Ethics and severe pandemic influenza: maintaining essential functions through a fair and considered response

The response to severe pandemic influenza will be managed by experts in public health and infectious disease and by government officials to whom the public will turn for information and direction. Nonetheless, there remain important ethical considerations that can shape what goals are given priority, how scarce resources are distributed, how the public is included, and how we treat the most vulnerable in our response to a pandemic. This article assumes that the secondary consequences of severe pandemic influenza could be greater than deaths and illness from influenza itself. Response plans, then, must consider threats to societal as well as medical infrastructures. While some have suggested that scarce medical countermeasures be allocated primarily to first responders and then to the sickest, we suggest that an ethical public health response should set priorities based on essential functions. An ethical response also will engage the public, will coordinate interdependent sectors as a core preparedness priority, and will address how plans affect and can be understood by the least well off.     

Corporate preparedness for pandemic influenza: a survey of pharmaceutical and biotechnology companies in Montgomery County, Maryland

Objectives: We conducted a survey of corporate preparedness for pandemic influenza among biotechnology and pharmaceutical companies in Montgomery County, Maryland, to determine the level of preparedness for this industry and geographic region. Methods: The survey, based on the HHS Business Pandemic Influenza Planning Checklist, established whether a company had a preparedness plan specific to pandemic influenza, the contents of its plan, or its reasons for a lack of a plan. Results: A total of 50 companies participated in the survey. Of these, 40 did not have any type of preparedness plan, 3 were drafting plans, 6 had general preparedness plans that could be applied to an influenza pandemic, and only 1 company had a preparedness plan specifically designed to address pandemic influenza. Conclusions: Biotechnology and pharmaceutical companies in this geographic region are currently not well prepared for pandemic influenza. Public health officials should offer more help, possibly in the form of a model small business preparedness plan, and collaboration between companies should be encouraged to foster sharing of preparedness plans.     

Ethical principles of management and planning during influenza pandemic

The article is dedicated to an actual problem of ethical component inclusion into the system of management and planning of epidemic control measures during threat emergence and in the course of influenza pandemic (epidemic) progress. Data regarding development of international ethical guidelines during influenza including WHO recommendations are presented and analysis of normative documents in Russian Federation is given. A necessity of comprehension and accounting of ethical values in pandemic preparedness is shown, main directions of action and responsibility are revealed. Key ethical positions of planning and implementation of measures during influenza pandemic are outlined, compliance with those determines the level of public support and thus provides the effectiveness of the implemented measures.     

The prospect of using alternative medical care facilities in an influenza pandemic

Alternative care facilities (ACFs) have been widely proposed in state, local, and national pandemic preparedness plans as a way to address the expected shortage of available medical facilities during an influenza pandemic. These plans describe many types of ACFs, but their function and roles are unclear and need to be carefully considered because of the limited resources available and the reduced treatment options likely to be provided in a pandemic. Federal and state pandemic plans and the medical literature were reviewed, and models for ACFs being considered were defined and categorized. Applicability of these models to an influenza pandemic was analyzed, and recommendations are offered for future ACF use. ACFs may be best suited to function as primary triage sites, providing limited supportive care, offering alternative isolation locations to influenza patients, and serving as recovery clinics to assist in expediting the discharge of patients from hospitals.     

Pandemic unpreparedness?

Analysis of national influenza pandemic preparedness plans reveals that the preparations for an effective response in the early stages of a pandemic, while a vaccine is still being prepared, are giving cause for concern.     

Focus: Vaccines: Achieving Global Vaccine Equity: The Case for an International Pandemic Treaty

This paper presents an ethical argument in support of an international Pandemic Treaty. It argues that an international Pandemic Treaty is the best way to mark progress on global vaccine equity and broader issues of global pandemic preparedness and response which came to light during the coronavirus disease 2019 (COVID-19) pandemic. Section I evaluates principles of multilateral charity, national security, and international diplomacy standardly invoked in debates about global vaccine allocation and argues that these approaches fall short. Section II explicates notions of solidarity, duties to the least well-off, and mutual aid as ethical values more fitting for an era of emerging infectious diseases. Section III relates the discussion to an international Pandemic Treaty and presents legal, pragmatic, and ethical reasons to support it. The paper concludes that in an interconnected world, fair sharing of vaccines between nations is morally mandatory.     

Emergence of avian H1N1 influenza viruses in pigs in China.

Avian influenza A viruses from Asia are recognized as the source of genes that reassorted with human viral genes to generate the Asian/57 (H2N2) and Hong Kong/68 (H3N2) pandemic strains earlier in this century. Here we report the genetic analysis of avian influenza A H1N1 viruses recently isolated from pigs in southern China, a host suspected to generate new pandemic strains through gene reassortment events. Each of the eight gene segments was of avian origin. Phylogenetic analysis indicates that these genes form an Asian sublineage of the Eurasian avian lineage, suggesting that these viruses are an independent introduction into pigs in Asia. The presence of avian influenza viruses in pigs in China places them in an optimal position for transmission to humans and may serve as an early warning of the emergence of the next human influenza virus pandemic.     

Avian influenza h6 viruses productively infect and cause illness in mice and ferrets

Influenza pandemic preparedness has focused on influenza virus H5 and H7 subtypes. However, it is not possible to predict with certainty which subtype of avian influenza virus will cause the next pandemic, and it is prudent to include other avian influenza virus subtypes in pandemic preparedness efforts. An H6 influenza virus was identified as a potential progenitor of the H5N1 viruses that emerged in Hong Kong in 1997. This virus continues to circulate in the bird population in Asia, and other H6 viruses are prevalent in birds in North America and Asia. The high rate of reassortment observed in influenza viruses and the prevalence of H6 viruses in birds suggest that this subtype may pose a pandemic risk. Very little is known about the replicative capacity, immunogenicity, and correlates of protective immunity for low-pathogenicity H6 influenza viruses in mammals. We evaluated the antigenic and genetic relatedness of 14 H6 influenza viruses and their abilities to replicate and induce a cross-reactive immune response in two animal models: mice and ferrets. The different H6 viruses replicated to different levels in the respiratory tracts of mice and ferrets, causing varied degrees of morbidity and mortality in these two models. H6 virus infection induced similar patterns of neutralizing antibody responses in mice and ferrets; however, species-specific differences in the cross-reactivity of the antibody responses were observed. Overall, cross-reactivity of neutralizing antibodies in H6 virus-infected mice did not correlate well with protection against heterologous wild-type H6 viruses. However, we have identified an H6 virus that induces protective immunity against viruses in the North American and Eurasian lineages.     

Public health strategies for distribution of influenza vaccine during an influenza pandemic

In order to consider the ethical issues around vaccine distribution during an influenza pandemic, it is critical to have an understanding of the role of influenza vaccine in a pandemic, the rate at which vaccine is likely to be come available, who will likely produce and "own" the vaccine, how vaccine distribution and administration might be accomplished, and which are the groups that might be deemed highest priority to be vaccinated against influenza. The United States and Connecticut have been considering the more challenging of these issues and have learned from Canada, which previously discussed and made decisions on the challenges related to vaccine distribution. Although there is still some critical advance thinking that needs to be done, planning for the response to an influenza pandemic is now at an advanced stage. The keys to preparedness at this stage are to be aware of the vaccine distribution options, to know the benefits and limitations of each option, and to be flexible but nimble in dealing with a real pandemic.     

Preparing for an influenza pandemic: ethical issues

In the near future, experts predict, an influenza pandemic will likely spread throughout the world. Many countries have been creating a contingency plan in order to mitigate the severe health and social consequences of such an event. Examination of the pandemic plans of Canada, the United Kingdom and the United States, from an ethical perspective, raises several concerns. One: scarcity of human and material resources is assumed to be severe. Plans focus on prioritization but do not identify resources that would be optimally required to reduce deaths and other serious consequences. Hence, these plans do not facilitate a truly informed choice at the political level where decisions have to be made on how much to invest now in order to reduce scarcity when a pandemic occurs. Two: mass vaccination is considered to be the most important instrument for reducing the impact of infection, yet pandemic plans do not provide concrete estimates of the benefits and burdens of vaccination to assure everyone that the balance is highly favorable. Three: pandemic plans make extraordinary demands on health care workers, yet professional organizations and unions may not have been involved in the plans' formulation and they have not been assured that authorities will aim to protect and support health care workers in a way that corresponds to the demands made on them. Four: all sectors of society and all individuals will be affected by a pandemic and everyone's collaboration will be required. Yet, it appears that the various populations have been inadequately informed by occasional media reports. Hence, it is essential that plans are developed and communication programs implemented that will not only inform but also create an atmosphere of mutual trust and solidarity; qualities that at the time of a pandemic will be much needed.     

Perspectives of immunization program managers on 2009-10 H1N1 vaccination in the United States: a national survey

In June and July 2010, we conducted a national internet-based survey of 64 city, state, and territorial immunization program managers (IPMs) to assess their experiences in managing the 2009-10 H1N1 influenza vaccination campaign. Fifty-four (84%) of the managers or individuals responsible for an immunization program responded to the survey. To manage the campaign, 76% indicated their health department activated an incident command system (ICS) and 49% used an emergency operations center (EOC). Forty percent indicated they shared the leadership of the campaign with their state-level emergency preparedness program. The managers' perceptions of the helpfulness of the emergency preparedness staff was higher when they had collaborated with the emergency preparedness program on actual or simulated mass vaccination events within the previous 2 years. Fifty-seven percent found their pandemic influenza plan helpful, and those programs that mandated that vaccine providers enter data into their jurisdiction's immunization information system (IIS) were more likely than those who did not mandate data entry to rate their IIS as valuable for facilitating registration of nontraditional providers (42% vs. 25%, p<0.05) and tracking recalled influenza vaccine (50% vs. 38%, p<0.05). Results suggest that ICS and EOC structures, pandemic influenza plans, collaborations with emergency preparedness partners during nonemergencies, and expanded use of IIS can enhance immunization programs' ability to successfully manage a large-scale vaccination campaign. Maintaining the close working relationships developed between state-level immunization and emergency preparedness programs during the H1N1 influenza vaccination campaign will be especially important as states prepare for budget cuts in the coming years.     

Introducing One Health to the Ethical Debate About Zoonotic Diseases in Southeast Asia

Pandemic plans recommend phases of response to an emergent infectious disease (EID) outbreak, and are primarily aimed at preventing and mitigating human‐to‐human transmission. These plans carry presumptive weight and are increasingly being operationalized at the national, regional and international level with the support of the World Health Organization (WHO). The conventional focus of pandemic preparedness for EIDs of zoonotic origin has been on public health and human welfare. However, this focus on human populations has resulted in strategically important disciplinary silos. As the risks of zoonotic diseases have implications that reach across many domains outside traditional public health, including anthropological, environmental, and veterinary fora, a more inclusive ecological perspective is paramount for an effective response to future outbreaks.     

The anticipated severity of a "1918-like" influenza pandemic in contemporary populations: the contribution of antibacterial interventions

Recent studies have shown that most of deaths in the 1918 influenza pandemic were caused by secondary bacterial infections, primarily pneumococcal pneumonia. Given the availability of antibiotics and pneumococcal vaccination, how will contemporary populations fare when they are next confronted with pandemic influenza due to a virus with the transmissibility and virulence of that of 1918? To address this question we use a mathematical model and computer simulations. Our model considers the epidemiology of both the influenza virus and pneumonia-causing bacteria and allows for co-infection by these two agents as well as antibiotic treatment, prophylaxis and pneumococcal vaccination. For our simulations we use influenza transmission and virulence parameters estimated from 1918 pandemic data. We explore the anticipated rates of secondary pneumococcal pneumonia and death in populations with different prevalence of pneumococcal carriage and contributions of antibiotic prophylaxis, treatment, and vaccination to these rates. Our analysis predicts that in countries with lower prevalence of pneumococcal carriage and access to antibiotics and pneumococcal conjugate vaccines, there would substantially fewer deaths due to pneumonia in contemporary populations confronted with a 1918-like virus than that observed in the 1918. Our results also predict that if the pneumococcal carriage prevalence is less than 40%, the positive effects of antibiotic prophylaxis and treatment would be manifest primarily at of level of individuals. These antibiotic interventions would have little effect on the incidence of pneumonia in the population at large. We conclude with the recommendation that pandemic preparedness plans should consider co-infection with and the prevalence of carriage of pneumococci and other bacteria responsible for pneumonia. While antibiotics and vaccines will certainly reduce the rate of individual mortality, the factor contributing most to the relatively lower anticipated lethality of a pandemic with a 1918-like influenza virus in contemporary population is the lower prevalence of pneumococcal carriage.     

Pandemic policy and planning considerations for universities: findings from a tabletop exercise

The potential for a novel influenza virus to cause a pandemic represents a significant threat to global health. Planning for pandemic flu, as compared to planning for other types of hazards, presents some unique challenges to businesses, communities, and education institutions. To identify and address the challenges that may be faced by major metropolitan universities during a flu pandemic, a tabletop exercise was developed, offered, and evaluated. Its purpose was to assess existing University of Washington (UW) plans and policies for responding to an influenza pandemic. On May 31, 2006, more than 50 participants, including UW administrators and unit leaders and a number of key external partners, participated in a tabletop exercise designed to simulate all phases of an influenza pandemic. This exercise revealed existing gaps in university pandemic influenza plans and policies, including issues related to isolation and quarantine, continuity of operations, disaster mental health services, integration of volunteers into a disaster response, tracking travel of university students and personnel, communication problems, and ways to meet the needs of resident and foreign students and faculty during an outbreak. Policy and planning recommendations are offered that address each of these challenges faced by UW as well as other major research universities and colleges.     

Compliance to Oseltamivir among Two Populations in Oxfordshire,United Kingdom Affected by Influenza A(H1N1)pdm09, November 2009 – A Waste Water Epidemiology Study

Antiviral provision remains the focus of many pandemic preparedness plans, however, there is considerable uncertainty regarding antiviral compliance rates. Here we employ a waste water epidemiology approach to estimate oseltamivir (Tamiflu®) compliance. Oseltamivir carboxylate (oseltamivir''s active metabolite) was recovered from two waste water treatment plant (WWTP) catchments within the United Kingdom at the peak of the autumnal wave of the 2009 Influenza A (H1N1)pdm09 pandemic. Predictions of oseltamivir consumption from detected levels were compared with two sources of national government statistics to derive compliance rates. Scenario and sensitivity analysis indicated between 3–4 and 120–154 people were using oseltamivir during the study period in the two WWTP catchments and a compliance rate between 45–60%. With approximately half the collected antivirals going unused, there is a clear need to alter public health messages to improve compliance. We argue that a near real-time understanding of drug compliance at the scale of the waste water treatment plant (hundreds to millions of people) can potentially help public health messages become more timely, targeted, and demographically sensitive, while potentially leading to less mis- and un-used antiviral, less wastage and ultimately a more robust and efficacious pandemic preparedness plan.     

Theoretical basis to measure the impact of short-lasting control of an infectious disease on the epidemic peak

Background  

While many pandemic preparedness plans have promoted disease control effort to lower and delay an epidemic peak, analytical methods for determining the required control effort and making statistical inferences have yet to be sought. As a first step to address this issue, we present a theoretical basis on which to assess the impact of an early intervention on the epidemic peak, employing a simple epidemic model.     

El Ni?o Southern Oscillation and Leptospirosis Outbreaks in New Caledonia

Leptospirosis is an important cause of seasonal outbreaks in New Caledonia and the tropics. Using time series derived from high-quality laboratory-based surveillance from 2000–2012, we evaluated whether climatic factors, including El Niño Southern Oscillation (ENSO) and meteorological conditions allow for the prediction of leptospirosis outbreaks in New Caledonia. We found that La Niña periods are associated with high rainfall, and both of these factors were in turn, temporally associated with outbreaks of leptospirosis. The sea surface temperature in El Niño Box 4 allowed forecasting of leptospirosis outbreaks four months into the future, a time lag allowing public health authorities to increase preparedness. To our knowledge, our observations in New Caledonia are the first demonstration that ENSO has a strong association with leptospirosis. This association should be tested in other regions in the South Pacific, Asia or Latin America where ENSO may drive climate variability and the risk for leptospirosis outbreaks.     

Health system resource gaps and associated mortality from pandemic influenza across six Asian territories

Background

Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia.

Methods and Findings

We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored.

Conclusions

The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.     

Avian influenza: an osteopathic component to treatment

Avian influenza is an infection caused by the H5N1 virus. The infection is highly contagious among birds, and only a few known cases of human avian influenza have been documented. However, healthcare experts around the world are concerned that mutation or genetic exchange with more commonly transmitted human influenza viruses could result in a pandemic of avian influenza. Their concern remains in spite of the fact that the first United States vaccine against the H5N1 virus was recently approved. Under these circumstances the fear is that a pandemic of avian influenza could result in the kind of mortality that was seen with the Spanish influenza pandemic of 1918–1919, where the number of deaths was estimated to be as high as 40 million people. Retrospective data gathered by the American Osteopathic Association shortly after the 1918–1919 influenza pandemic have suggested that osteopathic physicians (DOs), using their distinctive osteopathic manipulative treatment (OMT) methods, observed significantly lower morbidity and mortality among their patients as compared to those treated by allopathic physicians (MDs) with standard medical care available at the time. In light of the limited prevention and treatment options available, it seems logical that a preparedness plan for the treatment of avian influenza should include these OMT procedures, provided by DOs and other healthcare workers capable of being trained to perform these therapeutic interventions. The purpose of this paper is to discuss the characteristics of avian influenza, describe the success of DOs during the 1918–1919 Spanish influenza pandemic, describe the evidence base for the inclusion of OMT as part of the preparedness plan for the treatment of avian influenza, and describe some of the specific OMT procedures that could be utilized as part of the treatment protocol for avian influenza patients.