Bioethics and pandemic flu preparedness
Medscape recently published a comprehensive article on pandemic flu preparedness, discussing the history, epidemiology and basic preparedness principles connected with the pandemic flu. Helpful information on disease control and mitigation together with surge capacities in hospitals is also included. [full article below]
Dark Clouds on the Horizon: Preparing for the Next Influenza Pandemic
Infectious diseases have been a source of social disruption, misery, and death throughout human history, and reports of the effects of major epidemics appear early in recorded history. As medical and public health practitioners prepare for the next major influenza pandemic, it is interesting to review the writings of the Greek historian Thyucidides, who described what may have been the first recorded influenza pandemic: the Great Plague of Athens (ca. 430 BC). As Thyucidides (translated by Prof. Rex Warner) wrote:
At the beginning the doctors were quite incapable of treating the disease…[i]n fact mortality among the doctors was highest of all, since they came more frequently in contact with the sick…Words indeed fail when one tries to give a general picture of this disease; and as for the sufferings of individuals, they seemed almost beyond the capacity of human beings to endure…Some died in neglect, some in spite of every possible care being taken of them…no [recognized method of treatment] existed…Those with strong constitutions were no better able than the weak to resist the disease, which carried away all alike…The most terrible thing of all was the despair into which people fell when they realized that they had caught the plague; for they would immediately adopt an attitude of utter hopelessness.[1]
More than 2 millennia later, the devastating 1918-1919 influenza pandemic appeared, again in the context of a massive military conflict. The linkage between influenza pandemic and the mass movement of populations associated with the First World War is unlikely to be a coincidence. It has been suggested that a massive British supply depot at Etaples, in northern France, was the birthplace of the 1919 pandemic strain, with food animals (eg, chickens, ducks, and pigs) and large populations of soldiers living in close proximity necessary to provide opportunities for selection of an avian influenza strain characterized by efficient person-to-person transmission.[2]
At the start of the new millennium, the threat of a potentially devastating pandemic is again on the horizon. In this column, I provide a necessarily brief review of the current issues related to pandemic influenza, including the relationship between pandemic and seasonal influenza epidemiology and control; recent developments in the spread and evolution of the highly pathogenic avian influenza H5N1 virus subtype (HPAI); key concepts in pandemic influenza planning for communities, healthcare institutions, and businesses; and the utilization of both pharmacologic and nonpharmacologic measures for pandemic control. Finally, I review some valuable lessons for pandemic influenza planning in North America that were learned during the 2003 SARS outbreak in Toronto, Ontario, Canada.[3]
Epidemiology of Influenza: Seasonal vs Pandemic
The influenza viruses are orthomyxoviruses, pleiomorphic (variably shaped) negative-sense RNA viruses. The 2 major influenza subtypes that cause disease in humans are types A and B; both cause seasonal respiratory illness, but illness associated with circulating type A strains is often more severe. Influenza A viruses are actually avian (bird) viruses, and are characterized on the basis of the structure of 2 major surface antigenic determinants: hemagglutinin (H) and neuraminidase (N). Viruses containing all 15 known H types and all 9 known N types cause infection in wild waterfowl,[4] but currently, H3N2 and H1N1 viruses are the principal influenza A virus types causing seasonal human influenza infection. These viruses lack a “proofreading” function, and thus are prone to accumulation of mutations in H and N proteins (so-called “antigenic drift”), which causes sufficient variation in viral strains to allow repeated reinfection of humans with a given viral subtype (eg, H3N2); however, there is some degree of cross-immunity to strains of a given subtype.
The relationship between seasonal and pandemic influenza viruses extends beyond shared virology: Effective control of pandemic influenza strains will rely heavily on public health infrastructure and personnel currently charged with disease control activities related to the seasonal influenza epidemics that claim an estimated 40,000 lives each year in the United States alone.[7] Emerging data suggest that those at greatest risk for severe influenza requiring hospitalization are older adults and young (< 24 months) children.[8] Of concern, seasonal influenza control activities, including provision of influenza vaccine to at-risk populations and healthcare workers (HCW), consistently fall short of targets.[9-11] On a more positive note, investment in pandemic influenza activities and structures is likely to strengthen seasonal influenza control, even if the next pandemic is relatively nonsevere.
Current Epidemiology of Highly Pathogenic Avian Influenza (H5N1) in Humans
As noted above, influenza viruses of public health importance are derived from viruses that circulate in avian populations, and in the past decade, there have been numerous instances of avian influenza viruses causing infection in humans. The most alarming of these has been the emergence of HPAI as a cause of severe respiratory illness in humans. This virus now meets 2 of 3 important virologic characteristics that are necessary for a pandemic strain: First, the antigenic makeup of this virus is such that there is little preexisting immunity to infection in human populations. Second, the virus is capable of causing virulent infection in humans. The third characteristic of pandemic strains is their ability to be transmitted easily from person to person; although such transmission remains uncommon, it has occurred in Thailand, suggesting that emergence of this virus as a pandemic strain is a very real possibility.
As of August 2007, over 300 cases of HPAI infection have been reported in humans, with most of these occurring in developing countries with humans and poultry living in close proximity. The case-fatality rate for HPAI (ie, number of fatalities divided by number of cases) is an astounding 61%, with most fatalities occurring in individuals aged < 40 years. Although the overwhelming majority of cases have had direct contact with infected birds, there are now at least 2 instances in which HPAI is believed to have been transmitted directly between people, raising the specter of emergence of HPAI as a full-fledged pandemic strain. Of note, the virus has continued to evolve, with several distinct clades now identified in different geographic locales.
Pandemic Preparedness: Basic Principles
Preparation for the next influenza pandemic involves numerous tasks related to (1) surveillance and communication, such that decision makers are aware of the degree of threat posed by influenza; (2) disease mitigation and control strategies; (3) and development of “surge capacity” and the capacity to function in the face of large-scale staff absences and social disruption. The goals of such planning, whether at the institutional (eg, hospital or business), local, state, federal, or even global level, are to maximize the physical and mental health of the greatest number of individuals; to minimize the degree to which pandemic influenza strains infect susceptible individuals; and to minimize the extent to which a pandemic disrupts the social and economic fabric of the institution, community, or jurisdiction. Pandemic preparedness, like any other type of disaster preparedness, is based on the notion that planners should “hope for the best but plan for the worst.” As such, pandemic plans assume that the most effective tools for the control of a pandemic influenza strain (ie, a highly effective vaccine or antiviral drug that protects against infection with transmission of the pandemic strain) will be either unavailable or in short supply when the pandemic emerges, such strategies should aim to maximize health and minimize disruption for sufficient time to permit development, manufacture, and distribution of a highly effective vaccine.
Surveillance and Communication
Current influenza surveillance in the United States relies on data input from a variety of sources, which include “sentinel” physicians and clinics who report illness rates directly to public health authorities; approximately 130 laboratories that report influenza virus isolation; and mortality registers, which permit identification of excess seasonal mortality associated with severe influenza activity. In the United States, new initiatives in influenza surveillance that are likely to be important in a pandemic influenza scenario include new population-based surveillance efforts, the designation of influenza A infection due to novel viral strains, and influenza deaths in children (< 18 years) as nationally notifiable infectious diseases.
Of course, accurate surveillance for novel influenza viruses depends on linkage between human and animal health professionals because animal populations, particularly wild birds and poultry, may provide important information about the epidemiology of candidate pandemic viral strains. Linkage across the “human-animal divide” has not, traditionally, been well done, although some have noted that an integrative model of human-animal health (the so-called “one-medicine” paradigm) would be extremely valuable in the evaluation and control of emerging zoonotic threats, such as pandemic influenza (to say nothing of yellow fever, hemorrhagic fevers, and West Nile virus infection).[13] The threat of pandemic influenza has spurred several such integrative efforts, including the collaboration between the WHO and animal-health organizations, such as Office International des Epizooties (OIE) (now also known as the World Animal Health Organization) and the United Nations Food and Agriculture Organization (FAO). (See http://www.offlu.net for more details.) The CDC has recently funded Centers of Excellence for human/animal health, and some states (such as Georgia, home to both the CDC and a major component of the US poultry industry) have hired public health professionals to serve as liaisons between the human and animal health communities. Up-to-date information on influenza surveillance and surveillance systems, in the United States and internationally, can be obtained from the CDC via the Internet at http://www.cdc.gov/flu/weekly/fluactivity.htm.
Disease surveillance efforts necessarily go hand in hand with the ability to communicate surveillance data to public health decision makers, disease control personnel, and to the public as a whole. Risk communication in the face of an infectious disease outbreak or epidemic is a complicated topic addressed more fully elsewhere.[14] However, several key principals of risk communication in a pandemic situation are addressed in the US Department of Health & Human Services (HHS) Pandemic Influenza Plan, and include acknowledgment of uncertainty, coordination of message development/release by different agencies, advice on protection of self and family, and an emphasis on transparency.
Public health decision makers need to be able to communicate with each other at the local, regional, national, and international levels, and communication plans for crisis situations are a key component of pandemic planning. At regional and national levels, an important component of preparing for future crisis communications involves having local decision makers, care providers, and emergency responders know and trust each other before a crisis situation emerges. In the United States, recent “flu summits,” which have taken place at both the national and state levels, have allowed groups and individuals with a stake in pandemic planning to meet, exchange information and insight, and plan together. (For additional information, see http://www.preventinfluenza.org/.) An important source of complexity in surveillance and communications planning is the possibility that some countries or regions may not share information honestly, due to fears that such transparency would result in border closures, travel restriction, or economic losses. Although it may be hoped that this would not be the case in a pandemic scenario, experience related to both the 2003 SARS outbreak and to current HPAI surveillance efforts suggests that this is a distinct possibility.[3,15] (See also http://news.bbc.co.uk/1/hi/sci/tech/5034276.stm.)
Disease Mitigation and Control
The ideal tools for the control of an influenza pandemic would include a safe, effective, and widely available vaccine against the pandemic strain, and similarly safe, effective, and abundant drugs for the treatment of influenza in individuals infected despite vaccination efforts. Unfortunately, for reasons outlined below, these tools will not be available, at least in the first weeks and (likely) months of a future pandemic. Consequently, disease mitigation strategies, such as those contained in the CDC’s Influenza Pandemic Operations Plan, http://www.cdc.gov/flu/pandemic/cdcplan.htm include a variety of nonpharmacologic interventions aimed at stopping or slowing the spread of influenza, as well as strategies for prioritizing the use of such limited supplies of drugs and vaccines as do exist when a pandemic begins.
The CDC document ties specific US Federal Government actions to the “phase” of the influenza pandemic, as defined by the WHO. The world is currently faced with a “WHO Phase 3″ situation: Human infections now occur with a novel influenza subtype (H5N1), but with only limited instances of human-to-human transmission.
In the event that human-to-human transmission of H5N1 strains becomes increasingly frequent, local clusters of influenza due to this virus are likely to emerge, and are likely to be seen first in countries that currently have known H5N1 disease in domestic bird and human populations, although it is important to remember that the next pandemic may not be due to H5N1, and could in fact emerge anywhere, including North America. At this juncture (”WHO Phase 4,” corresponding to US Federal Response Stage 2), domestic efforts in many countries, including the United States, would be initiated in an attempt to avoid importation of pandemic influenza via infected travelers or imported animals. In addition to contributing to efforts to contain overseas outbreak, the US plan calls for screening activities targeted at incoming travelers and goods, activation of quarantine stations (such that, for example, individuals arriving from countries with pandemic influenza outbreaks can be observed before being admitted into the United States), and preparations for a massive increase in vaccine production capacity would begin. As widespread disease outbreaks emerge overseas (WHO Phase 5, or US Federal Response Stage 3), these measures would be strengthened, and activation of plans, personnel, and resources necessary to provide surge capacity (see below) would begin. Additionally, stockpiles of drugs and vaccines would be distributed, and resources diverted for vaccine production. Because individuals ill with pandemic strain influenza would be likely to seek medical care, and because hospitals provide fertile environments for the transmission of respiratory disease (see below), the CDC plan calls for heightened hospital surveillance at this juncture.
It should be noted that travel restrictions (eg, closing of borders or discontinuation of flights between the United States and countries with pandemic-strain influenza outbreaks) are likely to be quite ineffective in preventing the importation of a pandemic influenza strain into the United States or any other country, due to difficulty with both implementation and doubtful effectiveness.[16] For example, barring flights from a given country would not affect individuals from traveling to North America by transiting through other countries; indeed, travel restrictions may actually enhance migration by heightening the sense of panic in source countries.
If attempts to prevent the introduction of pandemic influenza into the United States were unsuccessful, there would be attempts to contain isolated cases of pandemic strain influenza — or small outbreaks — through the use of quarantine and isolation, vaccination and postexposure antiviral prophylaxis, and restrictions on domestic travel in order to prevent movement of disease across the country. Influenza is believed to be transmissible for approximately 24 hours prior to the onset of symptoms, which would make quarantine of exposed individuals key to successful containment. Ultimately, if these efforts were unsuccessful, efforts would turn toward prevention of widespread disease through production and administration of vaccine, support of a likely overwhelmed healthcare system, epidemiologic monitoring of disease spread, and maintenance of basic utilities and services — as well as public order.
In the absence of an abundant, highly effective vaccine, measures, such as “social distancing,” would likely be utilized to slow the spread of disease. Social distancing includes measures, such as closure of schools and cancellation of public gatherings (eg, concerts). Support for such measures derives largely from nonexperimental evidence derived from the 1918-1919 pandemic. Cities, such as St. Louis, Missouri, where school closure was implemented very shortly after first identification of influenza cases, experienced far less severe influenza epidemics than cities, such as Philadelphia, Pennsylvania, where implementation of such measures was delayed.[17] Although such attenuated epidemics may last longer, and ultimately affect nearly as many individuals as explosive epidemics — such as what occurred in Philadelphia — this attenuation is still attractive because it is less likely that healthcare facilities and communities will be overwhelmed.
Infection Control and Pandemic Influenza in Hospitals
Hospitals and other healthcare facilities would experience important and multidimensional challenges during an influenza pandemic. On the one hand, these facilities would struggle to provide adequate medical care to infected individuals. On the other hand, as demonstrated during the SARS outbreak of 2003, hospitals serve both as a magnet for infectious individuals and as an environment in which extensive transmission of respiratory disease may occur.[3] Because both HCW and patients are likely to be infected if adequate infection control measures are not in place, such transmission can lead to attrition of HCW, further stressing already overcrowded and underresourced facilities, or if infected HCW continue to work, acceleration of disease transmission in the hospital setting.
Surge Capacity
Planning for an influenza pandemic requires proper consideration of the marked increases in healthcare visits and hospital admissions that would accompany even a moderate pandemic. The resources required to accommodate increased patient volumes are commonly described as surge capacity. Although much of the existing literature on surge capacity focuses on hospitals,[20] it is important to realize that planning in order to maintain functioning in the face of pandemic-related disruption and employee absences is an important consideration for emergency service providers of all types, as well as both small and large business entities. The complexity of such planning exercises is compounded by the fact that the scope and severity of a future influenza pandemic are unknowable. Planning to identify, support, and activate resources necessary to maintain an “appropriate level” of care during an influenza pandemic is the key to framing surge capacity-related goals.
The HHS pandemic plan suggests that efforts to develop surge capacity be informed by data from prior pandemics (1918, 1957, and 1968). As Toner and colleagues[20] have pointed out, under “best case” (1957- or 1968-like pandemic) conditions, the US healthcare system would be “severely stressed [and would be] overwhelmed in the case of a severe [1918-like] pandemic.[20]” The status quo during our current, pre-pandemic phase gives additional reason for concern. Seasonal increases in patient volume associated with wintertime circulation of influenza viruses already place a strain on hospital resources in North America. Financial pressures and an institutional emphasis on efficiency result in many healthcare facilities operating near capacity much of the time. High-traffic areas, such as emergency departments, serve effectively as “bottlenecks” in an overcrowded healthcare system, with patients in some areas prone to prolonged stays in nonpatient care areas (such as hallways) awaiting admission to a bed.[21,22] Such overcrowding has an adverse effect on infection prevention and control efforts, and facilitates transmission of respiratory viruses, including influenza, and other pathogens.
In the presence of an influenza pandemic, this situation would be exacerbated tremendously, both due to increased patient volumes, the requirement for specialized care areas and equipment (eg, negative pressure rooms, ventilators) that exist in relatively small fixed numbers, and due to decreased numbers of HCW who might stay away from work due to illness, fear, or necessity of caring for family or friends. Maximizing the number of HCW available during a pandemic requires sensitivity to factors that are likely to motivate workers to avoid work; for example, it is extremely important that contingency plans be formulated for the care of children of HCW, particularly if schools are closed during a pandemic as an epidemic mitigation strategy. Other strategies, such as “cohorting” HCW with infected or uninfected patients, not permitting crossover of care, and “working quarantine” with restriction of exposed HCW to infected patients, may be helpful. Working quarantines were used in the 2003 SARS outbreak in Toronto, with some success.[23]
Approaches to augmenting staff levels under such circumstances may also include the use of recently retired staff and the use of nontraditional care providers (eg, emergency medical technicians) in patient care roles.
HHS recommendations on influenza planning, and a “checklist” for planners, are available via the Internet at PandemicFlu, http://www.pandemicflu.gov/plan/healthcare/hospitalchecklist.html although this guidance has been criticized as somewhat vague and lacking in detail.[20] HHS suggests regional coordination to leverage local resources, and optimizing existing infection control practices to reduce the likelihood of the rapid spread of influenza in the hospital environment. Of course, optimizing infection control practices will have an immediate benefit to hospitals in reducing the current high level of transmission of nosocomial pathogens (respiratory and others) in the healthcare environment. The bioethical dimensions to decision making in the face of a pandemic would be manifold. Clear, ethically sound planning for prioritization of use of lifesaving resources (eg, mechanical ventilation) should be made ahead of time, to avoid “on the spot” life-and-death prioritization by decision makers with potential conflicts of interest.
How many beds can a healthcare system create if all “nonurgent” medical care is deferred, and anyone who can be discharged is discharged? Data on this question emerged from Toronto’s experience with SARS in 2003. Schull and colleagues[24] found that in Toronto, the discharge of all individuals with nonurgent medical conditions in area hospitals had resulted in the creation of around 3700 empty, staffed beds (ie, around 12% of the city’s total beds). However, they showed that even a “mild” pandemic, with 15% of the population infected, would rapidly fill these beds, resulting in an overcapacity healthcare system even under the best of circumstances.[24]
It is possible under extreme conditions to consider providing care for patients in nontraditional areas, which may include hospital cafeterias; procedure rooms (eg, cardiac catheterization suites) might be used for intensive care. Clearly, the necessity of providing care in nonhealthcare settings (eg, schools and other large public buildings) is a frightening prospect, but local pandemic plans should consider the availability and accessibility of such sites.
A major impediment to the creation and implementation of pandemic plans and surge capacity is the limited funding available to support such activities. It has been pointed out that the average hospital is likely to need approximately $1 million for adequate pandemic preparedness, but Health Resources and Services Administration for bioterrorism and pandemic planning is currently set at approximately $100,000 per hospital per year.[20] The means whereby this gap may be overcome in the face of numerous other competing priorities is unclear.
By:David N. Fisman, MD, MPH http://www.medscape.com/viewarticle/565014_6
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