of death in influenza patients---a secondary infection of lethal pneumonia---oftentimes never had a chance to establish itself. Instead, the virus caused an uncontrollable hemorrhaging that filled the lungs, and patients would drown in their own body fluids.

Not only was the Spanish Flu strikingly virulent, but it displayed an unusual preference in its choice of victims---tending to select young healthy adults over those with weakened immune systems, as in the very young, the very old, and the infirm. The normal age distribution for flu mortality was completely reversed, and had the effect of gouging from society's infrastructure the bulk of those responsible for its day to day maintenance. No wonder people thought the social order was breaking down. It very nearly did.

But at the close of the First World War, when Spanish Flu appeared, the world was a very different place. Since then, outstanding advances in our knowledge of the germ world have been made, adding dramatically to our repertoire of medical wizardry. Surely what happened back then couldn't happen again.

Or could it?

During the 1918-1919 fall period the number of Americans who died from influenza is estimated at 675,000. Of those, almost 200,000 deaths were recorded in the month of October 1918 alone. Worldwide, the mortality figure for the full pandemic is believed to stand somewhere between 30 to 40 million. So, with the world population today having more than tripled in the intervening years, what is to stop a modern flu pandemic from claiming upwards of 100 million lives? The answer, it seems, is nothing at all.

Today, of course, we have vaccines and antiviral drugs. But in the Third World, at least, these combatants are in very short supply. In India, where the Spanish Flu is thought to have culled more than 10 million from the population, public health care is still notoriously deficient. In China, with a population one third larger again, the situation is not much better. Even for developed countries, where vaccines are readily available, the fraction of the population that routinely subjects itself to inoculation generally hovers around 10 percent. In the event that the public were to receive adequate warnings of an impending pandemic, it's likely of course that this number could be significantly increased. But even then, it may not matter. By their nature pandemics tend to take us by surprise. The next influenza strain that ravages the human population will probably not be the one we were planning to encounter.