An influenza pandemic occurs when a novel influenza A virus spreads from person to person around the world and affects a very large number of people. A novel flu A virus might cause a flu pandemic if the novel virus can spread efficiently from person to person (instead of just from animals to people or from one person to another, but then no further). Another condition for a pandemic to occur is that most people will not have immunity to the new virus. People can have some immunity to novel or pandemic flu A viruses that are similar to flu A viruses they’ve been infected by in the past. If a new flu A virus is very different from earlier flu A viruses, it may be more likely to cause a pandemic. Influenza B viruses do not cause influenza pandemics.

Seasonal Flu vs. Pandemic Flu

A novel influenza A virus is one that has caused human infection, but is different from current seasonal human influenza A viruses that circulate among people. Novel influenza A viruses are usually influenza A viruses that circulate among animals. Some novel influenza A viruses are believed to pose a greater pandemic threat than others and are more concerning to public health officials because they have caused serious human illness and death and also have been able to spread in a limited manner from person-to-person. Novel influenza A viruses are of extra concern because of the potential impact they could have on public health if they gain the ability to spread easily from person to person, which might cause the next influenza pandemic. Human infection with a novel influenza A virus is a nationally notifiable condition reportable to CDC. The text below summarizes the novel influenza A viruses that are currently most concerning to public health officials.

Avian Influenza A Viruses

• Avian influenza A viruses do not normally infect humans, but sporadic human infections have occurred.
• Illness in humans caused by avian influenza A virus infections has ranged from mild to severe (e.g. pneumonia).
• Several subtypes of avian influenza A viruses are known to have infected people (H5, H6, H7, H9, H10 viruses).
• Highly pathogenic Asian avian influenza A(H5N1) and low pathogenic Asian A(H7N9) viruses account for the majority of human infections with avian influenza A viruses.
• Human infections with avian influenza A viruses have most often occurred after exposure to infected poultry or their secretions or excretions, such as through direct or close contact, including visiting a live poultry market.

Avian influenza A H5 viruses

• Among H5 avian influenza A viruses, Asian highly pathogenic avian influenza (HPAI) A (H5N1) viruses have caused the most human infections. Asian H5N1 viruses are currently circulating among poultry in Asia and the Middle East and human infections with these viruses have been reported in 17 countries since 2003. Human infections are often associated with severe pneumonia and mortality greater than 50%. Probable, limited, non-sustained human-to-human spread of Asian H5N1 viruses has been reported in several countries. (HPAI H5 viruses detected in birds and poultry in the United States are different and have not caused human infections.)
• The World Health Organization (WHO) tracks the number of reported, confirmed, human infections with HPAI H5N1 viruses.
• On January 8, 2014, the first case of human infection with Asian HPAI H5N1 virus in the Americas was reported in Canada in a traveler returning from China. (No human infections with Asian H5N1 virus have ever been reported in the United States.)
• Sporadic human infections with HPAI H5N6 viruses also have been reported in China, resulting in severe illness and high mortality.

Avian influenza A H7 viruses

• Among H7 viruses, low pathogenic Asian lineage avian influenza A H7N9 viruses have caused the most reported human infections; with most of them occurring in China. The first human infections with H7N9 viruses were reported by WHO on April 1, 2013 and sporadic human infections continue to be reported in China. In late 2016, some low pathogenicity Asian H7N9 viruses developed mutations that made them highly pathogenic in poultry. These HPAI H7N9 Asian viruses continue to be associated with human infections in China. Many Asian H7N9 virus infected patients have had severe respiratory illness. During the past five annual epidemics of Asian H7N9 virus infections in people, the mortality rate in hospitalized patients has averaged about 40 percent. Probable, limited, non-sustained human-to-human spread of Asian H7N9 viruses also has been reported in China. Since the implementation of a large-scale H5-H7 poultry vaccination program in September 2017, few human infections with Asian H7N9 viruses have been reported.
• In January 2015, the Government of Canada and the Ministry of Health in British Columbia reported the first two cases of human infection in North America with Asian H7N9 virus in a husband and wife who had traveled to China. Cases of Asian H7N9 virus infection associated with travel to China also have been reported in Hong Kong, Taiwan and Malaysia.

Avian influenza A H9 viruses

• Sporadic human infections with some low pathogenicity H9N2 viruses also have been reported in China, Hong Kong, Bangladesh, and Egypt. Most H9N2 virus infections in people have occurred in children after poultry exposures. H9N2 virus infection of humans generally causes mild upper respiratory tract illness.

Swine Influenza/Variant Influenza A viruses

• Sporadic human infections with swine influenza A viruses circulating among pigs can occur. When this happens, these viruses are called “variant viruses.” They also can be denoted by adding the letter “v” to the end of the influenza A virus subtype designation.
• Illness associated with variant virus infection has been mostly mild with symptoms similar to those of seasonal flu. Like seasonal influenza, however, serious illness, resulting in hospitalization and death, is possible. In general, variant viruses have been associated with less severe illness and much lower mortality than human infection with avian influenza A viruses.
• Most commonly, human infections with variant viruses occur in people with exposure to infected pigs (e.g., children who have direct or close contact with pigs at a fair or workers in the swine industry), but limited, non-sustained spread from person to person of some variant viruses has been detected.
• Human infections with H1N1v, H3N2v and H1N2v viruses have been detected in the United States.

What is an influenza pandemic?

An influenza pandemic is a global outbreak of a new influenza A virus that is very different from current and recently circulating human seasonal influenza A viruses. Pandemics happen when new (novel) influenza A viruses emerge which are able to infect people easily and spread from person to person in an efficient and sustained way.

Where do pandemic influenza viruses come from?

Different animals—including birds and pigs—are hosts to influenza A viruses that do not normally infect people. Influenza A viruses are constantly changing, making it possible on very rare occasions for non-human influenza viruses to change in such a way that they can infect people easily and spread efficiently from person to person.

How do influenza A viruses change to cause a pandemic?

Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1 through H18 and N1 through N11). Theoretically, any combination of the 18 hemagglutinins and 11 neuraminidase proteins are possible, but not all have been found in animals and even fewer have been found to infect humans.

Influenza viruses can change in two different ways, one of which is called “antigenic shift” and can result in the emergence of a new influenza virus. Antigenic shift represents an abrupt, major change in an influenza A virus. This can result from direct infection of humans with a non-human influenza A virus, such as a virus circulating among birds or pigs. Antigenic shift also can happen when a non-human influenza A virus (for example an avian influenza virus) exchanges genetic information with other influenza A viruses in a process called genetic reassortment, and the resultant new virus is able to infect people. For example, an exchange of genes between a human influenza A virus and an avian influenza A virus can create a new influenza A virus with a hemagglutinin protein or both a hemagglutinin protein and a neuraminidase protein from an avian influenza A virus. If this new virus causes illness in infected people and can spread easily from person to person, an influenza pandemic can occur.

What happens when a pandemic influenza virus emerges?

When a pandemic influenza virus emerges, the virus can spread quickly because most people will not be immune and a vaccine might not be widely available to offer immediate protection. During the 2009 H1N1 pandemic, for example, a new H1N1 virus was first identified in April 2009. By June 2009, that novel H1N1 virus had spread worldwide and the World Health Organization declared a pandemic. Spread of a pandemic influenza virus may occur in multiple disease “waves” that are separated by several months. As a pandemic influenza virus spreads, large numbers of people may need medical care worldwide. Schools, childcare centers, workplaces, and other places for mass gatherings may experience more absenteeism. Public health and healthcare systems can become overloaded, with elevated rates of hospitalizations and deaths. Other critical infrastructure, such as law enforcement, emergency medical services, and transportation industry may also be affected.

Will seasonal flu vaccines protect against pandemic flu?

It is unlikely that seasonal flu vaccines would protect against a pandemic influenza virus. Seasonal flu vaccines that are used annually protect against currently circulating human influenza A and B viruses. They are not designed to protect against new influenza A viruses. A pandemic influenza virus would be very different from circulating seasonal influenza A viruses and thus seasonal vaccines would not be expected to offer protection.

Are there vaccines to protect against pandemic flu?

The federal government has created a stockpile of some vaccines against select influenza A viruses with pandemic potential that could be used in the event of a pandemic, including vaccines against certain avian influenza A (e.g. H5N1 and H7N9) viruses. If a similar virus were to begin a pandemic, some vaccine would already be available.

The Department of Health and Human Services (HHS) is the lead agency for public health preparedness and medical response to an influenza pandemic. Within HHS, the Biomedical Advanced Research and Development Authority (BARDA) Influenza Division is charged with the advanced development and procurement of medical and non-pharmaceutical countermeasures for pandemic influenza preparedness and response.

How long would it take to develop a new pandemic vaccine?

If a new pandemic influenza virus (not included in the pre-pandemic vaccine stockpile) were to emerge, it is likely that a vaccine would have to be developed against that virus in order for sufficient supply of vaccine to become available for everyone who wishes to be vaccinated. How long it would take to produce a pandemic flu vaccine would depend on many factors, including how long it would take to create a candidate vaccine virus (CVV) and what vaccine manufacturing process would be used.” For seasonal influenza vaccine, it usually takes at least six months to produce large quantities of flu vaccine. During the 2009 H1N1 pandemic, it took about the same amount of time. CDC began developing a CVV to make monovalent (one component) H1N1pdm09 vaccine in mid-April. The first doses of vaccine were administered in early October and large quantities of vaccine became available in late November. Efforts are underway now to shorten the time it takes to produce influenza vaccines but because of the current amount of time needed to make flu vaccine, early supplies of pandemic vaccine might not be enough to meet demand, especially if most people need two doses of vaccine for protective immunity.

How many doses of pandemic vaccine would each person need?

People with no immunity against a new influenza virus may need two doses to be fully protected against that virus. The first dose primes the immune system and the second dose creates the protective response. During the 2009 H1N1 influenza pandemic, CDC recommended that two doses of the vaccine be given to children 6 months through 9 years of age in order to increase the immune response.

What treatments are available for pandemic flu?

During a flu pandemic, antiviral drugs would be an important tool to treat and prevent the spread of influenza illness. Antiviral drugs are medicines (pills, liquid or an inhaled powder) that fight against the influenza viruses infecting the respiratory tract. Antiviral drugs are recommended to treat seasonal influenza in people who are very sick or who are at high risk of serious flu complications. These same drugs may be useful for treating pandemic influenza, depending upon whether the pandemic influenza virus is susceptible or resistant to available antiviral drugs. Antiviral drugs are prescription drugs (they are not sold over-the-counter) and are different from prescription antibiotics that treat bacterial infections.

Are there other ways to slow a pandemic?

Nonpharmaceutical interventions, or NPIs, are actions, apart from getting vaccinated and taking medicine, which people and communities can take to help slow the spread of respiratory illnesses, like pandemic flu. Again, these actions do not include medicines, vaccines, or other pharmaceutical interventions. Given that it may take months to produce a pandemic flu vaccine (not included in the pre-pandemic vaccine stockpile) and that antiviral drugs may be reserved for treatment, NPIs will likely be the only prevention tools available during the early stages of a pandemic and, thus, critically important to help slow the spread of infection.

How would nonpharmaceutical interventions (NPIs) be used during a pandemic?

NPIs, also known as community mitigation strategies, may be more efficient when used early in a flu pandemic and in a layered fashion. Public health officials will recommend that people practice everyday preventive actions at all times. These actions include staying home when sick, covering coughs and sneezes with a tissue, washing hands often, and cleaning frequently touched surfaces and objects. During severe, very severe, or extreme flu pandemics, public health officials may recommend additional actions, such as using facemasks when sick and in close contact with other people, temporarily dismissing child care facilities and schools, and increasing the space between people and decreasing the frequency of contact among people (that is, social distancing).

How do you plan for the use of NPIs during a flu pandemic?

CDC has developed an updated set of guidelines, called the Community Mitigation Guidelines to Prevent Pandemic Influenza – United States, 2017, supplemental plain-language guides for specific community groups, and online communication and education materials that outline strategies for planning and preparing for a flu pandemic and for using nonpharmaceutical interventions (NPIs). Additionally, CDC has developed an NPI 101 training for public health professionals to help them learn more about NPIs and share information with their communities on how to use NPIs.

Are there novel influenza A viruses that are of extra concern in terms of their pandemic threat?

A novel influenza (flu) virus is an influenza A virus that has caused human infection and which is different from current human seasonal influenza A viruses. Any novel influenza A virus, such as those of avian or swine origin, has the potential to cause an influenza pandemic. Some novel flu A viruses are believed to pose a greater pandemic threat and are more concerning to public health officials than others because they have already caused serious human illness and death and also have been able to spread in a limited manner from person to person. Novel influenza A viruses are of extra concern because of the potential impact they could have on public health if they gained the ability to spread from person-to-person easily and thus trigger an influenza pandemic. Examples of novel influenza A viruses of extra concern because of their potential to cause a severe pandemic include avian influenza A (H5N1) and avian influenza A (H7N9) viruses. These two different avian influenza A viruses have caused sporadic human infections, some limited person to person spread and resulted in critical illness and death in people.

Influenza viruses that normally circulate in pigs also have infected people; these viruses include influenza A (H1N1v), (H1N2v) and (H3N2v). When influenza viruses that normally circulate in swine are found in people, they are called “variant” viruses; the “v” after the virus name indicates a variant virus. Limited, unsustained spread from person to person also has been detected with these viruses, but in general, these variant viruses have been associated with less severe illness and fewer deaths than avian influenza viruses. In general, human infections with H5N1, H7N9, H1N1v, H1N2v and H3N2v viruses have occurred rarely, but if these viruses were to change in such a way that they were able to infect humans easily and spread from person to person in a sustained manner, a flu pandemic could result.

In the spring of 2009, a novel influenza A (H1N1) virus emerged. It was detected first in the United States and spread quickly across the United States and the world. This new H1N1 virus contained a unique combination of influenza genes not previously identified in animals or people. This virus was designated as influenza A (H1N1)pdm09 virus. Ten years later work continues to better understand influenza, prevent disease, and prepare for the next pandemic.

The 2009 H1N1 Pandemic: A New Flu Virus Emerges

The (H1N1)pdm09 virus was very different from H1N1 viruses that were circulating at the time of the pandemic. Few young people had any existing immunity (as detected by antibody response) to the (H1N1)pdm09 virus, but nearly one-third of people over 60 years old had antibodies against this virus, likely from exposure to an older H1N1 virus earlier in their lives. Since the (H1N1)pdm09 virus was very different from circulating H1N1 viruses, vaccination with seasonal flu vaccines offered little cross-protection against (H1N1)pdm09 virus infection. While a monovalent (H1N1)pdm09 vaccine was produced, it was not available in large quantities until late November—after the peak of illness during the second wave had come and gone in the United States. From April 12, 2009 to April 10, 2010, CDC estimated there were 60.8 million cases (range: 43.3-89.3 million), 274,304 hospitalizations (range: 195,086-402,719), and 12,469 deaths (range: 8868-18,306) in the United States due to the (H1N1)pdm09 virus.

Additionally, CDC estimated that 151,700-575,400 people worldwide died from (H1N1)pdm09 virus infection during the first year the virus circulated.** Globally, 80 percent of (H1N1)pdm09 virus-related deaths were estimated to have occurred in people younger than 65 years of age. This differs greatly from typical seasonal influenza epidemics, during which about 70 percent to 90 percent of deaths are estimated to occur in people 65 years and older.

Though the 2009 flu pandemic primarily affected children and young and middle-aged adults, the impact of the (H1N1)pdm09 virus on the global population during the first year was less severe than that of previous pandemics. Estimates of pandemic influenza mortality ranged from 0.03 percent of the world’s population during the 1968 H3N2 pandemic to 1 percent to 3 percent of the world’s population during the 1918 H1N1 pandemic. It is estimated that 0.001 percent to 0.007 percent of the world’s population died of respiratory complications associated with (H1N1)pdm09 virus infection during the first 12 months the virus circulated.

The United States mounted a complex, multi-faceted and long-term response to the pandemic, summarized in The 2009 H1N1 Pandemic: Summary Highlights, April 2009-April 2010. On August 10, 2010, WHO declared an end to the global 2009 H1N1 influenza pandemic. However, (H1N1)pdm09 virus continues to circulate as a seasonal flu virus, and cause illness, hospitalization, and deaths worldwide every year.

The 1968 pandemic was caused by an influenza A (H3N2) virus comprised of two genes from an avian influenza A virus, including a new H3 hemagglutinin, but also contained the N2 neuraminidase from the 1957 H2N2 virus. It was first noted in the United States in September 1968. The estimated number of deaths was 1 million worldwide and about 100,000 in the United States. Most excess deaths were in people 65 years and older. The H3N2 virus continues to circulate worldwide as a seasonal influenza A virus. Seasonal H3N2 viruses, which are associated with severe illness in older people, undergo regular antigenic drift.

The 1918 influenza pandemic was the most severe pandemic in recent history. It was caused by an H1N1 virus with genes of avian origin. Although there is not universal consensus regarding where the virus originated, it spread worldwide during 1918-1919. In the United States, it was first identified in military personnel in spring 1918. It is estimated that about 500 million people or one-third of the world’s population became infected with this virus. The number of deaths was estimated to be at least 50 million worldwide with about 675,000 occurring in the United States.

Mortality was high in people younger than 5 years old, 20-40 years old, and 65 years and older. The high mortality in healthy people, including those in the 20-40 year age group, was a unique feature of this pandemic. While the 1918 H1N1 virus has been synthesized and evaluated, the properties that made it so devastating are not well understood. With no vaccine to protect against influenza infection and no antibiotics to treat secondary bacterial infections that can be associated with influenza infections, control efforts worldwide were limited to non-pharmaceutical interventions such as isolation, quarantine, good personal hygiene, use of disinfectants, and limitations of public gatherings, which were applied unevenly.

The 1918 H1N1 flu virus caused the deadliest pandemic of the 20th century. To better understand this deadly virus, an expert group of researchers and virus hunters set out to search for the lost 1918 virus, sequence its genome, recreate the virus in a highly safe and regulated laboratory setting at CDC, and ultimately study its secrets to better prepare for future pandemics.