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An influenza pandemic is a global outbreak of disease that occurs when a new influenza A virus appears or “emerges” in the human population, causes serious illness, and then spreads easily from person to person worldwide. Pandemics are different from seasonal outbreaks or “epidemics” of influenza. Seasonal outbreaks are caused by subtypes of influenza viruses that already circulate among people, whereas pandemic outbreaks are caused by new subtypes, by subtypes that have never circulated among people, or by subtypes that have not circulated among people for a long time. Past influenza pandemics have led to high levels of illness, death, social disruption, and economic loss

There are many different subtypes of influenza or “flu” viruses. The subtypes differ based upon certain proteins on the surface of the virus (the hemagglutinin or “HA” protein and the neuraminidase or the “NA” protein.

Pandemic viruses emerge as a result of a process called "antigenic shift,” which causes an abrupt or sudden, major change in influenza A viruses. These changes are caused by new combinations of the HA and/or NA proteins on the surface of the virus. Such changes result in a new influenza A virus subtype. The appearance of a new influenza A virus subtype is the first step toward a pandemic; however, to cause a pandemic, the new virus subtype also must have the capacity to spread easily from person to person. Once a new pandemic influenza virus emerges and spreads, it usually becomes established among people and moves around or “circulates” for many years as seasonal epidemics of influenza. The U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have large surveillance programs to monitor and detect influenza activity around the world, including the emergence of possible pandemic strains of influenza virus.

During the 20th century, the emergence of several new influenza A virus subtypes caused three pandemics, all of which spread around the world within a year of being detected.

• 1918-19, "Spanish flu," [A (H1N1)], caused the highest number of known influenza deaths. (However, the actual influenza virus subtype was not detected in the 1918-19 pandemic). More than 500,000 people died in the United States, and up to 50 million people may have died worldwide. Many people died within the first few days after infection, and others died of secondary complications. Nearly half of those who died were young, healthy adults. Influenza A (H1N1) viruses still circulate today after being introduced again into the human population in 1977.
  
  
• 1957-58, "Asian flu," [A (H2N2)], caused about 70,000 deaths in the United States. First identified in China in late February 1957, the Asian flu spread to the United States by June 1957.



• 1968-69, "Hong Kong flu," [A (H3N2)], caused about 34,000 deaths in the United States. This virus was first detected in Hong Kong in early 1968 and spread to the United States later that year. Influenza A (H3N2) viruses still circulate today.

Both the 1957-58 and 1968-69 pandemics were caused by viruses containing a combination of genes from a human influenza virus and an avian influenza virus. The 1918-19 pandemic virus appears to have an avian origin.

A vaccine probably would not be available in the early stages of a pandemic. Scientists around the world work together when developing a new vaccine against influenza to select the virus strain that will offer the best protection against that virus. Manufacturers then use the selected strain to develop a vaccine. Once a potential pandemic strain of influenza virus is identified, it takes several months before a vaccine will be widely available. If a pandemic occurs, the U.S. government will work with many partner groups to make recommendations guiding the early use of available vaccine..

Four different influenza antiviral medications (amantadine, rimantadine, oseltamivir, and zanamivir) are approved by the U.S. Food and Drug Administration (FDA) for the treatment and/or prevention of influenza. All four usually work against influenza A viruses. However, the drugs may not always work, because influenza virus strains can become resistant to one or more of these medications. For example, analyses have shown that some of the 2004 H5N1 viruses isolated from poultry and humans in Southeast Asia are resistant to two of the medications for influenza (amantadine and rimantadine).