Abstract

There is a continued need to improve the state of preparedness for a potential influenza pandemic in the United States despite the publication of a pandemic influenza plan by the Department of Health and Human Services. Of particular importance are the sense of urgency for a coordinated response plan, an allocation of adequate funds to deal with this issue, and the need for a national leader to coordinate the development and execution of a national plan, including its relationship to the control of seasonal influenza. In addition, an infrastructure needs to be established in the United States to enable the rapid development and large-scale production of a safe and effective vaccine for new influenza strains; methods to treat influenza pneumonia need to be evaluated; a coordinated public health response needs to be defined; a nationally developed blueprint to deal with logistics of pandemic prevention is required; and there is a need to establish reliable communication systems on a national and local basis, to provide accurate information to the lay public, health care workers, and the agricultural sector

In the present article, we present the recommendations made by representatives from federal, state, and local governments; professional societies; academia; and the pharmaceutical industry who met in Washington, DC, in February 2006 to review the current state of preparedness in the United States for a potential influenza pandemic. The goal of the meeting was to extend the recommendations of the recently issued US Department of Health and Human Services (HHS) Pandemic Influenza Plan [1] and provide suggestions for the actualization of this plan at state and local levels. In addition, the group identified areas for further research and attention. The meeting attendees were assigned to 1 of 7 groups that were asked to evaluate specific components of the current HHS guidelines (vaccine development and production; education and communication; surveillance and diagnostics; distribution of vaccines, antiviral medications, and medical supplies; use of antivirals and antiviral development; containment procedures; and surge capacity for patient care). Each group was presented with a series of questions by a moderator, and a predetermined discussant led each group in constructing a response to the issues highlighted. At the end of the meeting, the recommendations of each group were presented to all of the meeting attendees for further discussion. Subsequently, the authors prioritized these recommendations and formulated a proposal for how they should be implemented. Plans to implement some of these recommendations have been made, at least in part, by HHS and its affiliated divisions. However, there are many additional important issues that require urgent attention

Recommendations

These recommendations are predicated on our view that avian influenza represents a major risk to society. Avian influenza is heavily impacting the global poultry industry, and it is likely that it will extend to infect poultry in the United States in the near future. It is possible that H5N1 will remain a devastating disease in birds, with only sporadic human cases. However, the lessons from the long history of influenza and the short history of the H5N1 influenza A strain indicate that there is a strong possibility that mutations capable of promoting sustained human-to-human transmission will occur. If this happens, the resultant influenza pandemic will quickly overwhelm the nation’s health care resources, as well as causing enormous economic losses and, potentially, social chaos. For the United States, basic, clinical, and epidemiological research in the science of influenza has been incredibly productive and represents a wise investment that may have substantial dividends. At the same time, this country has a fragmented, largely private health care system that makes planning for an integrated public health and medical management response uniquely challenging. Of particular importance are To our knowledge, none of these elements is currently in place—the sense of urgency, adequate budget, or coordinated leadership

  • the sense of urgency for a coordinated public health and clinical care response plan with consistency of decision-making and prioritization of actions across the country;

  • an allocation of adequate funds to deal with this issue;

  • the need for a respected, scientifically grounded national leader or commission to lead the development and execution of a national plan. It is assumed that this leadership would be well supported by an appropriate panel of experts in relevant fields, including public health, health care resources, basic and clinical virology, the pharmaceutical industry, and agriculture

Vaccine Production

High priority:An infrastructure needs to be established in the United States to enable the rapid development and large-scale production of a safe and effective vaccine for new influenza strains. Priority issues include the science of vaccine development and production capacity. The “science” refers to the ability to understand the immunology of effective immune responses, to rapidly produce vaccine against new antigenic strains, and to deliver it in a fashion that will elicit an effective protective response

Of the $3.8 billion approved by Congress for pandemic influenza preparedness, $2.6 billion was assigned to the Office of Public Health Emergency Preparedness for core preparedness activities. These activities include the development of a vaccine directed at the pandemic strain, of production capacity to rapidly respond to pandemic needs, and of alternative vaccine development methods to more efficiently provide large supplies of an effective vaccine, such as cell-based systems. At the time of the meeting, the national strategy was to stockpile 20 million doses of prepandemic vaccine and accelerate vaccine production capacity within the United States, to be able to produce intrapandemic vaccines within 6 months. Ultimately, there needs to be the capacity to vaccinate 300 million people, which will likely require 600 million doses of a pandemic vaccine for the US population. However, it is not clear how such a stockpile would be managed. In addition, there needs to be better discussion and communication of strategies being implemented and the stages of development. This needs to be done at the national level and coordinated on a global basis

Additional recommendationsThe development of new production platforms, such as cell-based vaccine technology, should be accelerated. In addition, research to identify novel vaccine approaches and develop dose-sparing strategies, through the use of adjuvants and/or intradermal inoculations, should be expanded. Multiple approaches must be pursued in parallel, with a rapid process for assessing progress and reallocating resources on the basis of emerging results

Additional incentives should be implemented for pharmaceutical companies developing and producing influenza pandemic vaccines, since these efforts would be conducted at the expense of other development and production, with no assurance of purchase and vagaries in the shelf life of vaccines or stockpiled concentrates. Regulatory requirements need to be transparent and clearly articulated to ensure more-rapid vaccine development. Plans for regulatory approval should encompass different scenarios. For example, during a pandemic, acceptable risk-benefit ratios may change. Liability protection may be particularly important. Other incentives could include recommendations for predictable, sustained uptake of vaccines and funding of vaccination during the interpandemic period. At present in the United States, most influenza vaccine for seasonal use is purchased and distributed through the private sector, unlike in most other countries. Expansion of guaranteed governmental purchase and of overall distribution through increasing the age ranges for receipt would boost production capacities

It should be determined whether it would be preferable to develop, produce, and stockpile a vaccine targeting a specific subtype of influenza or, alternatively, to prime the population or at least the high-risk segments of the population, like health care workers, with a vaccine that is directed against the highest-likelihood threat (i.e., H5N1 at present). Another consideration would be deployment of vaccines targeting multiple subtypes of influenza, switching the target yearly according to the subtype currently in circulation. The role of cross-protection against multiple subtypes or strains of influenza needs to be explored but remains a long-term goal at present. Better studies are needed to understand the correlates of immune response and protection. Finally, potential short- and long-term strategies need to be prioritized to guide research

Treatment and Prevention

High priority:Methods to treat influenza pneumonia by use of antiviral drugs, antibiotics, anti-inflammatory agents, and cytokine modulation need to be evaluated, because currently there is no influenza pneumonia treatment with established merit. In addition, the use of antiviral medications for therapy and prophylaxis requires further evaluation, with special attention given to efficacy; to safety in higher-risk populations, like infants, pregnant women, and immunocompromised hosts; and to antiviral resistance

Neuraminidase (NA) inhibitors and the M2 inhibitor adamantanes (amantadine and rimantidine) have established merit for treating and preventing seasonal influenza due to susceptible viruses. Although active against all H5N1 and other avian viruses in the laboratory, NA inhibitors have not been studied rigorously for efficacy in preventing avian influenza. The adamantanes have proven prophylactic efficacy in studies conducted during the 1968 Hong Kong pandemic and the 1977 Russian pandemic-like event. However, the rapid emergence of resistance to the M2 inhibitor adamantanes among current H3N2 strains casts doubt on the future role of these drugs

Antiviral medications are one cornerstone in the management of pandemic influenza, because it is unlikely that sufficient quantities of vaccines will be available to protect the majority of the population. They may be the only specific modality available early in a pandemic. However, antiviral medications alone may not be effective in treating patients with influenza pneumonia, because infection with the H5N1 influenza virus has resulted in a high rate of mortality in hospitalized patients, largely resulting from progressive respiratory failure despite high rates of oseltamivir usage in standard treatment regimens [2]. Nevertheless, the treatment data are anecdotal, and there are concerns that the medications have been given too late or in an inadequate dose. Furthermore, resistance emergence may have compromised efficacy in some patients [3]. Appropriate trials to address these issues should be planned and then implemented when feasible

Although oseltamivir and zanamivir have not been evaluated in a pandemic setting, they have demonstrated efficacy in the prevention of seasonal influenza. Adamantanes have also been used successfully for pandemic influenza prophylaxis. Mathematical models predict that a ring prophylaxis strategy, as was utilized in the smallpox eradication program, might contain local outbreaks of H5N1 influenza that is transmitting from person to person [4, 5]. Assumptions in the model are the ability to detect an outbreak early, adequate supply of the antivirals, lack of resistance, and antiviral efficacy. Although evaluation of the ring prophylaxis strategy may be difficult to perform, given the limited number of human-to-human transmissions that have occurred, plans should be in place to do so rapidly if there is increased evidence of such transmission, even at a low level. The World Health Organization and US government have such an initial antiviral stockpile, and plans for implementing rapid outbreak investigation and response strategies are in progress. During an established pandemic, the current limited availability of antiviral medications and the lack of manufacturing surge capacity would make implementing intervention strategies difficult unless drugs were pre-positioned

These limitations in supply and capacity for rapid distribution emphasize the need to develop manufacturing capacity to assure a national supply within the United States. The anticipated need is for therapeutic courses for at least 25% of the US population

Additional recommendationsThe capacity to rapidly obtain data on the development of antiviral resistance for seasonal and pandemic influenza should be increased to guide treatment. Combination antiviral therapy (2 NA inhibitors or an NA inhibitor and an M2 inhibitor) should be evaluated to determine whether it results in an improvement in virologic control, a decrease in the potential emergence of resistant variants, or an increase in efficacy. New targets for antiviral drug development need to be identified. Additional NA inhibitors, particularly those that could be given parenterally to assure adequate delivery and those that could be administered infrequently, should be put into clinical development. The barriers to the development of new agents need to be identified, and ways to lower these barriers need to be developed

Public Health Interventions

High priority:A coordinated public health response needs to be defined, with consistent application across constituencies. This will include national, state, and local planning

Our recommendations for pandemic influenza have substantial budget implications for state and local public health agencies. Also, it is emphasized that the burden of care will be local and will be the responsibility of the health care system that is largely private. Unfortunately, most health care workers and institutions in this country have little relevant experience in responding to any major epidemic. A key component of the local response is surge capacity for public health intervention, medical care, and logistical support. Coordination of care in the United States will be particularly challenging, because most health care systems and hospitals are private and financially stressed, often serve defined patient populations, operate with few excess beds, and have “just in time” supplies. Public health interventions, including ring and other prophylaxis strategies, travel restrictions, quarantines, social distancing, prioritization for limited vaccine and prophylactic and therapeutic antiviral agents, and health care worker safety, among others, need to be defined and evaluated. These have not been well studied for influenza control, and critical gaps in our knowledge remain. Studies performed now during seasonal influenza outbreaks will have the dual benefit of preparing for a pandemic and better addressing seasonal influenza, especially when there is antigenic drift or the vaccine supply is inadequate

Additional recommendationsThe federal government and national experts need to provide specific guidance to state and local authorities regarding the trigger points for nonpharmacological intervention, such as

  • social distancing—for example, closures of schools, businesses, restaurants, and other locations where there is potential for close social interaction;

  • cessation of public gatherings;

  • travel advisories and travel restrictions;

  • infection control policies, such as the use of masks and isolation procedures;

  • prioritization for predictable shortages in medications, including antivirals and antibiotics, as well as disposable and durable medical equipment, such as ventilators

The trigger points for quarantine should be clearly defined and justified in advance. There are no data on effectiveness of quarantine against influenza; the short incubation period renders quarantine and isolation of questionable value. Differences with the experience of severe acute respiratory syndrome (SARS) are critical here. SARS has a longer incubation period than influenza, and viral shedding does not occur before the onset of fever, which can be used as an effective way of identifying who should be isolated. As such, the experience with SARS was predominantly limited to intrainstitutional outbreaks in health care facilities. In contrast, infection with influenza primarily results in community-based epidemics. This is because viral shedding is at its highest before the onset of any clinical signs of illness, which makes it difficult to identify who should be isolated to prevent further infection

The role of travel restrictions, especially early in the pandemic, must be considered and managed at the federal level. Therefore, communication with and between airlines and other transport authorities must exist before a pandemic, to ensure cooperation

The unique needs of special populations need to be addressed. This includes populations such as health care workers and other essential personnel; first responders; jail and prison inmates; the elderly; persons who are institutionalized, homebound, or homeless; travelers; and undocumented persons. Health care workers and essential members of society (i.e., first responders, police, firefighters, etc.) and their families should be vaccinated or treated first, so that they will be available to work in the event of a pandemic. Special considerations and plans are required for elderly persons (residential facilities), the homeless, undocumented persons, and people living in impoverished areas, where there are limited health care resources

To ensure continuation of education, schools should consider how to facilitate home schooling through the use of online learning/homework networks. Telecommuting may be a possibility for some employees and will assist with self-protection and reverse quarantine, as well as maintaining business continuity. Therefore, employers should establish contingency plans and secure networking systems that employees can use from home to access applications and data

A broad education program in public health measures is required. Information should be disseminated from the federal to the state and local levels through many credible bodies, such as churches, schools, businesses, and local health departments, using multiple forums, including radio, television, newspapers, notices, mailings, the Internet, and other methods of mass communication. However, consistency of content is essential to avoid confusion. There should also be a public education campaign for seasonal influenza, as opposed to waiting for the pandemic to start. The public should be educated regarding likely effective means of preventing transmission of influenza through hand hygiene, cough etiquette, and social distancing

Protocols need to be developed for stockpiling food and medical supplies at home, utilizing experience gained in resource-poor countries. Household stockpiling of enough essential food supplies and water for at least 1 week of disruption should be encouraged. However, state and federal governments should be prepared to ensure that adequate food supplies are made available to the public during periods of disruption

Logistics

High priority:A nationally developed blueprint should be developed to deal with the logistics of pandemic mitigation, patient evaluation such as “fever clinics,” treatment, and critical care, including respirators

This requires addressing the surge capacity of the entire health care system with additional options, such as sports arenas, civic centers, and other large venues. Application will need to be local and involve collaboration between health care workers and public health personnel, presumably based on a generic blueprint. Pandemic influenza will be expected to quickly overwhelm the health care system. It is very unlikely that sufficient antiviral medications will be available early to provide substantial segments of the population with chemoprophylaxis. Prophylaxis for periods of 4–8 weeks requires considerably more drug supplies than does treatment of ill persons and is an inefficient means of using a limited resource. Projections for hospital care for pandemic influenza indicate that the current capacity in beds, in durable and disposable medical equipment, and in properly trained health care personnel are seriously inadequate. Thus, methods need to be developed for substantial expansion capacity. To our knowledge, few communities have done this with health care personnel, inpatient capacity, and intensive care unit capacity

The fragmented nature of the US health care system will make it difficult to coordinate an adequate local response to an influenza pandemic. The current HHS plan recommends that hospitals develop their own surge capacity plans but provides no guidance as to how to do so

Additional recommendationsNational guidelines need to be developed to address the approach and prioritization of limited medical resources. The following goals need to be achieved:

  • Identify who is responsible for developing surge capacity

  • Establish how different levels of needed excess capacity can be achieved for inpatients

  • Establish how surge capacity is achieved by health care providers in the outpatient setting for medical evaluations and, possibly, in an alternative setting for prophylaxis administration and/or distribution

  • Identify strategies to relieve hospital burden

  • Develop standards of care for special populations, including pregnant women, children, the elderly, and the immunocompromised

  • Convene an independent panel that will provide national guidance on triage of critical resources (hospital beds, oxygen, ventilators, antiviral medications, and antibiotics) that will inevitably be in inadequate supply during a pandemic; understanding the epidemiological profile of the pandemic (e.g., its impacts on children and young adults) will be central to determinations about the use of limited resources in different populations (e.g., nursing home elderly or those with chronic serious illness)

  • Establish national and global communication systems for hospitals, health care providers, and other personnel involved in any emergency medical response that address both altered standards of care and health system delivery models that might be implemented in the event of a disaster

  • Rapidly implement broadly applicable solutions to liability, regulatory, and financial issues, for both health care facilities and providers, that will allow effective delivery of care during health care emergencies; this would include licensing and liability protection for out-of-state and retired professionals

Alternative venues to those usually employed for distributing and administering interventions should be identified. Differences in distribution strategies between rapid access to antiviral treatments (i.e., for acutely ill persons) and vaccines need to be considered

Critical supplies, including those necessary for vaccination, oxygen therapy, antibiotics, and protection (masks, respirators) should be stockpiled in a fashion that will assure rapid access. The potential to reuse respirators needs to be studied. However, there is no technology currently available for disinfecting disposable respirators

Antiviral and antimicrobial drugs should be stockpiled and included in distribution planning, and guidelines should be established for their use. Different mechanisms for distributing medical supplies should be established, including local stockpiling of antiviral medications and supplies

To minimize disruption of medical supply chains, potential overlap of sources of supplies should be identified, and overseas supply chains that might have competing demands should be considered

The distribution process must be transparent; the data and logic used in decision making, including how ethical considerations have been implemented, should be clearly shown

Ongoing funding is needed to develop, maintain, and implement an acceptable level of health care surge capacity for any national health emergency. Private funding and public/private partnerships should be explored to meet this objective

A more aggressive national approach is needed to format and implement systems to utilize nonpracticing or retired medical personnel in times of national or local emergency. In addition, policy makers should reassess the potential use of both professionals and laypersons currently involved in local health emergency responses

Communications

High priority:There is a need to establish reliable communication systems on a national and local basis, to provide accurate information to the lay public, businesses, health care workers, and the agricultural sector

Health care workersHealth care systems need to develop a method of communication within their infrastructure. Academic institutions, health maintenance organizations, hospitals, health care networks, and other health organizations usually have networks that are established for purposes of emergency communications. These need to be reviewed, updated, refined, and made “pandemic flu relevant.”

The purpose is to transmit relevant information regarding organizational, local, regional, and national policies and other essential information. Multiple and overlapping communication methods must be established (phone, beeper, e-mail, and mail). Plans should include methods, such as the use of a blast e-mail system, beepers, phones, and other local communication devices, for immediate notification of preselected groups. The essential personnel anticipated for pandemic influenza will include those from infection control and intensive care; emergency medicine staff; and physicians and other professionals from infectious diseases, pulmonary/critical care, primary care, and respiratory care

Particularly important is a realistic appraisal of risks to health care workers and their families; they also need to know strategies to reduce such risks. Information for these groups and the public must be timely, consistent, clear, and credible. There needs to be a feedback mechanism, so that the flow of information is bidirectional between the national, state, and local health authorities. Some areas have sophisticated surveillance systems established, such as that used in New York City, which may be a good model for other cities. There must be a local communication leader who has substantial credibility, appropriate authorization from the organization leadership, and immediate access to relevant information

The publicThe private sector is expected to use its extraordinary network of resources to report timely information through standard methods, including radio, television, the Internet, print media, and so forth. However, the breadth and diversity of these media can lead to conflicting, confusing, or sensationalized information. Authoritative and publicly recognized information channels should be developed in advance of a pandemic event

At the national level, information should be provided about the epidemic and national policies/recommendations. At the local level, regular updates on the status of the local epidemic, resources, policies, and recommendations should be given. These might include recommendations for evaluation of influenza-like illness and use of and access to vaccines and/or antiviral medications

As was learned during the anthrax attacks, it is critical that an expert, trusted, and consistent spokesperson be identified. At the national level, this might be a health official with established credibility, such as the Director of the Centers for Disease Control and Prevention or the Director of the National Institute of Allergy and Infectious Diseases. There may be a need for several spokespersons, but they need to communicate similar messages, to ensure consistency. At the local level, there should be influenza spokespersons available who can report regional issues with expertise, credibility, and authority. The experience of Hurricane Katrina demonstrates the need for close liaison between federal, state, and local agencies with regard to public communication, to avoid contradictory messages being issued

The agricultural and veterinary sector must be kept informed in a fashion similar to the health care system. In turn, there needs to be excellent communication from the animal health sector to those involved in human public health

Seasonal Influenza Preparedness

Improving the management of seasonal influenza will, in turn, improve our preparedness for pandemic influenza. To help prepare for a pandemic, widespread and sustained interpandemic vaccination should be promoted. This requires public education, clear and expanded targets for influenza vaccination, and the establishment of better tracking and accountability. This will increase and stabilize the demand for vaccine, which will help to increase the supply in a pandemic. Employers should be encouraged to fund vaccination or, at least, to provide partial cost sharing with employees. In addition, an infrastructure needs to be established to ensure widespread delivery of vaccines to adults

The surveillance network for seasonal influenza should be expanded to provide timely influenza activity alerts and to better quantify influenza-specific morbidity. There needs to be increased testing for all respiratory viruses, to improve surveillance and patient care. Greater use of influenza diagnostics may prompt the development of new tests and the manufacture of greater numbers of existing tests. Efforts to develop rapid, accurate, and reliable point-of-care diagnostic tests should be increased, because current tests are of insufficient sensitivity in certain populations. Consequently, primary care physicians should be made aware of the limitations of current point-of-care tests. Efforts by laboratories and clinicians to recognize viruses with novel hemagglutinin subtypes should be scaled up

Clinicians require education regarding the potential clinical benefits of existing antiviral drugs during seasonal influenza. There should be an increase in the appropriate use of antiviral drugs, as well as vaccines, in children. Now that the adamantanes are known to have limited utility, physician education concerning the NA inhibitors has increased importance

Implementation

The implementation of these recommendations is beyond the ability of any individual organization and will require the fostering of collaboration between government departments and agencies, international bodies, academic bodies, professional societies, and the business world. In addition, there is a need for ongoing review and development of these plans and recommendations, to ensure that progress is made and that plans are refined in the event of new developments and that the decisions are well communicated. To achieve this, the authors recommend that a leader or Pandemic Influenza Advisory Board should be appointed by HHS, to advise and critically evaluate these activities

Financial Considerations

Although funding for pandemic preparedness has been provided by Congress, it is far less than the amount spent each year for seasonal influenza. The need is substantial if this is to be a serious effort. Key areas are not funded or are seriously underfunded. In particular, additional funding is required for state, local, and hospital preparedness; communications; and essential medical supplies, including antiviral medications, antibiotics, and respirators. To fully address all of the steps identified for pandemic influenza preparedness, the authors propose that a minimum of $30 billion in additional funding be provided. Specifically, funds are required for additional studies to identify methods to expedite vaccine development, for additional studies of novel and current antiviral medications, for stockpiling of antiviral medication(s) sufficient to treat 35% of the US population, for stockpiling of protective equipment (masks, gowns, respirators, gloves), to expand domestic vaccine production sources and increase seasonal use, to fund state and local health department preparedness, to provide resources for hospital/health care system planning, and to enable plans for surge capacity

The agricultural and veterinary medicine sectors have a critical and central role to play in the prevention and management of pandemic influenza. Unfortunately, because of time constraints, no substantive recommendations were generated for these important sectors at this meeting, although we clearly recognize their central role

The authors intend to review and revise these recommendations on an ongoing basis, to ensure that adequate preparations are being implemented to prevent or minimize the impact of a new influenza pandemic. In addition, we acknowledge that this initial set of recommendations is US focused. However, there is an intention to broaden the scope of this document in the future, to include additional recommendations for an international audience

Acknowledgments

We acknowledge the following individuals for their assistance in managing the breakout sessions: John Beigel, Lawrence Deyton, Jeff Duchin, Dan Hanfling, Linda Lambert, Jeffrey Levi, Anne Moscona, Michael Osterholm, Kristin Nicol, Cathy Petti, L. J. Tan, John Treanor, Tim Uyeki, and Isaac Weisfuse. In addition, we thank John Fry for his assistance in writing this manuscript. The “Seasonal and Pandemic Influenza 2006: At the Crossroads, a Global Opportunity” conference was sponsored by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the National Institute of Allergy and Infectious Diseases, and the Centers for Disease Control and Prevention. Funding for the conference was supplied through an unrestricted educational grant from Gilead Sciences, GlaxoSmithKline, Roche Laboratories, MedImmune, Sanofi Pasteur, Biota Holdings, and BioCryst Pharmaceuticals

Supplement sponsorshipThis article was published as part of a supplement entitled “Seasonal and Pandemic Influenza: At the Crossroads, a Global Opportunity,” sponsored by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the National Institute of Allergy and Infectious Diseases, and the Centers for Disease Control and Prevention

References

1.
US Department of Health and Human Services
HHS Pandemic Influenza Plan
  
Available at: http://www.hhs.gov/pandemicflu/plan/. Accessed 1 June 2006
2.
Writing Committee of the World Health Organization Consultation on Human Influenza A/H5
Avian influenza (H5N1) infections in humans
N Engl J Med
 , 
2005
, vol. 
353
 (pg. 
1374
-
85
)
3.
De Jong
MD
Tranh
TT
Khanh
TH
, et al.  . 
Oseltamivir resistance during treatment of influenza A (H5N1) infection
N Engl J Med
 , 
2005
, vol. 
353
 (pg. 
2667
-
72
)
4.
Ferguson
NM
Cummings
DAT
Cauchemex
S
, et al.  . 
Strategies for containing an emerging influenza pandemic in Southeast Asia
Nature
 , 
2005
, vol. 
437
 (pg. 
209
-
14
)
5.
Longini
IM
Nizam
A
Xu
S
, et al.  . 
Containing pandemic influenza at the source
Science
 , 
2005
, vol. 
309
 (pg. 
1083
-
7
)
Presented in part: Seasonal and Pandemic Influenza 2006: At the Crossroads, a Global Opportunity, Washington, DC, 1–2 February 2006 (for a list of sponsors and funding, see the Acknowledgments). The authors formed the independent committee that planned and coordinated the conference. A second conference on the subject will be held on 1–2 February 2007 in Washington, DC. For additional information, contact Joanne Jablonski at HealthMatters Communications, the logistical coordinators of this program. Please call 646-674-4882 or e-mail jjablonski@contacthmc.com
Potential conflicts of interest: R.J.W. is on the Scientific Advisory Board for Gilead Sciences and is a member of the GlaxoSmithKline and Novartis Speakers Bureaus. A.S.M. has received grant support from Roche and Sanofi Pasteur and the National Institutes of Health (grant U01 AI057853) and has served as an ad hoc consultant to Roche, MedImmune, and Chiron. M.T. has served as a consultant to Roche, Gilead Sciences, and GlaxoSmithKline. All other authors report no conflicts
Financial support: supplement sponsorship is detailed in the Acknowledgments