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Institute of Medicine (US) Forum on Emerging Infections; Knobler S, Lederberg J, Pray LA, editors. Considerations for Viral Disease Eradication: Lessons Learned and Future Strategies: Workshop Summary. Washington (DC): National Academies Press (US); 2002.

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Considerations for Viral Disease Eradication: Lessons Learned and Future Strategies: Workshop Summary.

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6The Challenges to Post-Eradication Outbreaks

OVERVIEW

As the United States enters the post-eradication era, it is critical that we develop thoughtful institutional strategies to meet the challenges of potential reintroduction or re-emergence of disease. The waning of surveillance and laboratory diagnostic capability, reduced medical awareness, lack of vaccine supply and production capacity, limited institutional response capacity, decreased immunity in the population at large, and increased threats of bioterrorism all leave the non-immunized populace highly vulnerable to a post-eradication outbreak. Planning for the post-eradication era will likely warrant consideration of major outbreak scenarios and the required capacity for response.

Hospitals serve as a major hub in the U.S. health care system and can and should play a major role in an outbreak response. However, they have neither the capacity nor infrastructure to handle such a crisis, and there are no financial incentives or mandates in place to encourage them to devote efforts to anticipate potential outbreak scenarios. There is an enormous amount of work to be done to prepare hospitals for the post-eradication era.

Because of the increasing threat of bioterrorism, especially with regard to smallpox, planning for potential outbreaks in a post-eradication era should involve consideration of national security implications in addition to public health considerations. Although health care workers would be the sentinels of any outbreak response, no matter what the security implications, a bioterrorist act may require the involvement of other communities, such as intelligence and defense and arms control, that may not typically be involved in outbreak response. The appropriate agencies and institutions must be prepared to offer a swift and effective collaborative response.

Preparing for unexpected disease outbreaks also requires a flexible and adaptive post-eradication vaccine program involving continued vaccine production, research, and development. Vaccine manufacture must keep up with changing regulatory requirements (e.g., safety issues concerning the threat of prion-mediated diseases from animal protein components of vaccines), new scientific challenges (e.g., alterations to the virus), and changes in the manufacturing process.

Institutions must be prepared to deal with the psychological challenges expected to surface during a post-eradication outbreak, namely, fear and panic. Well-trained responder staff, effective communication regarding the risks of infection and exposure, and a swift, well-coordinated public health response will be key in promoting a healthy public reaction.

Although U.S. institutions may be starting to take some steps in preparation for a post-eradication era, much of the developing world lags far behind. Many countries are not only still struggling with early eradication initiatives—for example, immunizing all children and developing effective communications networks—they are doing so in the face of adversity. Many developing countries lack not only immunization services but basic health care services as well, and are in the midst of conflict situations where vaccinators are being killed in the field.

This issue of equity has increasingly become a component of global health concerns. Access to limited quantities of vaccines has been debated as a human rights issue. Within the United States, this focus has been on the uninsured and underserved populations. More broadly, in developing countries—where the ability to pay for vaccines and maintain appropriate infrastructure for vaccine delivery remains quite limited—the responsibilities of international organizations, national governments, development banks, and private-sector suppliers are raised as a challenging ethical question.

READY OR NOT: THE U.S. HEALTH CARE SYSTEM AND EMERGING INFECTIONS

, M.P.H.

Senior Fellow, The Johns Hopkins University Center for Biodefense Studies, Baltimore, MD, and Former CEO, Georgetown University, Medical Center, Washington, DC

The preparedness of the U.S. health care system to respond to future disease outbreaks—accidental or intentional—deserves careful consideration. A caveat may be in order here, however, as this topic will force us to descend from the Olympian heights of scientific discourse to the arid plains of bureaucracies, institutions, and politics. This presentation will focus on hospitals, clinics, and home care agencies—what is commonly termed the “U.S. health care system”—as opposed to the public health system, whose readiness is addressed elsewhere in this report.

To the question, “Are we prepared?” the answer, in my opinion, is emphatically negative. This lack of readiness is characterized by:

  • lack of capacity and infrastructure,
  • lack of incentives and mandates,
  • absence of networks of collaborating institutions, and
  • unresolved staffing and legal policy issues.

It is worth noting that there may be legitimate conflicting perspectives on what role the U.S. health care delivery system should play in response to an epidemic that constitutes a major public health threat. This paper supports the notion that the acute health care system can and ought to play a very important, but delimited, role in helping the nation respond to future outbreaks. Following is an assessment of the four problems listed above. Their solutions are critical to an effective health care system response.

Capacity and Infrastructure Issues

In order for the health care system to respond effectively to a potential disease outbreak, the health system must be operating reasonably effectively prior to the outbreak. That is, a certain amount of basic functionality, organizational infrastructure strength, and extra capacity (i.e., availability of drugs, equipment, supplies, and personnel) will be a sine qua non of an effective response. If hospitals and physicians are already struggling to handle day-to-day operations due to a lack of staff, equipment, and other core capacities, it will be impossible for them to respond effectively to a significant crisis.

Unfortunately, U.S. hospitals are currently experiencing tremendous economic pressures. One-third of all hospitals are losing money. Of the two-thirds that are still profitable, their margins declined by a third between 1998 and 1999. Their profitability is only 4.7%, which is only slightly above the medical Consumer Price Index (CPI). In addition to the Balanced Budget Act of 1997, which reduced aggregate hospitals' Medicare payments by more than Congress intended, hospitals face a host of new regulatory demands including HIPAA (Health Insurance Portability Act), which industry analysts estimate will cost the sector more than did Y2K preparedness efforts. Other regulatory pressures include ergonomic regulations, patient safety regulations, and major seismic upgrades (for California hospitals), to cite just a few.

The problems hospitals currently face are not only financial. The most acute operational issues relate to staff shortages—including nurses, technologists, pharmacists, technicians, nurses' aides, housekeepers, medical records coders, and others. Current staff levels are insufficient for hospitals to cope even with the small and entirely predictable seasonal influenza epidemics. To cite a few examples:

  • In December 1999, during the flu season, three-quarters of the Los Angeles emergency rooms were so full that, for 10 days, they had to reroute ambulances to other hospitals.
  • In Maryland, the amount of time that hospitals are on “emergency by-pass” has doubled each year for the past three years.
  • In San Antonio, the city's Emergency Medical Services physiciandirector was quoted in a New York Times article by C. Goldberg, “Emergency Crews Wary as Hospitals Say, ‘No Vacancy,’” December 17, 2000, as saying “We're dying; I got called nine times yesterday to divert my ambulances—and that wasn't an unusual day. We've got an epidemic of the nonavailability of acute care beds, and the epidemic is becoming a pandemic.”

Because the population is aging and academic enrollments in key health care professions have declined, most observers are worried that these infrastructure problems will only become worse. In the same New York Times article mentioned above, the director of a suburban Boston ER, for example, likened ERs to canaries in the coal mine: “We are basically the canary that's telling the story that the whole system is in trouble, its capacity is inadequate to meet the peak demands.”

In addition to chronic infrastructure deficiencies, hospitals lack the capacity to handle “surges” of new patients. For example, a 1998 survey of medical resources for the state of Minnesota revealed that only 60 of 144 acute care hospitals—only 465 beds state-wide—had negative air pressure rooms, which are critical tools for managing patients with highly contagious diseases (Osterholm and Schwartz, 2000). As another example, a recent fire in a downtown high-rise motivated the Maryland Secretary of Health to commission a study which revealed that the city of Baltimore, home to two major medical centers and medical schools, could not handle a situation involving only 100 casualties needing overnight ventilators (O'Toole, 2000).

After two decades of hospital reimbursement policies based exclusively on market principles, hospitals now operate on a “just in time—just what's required” basis which governs the availability of drugs, supplies, equipment, and staffing. In the process, we have lost sight of the historic concept of the hospital as a community resource that is always ready in the event of disease outbreak.

Incentives and Mandates

Among the range of issues with which hospital executives deal on a daily basis, a potential disease outbreak—whether accidental or as a result of bioterrorism—is a low-probability event that competes for attention with more pressing, and more certain, matters. Currently, hospitals have neither incentives, such as funding, to prepare for future outbreaks, nor a legal mandate to do so.

Since the Reagan administration, the United States' policies governing hospital reimbursement have been fundamentally free-market-based. This has led to economic competition among hospitals within a community, as well as the notion that hospitals that support “issues of the commons” (e.g., care for the poor, medical education, biomedical research) without receiving full reimbursement are doing something “economically irrational.” Spending significant dollars preparing for bioterrorism, or a similar event on behalf of the community, would trigger a red flag to a hospital's managed care payers, who would think they were overpaying (Bentley, 2000).

This does not imply that hospitals would not respond in the event of a crisis. In fact, American hospitals have a record of extraordinary response when disaster strikes. The point is that, without preparedness funding, it is economically irrational to expect or hope for preparatory efforts on the part of any individual health care organization.

In addition to a lack of incentive for hospitals' preparatory efforts, there is no mandate requiring such activity. Currently, the closest thing to a hospital mandate is a Joint Commission on the Accreditation of Health Care Organizations (JCAHO) requirement that every hospital have emergency plans and drills in place to cover a broad range of potential disasters.

Legal mandates and financial incentives will likely be required to catalyze hospital response on this issue. At least four types of financial protection will be necessary:

  • Funds to help hospitals address fundamental capacity and infrastructure deficiencies,
  • Funds for outbreak response planning and preparedness,
  • Compensation for direct patient care in the event of an outbreak, combined with a loosening of the usual requirements for detailed corroborating documentation, and
  • Reimbursement for extraordinary institutional costs.

In addition, immunity from liability will be necessary in the context of actions that outbreak management typically entails: triage decisions, dealing with immuno-suppressed populations, mandatory vaccination, and quarantine.

Regional Collaborative Networks

An effective community response to an outbreak will require that multiple health organizations and the public and private sectors respond in a highly integrated fashion. This collaboration must bridge at least three distinct health communities—public health, emergency management/first responders, and medical care delivery—each of which has its own culture, language, and decision-making processes. All three communities will need to be linked with local and state elected and government authorities, law and order institutions, state laboratories, military hospitals, the Centers for Disease Control and Prevention (CDC), and other agencies.

However, substantial communications and knowledge barriers exist within and among all of these various health agencies. For example, a recent TOPOFF exercise, named for its engagement of top officials of the U.S. government, was held in Denver in spring 2000. It tested the readiness of government officials and agencies to respond to a bioweapons event. In an assessment of TOPOFF, a number of the participants noted that different professions practiced different decision-making processes. One observer commented that, “In public health, most decision-making is through democratic processes and consensus-building, but for some decisions, this cannot work.” Another observer remarked, “The time frame that public health is accustomed to dealing with is not what is needed for bioterrorism. In this type of crisis, one needs to make decisions quickly. You don't have the luxury of time to do more research.” One public health official noted a widespread lack of familiarity with terms—such as a JIC (Joint Information Center), a JOC (Joint Operations Center), or DMORTs (Disaster Mortuary Assistance Teams)—used by the emergency management community (Inglesby et al., 2001).

As another example of a communications barrier, during the West Nile outbreak in New York City in 1999, an infectious disease physician from one of the boroughs notified the New York City Department of Health about two suspected cases of encephalitis. In the meantime, 20 other patients with encephalitis had already been admitted to other NYC hospitals. Although encephalitis is clearly recognizable and is considered a legally reportable disease in New York, none of those other 20 cases had been called in (O'Toole, 2000). Even if these cases had been called in, the capacity of the health agency to respond adequately is uncertain. Dr. John Bartlett, Chief of Infectious Disease at Johns Hopkins University School of Medicine, conducted an experiment two years ago in the Hopkins emergency department, during which he simulated a patient with a case of inhalational anthrax. During this exercise, which occurred during a summer weekend, no one he contacted either inside or outside the Hopkins hospital was certain about which telephone number to use or which state official to notify (Osterholm and Schwartz, 2000). Finally, a call was made to the state public health officer and an urgent message left on an answering machine. Due to a lack of beepers in the public health department, the call was not answered until three days later.

Although the federal government has initiated efforts to create linkages among the emergency management and public health services in 50 to 60 cities nationwide, no region has yet truly integrated emergency management, public health, and medical services. An effective regional network requires adequate funding, designation of an in-charge organization and individual, and development of a regional response plan that would need to be rehearsed, critiqued, and modified as appropriate. Among the many challenges to overcome are the climate of competition among hospitals, distrust across the public-/private-sector divide, and communications and cultural obstacles among the multiple health communities.

Staffing and Legal/Policy Issues

Several groups of hospital executives have assembled over the past year under the auspices of the Johns Hopkins Center for Civilian Biodefense and the American Hospital Association (supported by the Department of Health and Human Services' [DHHS'] Office of Emergency Preparedness). Their objective has been to identify issues and barriers to hospitals' response to bioterrorism. One set of concerns pertains to hospital staffing, specifically:

  • Staff shortages, which cut across multiple professional and nonprofessional categories, are national in scope (in the case of nursing, international) and, given declines in academic enrollments for some professions, will likely be long-lasting.
  • For many health care professions (including physicians, nurses, and pharmacists), licensing restrictions prohibit individuals from practicing across state borders. If unaddressed, this will act as a barrier to importing physicians and nurses from outside crisis areas.
  • Seventy to eighty percent of hospital staff are female, the majority of whom are heads of households or are responsible for the care of family members. In the event of a major epidemic, which could last for weeks or months, the issue of family support becomes critical (Bentley, 2000).
  • Personal protection in the form of immunizations and access to antibiotics for staff and their families is a critical issue. It is unclear how health care staff will respond to future outbreaks, though it may be instructive to look back at workers' and professionals' concerns during the early days of the AIDS epidemic.

A second set of concerns pertains to legal issues. For example, the Emergency Medical Treatment and Labor Act (EMTALA) was designed to prohibit hospitals from refusing treatment to uninsured patients and sending them to other hospitals. The legislation requires each hospital to screen and stabilize every patient, even during a disease outbreak when it is likely that a hospital's emergency room may be closed for containment purposes. Also, different hospitals may have different roles in a public health emergency; for example, some may be used solely for quarantine, others for triage, and still others for specialized treatment. Thus, during an outbreak, not all hospitals may be capable of screening and stabilizing every patient. The EMTALA was not designed with an era of emerging infections in mind (Bentley, 2000).

EMTALA may be just the tip of the iceberg of unresolved legal and public policy issues, many of which relate to the fragmented U.S. legal system. For example, the legal powers that authorize response in a public health emergency are divided between the national and local levels. Interestingly, legal power may depend on whether an epidemic is deemed to be natural or intentional; national security law might apply in the case of the latter (Fidler, 2000).

A legal system that emphasizes protection of individual rights, while restricting government powers from impinging on such rights, creates additional potential barriers to an effective public health response. For example, citizens might ignore government orders, such as travel bans, quarantine, or compulsory treatment directives, which could, in turn, increase the likelihood that military intervention would be necessary to enforce public health (Fidler, 2000).

Conclusion

It would be inappropriate to conclude without putting into a larger context the challenge of preparing our health care system to respond to future epidemics. As previously mentioned, there may be legitimate conflicting perspectives on what role the health care system should assume in the event of a major public health crisis. These perspectives are buttressed by age-old differences in skill sets and attitudes between the medical and public health disciplines, and by large cultural gaps between triage and treatment, containment and continuous quality improvement, and isolation and architectural openness. A Stanford University Hospital analysis found that the routine hospitalized patient encounters over 30 different hospital employees during an average 24-hour period—hardly an ideal environment from which to try to contain an epidemic. Nonetheless, hospitals can and should play a major role in outbreak response:

  • The population will undoubtedly continue to seek hospital care for diagnosis, treatment, and prophylaxis. The absence of treatment facilities could contribute to public panic.
  • Hospitals are socially and geographically well-established arsenals within their communities, constituting well-known loci where professionals, equipment, supplies, and information technology come together in the service of local communities.

However, it is remarkable how quickly local hospital capacity is overwhelmed in many, if not all, epidemic-response scenarios. There is a need for sophisticated modeling of a range of hypothetical outbreaks, using current hospital capacity data. More importantly, we should explore all reasonable mechanisms to help hospitals substantially expand their capacities to handle mass surges of people (by incremental hundreds or even thousands) in the event of a major epidemic. One option, for example, might be to create expandable bio-containment units, which would be selfcontained but placed adjacent to hospitals. Such units might enable the use of the existing hospitals' organizational infrastructures, supplies, and personnel, while providing a simple but epidemiologically sound setting for the triage and treatment of far more individuals than the institutions' emergency rooms or clinics could safely handle. Similarly, we might explore the feasibility of training a cadre of hospital-based epidemiologists, current EMS physicians, and new staff. These suggestions and speculations are offered as a point of departure for future discussions on how best to help America's health care system prepare for inevitable disease outbreaks.

VACCINES FOR POST-ELIMINATION CONTINGENCIES

, M.D.

Vice President, Research and Medical Affairs, Acambis Inc., Cambridge, MA

Vaccines have been by far the most efficient means to prevent and control infectious diseases. Smallpox eradication was achieved through vaccination, and the eradication of poliovirus and measles will be achieved when the prevalence of artificial immunity is sufficiently high to preclude interhuman transmission. The benefits of disease eradication achieved through vaccination include life years gained; savings to patients, families, and society due to reduced morbidity and mortality; avoidance of costs for treatment and continued vaccination; indirect cost savings due to increased productivity; and the freeing-up of health care resources for other interventions. Following successful eradication, a responsible policy must include provisions for vaccine reserves and contingency planning in case the disease re-emerges; surveillance and diagnostic activities; and research on and development of new vaccines and therapeutic drugs.

Rationale for Vaccine Reserves

Because surveillance and case-finding may be difficult, particularly in medically underserved regions, disease eradication may be uncertain for several years after the last reported case. During this period of watchfulness, rumors of disease and case and outbreak investigations will continue, and vaccine must be available in the event of re-emergence. The means by which a disease could be reintroduced after presumptive elimination are listed in Table 6-1. For smallpox and other diseases under consideration for potential elimination—polio, measles, and rubella—no enzootic or nonhuman reservoir has been identified as a source of reintroduction; thus, the principal risks are human factors, inadvertent escape of laboratory stocks, and intentional release (bioterrorism or biowarfare). The consequences of reintroduction become increasingly grave over time due to the decline of herd immunity, susceptibility of the population to a pandemic, senescence of surveillance and laboratory diagnostic capability, and reduced medical awareness.

TABLE 6-1. Sources of Disease Re-Emergence After Eradication.

TABLE 6-1

Sources of Disease Re-Emergence After Eradication.

Smallpox as a Case Study

When smallpox was eradicated in 1979, re-emergence was dismissed as highly unlikely for several reasons:

  • There was no enzootic reservoir; monkeypox and other zoonotic poxviruses related to the smallpox virus were not considered a significant source for the reintroduction of human pox virus.
  • There were only a limited number of laboratories working with smallpox, and confidence was high that all laboratory stocks had been identified and destroyed. Reference materials were deposited in only two laboratories, one in the United States and the other in the Soviet Union.
  • There was no evidence that smallpox virus could persist or be reactivated in previously infected humans.
  • There was a high degree of confidence that vaccine reserves (approximately 200 million doses deposited at WHO) were adequate for any contingency and vaccine manufacture could be reinstated if necessary.
  • There was little concern about any threat posed by biowarfare (BW).

In the United States, vaccine manufacture ceased in 1982, and immunization of soldiers ceased in 1989 (Table 6-2).

TABLE 6-2. Smallpox Vaccination History, United States.

TABLE 6-2

Smallpox Vaccination History, United States.

Smallpox was dismissed as a bioweapon in part because all countries, including the USSR, had participated actively in eradication of the disease. It was, therefore, a surprise to learn that the Soviet Union, a nation engaged in the eradication effort, would simultaneously engage in surreptitious, state-sanctioned activities that could result in disease reintroduction. Moreover, smallpox has undesirable features as a bioweapon for several reasons: the disease is easily diagnosed; attribution of an attack would be obvious; the virus is transmissible and could backfire on non-target populations; the incubation period is long and its effect on a target population delayed; and a vaccine is available and routinely used to protect military forces.

The fallacy of these conclusions was not apparent until the early 1990s, after a defector from the former USSR revealed that smallpox was considered a strategic (not tactical) weapon. Development of smallpox as a BW agent had begun shortly after World War II, and the virus had been fully deployed in strategic weapons (Alibek, 1999). Intelligence leaks suggested that countries other than the former USSR were investigating smallpox as a BW agent as well, and by 1998, smallpox was widely considered the preferred biological weapon for terrorist activities (Henderson et al., 1999). By this time, it was recognized that U.S. vulnerability was enhanced by a deficient vaccine reserve since no vaccine had been produced since 1982, and the remaining static stockpile had partially deteriorated (LeDuc and Becher, 1999). The result was a complete shift in the policy for vaccine reserves within the public health sector (Table 6-3). In September 2000, the Centers for Disease Control and Prevention issued a contract to Acambis, Inc. (formerly known as OraVax, Inc.) for manufacture of a national stockpile of 40 million doses of a modern cell culture vaccine approved for use by the U.S. Food and Drug Administration (FDA).

TABLE 6-3. Vaccine Policy After Smallpox Eradication.

TABLE 6-3

Vaccine Policy After Smallpox Eradication.

Meanwhile, motivated by the hypothetical BW threat, the deteriorating vaccine reserves, and unacceptable characteristics of the original calf-lymph vaccine, the U.S. military had reinstated a vaccine development program in 1988. Its original objective was to produce a new cell culture-derived vaccine that could be administered by parenteral injection (thus avoiding the local cutaneous lesion responsible for auto- and accidental inoculation). Although some headway was made over the following twelve years and three small clinical trials conducted, the military program did not advance beyond pilot lot manufacture and investigational status, and it did not address the larger public health concerns.

Bioterrorism and Vaccine Reserves

These events emphasize how the changing landscape following disease eradication affects vaccine policies. The threat of deliberate release will remain the most significant rationale for a responsible and conservative policy. Measles, a highly infectious agent that would cause significant morbidity in non-immune adult populations, is another potential BW agent. Even poliovirus, which is far less transmissible and has a high infection:case ratio, should not be dismissed. The pathogenesis of poliovirus delivered as an aerosol could be fundamentally different from that of the naturally occurring disease.

The size of a vaccine reserve after elimination of these diseases must be carefully considered. The stockpile should be disease-specific and dependent on the prevalence of immunity required to break transmission. Transmission dynamic modeling may be useful in determining the size of the vaccine reserve. In the case of smallpox, limited data from the pre-vaccine era may provide a baseline for prediction. For measles, data on outbreaks in developing country populations with very low immunization coverage could be used. Similarily, polio outbreaks prior to the introduction of vaccine could provide data from which the spread of the the disease in an unprotected population may be modelled. While these examples may not offer exact models, they provide some basis for estimating the potential impact of outbreaks in the post-eradication era and thus, an appropriate size of a vaccine reserve.

Rationale for Continued Manufacture, Research, and Development

In retrospect, the decision to terminate smallpox vaccine manufacture, research, and development at the time of disease eradication and, instead, rely on existing stocks of vaccine to meet emergent contingencies was fallacious. The political, regulatory (i.e., regulatory requirements pertaining to vaccine safety), and scientific (e.g., genetic modifications to the disease agent) landscapes are expected to change significantly over time after elimination of any infectious disease agent. These changes require a supply of indate vaccine, combined with continued vaccine research and development.

As examples of changing regulatory requirements, several unforeseen safety issues have arisen within the last decade:

  • The risk of prion-mediated diseases resulting from the incorporation of bovine and human derivatives (fetal calf serum, human serum albumin, gelatin, and lactose) into vaccines.
  • Concern about mercury, which has resulted in the removal of thimerosol from vaccines.
  • Concern about adventitious agents, which has resulted in new quality control tests, including assays to detect replication-competent retroviruses and new standards for residuals (in particular, DNA). For example, in the case of smallpox vaccine, the static stockpile preserved at the time of eradication was produced in bovine tissue from individual animals that had not been tested for adventitious agents. Given the popular concerns about vaccine safety, it is easy to imagine the outcry of concern if the smallpox vaccine stockpile were to be activated.

Vaccine Manufacture After Disease Elimination

To ensure an adequate supply of vaccine that meets current good manufacturing practices requirements, at least one U.S. manufacturer of the vaccine in question should maintain active production and testing after disease eradication. This would require that master and working seed viruses be periodically tested under a formal stability program, and that the volume and number of containers of working seed are adequate to meet contingencies for scaled-up production. Since bulk can be stored for longer periods than final containers, a large supply of bulk vaccine should be kept frozen and ready for filling and finishing, although the filled vaccine stockpile must be sufficient to meet emergency requirements. As noted previously, the number of vials stored for this purpose will be determined by transmission modeling based on a worst-case scenario. New bulk vaccine and filled containers will be replenished on a schedule determined by stability data; expertise and experience of the corporate manufacturing and control personnel will be maintained; and the facilities, equipment, production process, and quality control methods will be continually validated. The Biologics License should be maintained, and regulatory staff (at FDA) should remain familiar with the product. By following these guidelines, the capability for surge production will be ensured.

Change from profitable to orphan product

Elimination of the disease will have a profound effect on the commercial status of the respective vaccine(s). In particular, vaccine status will change from large-volume, profit-driven markets to an orphan product. Large-scale continuous production will need to be modified in order to meet the demands of the new, smaller scale of the vaccine reserve program, which might entail campaigned production in shared facilities. This smaller scale will undoubtedly increase unit dose costs. Moreover, new security requirements will need to be imposed to protect seeds and vaccine, and biocontainment levels may increase in order to prevent escape of the virus from the facilities. These changes are likely to make the vaccine reserve program less profitable and more troublesome, with the result that the original manufacturer(s), typically large pharmaceutical companies, may lose interest. Therefore, it will be necessary to supplant commercial sales with a government supply contract. If smaller, “hungrier” biopharmaceutical companies become engaged in the government-sponsored vaccine production, a period of technology transfer, process validation, and possibly bridging clinical trials, may be required. Technology transfer requires infrastructure and expertise and may take several years (or longer) to accomplish.

Vaccine stability

Vaccine stability is the key factor in determining the scale and schedule of vaccine reserve manufacture. Stability is both vaccine- and virus-specific, as well as temperature-dependent. Bulk vaccine can be stored for considerably longer than can final, filled containers. For example, polio and measles vaccine bulks can be stored frozen for ten years, whereas final filled containers of measles and inactivated polio vaccines have shelf lives of two and three years, respectively. Real-time stability studies are necessary to establish expiration dating and would need to be repeated if vaccine manufacturing were transferred from one company to another.

Surge capacity

A key element in planning for post-elimination contingencies is the capacity of the vaccine manufacturer to scale-up production without changing the validated manufacturing process. The primary response to an emergency would involve using stored bulk vaccine to produce filled vials. However, it should be noted that approximately three months are required to fill vaccine and complete release tests. Seed stocks and cell banks must be available in sufficient supply. Manufacturing could be expanded by simply increasing the number of bioreactors (production vessels) and production suites. However, surge manufacturing must conform to validated processes so that no new regulatory problems arise. Production scale could be modestly increased (e.g., tenfold) without significantly changing the manufacturing process, although it is advised that the scaled-up process be tested and validated in advance.

New distribution requirements

In the post-elimination era, the fundamental approach to vaccine distribution will change, from routine childhood immunization programs to emergency mass immunization campaigns. In lieu of direct sales to private physicians, sales through physician supply houses, and local health department routine immunization programs, the federal government will prepare to distribute vaccine in the context of an emergency program. The storage and distribution system must be consistent with federal emergency planning, and packaging and labeling must be consistent with the intended use under emergency conditions. Methods for rapid large-scale vaccine administration must also be considered, since safety concerns preclude use of the multi-dose jet-injector. If new devices replace the original jet-injector, it will be necessary to conduct clinical trials with the reserve vaccine(s) to demonstrate immunogenicity.

Vaccine liability

After disease elimination, the vaccine status under the National Vaccine Injury Compensation Program would change, since the program currently applies only to routine pediatric vaccines. In the case of smallpox vaccine, which was never covered by the program, the manufacturer (Acambis, Inc.) contracted by CDC to produce new vaccine in response to bioterrorism threats was required to indemnify the government against tort claims. This was especially difficult because of the relatively high incidence of serious adverse events expected with widespread vaccine usage. Private insurance was obtained at a high cost to the government. A more costeffective alternative would be to amend the Public Health Service Act so the government could indemnify the manufacturer.

Re-Initiating or Changing Vaccine Production

Since biological products cannot be characterized as discrete, singlecomponent chemical structures, they are controlled primarily by demonstrating consistency of manufacturing. Changes to the manufacturing process or vaccine composition, which may affect vaccine performance, require significant effort in terms of validation and clinical testing. Old vaccines that undergo such changes are considered new vaccines by the regulatory authority, and new requirements not applicable under grandfather approvals may be imposed. Examples include: 1) programs for redevelopment after lapsed production (e.g., vaccinia virus formerly made by Wyeth and now redeveloped by Acambis); 2) modernization of the vaccine manufacturing process and facilities (e.g., anthrax vaccine formerly made by Michigan State Laboratories and now by Bioport); and 3) transfer of manufacturing (e.g., influenza from Parke-Davis to King Pharmaceutics, and yellow fever vaccine from Wellcome to Evans Vaccines). Each of these cases required a considerable, lengthy effort. For example, Acambis' accelerated vaccinia production will require approximately five years from project initiation to establishment of a new national vaccine stockpile. Problems associated with changes in the manufacturing process should be anticipated in the event that old vaccines, such as polio, are transitioned from routine use to a vaccine reserve status.

Vaccine Research and Development After Disease Elimination

After a disease has been eliminated, the natural tendency is to reduce both public and private funding for research and development. This causes a rapid erosion of technical expertise and capabilities to meet new and unforeseen contingencies. In the case of smallpox, this erosion was mitigated by the use of vaccinia as a live vector for vaccines and gene therapy. However, it is unlikely that polio and measles virus expertise will be maintained after eradication without a dedicated effort. Future threats may require modifications to the antigenic profile of vaccines; new studies on the immunological basis for protection; and the ability of vaccines to protect against strains having altered pathogenesis or route of infection. To meet these needs, a strong federally-sponsored research program must be maintained.

STRATEGIC PRIORITIES FOR ADDRESSING POST-ERADICATION OUTBREAKS

, M.D.

Colonel, U.S. Air Force and Professor, Military Strategy and Operations, National War College, National Defense University, Washington, D.C.

The eradication of globally significant diseases is properly entrusted to the public health and medical communities. However, the long-term implications of such efforts, including the possibility of natural or deliberate post-eradication outbreaks, may have security as well as public health consequences. The possible security implications of disease eradication should be assessed at the outset. This involves determining what, if any, bioterrorism, biological warfare or serious epidemic risk the agent represents and what steps should be taken to minimize those risks.

Five strategic priorities that should be addressed in a post-eradication outbreak are:

  1. recognize that it is occurring;
  2. contain its possible spread and mitigate its effects;
  3. characterize it;
  4. if possible, prevent its recurrence; and,
  5. if necessary, hold those responsible accountable.

Since the last documented endemic case of smallpox in 1977, the only other known occurrence was limited to a laboratory accident in 1978. The smallpox success story, however, illustrates the possible paradoxical security outcome of viral eradication. While the natural occurrence of this disease is a distant memory, the prospect of a deliberate post-eradication outbreak as the result of a terrorist attack or act of war is now considered credible. The non-immune status of the majority of Americans, coupled with a limited national capacity to respond to an outbreak, leaves a significant vulnerability which terrorists or adversaries could threaten to exploit.

The later stages of the public health effort to eradicate smallpox were not effectively synchronized or coordinated with the Department of Defense (DoD) attempt to assess the national security implications of the overall effort. This asynchrony left several notable shortfalls. The U.S. government did not invest in the preservation of capacities to produce and maintain adequate supplies of smallpox vaccine; it did not ensure the development of appropriate diagnostics; and it did not conduct research into antiviral therapies or assess the efficacy of existing vaccine to counter a smallpox biowarfare or terrorist threat. These issues contributed to the U.S. policy decision to delay the ultimate destruction of the remaining known smallpox cultures.

Eradication-Associated Security Assessment

Without careful consideration, the successful eradication of other diseases could result in similar scenarios, where the suspension of immunization practices and loss of vaccine production capabilities could lead to increased public health vulnerability and possible national security consequences. Prudent public health and national security policies require a formal assessment process to determine if eradication could lead to such a paradoxical security outcome. Central to this assessment is consideration of a possible natural or deliberate post-eradication outbreak. Eradication is a public health and medical responsibility, but assessing the possible security implications is a multidisciplinary process involving several non-health participants—including intelligence, arms control, law enforcement, and defense communities—whose roles would be distinct from but supportive of the actual eradication process.

The fundamental question to answer in an eradication-associated security assessment is, what is the disease's biowarfare and epidemic potential? Most of the information needed to answer this question should already be available. Factors that need to be considered include disease virulence, transmissibility, environmental stability, and the availability of diagnostics, prophylaxis, and treatment. Infectious agents that lend themselves to biowarfare or bioterrorism should receive greater security scrutiny than ones that do not in an effort to narrow the list of agents requiring further review, contingency planning, and possible resource investment.

Intelligence and Arms Control Issues

If the disease agent has biowarfare potential, its inclusion in formal biological arms control negotiations could be a logical next step. A legally binding protocol to the Biological Weapons and Toxins Convention (BWTC), which is currently being negotiated, may include provisions that take into account disease eradication efforts. It may be possible and desirable to give special prohibited status to eradicated diseases. The nature of the prohibitions, and possible consequences for violating such provisions, would be determined largely by the terms of the eradication agreement and the nature of the disease agent. Linking the arms control process with the eradication effort combines the formal legally and politically binding commitments of a multilateral arms control treaty with the moral commitment of a public health action.

Verification and transparency are additional arms control concepts worth considering during disease eradication efforts. Verification is a formal, legally binding certification mechanism between participating parties. It is the process one uses to ascertain the compliance of parties with an agreement, and it represents the confidence one has about that compliance. It also serves as a potential incentive for compliance. For the purposes of eradication, the verification process could assist in determining, with a high level of certainty, whether a disease has been eliminated from all natural reservoirs and been accounted for in laboratories and all other possible repositories.

Arms control verification can never be 100%. It may, however, serve as a useful theoretical framework and possible metric when considering possible security implications. For example, if one's verification process is strong and confidence in verification high, possible security issues are different than if the process were weak and confidence low. Historically, biological arms control verification has been considered problematic, if not impossible. Microbial agents, equipment, and processes to produce them can be used for both peaceful as well as prohibited uses. The dual-use nature of microbial research, development, and production are considered major impediments to achieving effective verification. Instead, biological arms control promotes the concept of transparency that provides openness about certain activities, like biodefense for example, that could be matters of concern but refrains from making any formal treaty determination about those activities. Transparency of only selected activities can build confidence in compliance while implicitly acknowledging the inherent limits of and low confidence about verification.

Intelligence and arms control issues should be considered and addressed appropriately. The intelligence community has the ability to collect and assess information that can help determine whether the disease agent in question has biowarfare potential or has been researched or developed as such, and whether nations or groups may seek to develop that agent as a weapon. Most importantly, intelligence can assist in assessing compliance with the terms of the effort. By collecting all source information, they may be able to determine whether the intent of participating parties is consistent with their overt actions. Thus, their involvement is vital to helping establish a level of confidence in compliance with the eradication process.

Department of Defense's Role in the Eradication Process

The DoD has both the clinical and laboratory resources to play several possible roles in the eradication process. For example, as part of theater engagement plans, military medical units provide medical support and assistance, including vaccination, to developing nations on an on-going basis. Similarly, several overseas military laboratories offer regional laboratory expertise that can, and has, supported eradication efforts.

The DoD is responsible for assessing the potential impact of eradication campaigns on the future health and operational effectiveness of U.S. military personnel. Immunizations are administered either upon entry into the armed forces or prior to deployments into areas where endemic or biowarfare threats are considered significant. While the natural foci of disease may be eliminated, suspension of immunizations for active and reserve military personnel follow a different set of priorities than in the civilian sector. The nature of the disease and its potential operational impact must be considered, as well as any and all intelligence that may provide insight into adversaries' intentions or capabilities to use the agent for biowarfare purposes.

The military's need to protect its troops goes beyond vaccines; it also involves diagnostic capabilities, possible biodetection technologies, chemoprophylaxis, and therapeutics. The military has an obligation to engage early in the eradication process. A security review offers an opportunity to assess what capabilities are needed to protect America's armed forces from future threats.

With the current concern about bioterrorism and asymmetric warfare, the public health community may find the defense approach to threat assessment and capabilities development relevant. If the agent subject to eradication is deemed to be of biowarfare or serious epidemic potential, the DoD's requirements for diagnostics, detection technologies, vaccines, and prophylactics may also be applicable. From a public health perspective, it may also be valuable to conduct age-stratified longitudinal studies to assess and monitor the changing status of the population's immunity. Over time, the population's immune status may become an indicator of vulnerability, which may help guide policy-making and later resource allocation.

Planning for Future Security Risks

Once it has been determined that a disease may have future security implications, the five priorities cited earlier become the functional basis for planning. Recognizing a possible post-eradication outbreak is the first and foremost priority. An extensive, interconnected global and national surveillance and laboratory system must be able to recognize and confirm the event. The sentinels of this system, however, are health care workers. While a disease may be eradicated, there may still be a need to ensure that primary care providers have sufficient clinical knowledge and index of suspicion about the disease to include it in their differential diagnosis. To this end, laboratory diagnostics that can confirm the diagnosis must be available.

Following immediate recognition, a prompt response is necessary to contain and mitigate the outbreak's morbidity and mortality. Depending on the agent, an international response may be required to augment individual national capabilities, as well as address the possible risk of regional or global spread. Vaccines and other products may be required. Stockpiles, pharmaceutical surge capacities, and logistics to move these supplies will determine the timeliness and effectiveness of the response.

Outbreak characterization and containment should occur simultaneously. In addition to traditional “shoe leather” and molecular epidemiology, other types of information, including intelligence sources, may be required to help determine whether the outbreak was a natural occurrence, suspicious, or deliberate. If suspicious or deliberate, there may be a requirement to collect evidence for legal or arms control purposes. Prevention of recurrence is largely dependent on the results of epidemiological and other investigations. Finally, holding responsible parties accountable may depend on the outcome of arms control, law enforcement, and even intelligence investigations. The response to a deliberate outbreak falls into the domain of political and possible legal action beyond the scope of this discussion.

Security Issues Related to Measles Eradication

The case of measles offers a brief illustration of the range of possible security issues related to disease eradication. Measles is an infectious disease agent that offers a realistic target for future eradication: humans are the only natural host for wild-type measles virus; an effective measles vaccine is available; following immunization, immunity to natural infection is long-lived; accurate diagnostic tests are available; and recent regional efforts have demonstrated success in interrupting measles transmission in the United States and Western Hemisphere.

Should a concerted effort be initiated to achieve global eradication, a first step in assessing the possible security implications would be to assess the biowarfare potential of measles. Measles is transmitted by respiratory droplets and is highly contagious. It can remain infective in droplet form in air for several hours, especially in low relative humidity (CDC, 1992), and can be transmitted by airborne spread as aerosolized droplet nuclei. Under these conditions, it is possible that a biowarfare aerosol release of measles virus could result in infection in exposed, non-immune individuals. Measles causes significant morbidity and mortality in children and is even more severe in adults. In one study, 30% of adult cases exhibited bacterial superinfection of the respiratory tract, 17% exhibited evidence of bronchospasm, and 3% developed pneumonia requiring hospitalization (Gremillion and Crawford, 1981).

The biowarfare potential of measles would probably figure prominently into the defense community's assessment of measles elimination. Given the likelihood of significant complications in military-age populations and the possibility of natural or other reservoirs, future DoD vaccination policies would probably have to take into account possible post-eradication outbreaks.

Properly administered measles vaccine results in immunity lasting for at least 16 years (Markowitz and Katz, 1994), but possible security concerns may require further longitudinal studies evaluating the duration of vaccineinduced immunity. Even if civilian vaccine practices were curtailed or discontinued, it may still be necessary to immunize the military or at least maintain a stockpile of measles vaccine, which would require planning and budgeting for an uninterrupted or standby surge production capacity. If the biowarfare threat from measles were deemed credible, the efficacy of the current vaccine might have to be assessed in the context of aerosolized transmission, which would depend on identifying an appropriate animal model for human measles. If researchers found that the vaccine were not entirely protective, research into possible antiviral therapies may be warranted. Surveillance systems would have to be geared to meet a possible measles threat, and rapid clinical diagnostics and detector technologies may have to be researched and developed. These are only a few of the possible issues that may have to be addressed during a security-based review.

Conclusion

Incorporating a national security process into an eradication effort introduces a dimension not commonly encountered in public health debates. On the one hand, it involves activities that strengthen the objective and purpose of the eradication effort. On the other hand, it raises concerns that may be new to public health practitioners. Security reviews may alter the public health community's fundamental expectations for eradication, and raise questions about traditional assumptions concerning disease eradication. For example, the conventional wisdom associating significant financial savings with ending routine immunizations may be challenged. Money saved on immunizations may have to be spent on expanded surveillance and vaccine stockpiling programs, for example. As America enters the 21st century, cognizant of the revolutions in biotechnology and genetics and the prospect of biowarfare, the health and security communities must work together to ensure both public health and national security. Disease eradication supports both imperatives, but the long-term consequences must be anticipated from the outset.

UNDERSTANDING THE PUBLIC AND MEDIA RESPONSE TO AN OUTBREAK

, M.D.

Colonel, U.S. Army Medical Corps, Associate Professor and Associate Chair, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD

A swift, well-coordinated, and effective public health response is the most powerful psychological intervention in a post-eradication outbreak. Through their actions and comments, political leaders, public health experts, and other key figures at the local, state, and federal levels will shape individual and community expectations, beliefs, and behaviors. In particular, the management of the outbreak in the first hours to days sets the tone for societal responses.

Fear and the Public Reaction

Infection by a microorganism taps into very deep-rooted fears of being invaded and destroyed by an invisible force. The lack of sensory cues associated with infection makes it impossible to discern whether or not one has been infected. Many organisms produce ubiquitous symptoms that can go undiagnosed until it is too late to save the victim. A delayed onset between exposure and illness produces tremendous anxiety and uncertainty in those fearing they have been infected. Moreover, much of the public does not have the scientific background with which to understand the outbreak.

By definition, post-eradication outbreaks would produce diseases rarely seen in medical practice. There would be limited medical knowledge about diagnosis, treatment, and outcome in the general community. This poses considerable uncertainty for both physicians and patients. In many countries, an epidemic of a disease that produces a high acute mortality rate will be a new experience. While people can become accustomed to quite terrible circumstances, there is a great possibility of panic when they are exposed to an unfamiliar threat for the first time. For example, the first use of gas and the introduction of machine guns in war both produced panic in the troops. As soldiers became familiar with these weapons, however, panic dissipated. Exposure to the dead and disfigured also produces strong psychological responses and is a potent psychological stressor.

Understanding which aspects of biological agents invoke terror can aid in developing intervention strategies. For example, unrealistic beliefs about microbes and viruses can be addressed through education. Informing people about what they can expect, thereby lessening surprise and affording them a sense of control through predictability, can alleviate uncertainty.

Fear-producing aspects of outbreaks include:

  • the potential for high numbers of casualties;
  • a potentially limited availability of treatments;
  • in some cases, uncertainty about the effectiveness of medical interventions;
  • the possibility of an epidemic involving person-to-person transmission; and
  • dispersion of the ill, which can erode the sense of safety in regions far from the original source of infection.

Based on data gleaned from studies of disasters and observations of past outbreaks, there are certain elements of an outbreak that influence the public's reaction. How an outbreak has arisen has major implications for behaviors. An act of bioterrorism, for example, can be expected to provoke widespread rage which can be difficult to manage with respect to scapegoating. It could also result in ill-advised policy decisions made in the heat of the moment. Grotesqueness has been demonstrated to be a powerful predictor of strong emotional responses. Diseases like smallpox and hemorrhagic fevers, such as Ebola, evoke terror in many people. The larger the outbreak, the more strain it places on the community. The disruption of basic community functions and normal activities adds secondary psychological and behavioral stressors.

The media will play a major role in determining how the public reacts following an outbreak. In a climate of uncertainty and fear, the public will thirst for information to help them gauge their personal risks. Radio, television, and the Internet should be used to provide accurate, non-sensationalized information in order to control rumors and provide instructions on personal safety measures.

Psychological responses to outbreaks of eradicated disease can include: the attribution of somatic symptoms to intoxication and infection, scapegoating and stigmatization, and social isolation and paranoia, which contribute to the development of conspiracy theories and mistrust. As the outbreak continues, people may become demoralized and lose their faith in the institutions that are supposed to protect them. All of these responses are influenced by cultural and religious views about causality, death, and dying. Therefore, it is very difficult to generalize findings across cultures and over time.

The Nature of Panic

The word “panic” is often used to describe psychological responses to disease outbreaks. Panic refers primarily to a group phenomenon in which intense, contagious fear causes individuals to think only of themselves. They become paralyzed by fear or seek to escape by any means necessary. Panic also refers to an individual response characterized by the loss of rational thought due to overwhelming terror. A major goal of preparation and response for a post-eradication outbreak is the prevention of panic and the preservation of individual, group, and community function.

In examining historical responses to epidemics, Garrett (1994) has made the following observations:

Panic does not always go hand in hand with epidemics, nor does its scale correlate with the general gravity of the situation. Indeed, history demonstrates that population responses to diseases are rarely predictable, often peculiar.… Where a hefty dose of public concern was warranted, as in the case of the 1918–19 [influenza] pandemic, an oddly common feature was nonchalance.… In contrast, public reaction to the 29 deaths in Philadelphia [Legionnaires' disease] was extraordinary.… Phrases like “explosive outbreak,” “mysterious and terrifying disease,” “Legionnaire killer,” and “killer pneumonia” filled press accounts as well as the oncamera statements of Philadelphians and politicians.

As this statement implies, the way the news is covered shapes the public response to an outbreak.

Panic is rare following disasters. For example, panic did not occur following the Tokyo sarin attack; although thousands of people sought medical care after the sarin attack, they were orderly and obeyed instructions, and first responders and hospital staff managed their responsibilities well. However, this may not happen during an epidemic. The risk factors for panic are:

  • surprise and novelty,
  • the belief that there is only a small chance of escape,
  • seeing oneself as high risk for becoming ill,
  • available, but limited, resources in which there is a situation of “first come, first served,”
  • a perceived lack of effective management of the catastrophe, and
  • loss of credibility of authorities.

The government and medical community will play large roles in shaping the public's reaction. Medical responses will be scrutinized for efficacy and fairness. For example, political and medical decisions about what groups to vaccinate first, or which groups will be given highest priority for a limited supply of vaccine, may have a chilling effect. These decisions may also affect those responsible for providing medical care and other essential community services. For example, a question that frequently arises in the first responder community is, “In the event of a contagious agent, would our families be given high priority as well as us?” Policy makers must address how decisions in this area will be made and explained to the public. Protocols should be developed for these scenarios in order to mitigate panic and minimize the risk of poor decisions in the midst of a crisis.

The provision of accurate knowledge is an important determinant in whether panic will occur. Even if the news is very bad, knowledge is preferable to uncertainty in which fantasies and rumors run rampant. Providing inaccurate news or lying to the public results in loss of credibility that cannot be regained, as was seen at Three Mile Island and in Surat, India.

Untrained or mistrained responders can cause group breakdown and institutional panic, which would not be reassuring to the public if it occurred in a hospital, for example. There are several factors that could contribute to group disorganization and institutional breakdown:

  • distrust prior to the event,
  • a breakdown in communication,
  • failure of critical elements,
  • poor leadership, and
  • a perception that there is no effective response.

Realistic simulation training maximizes the probability of people performing their roles well by identifying key personnel and facilitating the development of personal relationships. It minimizes panic by teaching decision- making and problem-solving skills under calm conditions, rather than during the chaotic time of an actual response.

While panic may not be evident during a crisis, there will likely be significant numbers of the “worried well” seeking medical evaluation. The signs and symptoms of anxiety are protean and ubiquitous. People who have been exposed to infection often worry that they are becoming ill when they experience anxiety symptoms. Following an outbreak, well-designed risk communication can reassure low-risk citizens that they are not sick, thereby reducing the number of people seeking hospital evaluation.

Now, despite having devoted so much time to a discussion of the multidimensional nature of panic, it may be wise to strike the word “panic” from our lexicons. Telling people not to panic may, in fact, reinforce the behaviors we are trying to prevent. Also, in terms of trying to understand and develop predictive models about how the public will behave, it is far more helpful to explicitly describe the behaviors rather than lumping them under the rubric of “panic.”

Historical Examples and Post-Outbreak Interventions

Following the SCUD attacks on Israel during the Gulf War, for every ill or injured casualty seeking medical assistance, there were four non-ill behavioral casualties seeking aid. This phenomenon has also been observed during disease outbreaks. Furthermore, medical and hospital support personnel are not immune from fear-organized behaviors, such as absenteeism and decreased performance, especially in circumstances where emergency and health personnel are worried about their families.

The 1994 outbreak of pneumonic plague in Surat, India, illustrates how fear-organized behaviors can dominate the public's response to an epidemic. This is true despite the fact that, in this case, the organism was susceptible to antibiotics. Stigma and social isolation had economic as well as psychological consequences, and fear of disease dissemination eroded feelings of safety in many parts of the world. Communicating the risks and managing fear, anger, and paranoia should be major intervention objectives in the wake of a post-eradication outbreak.

Overdedication—people continuing to work despite suffering the effects of fatigue from sleep deprivation and intense mental and physical activity—is a common problem in crisis situations. There are scores of case examples in which exhausted leaders have made poor decisions which have endangered others. Protocols need to specify plans for rotating all personnel. This is especially critical in situations in which the outbreak may extend from days to weeks to months.

The tendency of the science community to debate and criticize as a way of seeking the truth will not reassure the public and may actually lead to the loss of credibility. A number of experts have emphasized the need for “one voice” to provide information to the public. While this is a laudable goal, it may be unreachable given the long-standing traditions of scientific discourse. We need a better understanding of how the public should be trained to anticipate and cope with the diverse, and often conflicting, information that will be disseminated in the wake of an outbreak. For example, following the midwestern U.S. floods in 1997, there were discrepancies in the amount of time residents were told to boil their water by different government agencies. In the face of this confusion, how did people decide what to do? Discrepancies between what leaders and experts are telling people to do and what they, themselves, are doing, will not escape media notice and will undermine the credibility of the authorities.

Recommendations

  • Multiple research methodologies must be employed to address the psychological and behavioral consequences of a post-eradication outbreak.
  • Policies on the distribution of limited resources, such as vaccine and antibiotics, should be informed by behavioral research and ethical review.
  • Planning for the behavioral and psychosocial aftermath of a posteradication outbreak requires a multidisciplinary effort involving political, medical and mental health leaders, governmental and social institutions, and the citizenry.
  • While developing outbreak policies, the emotional and physical impact of a major disease outbreak on leaders must be taken into account in order to ensure rational, informed decision-making during the crisis.
  • Research should be directed toward delineating how best to enlist media support in the management of outbreaks.
  • The behavioral and societal effects of past infectious disease outbreaks should be studied systematically and a taxonomy developed which can be used to identify the effects and course of responses to outbreaks. These studies should examine responses in individuals, families, small groups, hospitals, and communities. The review should also examine the response to past uses of mass quarantine, evacuation, immunization, and isolation. Information gleaned from these studies can serve as the basis for hypotheses which can be tested in future outbreaks.
  • Infectious disease specialists, risk communication experts, public officials, and members of the media should develop communication and information programs for each disease of concern. Effective risk communi- cation after an attack will be key in promoting healthy and constructive public behaviors and reducing fear-organized behaviors. These programs should designate who will inform the public, and they should delineate the specific actions recommended for citizens to minimize their possibility of falling ill. Messages must be specifically designed for each segment of the population, based on available information and input from credible community leaders.

POST-ERADICATION CHALLENGES IN THE DEVELOPING WORLD

, M.P.H.

Worldwide Polio Eradication Coordinator and Senior Technical Advisor for Health and Child Survival. Bureau for Global Programs, U.S. Agency for International Development, Washington, D.C.

The U.S. Agency for International Development (USAID) provides foreign assistance to developing countries and maintains offices and ongoing programs in nearly every country of the developing world. Immunization has long been a hallmark of AID's child survival activities. In 1996, at the urging of Rotary International, Congress directed USAID to establish a global polio eradication program that would provide a minimum of $25 million per year for polio-specific activities. The rationale for this earmark was based on the success of the eradication efforts in the Americas, where USAID had been the largest external donor, and on the belief that savings would come once vaccination could stop. Annual estimated savings from vaccination costs alone ranged from $230 million per year in the United States to $1.5 billion globally, in perpetuity, once immunization ceased. Because of a complex budget structure and earmarks for USAID, much of the funding had to come out of existing resources, primarily routine immunization programs. Knowing the enormous challenge of immunizing children and establishing certification-standard surveillance in the most difficult- to-reach areas of Africa and South Asia, often under conflict situations, as well as concerns regarding cessation of immunization, USAID entered into this commitment with skepticism. However, once engaged, the commitment has been strong and visible, with hopes that USAID, working closely with its partner organizations, would leave a long-term legacy behind.

I have listened carefully to the presentations over the last few days and the doubts being raised about the feasibility of stopping polio immunization. If true, USAID is in a very difficult position. We have pledged to maintain political, financial, and technical involvement until the world is certified polio-free, even if the road is bumpier and longer than originally planned. Any lessening of the effort at this point in the eradication program would be a signal to other donors and to host country governments that they can retreat. This risks halting the momentum currently enjoyed by the program as well as setting the stage for polio cases to resurge to pre-eradication levels—100 times what they are today. USAID does not want to send this signal without seriously considering all of the scientific data and opinions, how the public and Congress would perceive it, and what it would mean in terms of USAID's credibility.

While many reputable scientists and virologists are firm in their belief that polio eradication is feasible and immunization can safely stop at some point in the near future, others, equally strongly, believe that polio immunization may never cease. If the funds spent on eradication cannot be recouped, then how do we tell our constituents—the children in developing countries—that we have invested nearly $1.8 billion thus far, and that this amount is increasing, for an activity that may never be stopped. In the meantime, in a district in Zambia, for example, it costs about $11 per capita to provide an essential package of basic health services, but currently available resources amount to only $5 per capita. Access by developing countries to limited supplies of vaccine stockpiles and costs to contain potential outbreaks in the post-eradication era, raise additional issues of equity and public health priority.

This is a very serious issue. The need for eradication and anticipating post-eradication needs must be balanced with the general health needs of the children, while at the same time maintaining USAID's integrity and credibility in the eyes of the public, Congress, host countries, and other stakeholders.

There are a number of other important issues that must also be addressed while considering eradication. Eradication programs have consequences, both opportunities and threats, beyond wiping out a virus. First, the great need to provide every child with basic preventive health care, including immunization. House-to-house strategies are no longer enough for delivering polio vaccine, so USAID and its partners are now going childto- child, which requires intensive effort looking for children in places where we have never looked before. Like the homeless here on the streets in Washington, D.C., it is easy to simply walk by them. But we cannot do this in the slums of Calcutta, for example. To achieve polio eradication we must find and immunize every child. Once we find them how can we ignore them for other services? How do we bring the same intensity of effort and find the resources to bring basic preventive services to them as well?

Second, polio eradication is helping to build or revitalize many aspects of health infrastructure in developing countries. One example is the important area of communications. Most laboratories in developing countries did not have dedicated phone and fax lines until USAID helped pay for them in their effort to establish an effective laboratory network for acute flaccid paralysis (AFP) surveillance. With foresight and planning, the laboratory network will extend beyond AFP, but in order for this to happen, objectives need to be outlined from the beginning. Even if eradication efforts fail, the network is a legacy that must continue if we are ever to build a stronger system of health services. It is this type of global communication system that will alert us to outbreaks of disease and enable us to take corrective action. USAID considers this a good investment for polio eradication and for protecting the United States.

Finally, conflict situations are posing tremendous challenges in many developing countries. In the Eastern Congo, for example, administering vaccinations requires negotiating with the Congolese rebels to set aside certain days of peace—something I have personally done. Despite all goodfaith negotiations, it is impossible to control all factions or undisciplined soldiers who shoot anybody they see. Everyone from volunteers, to health workers, to staff of U.N. organizations, to donors, regularly demonstrate acts of courage and put themselves at risk in an effort to vaccinate children. Sometimes, these acts of bravery are a step toward peace-building. Sometimes, vaccinators die while conducting eradication activities. CDC, to their credit, has established a Heroes Fund for the many vaccinators who have died since polio eradication started. We should not enter eradication efforts lightly without thinking of these people who are giving up their lives for the sake of eradication.

USAID is proud of our involvement in polio eradication and our contribution to reducing the death, disability, and social stigma that accompanies the disease. The global program can be proud of the success so far; thousands of cases of polio have been prevented; children that might have been paralyzed are walking, will marry, be involved in economic activities, and be vital members of their communities. USAID leadership to maximize the benefits of polio eradication, to raise awareness of the health needs of children, and to seek peace will have provided a great service—regardless of whether immunization can cease or not.

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Copyright © 2002, National Academy of Sciences.
Bookshelf ID: NBK98115

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