Pandemics occur when an influenza virus mutates into a novel strain that is highly transmissible among humans, leading to outbreaks worldwide. Because there is little or no pre-existing immunity in the population, the strain is highly pathogenic, thus causing disease among those who become infected. Infected individuals may be capable of transmitting the virus strain for 1 to 2 days before developing symptoms. Pandemics arise periodically but unpredictably and can cause successive waves of disease lasting for up to 3 years. In recent years, the H5N1 strain and other strains of the influenza virus have emerged or re-emerged. Experts are concerned because of similarities between the H5N1 strain and the H1N1 strain, which caused the 1918-19 pandemic. For example, research suggests that both the H5N1 and H1N1 strains prompt an over-reaction of the inflammatory response in humans, causing rapid and severe damage to the lungs. Although the H5N1 strain has not been easily transmitted among humans, influenza experts believe that H5N1 or another new influenza strain may eventually mutate to become highly transmissible. Pharmaceutical interventions available during a pandemic include vaccines and antivirals. Pharmaceutical interventions are the primary methods used to prevent the spread of disease as well as to reduce morbidity and mortality caused by the influenza virus. See table 1. Vaccination is the primary method for preventing infection with the influenza virus. Vaccines reduce the severity of disease or provide immunity by causing the body to produce protective antibodies to fight off a particular virus strain. In order for a vaccine to be most effective, it needs to be well-matched to a particular strain of the influenza virus so that the antibodies formed in response to the vaccine protect against that strain. However, existing strains of the influenza virus can mutate into new strains; in part, this is why a new vaccine is created each year for the upcoming influenza season. Much of what is known about the anticipated effectiveness of a pandemic vaccine is based on evidence from the annual seasonal vaccine. During a pandemic, it may be necessary to use a vaccine that was developed prior to a pandemic and therefore may not be well-matched to the pandemic-causing strain. This vaccine, called a pre-pandemic vaccine, is developed using an influenza strain that experts believe is likely to cause the next pandemic. Research exploring the use of a pre-pandemic vaccine based on strains of the H5N1 virus suggests that it may provide some protection against serious illness and death. In contrast, a pandemic vaccine would be developed against an identified pandemic- causing strain and would likely provide better protection against the pandemic strain. It is likely that seasonal influenza vaccine manufacturers will produce the vaccine used during a pandemic. However, for the 2007-08 influenza season, only five vaccine manufacturers were licensed to produce seasonal influenza vaccine for the United States and only one manufacturer produced its vaccine from start to finish in facilities within U.S. borders. We also recently reported that experts are concerned that countries without domestic manufacturing capacity will not have access to vaccine in the event of a pandemic if the countries with manufacturing capacity prohibit the export of pandemic vaccine until their own needs are met. Antivirals can reduce symptoms and help prevent the spread of influenza by suppressing the growth of the influenza virus. Unlike the immune response triggered by a vaccine, antivirals target the virus itself. For example, some antivirals interfere with the virus’s ability to attach to cells, thereby preventing infection of human cells. Antivirals also differ from vaccines in that they do not need to be reformulated to match a specific influenza strain in order to be effective. In addition, antivirals can be manufactured and stockpiled in advance, making them potentially available at the beginning of a pandemic. HHS currently maintains a stockpile of antivirals in the SNS. However, as we have previously reported, there are limitations associated with relying on antivirals during a pandemic. For example, the effectiveness of antivirals during seasonal influenza has been limited if they are used more than 48 hours after the onset of symptoms in an infected individual. For prophylactic use against seasonal influenza in healthy individuals, antivirals may not be as effective if they are not taken throughout the entire time an outbreak is present in a community. Some influenza strains have become resistant to the antivirals currently approved for prevention and treatment, and thus, the antivirals may not always be effective in preventing disease. In addition, antivirals, like vaccines, take several months to produce, and the lead time needed to scale up production capacity may make it difficult to meet any large-scale, unanticipated demand immediately. As we recently reported, current antiviral production capacity is inadequate to meet expected demand during a pandemic. Further, antivirals can be expensive to stockpile and difficult to administer, depending on the form in which they are given. For example, Tamiflu is given as a capsule or liquid and is relatively easy to administer, whereas, Relenza, is more difficult to administer because it is a powder that must be inhaled using a special device. Since 2000, we and others have reported that federal, state, and local officials need to have information on target groups that have priority for receiving pharmaceutical interventions to know how, where, and to whom to distribute the interventions. We reported that having established target groups is particularly crucial in times of limited supply, such as during a pandemic, when a lack of specific guidance makes it difficult for federal, state, and local officials to plan. For example, in a prior report, we noted that health officials in one state did not know exactly how many individuals were considered a priority for receiving a vaccine. In that case we found that it took state officials nearly a month to compile data on high-risk individuals, to decide how many doses of vaccine were needed in local areas, and to receive and ship vaccine to counties. State and local officials rely on federal guidance when making decisions on which groups should be targeted first for vaccination. For example, in a prior report on the 2004-05 influenza season, when the United States lost approximately half of its seasonal vaccine supply because of manufacturing difficulties, we found that CDC quickly revised its recommendations on who should be prioritized for vaccine. CDC’s changes decreased the targeted population from approximately 188 million to 98 million. State and local officials we spoke with for this report told us that they quickly adopted CDC’s revised recommendations. Since the terrorist attacks on September 11, 2001, public health departments and hospitals have been considered vital elements of emergency preparedness and response efforts. Surge capacity in public health departments and hospitals will be critical to pandemic response given the large number of people expected to require medical care. During a pandemic, hospitals will need to provide care for influenza patients as well as continue providing care for other patients. A pandemic will put a severe strain on the health care system, which already is easily overwhelmed by seasonal influenza outbreaks. Seasonal influenza results in more than 200,000 hospital admissions and 36,000 deaths in the United States every year, and hospitals were stretched to capacity in some past seasonal influenza outbreaks. A severe pandemic would overwhelm hospitals in the United States. For example, using HHS’s planning assumptions, authors of one study estimated that influenza patients would need the equivalent of 191 percent of available staffed non- ICU beds and 461 percent of available staffed ICU beds. A pandemic would occur in the context of existing health care provider shortages. Shortages of health care providers, including physicians and nurses, have been reported for many years by GAO and others. For example, the Association of American Medical Colleges recently released a report summarizing studies issued by 15 states between 2000 and 2007 regarding physician shortages in the United States. That report found that many of these states reported shortages of physicians in specialties such as primary care, cardiology, and endocrinology. Similarly, a recent survey of chief executive officers by the American Hospital Association found that as of December 2006, hospitals across the country reported having an estimated 116,000 registered nurse vacancies. That survey also found that nearly half of emergency departments are operating at or above capacity. Partly in response to these workforce shortages, Congress passed the Pandemic and All-Hazards Preparedness Act (PAHPA) in December 2006. Among other things, the law requires the Secretary of HHS by 2009 to identify strategies to recruit, retain, and protect the public health workforce from workplace exposures during public health emergencies, which would include pandemics. In addition, PAHPA established the Office of the Assistant Secretary for Preparedness and Response to coordinate activities between HHS and other federal departments, agencies, and offices and state and local officials responsible for emergency preparedness. Nonpharmaceutical interventions are measures used to reduce the impact of a communitywide infectious disease outbreak without the use of pharmaceuticals. Examples of nonpharmaceutical interventions include isolation, quarantine, social distancing, and infection control (see table 2). Slowing the spread of disease during a pandemic will be particularly important given anticipated shortages of pharmaceutical interventions and the expectation that a severe pandemic will overwhelm the health care system. Experts have suggested that nonpharmaceutical interventions can help the health care system by reducing the anticipated influx of patients by limiting the rate of disease transmission (see fig. 1). In the past, nonpharmaceutical interventions have been used in some cases to successfully slow the spread of infectious disease outbreaks. For example, during the 1918-19 pandemic, local public health officials relied on nonpharmaceutical interventions—including rules forbidding overcrowding in streetcars and bans on public gatherings—to slow the spread of disease. More recently, during the global outbreak of severe acute respiratory syndrome (SARS) in 2003, nonpharmaceutical interventions were also implemented to slow the spread of disease. For example, we reported that nonpharmaceutical interventions, such as closing two hospitals to new admissions, appeared to be useful in Canada’s management of the SARS outbreak.