Pandemics and Preparations

The history of humankind is replete with plagues [1, 2], but it is tempting to believe that we are now so advanced that lethal epidemics can be easily prevented and controlled. Can new plagues still emerge in this modern world? Without a doubt, the answer is “yes.” We must only consider AIDS to understand that the spread of HIV has been facilitated by many of the central characteristics of modern life. In reality, the extraordinary advances in modern civilization and medicine offer only partial protection against plagues, substituting control of some (e.g., smallpox) with the emergence of others (e.g., bioterrorism). Our means to control plagues are both ancient (taboos, quarantine, and isolation) and modern (vaccinations, mathematical modeling, and molecular epidemiology).

We now are grappling with issues surrounding influenza. Once established, influenza is highly contagious among humans and, as with other communicable diseases, often difficult to predict in its occurrence and scale [3, 4]. Are we really at risk for pandemic influenza? Most experts believe that we are, but they are uncertain about when, where, and how severe the next pandemic will be. Influenza virus strains are always circulating among humans, and there is a large and variable reservoir of animal strains with the potential to jump to humans or to recombine with human‐adapted strains. Currently, there is an extensive epizootic of avian influenza due to an H5N1 strain that already has jumped to humans, although relatively infrequently, but with apparent high mortality and with occasional spread from human to human. On a global scale, the effects on humans have been minor, but there is great concern that we are at risk for something worse, analogous to the 1918–1919 influenza pandemic [5, 6]. The “Seasonal and Pandemic Influenza 2006” meeting held in Washington, DC, on 1–2 February 2006 and this supplement of the Journal of Infectious Diseases address these issues.

Our vulnerabilities to plagues such as pandemic influenza can be summarized. We live in an increasingly smaller world where, thanks to the advances in transportation, an outbreak in a remote village can be spread to major cities of the world in days, and from there, everywhere. Because of the progress of public health and modern medicine, there are probably more people alive today who are compromised—the elderly, infirm, and immunocompromised, as well as people living with compensated chronic diseases—than ever before. Not only would they be among the hardest hit by a communicable disease, but they also very possibly could preferentially spread the infection to others. The public health infrastructures in the United States and across the world have not kept pace with our growing vulnerabilities.

Faced with a threat of unknown timing and severity, what can we do? Our national government and many state and local public health departments have begun to prepare. They should be commended for doing so. I submit that those efforts must be strengthened, and we must do so now. Even if pandemic influenza does not arrive for decades, planning and preparation can help in many ways. Preparing for pandemic flu is like living in a floodplain and building levees: it is a great deal of effort, and for 49 years of 50, there is no real benefit. But in that fiftieth year (which could be any year), if you do not have the levee, you are in trouble. Preparedness is like insurance: you pay an annual premium to guard against catastrophic consequences. But preparedness is more than that, because it is not merely an averaging of risk but a means to mitigate a crisis. Our nation recently witnessed another natural calamity, Hurricane Katrina, in which failures in long‐term preparations and in short‐term coordination and communication led to catastrophic outcomes. We must learn from this disaster, because, unlike the experience of Hurricane Katrina, in which one locality was devastated but the rest of the country was intact and could respond, with a pandemic virtually all areas are affected; there are no reinforcements, except as planned and organized in advance. This is a somber reality.

However, preparation for pandemic influenza has many collateral benefits for dealing with the ordinary seasonal influenza, other infectious diseases, outbreaks, and other natural and human‐made disasters. A few examples should be illustrative. Rapid and type‐specific clinical diagnosis of influenza and of resistance to antiviral agents is currently not adequate for managing a pandemic [7]. Improved diagnostic technologies not only would help us in a pandemic but also would provide models to use for control of other infectious diseases. Research to develop new antiviral agents should help to combat seasonal influenza and other viral diseases for which our therapeutic armamentarium is limited [8]. Advances in the technologies involved in rapidly preparing large quantities of high‐quality vaccines to abort a pandemic will improve our ability to combat seasonal influenza and many other vaccine‐preventable illnesses. Efforts to improve vaccine manufacturing and distribution capabilities will have similar benefits [9]. Establishing effective surveillance systems will lead to the creation of new cooperative networks with veterinarians [10] and between countries, as well as to the development of new mathematical, epidemiological, and molecular tools for understanding pathogen transmission and evolution [11]. Greater understanding of the pathogenesis of influenza, especially with pandemic strains [12, 13], will expand the knowledge base relevant to other infectious diseases. Knowledge of the ecological issues underlying avian influenza [10] provides models of global and local ecology, as well. Finally, a concerted effort to combat pandemic influenza could lead to a more widespread understanding among the general public about infectious disease risk and control, public health, the need for cooperation across political boundaries [14], and, with luck, to a greater appreciation of Darwinian evolution, which underpins not only influenza emergence but all of biological science and medicine.

How do we get from here to there? In this supplement, the authors provide a number of intermediate steps that can be introduced as they become ready. Notable examples include universal seasonal influenza immunization [15], which creates the political, social, medical, and economic infrastructure on which to build a pandemic control program. Development and deployment of a stockpile of current antiviral agents [8] and materials [16] and practice drills to optimize distribution are critical. Training health care workers and educating the general public will also be key. Surveillance of influenza cases [4], extending our library of molecular genotypes [17] and of their patterns of spread [18, 19], and examining their development of resistance [20] all build our knowledge base. The existing US government doctrines [21] provide a framework for a program of responses, which the Infectious Diseases Society of America has worked to shape (for the Society's comments on the US Department of Health and Human Service's Pandemic Influenza Plan and other policy statements, see the organization's Web site, available at: http://www.idsociety.org/Content/NavigationMenu/Resources/Avian_Pandemic_Flu/Avian_Pandemic_Flu.htm). Central to all these efforts is the need for funding and for legislation that would support advanced development of critical products, such as vaccines and drugs.

There are large challenges, and the forecast requires an ambitious agenda of work. If the storm comes tomorrow, we must do the best we can. But if the storm comes 10 years from now, we will not want to know that we were warned but wasted the opportunity to build our levees. In 1905, Santayana wrote, “Those who cannot remember the past are condemned to repeat it” [22]. More than a century later, we must apply this admonition to the challenge of pandemic influenza. We also must remember that epidemics strain the social fabric. The disease and dislocation themselves impede the control measures and also destabilize community norms; epidemics have been catalysts for social disintegration and revolution [1, 2]. Preparation involves not only the scientific and medical components but also the legal, economic, and security aspects. A strong governmental presence is needed, but, to accomplish that, a fully authorized plan that has been well vetted and well rehearsed must be in place. This involves commitment from the highest levels of government, as well as the coordination of the different international bodies and private agencies. The latter is not a simple task and would ordinarily lag, unless we consider the peril of failure.

For the United States, we need a program on the scale of the Manhattan Project. I estimate that the cost in today’s money is in excess of $25 billion. Thus far, $5 billion has been appropriated through emergency supplemental legislation. This is one‐time funding; we need a sustained effort. Such a commitment, over a period of several years, with cooperation and coordination with other countries should have a strong and lasting impact. The needs are great, but the opportunities are greater still. The meeting and this supplement of the Journal of Infectious Diseases are an admirable effort to both summarize the state of the art and advance our mobilization. Whitley et al. [16] indicate a sense of urgency. I agree; let us not hesitate before it is too late.

Acknowledgments

Supplement sponsorship. This article was published as part of a supplement entitled “Seasonal and Pandemic Influenza: At the Crossroads, a 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.

Potential conflicts of interest: none reported.

Financial support: supplement sponsorship is detailed in the Acknowledgments.