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Appendix C: Influenza BackgroundPandemics are explosive global events in which most, if not all, populations worldwide are at risk for infection and illness. In historical pandemics of influenza, the disease spread worldwide within months, and with modern travel patterns and increased population density, a pandemic of influenza is expected to spread much faster in present day. A pandemic has the potential to be a catastrophic disaster of unprecedented scale. Influenza pandemics are believed to have occurred for at least 300 years at unpredictable intervals. It is difficult to predict when the next influenza pandemic will occur or how severe it will be - wherever and whenever a pandemic starts, everyone around the world is at risk. Defining the potential magnitude of a pandemic is difficult because of the large differences in severity for the three 20th Century pandemics. The 1918 pandemic resulted in an estimated (at least) 500,000 deaths in the United States, the 1958 pandemic killed approximately 70,000 Americans, and the 1968 pandemic caused an estimated 34,000 U.S. deaths. This difference largely relates to the severity of infections and the virulence of the influenza viruses that caused the pandemics. The 20th Century pandemics also have shared similar characteristics. In each pandemic, about 30 percent of the U.S. population developed illness, with about half of those Americans seeking medical care. Children under the age of 18 have tended to have the highest rates of illness, though not of severe disease and death. Geographical spread in each pandemic was rapid and virtually all communities experienced outbreaks. An especially severe pandemic of influenza could lead to high levels of illness, death, social disruption, and economic loss. Everyday life will be disrupted because so many people in so many places become seriously ill at the same time. Impacts can range from school and business closings and the cancellation of social/mass gatherings (such as concerts and movies) to the interruption of basic services such as public transportation and food delivery. While an annual influenza season in the U.S., on average, results in approximately 36,000 deaths, 226,000 hospitalizations, and between $1 billion and $3 billion in direct costs for medical care, it is predicted that the number of illnesses, deaths, hospitalizations, and the direct costs will be significantly higher during a pandemic. A substantial percentage of the world's population will require some form of medical care. 2 Health care facilities will likely overwhelmed, creating a shortage of hospital staff, beds, ventilators, and other supplies. Surge capacity at non-traditional sites (such as schools) may need to be created to cope with demand. In addition, in this scenario, the need for vaccine is likely to outstrip supply and the supply of antiviral drugs is also likely to be inadequate early in a pandemic. Difficult decisions will need to be made regarding who gets antiviral drugs and vaccines. As described in the Interim Pre-pandemic Planning Guidance:Community Strategy for Pandemic Influenza Mitigation in the United States - Early, Targeted, Layered Use of Nonpharmaceutical Interventions, without implementing mitigating interventions, even a less severe pandemic would likely result in dramatic increases in the number of hospitalizations and deaths. In addition, an unmitigated severe pandemic would likely overwhelm our nation’s critical healthcare services and impose significant stress on our nation’s critical infrastructure. Therefore, communities, individuals and families, employers, schools, and other organizations must plan for the use of non-pharmaceutical interventions (NPI) to help limit the spread of a pandemic, prevent disease and death, lessen the impact on the economy, and keep society functioning. For additional information on these NPIs, refer to Section D of this appendix.
A. Influenza VirusesInfluenza viruses are negative-stranded ribonucleic acid (RNA) viruses that have been divided into types: A, B, and C viruses. Type C is not known to cause disease in humans, and only type A viruses are known to cause pandemics. Type A viruses are further divided into subtypes based on the specific hemagglutinin (H) and neuraminidase (N) proteins on the virus surface. Two subtypes of A viruses are currently circulating among humans - H3N2 and H1N1. When these subtypes in emerged in the 20th Century, humans had not been exposed to them previously and resulted in the pandemics of 1918 pandemic (H1N1) and 1968 (H3N2). In addition, the 1957 pandemic was associated with the emergence and spread of the H2N2 virus; however, this virus subtype stopped circulating in 1968. Pandemics of influenza are unusual events and their timing cannot be predicted. For example, only three pandemics occurred in the 20th Century (1918, 1957, and 1968). The infrequency and unpredictable timing of these events is explained by the fact that influenza pandemics occur only when a new (or novel) influenza virus emerges and spreads globally. By definition, most people have never been exposed to these viruses; and therefore, are susceptible to infection by them. In contrast, seasonal influenza virus strain variants are modified versions of influenza viruses that are already in widespread circulation. Therefore, there is usually some level of pre-existing immunity to strain variants. Antigenic drift and shift account for the differences described here between seasonal and pandemic strains of influenza.
1. Drift and ShiftInfluenza viruses replicate their RNA sloppily, and as a result mutate fairly easily. Mutations of these viruses can result in either modification (drift) or replacement (shift) of the hemagglutinin and neuraminidase on the viral surface. Because these proteins are the main targets for the immune system, changes in these proteins can have minor to profound effects on the influenza virus’ ability to spread throughout human and animal populations.
a) DriftWhen influenza viruses undergo antigenic drift, mutations to the virus genome produce changes in the viral hemagglutinin and neuraminidase. As noted earlier, since RNA replication in influenza virus is sloppy, drift is a continuous ongoing process, and results in the emergence of new strain variants. The amount of change can be subtle or dramatic, but eventually one of the new variant strains becomes dominant, usually for a few years, until a new variant emerges and replaces it. In essence, drift affects the influenza viruses that are already in worldwide circulation. This process allows influenza viruses to change and re-infect people repeatedly through their lifetime. Since influenza virus strains shift dominance on such a constant basis, each year, many laboratories, including in the United States, collect influenza viruses circulating in different parts of the world. Some of these virus samples are sent to one of four WHO reference laboratories (one of which is at the CDC in Atlanta) for detailed testing. The testing includes determining how well antibodies in the current seasonal influenza vaccine react to the circulating virus and new influenza viruses (how well the current vaccine protects against from getting sick). This information, along with information about global influenza activity, is used by the WHO and an advisory committee of the FDA to select three viruses (two subtypes of influenza A viruses and one influenza B virus) to be the components of the annual influenza vaccines produced for the following fall and winter. Usually, one or two of the three virus strains in the vaccine are changed each year. (This is why it is so important to get the seasonal vaccine every year.)
b) ShiftIn contrast to drift, in antigenic shifts, the surface existing viral hemagglutinin and neuraminidase proteins are not modified, but are replaced by significantly different hemagglutinin and neuraminidase proteins. As a result, the influenza A viruses bear entirely new (or novel) H or H/N combinations which are perceived by our immune systems as something majority of people do not have pre-existing antibody protection against. As a result, there is widespread illness and mortality among populations as the disease spreads around the world in a pandemic.
B. Animal ReservoirsWild birds are considered the reservoir for influenza viruses because more influenza A subtypes (15) circulate among wild birds than humans or other animal species. Normally, animal influenza viruses do not infect humans. However, avian influenza viruses can sometimes cross this barrier and directly infect humans. Pandemic viruses can also arise when some of the genes from animal influenza viruses mix (or re-assort) with some of the genes from human influenza viruses to create a new hybrid influenza virus. Re-assorted viruses have been frequently identified and are thought to have been responsible for the 1957 and 1968 pandemic viruses. There are three requirements for influenza (or any infectious disease) to become pandemic in humans:
As described below, the first two requirements have been met.
a) H5N1 Strain of Influenza and Current SituationAlthough it is unpredictable when the next pandemic will occur and what strain may cause it, the continued and expanded spread of a highly pathogenic - and now endemic - avian H5N1 virus across much of Asia, Russia, and Europe, and parts of Africa, represents a significant pandemic threat. Human H5N1 influenza infection was first recognized in 1997 when it infected 18 people (and caused 6 deaths) in Hong Kong. Since 2003, over 320 human H5N1 cases (and over 190 deaths; with a mortality rate of approximately 60 percent) have been confirmed (by WHO) in a growing list of countries, including Thailand, Vietnam, Cambodia, Indonesia, China, Egypt, Turkey, Azerbaijan, Djibouti, Iraq, Laos, and Nigeria. Additional concerns that the H5N1 virus currently circulating has significant potential in triggering a pandemic because: While H5N1 is the greatest current pandemic threat, other avian influenza subtypes have also infected people in recent years. In 1999, H9N2 infections were identified in Hong Kong; in 2003, H7N7 infections occurred in the Netherlands; and in 2004, H7N3 infections occurred in Canada. Such outbreaks/strains also have the potential to give rise to the next pandemic, reinforcing the need for continued surveillance and ongoing vaccine development efforts against these strains.
C. Impact of Influenza and Influenza PandemicsPandemic strains of influenza viruses have demonstrated their ability to spread worldwide within months, or weeks, and will cause illness and deaths in all age groups. The pandemic will likely spread around the world in multiple waves (periods during which community outbreaks occur across the country) of illness with each wave taking 2 - 3 months to spread the globe. As each wave is spreading, it is estimated that epidemics of influenza will remain in affected communities for 6 – 8 weeks. While the ultimate number of infections, illnesses, and deaths is unpredictable, it is nonetheless certain that without adequate planning and preparations, an influenza pandemic in the 21st Century has the potential to cause enough illnesses to overwhelm current public health and medical care capacities at all levels, despite the vast improvements made in medical technology during the 20th Century. Certain modern trends will likely increase the potential for pandemics to cause more illnesses and deaths than in previous pandemics:
This combination of factors suggests that the next pandemic may lead to influenza spreading among the population and around the world faster than in the past, overwhelming countries and health systems that are not adequately prepared. The 1957 pandemic, during an era with much less globalization, spread to the U.S. within 4 - 5 months of its detection in China, and the 1968 pandemic spread to the U.S. from Hong Kong within 2 - 3 months. As the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003 demonstrated, modern travel patterns may significantly reduce the time needed for pandemic influenza viruses to spread globally to a few months or even weeks. The major implication of such rapid spread of an infectious disease is that many, if not most, countries will have minimal time to implement preparations and responses once pandemic viruses have begun to spread. While SARS infections spread quickly to multiple countries, the epidemiology and transmission modes of the SARS virus greatly helped to contain the spread of this infection in 2003, along with quarantine, isolation, and other control measures. By contrast, because influenza spreads more rapidly between people and can be transmitted by those who are infected but do not yet have symptoms, the spread of pandemic influenza to multiple countries is expected to lead to the near simultaneous occurrence of multiple community outbreaks in an escalating fashion. No other infectious disease threat, whether natural or engineered, poses the same current threat for causing increases in infections, illnesses, and deaths so quickly in the U.S. and worldwide.
D. Interim Pre-pandemic Planning Guidance: Community Strategy for Pandemic Influenza Mitigation in the United States - Early, Targeted, Layered Use of Nonpharmaceutical InterventionsNon-pharmaceutical interventions (NPIs) will likely reduce influenza transmission, and therefore impact the severity of the pandemic, by reducing contact between sick and uninfected persons, thereby decreasing the number of those who become infected. This will, in turn, lessen the need for healthcare services and minimize the impact of a pandemic on the economy and society. To have the greatest effect, NPI measures should be implemented in the early stages of the pandemic. NPIs described in the Community Strategy for Pandemic Influenza Mitigation guidance document include:
Decisions about what tools should be used during a pandemic should be based on the observed severity of the event, its impact on specific subpopulations, the expected benefit of the interventions, the feasibility of success in modern society, the direct and indirect costs, and the consequences on critical infrastructure, healthcare delivery, and society. The most controversial elements (e.g., prolonged dismissal of students from schools and closure of childcare programs) are not likely to be needed in less severe pandemics, but these steps may save lives during severe pandemics. Just as communities plan and prepare for mitigating the effect of severe natural disasters (e.g., hurricanes), they should plan and prepare for mitigating the effect of a severe pandemic. To further assist in pre-pandemic planning, the Community Strategy for Pandemic Influenza Mitigation also introduces the Pandemic Severity Index (PSI), which is five discrete categories of increasing severity (Category 1 - 5), similar to the Saffir-Simpson Scale for measuring hurricane strength/intensity (which is also Category 1 – 5). All future pandemics will be assigned to one of these categories. The PSI is based on the case fatality ratio, and other key epidemiological characteristics that define outbreaks/pandemics of disease, as shown below.
The timing of initiation, which PSI Categories to implement, and length of duration of the NPIs outlined in the Community Strategy for Pandemic Influenza Mitigation will influence their effectiveness; and Table C-3 below provides guidance.
Historical data from the 1918 pandemic suggests that the duration of implementing NPIs significantly impacts mortality rates. Stopping or limiting the intensity of NPIs while pandemic virus was still circulating within the community caused increases in mortality due to pneumonia and influenza in some communities. As long as susceptible individuals are present in large numbers in a particular area, spread of influenza will continue. While NPIs may limit or slow community transmission, persisting pandemic virus circulating in a community with a susceptible population is a risk factor for re-emergence of the pandemic. Therefore, while the duration of NPI implementation will depend on the severity of the pandemic, and the duration of the pandemic wave (about 6 – 8 weeks) within the particular area, communities should be prepared to maintain these measures for up to 12 weeks in a Category 4 or 5 pandemic, as shown above in Table C-3. Monitoring of excess mortality, case fatality ratios, or other surrogate markers over time will be important for determining both the optimal duration of implementation and the need for resumption of these measures.
E. Pandemic Influenza Planning ChecklistsIn the event of an influenza pandemic, many sectors play a key role in protecting the health and safety of their employees, as well as limiting the negative impact to the economy and society. Planning for pandemic influenza is a critical aspect of this. HHS and CDC developed guidelines, including checklists, to assist businesses, industries, and other employers in planning for a pandemic. These checklists cover multiple key sectors, including:
Appendix O contains the checklists that are most applicable to DOI and its equities; these are the EMS, Law Enforcement, Correctional Facilities, Individual/Families, Schools (Kindergarten -12th Grade), and Colleges/Universities checklists. Those checklists that are not included in this appendix can be found at www.pandemicflu.gov. The checklists identify key areas that DOI equities should address, in addition to the guidance laid out in the DOI Pandemic Influenza Plan, in their pandemic planning. The checklists also enable those responsible for pandemic influenza planning to assess and improve their preparedness efforts. Given the differences within sectors, individual facilities/equities should adapt the checklists to meet their unique needs. In addition, when developing pandemic plans and preparations, sectors and individual facilities/equities should also utilize information and guidance from State, regional, and local health departments and emergency management agencies/authorities.
F. Internet Resources on InfluenzaThe links listed below were active as of November 2007. However, because web sites can change without notice, no site can be guaranteed active or accurate indefinitely.
U.S. Government:
Nongovernmental Organizations:
Background & Historical Information:
Additional Preparedness & Response Resources:
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