SUPPLEMENT ARTICLE Pandemic Preparedness: Pigs, Poultry, and People versus Plans, Products, and Practice Julie L. Gerberding Centers for Disease Control and Prevention, Atlanta, Georgia Influenza pandemic preparedness planning is critical for reducing human suffering and negative effects on the economy and society. The Centers for Disease Control and Prevention (CDC) is working to ensure a rapid, efficient, and successful response to an outbreak if, when, and where it appears. The CDC s context for strategic planning is based on experiences with seasonal influenza and what is known about past influenza pandemics. From a public health perspective, pandemic preparedness can be achieved with a plan that builds a network of shared responsibility from the local to the global level, with a focus on saving lives with vaccines, antiviral drugs, medical supplies, containment, and communication. Seasonal influenza results in 36,000 deaths and 1200,000 hospital admissions in the United States every year [1, 2], resulting in significant economic impact. Despite the availability of an effective vaccine, there continues to be significant morbidity and mortality as a result of seasonal influenza. Why people choose not to receive the influenza vaccine and why society has allowed this infectious disease to remain such a major force of morbidity and mortality are important questions that need to be addressed. Influenza pandemics have occurred regularly throughout history, but it is not possible to predict when the next pandemic will occur. Novel strains of the influenza virus have crossed over into the human population at several points in recent history (figure 1). The emergence of the H5N1 variant presents the possibility of another pandemic. Forty million people died during the 1918 influenza pandemic. Establishing why these people died may provide valuable information that could assist in prepa- Presented in part: Seasonal and Pandemic Influenza 2006: At the Crossroads, a Global Opportunity, Washington, DC, 1 2 February 2006 (for a list of sponsors and funding, see the Acknowledgments). Potential conflicts of interest: none reported. Financial support: supplement sponsorship is detailed in the Acknowledgments. Reprints or correspondence: Dr. Julie L. Gerberding, 2072 Somervale Ct., Atlanta, GA 30329 (jlouisemd@yahoo.com). The Journal of Infectious Diseases 2006; 194:S77 81 This article is in the public domain, and no copyright is claimed. 0022-1899/2006/19409S2-0004 ration for the next pandemic. However, little is known about the clinical events that contributed to these deaths that is, about the precise cause of mortality. The traditional view has been that infectious diseases of a bacterial nature were the proximal causes of death in many patients, particularly in the preantibiotic era. A review of the clinical data available from 1918 1919 revealed that bacterial superinfection was not the cause of death for the majority of people [3]. A variety of other causes have been suggested, but it is not clear which are the most likely mechanisms and whether any could present further opportunities for treatment or intervention in a future pandemic. The H5N1 virus, like the 1918 H1N1 virus, is a particularly virulent strain and is capable of causing high mortality, often from acute respiratory distress syndrome. Table 1 presents the potential impact of a pandemic today, on the basis of the prior experience of a relatively moderate pandemic, such as the one that occurred in 1957, and a more severe pandemic, such as that which occurred in 1918. Regardless of viral virulence, a similar percentage of the population would become infected under either scenario. The virulence of the virus would determine the proportion of patients that would require hospitalization or mechanical ventilation and who may die. Even the effects of a moderate pandemic would exceed the surge capacity of US hospitals, intensive care units, supply chains, and domestic production systems. Therefore, in addition to stockpiling strategies for vaccines and antiviral drugs, there is an urgent need to Pandemic Preparedness JID 2006:194 (Suppl 2) S77
Figure 1. address the whole production and supply chain for the durable medical goods that would be required in the event of a pandemic. As a consequence of the lack of surge capacity in medical supply production, the Centers for Disease Control and Prevention (CDC) is considering support for research into controversial areas, such as evaluating whether washing masks for reuse provides some level of protection to health care workers. The more severe pandemic scenario presents an enormous challenge in determining how medical supplies, in a just-in-time delivery system, would be made available for patient care. Infection with the H5N1 virus has resulted in a regional pandemic in poultry, which now includes Europe and Africa (figure 2). The proximity of humans to domestic poultry and pigs in parts of Southeast Asia presents a major challenge for controlling the evolution of a pandemic. Most attention has been devoted to direct bird-to-human transmission. However, pigs have also been infected with the H5N1 virus. The H5N1 strains in clade 2 are genetically distinct from those in clade 1. Likely, there will be continued progression and evolution of the H5N1 virus, resulting in a combination of changes that leads to more sustained human-to-human infection. To summarize avian influenza today, there is widespread prevalence in migratory birds, continued outbreaks among domestic poultry in expanding geographic locations, documented mammalian infection, and continued evolution of the virus. There have been 1200 human cases, with a case fatality rate 150% and rare cases of person-to-person transmission. The Evolution of novel influenza subtypes only remaining factor that would facilitate a pandemic is the ability of the virus to cause sustained and rapid person-toperson transmission. The US government has a specific doctrine, which provides a framework for planning. This includes the following: If there is a threat anywhere, then there is a threat everywhere. In the event of an outbreak of a novel strain of influenza in humans, the CDC will collaborate with global health authorities to attempt to quench it, regardless of country of origin. This requires the preparation of CDC international response teams to work bilaterally, regionally, or in collaboration with the WHO; the ability to detect and diagnose the virus and to have reliable and accurate information available as quickly as possible on Table 1. Event Planning assumptions. Moderate pandemic (1957-like) Severe pandemic (1918-like) Illness 90 million (30%) 90 million (30%) Outpatient medical care 45 million (50%) 45 million (50%) Hospitalization 865,000 9,900,000 ICU care 128,750 1,485,000 Mechanical ventilation 64,875 745,500 Death 209,000 1,903,000 NOTE. Data are estimated nos. of events and are from [4]. ICU, intensive care unit. S78 JID 2006:194 (Suppl 2) Gerberding
Figure 2. H5N1 surveillance
the front line; and strategies for implementing isolation for sick patients, administering antiviral prophylaxis, social distancing, and animal culling. If an outbreak happens in a small geographic area, it may be possible to quench it with these strategies. However, if an outbreak occurs in a large metropolitan area, involves many people, or has gone undetected for some time, then these strategies will not do any more than slow the progress of a pandemic, and other measures will be required to mitigate its effects. Prevent or at least delay introduction into the United States. Strategies to protect the US population could involve the introduction of travel advisories or possible entry or exit screening. The CDC s Quarantine and Border Health Stations are situated at strategic entry points into the United States and could be involved in identifying individuals entering the United States who required isolation or quarantine. More border health stations are being established. Slow spread, decrease illness and death, buy time. The United States will not be immune to a pandemic, so the third phase of the strategy is to slow down the spread of the disease and reduce illness and death, allowing time for the development of pandemic vaccines. Actions implemented locally by public health officials and infection control professionals may include antiviral treatment and isolation for people infected with influenza, quarantine for those exposed, social distancing, and vaccination. Clearly communicate to the public. Training in emergency risk management is being implemented at the state and local level. The CDC has produced resources to facilitate emergency risk management, which can be found on its Web site (http://www.cdc.gov/flu). Most people prefer to receive information from their personal doctors during health emergencies. Therefore, efforts are in progress to ensure that the medical community is engaged before a pandemic and that it is kept up to date with developments during the course of one. Preparedness for influenza is a network of shared responsibility and must be much broader than a federal activity. This will require a bigger and broader effort than any prior health care initiatives that have previously been undertaken in the United States. All sectors of communities, including the business community, the education sector, health care delivery organizations, faith-based organizations, and community organizations, must be engaged to assist in planning at a local level. The federal government will take the lead with the stockpiling of antiviral drugs and vaccines and in the development of other countermeasures, such as new vaccines. Resources have been developed to assist in involving other governmental and societal bodies in the planning process. These include checklists and performance metrics, which are available at http://www.pandemicflu.gov/. Allocation and distribution of these countermeasures will need to be planned and coordinated by state and local leaders. Pandemic preparation will also result in greater preparedness for seasonal influenza. Only 86 million doses of vaccine were manufactured in preparation for the 2005 2006 influenza season in the United States. Even so, more vaccine is produced each year than is administered. On the basis of evidence-based guidelines, the CDC estimates that 180 million people in the United States require annual vaccination. There is a significant gap between the amount of vaccine that is needed, the amount that is requested by individuals, and how much can be produced. Additional effort is required to educate and motivate a greater proportion of the population, especially those at greater risk, to request vaccination. Ultimately, consumer demand will lead to increased production and uptake of vaccines. In comparison, childhood vaccination programs in the United States routinely have 190% success rates. These programs are largely financed by the public sector, with the CDC and states having a large role in controlling the distribution and administration of vaccines. In contrast, the CDC and states have a limited role in the distribution and administration of adult vaccines. As a result, there are larger financial risks for adult vaccine providers, because of the reimbursement nature of health care provision, and there is no clear lead for accountability for the success or failure of a program. Therefore, it is important that, in addition to focusing on developing more vaccines, the practical elements of administering a large-scale influenza vaccination program are also addressed. Preparing for an influenza pandemic is a wise investment that is highly likely to pay off. First, we save lives with modern vaccines and antiviral drugs during seasonal influenza outbreaks. In addition, communities will be better prepared for a pandemic and other large-scale health threats. And, perhaps most importantly, we will have peace of mind, knowing that we have vaccines ready when we need them, where we need them, for all who need them. Acknowledgments I thank Richard Whitley and John Fry for their assistance in the preparation of this manuscript. The Seasonal and Pandemic Influenza 2006: At the Crossroads, a Global Opportunity conference was sponsored by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the National Institute of Allergy and Infectious Diseases, and the Centers for Disease Control and Prevention. Funding for the conference was supplied through an unrestricted educational grant from Gilead Sciences, GlaxoSmithKline, Roche Laboratories, MedImmune, Sanofi Pasteur, Biota Holdings, and BioCryst Pharmaceuticals. Supplement sponsorship. This article was published as part of a supplement entitled Seasonal and Pandemic Influenza: At the Crossroads, a S80 JID 2006:194 (Suppl 2) Gerberding
Global Opportunity, sponsored by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the National Institute of Allergy and Infectious Diseases, and the Centers for Disease Control and Prevention. References 1. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289:179 86. 2. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004; 292:1333 40. 3. Stevens KM. Cardiac stroke volume as a determinant of influenzal fatality. N Engl J Med 1976; 295:1363 6. 4. US Department of Health and Human Services. HHS Pandemic Influenza Plan part 1: strategic plan. Available at: http://www.hhs.gov/ pandemicflu/plan/part1.html. Accessed 16 August 2006. Pandemic Preparedness JID 2006:194 (Suppl 2) S81