National Vaccine Program Office

Influenza Pandemics: How They Start, How They Spread, and Their Potential Impact

How Does an Influenza Pandemic Start?

There are three main types of influenza viruses: A, B, and C. Influenza C causes only mild disease and has not been associated with widespread outbreaks. Influenza types A and B, however, cause epidemics nearly every year. Influenza A viruses are divided into subtypes, based on differences in two surface proteins: hemagglutinin (H) and neuraminidase (N). Influenza B viruses are not divided into subtypes. During an influenza flu season, usually one or more influenza A subtype and B viruses circulate at the same time.

A pandemic is possible when an influenza A virus makes a dramatic change (i.e., "shift") and acquires a new H or H+N. This shift results in a new or "novel" virus to which the general population has no immunity. The appearance of a novel virus is the first step toward a pandemic. However, the novel influenza A virus also must spread easily from person to person (and cause serious disease) for a pandemic to occur. Influenza B viruses do not undergo shift and do not cause influenza pandemics.

The reservoir for Type A influenza viruses is wild birds, but influenza A viruses also infect animals such as pigs and horses, as well as people. The last two pandemic viruses were combinations of bird and human influenza viruses. Many persons believe that these new viruses emerged when an intermediate host, such as a pig, was infected by both human and bird influenza A viruses at the same time. A new virus was created. Events in Hong Kong in 1997, however, showed that this is not the only way that humans can become infected with a novel virus. Sometimes, an avian influenza virus can "jump the species barrier" and move directly from chickens to humans and cause disease.

Since, by definition, a novel virus is a virus that has never previously infected humans, or hasn't infected humans for a long time, it's likely that almost no one will have immunity, or antibody to protect them against the novel virus. Therefore, anyone exposed to the virus--young or old, healthy or weak--could become infected and get sick. If the novel virus is related to a virus that circulated long ago, older people might have some level of immunity. It is possible that the novel virus may be especially dangerous to some age groups that are not usually at risk of severe illness or death from annual influenza (such as healthy young adults). Such widespread vulnerability makes a pandemic possible and allows it to have potentially devastating impact.

How Does a Pandemic Spread?

Although all pandemics begin with the appearance of a novel virus, most novel viruses do not spread and cause pandemics. It's more common for a novel virus to be detected and cause illness in a few people, but not go on to infect large numbers of people.

For a novel virus to cause a pandemic, a sequence of events must occur over time. A planning tool, developed by pandemic planners, of how those events might unfold can be found at the following web site: www.who.int/emc-documents/influenza/whoccscsredc991c.html. However, the phases will not occur simultaneously around the world.

The Phases of a Pandemic

To help prepare and respond to a pandemic, WHO has developed a series of "phases" that can be used by planners.

• Phase 0, Preparedness Level 0
  ( Inter-Pandemic Period )
   
  Every year, there are three or four strains of influenza viruses moving around the world and causing illness. In a normal year (the pre-pandemic period), all of these viruses will be previously identified strains and will be similar to other strains recently circulating. A vaccine, that covers the strains most likely to circulate during the influenza season, is developed each year. Vaccine is usually administered between October and December each year in the U.S.
   
• Phase 0, Preparedness Level 1
  (Initial Report of a New Strain in Humans)
   
  Occasionally there are reports of isolation of a novel virus from humans without clear evidence of spread from person to person or of outbreak activity. Each report of a novel virus is investigated and, depending on what is learned, we may or may not advance to the next stage of the model.
   
• Phase 0, Preparedness Level 2
  (Novel Virus Alert - Human Infection Confirmed)
   
  A Novel Virus Alert occurs when two or more human infections (with a novel virus) have been confirmed. The ability of the virus to spread from human to human and cause serious disease, however, is still questionable. Human infections with novel viruses have often been seen in Asia first, but a novel virus can be found anywhere. For example, the 1976 novel virus, known as swine flu, originated in Fort Dix, New Jersey.
   
• Phase 0, Preparedness Level 3
  (Human Transmission Confirmed)
   
  This Preparedness Level will exist when human transmission of the new virus sub-type has been confirmed through clear evidence of person-to-person spread in the general population, such as secondary cases resulting from contact with an index case, with at least one outbreak lasting over a minimum two week period in one country. Identification of the new virus sub-type in several countries, with no explanation other than contact among infected people, may also be used as evidence for significant human transmission.
   
• Phase 1
  (Confirmation of Onset of Pandemic)
   
  To progress from a Novel Virus Alert to Pandemic Imminent, a novel virus must be able to spread efficiently from one person to another. In this phase, the virus is causing several outbreaks in at least one country; it has spread to other countries and disease patterns indicate that severe morbidity and mortality (sickness and death) are likely in at least one segment of the population. The 1997 avian flu virus never efficiently spread from one person to another, so Pandemic Imminent was never declared.
   
• Phase 2
  (Regional and Multi-Regional Epidemics)
   
  The Pandemic phase occurs when the novel virus is causing outbreaks and epidemics in multiple countries around the world. If a community has not prepared itself well before this phase, it may be suddenly facing some very serious public health, social, and economic problems. Fortunately, it is extremely rare for a novel virus to progress to the Pandemic phase. It hasn't happened since the Hong Kong flu of 1968.
   
• Phase 3
  (End of First Pandemic Wave)
   
  Influenza activity in initially affected countries/regions has stopped while outbreaks of the new viruses are continuing elsewhere. During this "downtime," it is important to maintain enthusiasm for the pandemic response by continuing vaccination campaigns and other response efforts. This may be the time when we have a chance to "catch up" to the virus.
   
• Phase 4
  (Second or Later Waves of the Pandemic)
   
  Based on past experiences, at least a second wave of outbreaks caused by the novel virus would be expected to occur within 3-9 months of the initial epidemic in a particular country or region.
   
• Phase 5
  (End of the Pandemic - Back to Phase 0)
   
  The pandemic is declared "over" when the infection rate of influenza returns to pre-pandemic levels, and no more large-scale "waves" of illness are expected. Based on history, it could take two years for this to happen. Once it happens, the cycle begins again.

While there is no way to identify exactly when each of the phases will occur, it is estimated that an average pandemic could progress from a Novel Virus Alert to a Pandemic in a matter of months. This time frame could be much longer if the disease is not readily contagious, or it could be shorter if the virus spreads quickly.

The phases described above have been developed to help pandemic planners figure out what to do in conjunction with the changing epidemiology of a novel virus. It's important to understand that actual spread of the virus may or may not be described by these phases. For example, we may not be aware of a novel virus until after it has caused widespread disease. For this reason, pandemic plans must include the flexibility to respond to the specifics of each pandemic virus.

The Impact of a Pandemic: How Serious Might It Be?

There's no simple answer to the question of how serious a pandemic might be. It all depends on how virulent (severe) the virus is, how rapidly it can spread from population to population, and the effectiveness of pandemic prevention and response efforts. The 1918 Spanish flu is an example of a worst-case scenario because the strain was highly contagious and quite deadly. This pandemic killed more Americans than all the wars of the 20th century. Since our world today is vastly more populated, and people travel the globe with ease, the spread of a next pandemic could be more rapid than that of previous pandemics.

The impact of a pandemic isn't measured only by how many people will die. If millions of people get sick at the same time, major social consequences will occur. If many doctors and nurses become ill, it will be difficult to care for the sick. If the majority of a local police force is infected, the safety of the community might be at risk. If air traffic controllers are all sick at once, air travel could grind to a halt, interrupting not only business and personal travel, but also the transport of life-saving vaccines or anti-viral drugs. Therefore, a vital part of pandemic planning is the development of strategies and tactics to address all these potential problems.

Next Section: Pandemics and Pandemic Scares in the 20th Century

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