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Avian Flu: Is a Pandemic Coming?

The editors of Journal Watch (General) present their selections for Top Medical Stories of 2005, beginning with a look back at the avian flu data that was published in 2004. Most authorities believe that an H5N1 human pandemic is likely, although how severe it might be is unknown.

Three avian influenza pandemics occurred in the 20th century. The 1957 and 1968 pandemics were caused by avian viruses that recombined with human flu viruses, creating viruses that were both virulent and easily transmissible among humans. In contrast, the 1918 virus was an avian virus that had not swapped genes with a human flu virus. Rather, it had mutated in some other way — still unclear — that allowed it to be transmissible among humans (Journal Watch Oct 14 2005).

Since a 1997 outbreak of bird and human disease caused by a new avian virus (called H5N1) in Hong Kong, people have feared that a new pandemic would emerge. Although the Hong Kong outbreak and several others were stifled by killing hundreds of millions of domestic poultry, the virus did not disappear. Indeed, since 2003, it has adapted to infect migratory birds and has spread to many Asian countries and to Europe. The H5N1 virus is virulent in birds and humans. More than 100 humans who were in close contact with sick birds have become infected with H5N1, and about half of them have died. So the good news is that the current H5N1 virus does not easily infect humans, but the bad news is that it’s lethal when it does (Journal Watch Feb 18 2005).

How bad could a pandemic be? The 1918 virus infected approximately 40% of the human race in a matter of months and had a mortality rate of about 2% to 3%, leading to 20–50 million deaths. In 2005, a team at the CDC reconstructed the 1918 virus, based on its RNA sequence, and tested its virulence in mice. All infected mice died, with their alveoli filled with mucin and blood cells — a pathological picture similar to that seen in humans who died in 1918. The virulence genes of the 1918 virus are similar to those of the current H5N1 virus (Journal Watch Oct 14 2005).

What can be done to prevent an H5N1 pandemic? In vitro, most strains are susceptible to oseltamivir (Tamiflu). However, a recent case report demonstrates that the virus can rapidly develop resistance to this drug (Journal Watch Nov 4 2005). Experimental vaccines have elicited an antibody response against H5N1, but that fact does not assure clinical efficacy. And, production of either antivirals or vaccine on the scale that would be required to protect the world population would take years.

Most authorities believe that an H5N1 human pandemic is likely, although how severe it might be is unknown. If H5N1 recombines with a human flu virus, it could produce less severe disease than if it leaps directly to humans, as the 1918 virus did. Some experts argue that the risk of a pandemic is overblown. They note that the technologies for diagnosis, treatment, and immunization today are vastly superior to the technologies available during the 20^th-century pandemics. They take comfort in the facts that H5N1, although now widespread, is not yet spread easily among humans and that all known past pandemics involved H1, H2, and H3 flu viruses, not H5 strains. Time will tell.

— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine December 30, 2005

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