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The influenza virus wreaks havoc on our healthcare system and infrastructure and regularly requires significant public health resources for the fairly predictable seasonal influenza, and in addition in an unpredictable manner for pandemic influenza. The influenza virus and its epidemiology create optimal conditions for the development of an unanticipated pandemic of unforeseeable severity.

Influenza viruses, 0.08–0.12 microns, belong to the Orthomyxoviridae family and can be classified as types A, B, C, and D. Influenza A and B viruses cause seasonal influenza whereas only influenza A viruses have resulted in pandemics. Influenza C is infrequently recognized as causing relatively mild respiratory disease in humans and is not included in routine influenza virus testing. Influenza D is newly recognized and shares about 50% homology with influenza C.

Influenza A viruses are subclassified based on two surface glycoproteins—hemagglutinin (HA) and neuraminidase (NA). There are currently recognized 18 subtypes of HA (designated H1-18) and 11 subtypes of NA (N1-11). These subtypes circulate in birds. Influenza A(H1N1), A(H2N2), and A(H3N2) have caused seasonal influenza outbreaks. Influenza B has no recognized animal reservoir. The unique features of the influenza A viruses—their ability to undergo antigenic change and ability to infect other species—contribute to their threat as a novel pandemic virus.

Newer scientific methods have permitted the study of past pandemics that was not possible at the time of occurrence or even decades ago. With the recent attention to the 100th anniversary of the 1918–1919 influenza pandemic, it is instructive to look at influenza as a model of a pandemic pathogen that might prove useful in preparing for future pandemics.


Human influenza viruses are transmitted from person to person via the respiratory tract by coughing and sneezing. Small particle aerosol, large droplet, and fomite are all potential routes of infection. Species of influenza viruses from animals could reach humans via the same routes.

Birds, such as migratory waterfowl, can become infected by influenza viruses. The avian illness may be very mild or asymptomatic; virus shed in the feces has the potential to infect domestic poultry, swine, horses, and marine mammals, which may transmit infection to humans as a zoonosis.

Swine are also recognized as having an important role in the potential development of a pandemic influenza strain. The swine respiratory tract has receptors for both human and avian influenza viruses, which allow for infection with human and avian strains. The pig has been considered a mixing bowl where reassortment of human and avian influenza viruses may occur.

A unique feature of the influenza viruses is their spontaneous antigenic variation. Mutations resulting in minor changes in the protein structure of influenza viruses allow the virus to evade the host immune response. These changes, called antigenic drift, lead to outbreaks with new virus strains, and occur with influenza A and B viruses. ...

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