The Threat of Pandemic Influenza Are We Ready? Workshop Summary (2005) / Chapter Skim
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Summary and Assessment
Summary and Assessment
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A recent expert consultation convened by the World Health Organization (WHO) concluded that "the unpredictability of influenza viruses and the speed with which transmissibility can improve means that the time for preparedness planning is now" (WHO, 2004a)
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ORGANIZATION OF WORKSHOP SUMMARY This workshop summary report is prepared for the Forum membership in the name of the editors as a collection of individually authored papers and commentary. Sections of the workshop summary not specifically attributed to an individual reflect the views of the editors and not those of the Forum on Microbial Threats, its sponsors, or the Institute of Medicine.
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," the answer is "no." Addressing Unmet Needs Close Gaps in Global Surveillance3 Many countries lack infectious disease surveillance capabilities. Disturbingly, some of the most glaring gaps in surveillance occur in Asia, where H5N1 avian influenza has infected and killed scores of people since 1997.
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It will be important to include in that message the distinction between the protective effect of an antiviral influenza vaccine and additional vaccination that would be necessary to respond to a pandemic strain. A similar argument can be made for increasing interpandemic demand for antiviral drugs, which to date have low demand.
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. This plan would probably require a smaller investment, and possibly offers greater benefit in relation to cost, than the aforementioned strategy of compensating farmers for preemptive culling of poultry or livestock in areas affected by avian influenza.
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" Risk assessment tools based on influenza viral genomics may one day provide an answer -- and perhaps prevent the unnecessary culling of poultry or livestock following outbreaks of avian influenza. Increase the Efficacy of Influenza Vaccines12 Limited supplies of vaccine could go further if their antigen content could be adjusted to provide the lowest effective dose to each recipient, and if they could be safely made more effective with an adjuvant.
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As a result of its staggering mortality, the brunt of which was borne by young adults, the 1918 influenza pandemic remains a focus of scientific inquiry; the origin of the virus remains to be determined. Most recently, the "source" of its exceptional virulence has been discovered, and these findings suggest it is due to the hemagglutinin (HA)
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Similar age shifts in mortality also marked the two subsequent influenza pandemics in 1957 and 1968, which caused far fewer deaths than the 1918 flu.
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. Clues to Lethality and Adaptation It remains unclear why the 1918 influenza virus was so deadly to otherwise healthy young adults.
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Applying Lessons Learned from Past Pandemics There is particular pressure to recognize and heed the lessons of past pandemics in the shadow of the worrisome 20032004 flu season. At the time of this report's release, 44 confirmed human cases of H5N1 avian influenza occurred in Thailand and Vietnam; 32 (72 percent)
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. It was also noted that although there is no historical precedent for an influenza pandemic spawned by highly pathogenic avian influenza virus in poultry, flu "does something different every time" (Taubenberger, 2004)
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than the social chaos visited on the United States during the 1918 influenza pandemic. TODAY'S PANDEMIC THREAT: H5N1 INFLUENZA The past decade has seen increasingly frequent and severe outbreaks of highly pathogenic avian influenza (Webby and Webster, 2003)
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By acting quickly to cull every domestic bird in the country -- about 1.5 million animals -- Hong Kong thwarted the continued progress of this deadly strain, which has not since been detected. The parental H5N1 strain continued to evolve in geese and recombine with other avian influenza viruses, however, yielding more novel viruses that infected additional bird species and, eventually, humans.
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14 THE THREAT OF PANDEMIC INFLUENZA FIGURE S-2 The map displays the most recent reporting of avian influenza outbreaks in Thailand as published by the Office International des Epizooties (OIE, 2004)
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. Throughout Asia, affected countries responded to the avian flu epidemic with time-tested strategies: surveillance to detect the outbreak and monitor the progress of control efforts; culling potentially infected birds; disinfection of affected facilities, including the safe disposal of dead and culled birds; and educating poultry farmers and the general public about the threat posed by H5N1 avian influenza.
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. Vietnam In Vietnam, the avian influenza outbreak was recognized comparatively quickly, but several factors hindered effective action to control influenza (see Nguyen in Chapter 2; Nguyen, 2004)
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The Puzzling Present and Worrisome Future of Avian Flu In addition to the Asian epidemic, unprecedented numbers of outbreaks of diverse subtypes of avian influenza arose during the 20032004 flu season in locations including British Columbia and three separate regions of the United States (Figure S-3) (Webster, 2004a)
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. Between 1999 and 2002, researchers periodically isolated samples of the virus from asymptomatically infected southern Chinese ducks (a natural reservoir for the H5N1 and other avian influenzas)
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. Recognizing that new influenza strains may infect and even kill humans without causing a pandemic -- as was the case with swine flu in the United States in 1976 and avian influenza in Hong Kong in 1997 -- the plan presents a range of responses ("preparedness levels")
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. Such an effort would necessitate balancing agricultural and public health interests -- which frequently conflict with regard to infection control measures for zoonoses-and a coordinated approach by animal and human health authorities to influenza surveillance and reporting (Stöhr, 2004)
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pandemic plan has been under construction since the release of its predecessor nearly 25 years ago, but looming threats of avian influenza and bioterrorism, along with recent sobering estimates of the potential impact of pandemic influenza on the United States (Table S-1) have raised the plan's profile considerably (Gellin, 2004)
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This H5N1 vaccine production will provide a critical pilot test of the pandemic vaccine system; it will also be used for clinical trials to evaluate dose and immunogenicity and can provide initial vaccine for early use in the event of an emerging pandemic. Other efforts include the introduction into the U.S.
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. Several states, including Texas, Wisconsin, and California, are preparing for the next influenza pandemic as a complement or adjunct to preparations against bioterrorism (Perrotta, 2004; Shult, 2004; State of California, 2003)
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should be addressed in local pandemic planning and in infection control. State and Local Surveillance In addition to serving on the "front lines" of the response to pandemic influenza, state and local public health officials and health care providers are also largely responsible for implementing influenza surveillance in the United States.
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TOWARD PREPAREDNESS: OPPORTUNITIES AND OBSTACLES Addressing Avian Influenza Considerations of the pandemic threat posed by H5N1 avian influenza in Asia were augmented and enriched by further discussion of the global phenomenon of avian influenza, its impact on the poultry industry, and possible strategies for preventing and controlling its spread among birds and mammals, including humans. Participants noted the importance of surveillance to the effective control of influenza, as well as the limitations of predominant models of surveillance that focus on a single species or industry.
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. Immunization of Poultry Avian influenza vaccines increasingly are being viewed as a means of reducing the necessity for massive poultry culls, particularly in Asia.
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Shortly thereafter, three egg-laying flocks in the Turlock region were found to be positive for avian influenza detected through passive surveillance; a drop in egg production prompted the pro ducers to have the birds tested. One week later a broiler flock was found to be positive for avian influenza at slaughter.
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These sorts of protections need to be offered to the industries that raise much of the poultry (and swine) in the United States in order to achieve complete surveil lance and their cooperation in addressing avian influenza.
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. Preventing Interspecies Transmission The intersecting and sometimes conflicting interests of commerce and public health were also evident in discussions on preventing transmission of avian influenza from wild to domestic birds, and from poultry to domestic animals and humans (for transmission pathways between species, see Figure S-4)
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. During the development of this report, it was reported that H5N1 avian influenza had been discovered in migratory birds in the Novosibirskaya region of Russia (ProMED-mail, 2004t)
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These facilities analyze and compare thousands of viral strains each year in order to determine the antigen content of the three annual influenza vaccines, then prepare and distribute the candidate vaccine strain to manufacturers. While this network is strong in Western countries and was characterized as "sufficient" in Eastern Europe and the Middle East, it is riddled with strategic gaps in Africa as well as in Asia -- an area of particular concern due to H5N1 (Stöhr, 2004)
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The global threat posed by influenza necessitates international collaboration that balances the health and economic needs of developing countries -- essential participants in influenza surveillance -- with the medical, scientific, and financial resources of developed countries. Vaccines Widely accepted as the most effective intervention against influenza in humans, vaccines significantly reduce morbidity and mortality during annual (interpandemic)
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Because influenza vaccine cannot be stockpiled (due to antigenic shift and drift) , it was also suggested that the federal government share the risk of investing in producing vaccine reserves, in preparation for either a severe annual flu season or in response to a threatened pandemic.
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Pandemic vaccine production is expected to displace production of all other vaccines for 1 to 2 years; thus pediatric and other routinely used vaccines would require stockpiling to ensure their uninterrupted availability. H5N1 "Pandemic-Like" Vaccines In response to the threat posed by H5N1 in Asia, both the European Union (under the auspices of the European Medicines Evaluation Agency)
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Avian influenza viruses often grow poorly -- and some kill -- the embryonated eggs in which commercial viral seed stocks are grown (see Fedson in Chapter 3)
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. In 1997, this method produced 1,700 doses of a vaccine against "Hong Kong" avian influenza in a total of 8 weeks.
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and neuraminidase inhibitors (zanamivir and oseltamivir) , only the latter appear to be effective against current H5N1 avian influenza, considered to be the likeliest source of the next pandemic.
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that could be made available to slow or contain a potential pandemic -- or any emerging zoonosis -- at an early stage. The effectiveness of such targeted antiviral prophylaxis has been suggested by studies of influenza transmission within families, and has also been explored through mathematical models of infectious disease transmission (see subsequent discussion on emerging technical tools)
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The Role of the Private Medical System Although the American health care system is overwhelmingly privatized, little attention has been paid to private medicine's potential role in preparing for pandemic influenza. Thus the workshop presentation and discussion led by Gordon Grundy -- a regional medical director for Aetna, one of the country's largest managed care insurance corporations -- introduced a novel perspective and several new ideas to discussions of pandemic planning (see Chapter 3)
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Although these policies are generally effective in holding down health care costs, health plan administrators realize these policies would hinder the medical response to a public health crisis such as pandemic influenza. Aetna and other insurers have therefore waived certain cost-containment measures in response to emergencies including the September 11, 2001, terrorist attacks, the 2003 blackout of the northeastern United States, and various natural disasters, and they could be expected to do so in the event of an influenza pandemic.
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pandemic influenza, and particularly how health care providers will be compensated for the services they provide during a pandemic. In addition to encouraging participation by the private medical system in pandemic planning at all levels of government, workshop participants also urged private care providers -- particularly hospitals and hospital systems -- to make their own preparations for pandemic influenza.
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. It can be induced in mouse models with live, wild-type viruses or inactivated viruses given mucosally, but has not been studied for the live attenuated viruses sometimes used in influenza vaccines.
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By combining these strategies, researchers hope to achieve complete blockage of influenza replications and prevent the development of resistant viral strains; if they fall short of this goal, dangerous "silent epidemics" of sub-clinical infection could occur (see the earlier discussion of this phenomenon in relation to avian influenza vaccines)
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As several of the previously discussed pandemic plans have anticipated, a pandemic will introduce a plethora of legal and ethical dilemmas and political and economic consequences. It will also take place in a social context in which public perception of and reaction to an emergency strongly influences its impact.
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and severe (35 percent attack rate) influenza pandemic, then calculated annual "premiums" to be paid on preparations against these losses based on the cost of vaccination (Meltzer et al., 1999)
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At the international level, efforts to ensure strong surveillance and response to infectious disease outbreaks are hampered by the outdated International Health Regulations, which are currently undergoing revision (Gostin, 2004a)
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The most effective way that public officials can avoid a damaging credibility problem in a pandemic, participants advised, is by sharing the dilemmas of pandemic control with the public in a productive and effective way -- that is, by doing more than simply furnishing facts and figures. More research is needed to learn how to do this well; in the meantime, public health officials are advised to invest in targeted (as opposed to nuanced)
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2002. Nature's Terrorist Attack: Pandemic Influenza; Preparedness Planning for State Health Officials.
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. Avian Influenza Outbreak in Thailand 2004.
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2003. Influenza pandemic prepared ness.
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2004. Effect of vaccine use in the evolution of Mexican lineage H5N2 avian influenza virus.
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. Retrospection into Avian Influenza Outbreak in Vietnam during 2003-04.
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. PRO/AH/EDR> Avian influenza -- Eastern Asia (92)
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2004t. PRO/AD/EDR> Avian influenza A/H5N1, migratory birds -- Russia (Siberia)
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2004. Avian influenza: A new pandemic threat?
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