October 02, 2006
1918 Influenza Death Toll From Excessive Immune Response

H5N1 avian flu might have the potential to mutate into a killer epidemic. So an understanding of how the most lethal modern flu epidemic killed its victims may yield information that'll help protect us. Reconstructed 1918 Influenza viruses delivered into lab mice in biosafety level 3-enhanced laboratory at the CDC in Atlanta caused run-away inflammation that explains the lung damage seen in 1918 flu victims.

Unlike typical seasonal flu, which strikes hardest at the very young, the elderly and those with compromised immune function, the 1918 flu disproportionately killed young people in the prime of life. Modern analyses of 1918 flu victim autopsy samples show extreme and extensive damage to lung tissues. This observation gave rise to the hypothesis that the 1918 flu virus infection provoked an uncontrolled inflammatory response leading to rapid lung failure and death.

To test this idea, Dr. Tumpey infected mice intranasally with one of four types of flu virus: human seasonal flu virus from a strain that circulated in Texas in 1991; lab-made viruses containing either two or five of eight viral genes from the 1918 virus; or a reconstructed virus containing all eight 1918 flu virus genes. Lung tissue from three infected mice in each group was removed on days 1, 3 and 5 post-infection and processed to destroy any virus. The mouse genetic material (RNA) was then extracted from these lung samples and sent to the University of Washington team for analysis.

Drs. Katze and Kash and colleagues examined the mouse RNA using microarrays to determine which genes were activated when exposed to each of the four viruses. This analysis showed that the immune response to the reconstructed 1918 virus containing all eight flu genes was much greater than to any of the other viruses with all eight genes, says Dr. Katze. In particular, genes involved in promoting inflammation were strongly and immediately activated following infection by the reconstructed 1918 virus. "We clearly see a dramatic and uncontrolled immune response in the mouse lungs as early as one day following infection with the reconstructed 1918 virus," he says. A complete understanding of the host's response to the 1918 flu virus, adds Dr. Katze, requires use of a fully reconstructed virus.

If the H5N1 bird flu virus mutates into a form easily transmissible between humans it might cause death by the same general mechanism. If that turns out to be the case then many of those who get infected and manage to recover are probably going to live with some permanent damage to their bodies. Severe inflammation is going to leave behind damaged and scarred tissue.

If a highly lethal flu pandemic breaks out your best bet is to isolate yourself for months while vaccine production gets ramped up. Whether you go into solitary isolation or as part of a family, group of friends, or small job work team, cut yourself off from the chains of transmission of the virus. If you need to go to stores or meetings use N95, N100, or P100 face masks. Avoid touching surfaces. Try to avoid going in-doors with people who are not in your personal isolation group.

If you want to prepare for a pandemic here are my top suggestions:

  • Have at least 3 months of food and of anything else you would use over a period of a few months.
  • Stockpile some N95 and N100 face masks.
  • Build up your savings. Be able to pay the rent or mortgage and other bills for months without going to work.
  • If you have a lot of money get a self-contained place you can retreat to that is in a rural area.

If you can isolate yourself you won't get infected. It is as simple as that.

The longer we go without a flu pandemic the less the risk of an eventual pandemic killing any of us. Drugs that prevent extreme inflammation response will be found. Methods to scale up vaccine production more rapidly are on the way too. In 10 years I do not expect pandemic flu strains to pose a major threat to industrialized countries. We'll have the biotechnologies needed to protect ourselves pretty rapidly from deadly strains of influenza.

Share |      Randall Parker, 2006 October 02 04:54 PM  Dangers Natural Bio

BBM said at October 3, 2006 6:05 PM:

We're also much better at modulating the immune system than in 1918, and good supportive intensive care really has only been around for a few decades.

Randall Parker said at October 3, 2006 6:22 PM:


In a major pandemic I doubt there'd be intensive care beds for even 5% of the seriously ill.

Modulating the immune system: Yet so far the death rate from H5N1 has been quite high for the rare cases even where modern medical treatments were available.

Your best bet is isolation to avoid exposure.

remo williams said at October 3, 2006 7:52 PM:

It makes one realize how much better off the world is if the flu hit in 2017 instead of 2007. (I don't think Asian flu will turn into an epidemic, but other bad news might be out there....)

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