Influenza Pandemics

Pandemic: A Worldwide Outbreak of Influenza

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 are already in existence among people, whereas pandemic outbreaks are caused by new subtypes or by subtypes that have never circulated among people or 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.


Appearance ("Emergence") of Pandemic Influenza Viruses

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 appear (or "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. This change results in a new influenza A virus subtype. The appearance of a new influenza A virus subtype is the first step toward a pandemic, but the new virus subtype also must spread easily from person to person to cause a pandemic. Once a new pandemic influenza virus emerges and spreads, it normally 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 and the World Health Organization have large surveillance programs to monitor and "detect" influenza activity around the world, including the emergence of possible pandemic strains of influenza virus.

Influenza Pandemics During the 20th Century

During the 20th century, the emergence of new influenza A virus subtypes caused three pandemics, all of which spread around the world within 1 year of being detected.

  • 1918-19, "Spanish flu," [A (H1N1)], caused the highest number of known influenza deaths: 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 complications later. 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 the 1970s.
  • 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 origin of the 1918-19 pandemic virus is not clear.

Stages of a Pandemic

The World Health Organization (WHO) has developed a global influenza preparedness plan, which defines the stages of a pandemic, outlines WHO's role and makes recommendations for national measures before and during a pandemic. The phases are:

Interpandemic period


Phase 1: No new influenza virus subtypes have been detected in humans. An influenza virus subtype that has caused human infection may be present in animals. If present in animals, the risk of human infection or disease is considered to be low.

Phase 2: No new influenza virus subtypes have been detected in humans. However, a circulating animal influenza virus subtype poses a substantial risk of human disease.

Pandemic alert period

Phase 3: Human infection(s) with a new subtype, but no human-to-human spread, or at most rare instances of spread to a close contact.

Phase 4: Small cluster(s) with limited human-to-human transmission but spread is highly localized, suggesting that the virus is not well adapted to humans.

Phase 5: Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly better adapted to humans, but may not yet be fully transmissible (substantial pandemic risk).

Pandemic period

Phase 6: Pandemic: increased and sustained transmission in general population.

Notes: The distinction between phase 1 and phase 2 is based on the risk of human infection or disease resulting from circulating strains in animals. The distinction is based on various factors and their relative importance according to current scientific knowledge. Factors may include pathogenicity in animals and humans, occurrence in domesticated animals and livestock or only in wildlife, whether the virus is enzootic or epizootic, geographically localized or widespread, and/or other scientific parameters.

The distinction between phase 3, phase 4 and phase 5 is based on an assessment of the risk of a pandemic. Various factors and their relative importance according to current scientific knowledge may be considered. Factors may include rate of transmission, geographical location and spread, severity of illness, presence of genes from human strains (if derived from an animal strain), and/or other scientific parameters.


Vaccines to Protect Against Pandemic Influenza Viruses

A vaccine probably would not be available in the early stages of a pandemic. When a new vaccine against an influenza virus is being developed, scientists around the world work together to select the virus strain that will offer the best protection against that virus, and then manufacturers 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, it is expected that the U.S. government will work with many partner groups to make recommendations to guide the early use of vaccine.

Antiviral Medications to Prevent and Treat Pandemic Influenza

Four different influenza antiviral medications (amantadine, rimantadine, oseltamivir, and zanamivir) are approved by the U.S. Food and Drug Administration for the treatment and/or prevention of influenza. All four work against influenza A viruses. However, sometimes influenza virus strains can become resistant to one or more of these drugs, and thus the drugs may not always work. For example, the influenza A (H5N1) viruses identified in human patients in Asia in 2004 and 2005 have been resistant to amantadine and rimantadine. Monitoring of avian viruses for resistance to influenza antiviral medications is continuing.

Preparing for the Next Pandemic

Many scientists believe it is only a matter of time until the next influenza pandemic occurs. The severity of the next pandemic cannot be predicted, but modeling studies suggest that its effect in the United States could be severe. In the absence of any control measures (vaccination or drugs), it has been estimated that in the United States a "medium-level" pandemic could cause 89,000 to 207,000 deaths, between 314,000 and 734,000 hospitalizations, 18 to 42 million outpatient visits, and another 20 to 47 million people being sick. Between 15% and 35% of the U.S. population could be affected by an influenza pandemic, and the economic impact could range between $71.3 and $166.5 billion.


Recent examples of avian influenza outbreaks and infections in Hong Kong in 1997, 1998, and 2002 and the ongoing widespread outbreaks of avian influenza among poultry in Asia, show the importance of preparing for a pandemic. It has been 36 years since the last pandemic.

Influenza pandemics are different from many of the threats for which public health and the health-care system are currently planning:

  • The pandemic will last much longer than most other emergency events and may include "waves" of influenza activity separated by months (in 20th century pandemics, a second wave of influenza activity occurred 3 to 12 months after the first wave).
  • The numbers of health-care workers and first responders available to work can be expected to be reduced; they will be at high risk of illness through exposure in the community and in health-care settings, and some may have to miss work to care for ill family members.
  • Resources in many locations could be limited because of how widespread an influenza pandemic would be.

Because of these differences and the expected size of an influenza pandemic, it is important to have completed planning and preparedness activities to be able to respond promptly and adequately. For this reason, the U.S. Department of Health and Human Services (HHS) supports pandemic influenza activities in the areas of surveillance ("detection"), vaccine development and production, antiviral stockpiling, research, and public health preparedness. In addition, a draft National Pandemic Influenza Preparedness Plan was issued by HHS for public comment in August 2004. To view the draft plan or to obtain more information about pandemic influenza, visit the HHS Web site at

centers for Diseases Control and Prevention

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