Conference organized by:

Center for Biosecurity of UPMC

World Health Organization Communicable Disease Surveillance and Response Office

Conference sponsored by:

The Nuclear Threat Initiative

Influenza: A Developing Crisis
Presenter: Robert G. Webster, Ph.D.

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Dr. Webster came to Lyon directly from Vietnam, a trip that took less time than the incubation period of H5N1, meaning that, theoretically, he could have been carrying the seed of a new pandemic—a sobering thought he shared with the group. The 1918 pandemic which, he stated, killed 100 million people, resulted from an avian influenza virus that had evolved to a form capable of efficient human-to-human transmission and that had a much lower human mortality rate than the current H5N1 strain. Influenza A viruses can evolve by exchanging genes (reassortment) or without reassortment by virtue of the constant mutation that occurs with each replication of an influenza virus. The 1918 virus evolved without reassortment. The other pandemics of the 20th century (1957 and 1968), he noted, were due to reassortment between avian viruses and circulating human influenza viruses, and Webster explained that there is significant evidence that the 1977 H1N1 pandemic was due to an accidental lab release, as it was genetically identical to a strain that circulated naturally decades before.

Whether the current H5N1 strain reassorts with a human adapted influenza strain or simply evolves efficient human to human transmission through mutation, the risk of a pandemic from this virus is very real, Webster said. He traced the evolution of H5N1 over the last 8 years, highlighting the chain of multiple episodes of reassortment resulting in the current dominant "Z" genotype. This virus readily infects pigs but, at least at the moment, cannot be transmitted by them. He pointed out the expanding host range of this strain, including tigers and domestic cats, and the rapid evolution of the virus in ducks.

Reverse genetic techniques are being used to develop vaccines and to understand the molecular basis of disease caused by influenza viruses. This technique employs plasmids to insert genetic material from one virus into another. In so doing, a new virus is created that expresses some, but not all, of the characteristics of the original virus. Thus, a benign virus can be created that carries the surface antigens of the pathogenic virus. A vaccine developed using this technology is currently being tested. While this vaccine may or may not be a perfect match for whatever H5N1 strain develops in the near future, the hope is that it will impart sufficient immunity to prevent death, if not infection, should a human epidemic occur. While much has been learned about the H5N1 virus, key information—such as the determinants of transmissibility—has yet to be elucidated.

The only antiviral treatment for the current strain is oseltamivir. Since 1997, H5N1 has developed resistance to amantidine due to its use in chicken feed. In order to reduce the risk of resistance to oseltamivir, Dr Webster advocates limitation of its use for routine influenza. He also advocates the large scale stockpiling of oseltamivir.

- Summary by Eric Toner, M.D. 

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