Publications

In this article, we review the clinical management of deliberate infection with several pathogens of greatest bioweapons concern. On the basis of historical incidents coupled with information on ease of dissemination, contagiousness, mortality rates, public health impact, ability to engender panic, and the need for special preparedness,1-3 the Centers for Disease Control and Prevention (CDC) stratifies pathogens and toxins into three risk categories — A, B, and C — with category A meriting the highest level of concern and preparedness.4,5 In this review, we consider diseases that are caused by category A agents for which there are high-quality clinical data in the unclassified literature (see the Supplementary Appendix, available with the full text of this article at NEJM.org). The category A viral hemorrhagic fever viruses are beyond the scope of this review.

The White House recently called for a “robust and broad deliberative process” to assess the risks and benefits of select gain-of-function studies, pausing current experiments and further grants until new federal policy on research funding and oversight is developed. At issue is whether and under what conditions laboratory studies that enhance the transmissibility and/or virulence of potential pandemic pathogens such as the H5N1 avian influenza virus should go forward. To date, professionals from medicine, public health, and the life sciences have dominated the debate, and each side of the controversy has cited the public's well-being as the principal motivator for their position. A major stakeholder, the general public, has not yet actively and systematically weighed in on the matter. This commentary considers in what form and with what benefit public participation may materialize in the current debate regarding the governance of gain-of-function research.

For this second round of commentary, I focus on the grave risks of relying on nuclear weapons as a deterrent, and what is actually being done—and could be done—about those risks. While it can be imagined that a “safer” weapon could be switched out for nuclear weapons in our strategy of deterrence, in practice this will not happen. The myriad challenges of reducing nuclear weapons numbers across the globe would remain. In any case, governments need to do something to diminish the potential for armed nuclear conflict, for accidental launch, and for the increasing likelihood of nuclear-armed terrorist groups, which threatens to upend the strategic balance between nuclear armed and protected nations in ways that cannot be deterred. Adding another weapon of mass destruction to the mix does nothing to decrease this strategic risk.

A recent Bulletin column has suggested that non-contagious biological weapons may be a useful alternative to nuclear weapons as a deterrent, and could reduce the threat of nuclear devastation. While the United States may consider a variety of mechanisms toward a more stable deterrence strategy with fewer nuclear risks, biological weapons development will not be one of them. Doing so would violate US and international law and would be morally reprehensible. It would also leave the United States less secure.

Synthetic biology—often called “genetic engineering on steroids”— is on track to become an economically vibrant industry with national security implications. The rapidly expanding synthetic biology market is projected to grow to $16 billion by 2018.

While it is a relatively new field, synthetic biology has already been used to develop an antimalarial drug, make flu vaccines more rapidly, and to produce biofuels, detergents, adhesives, perfumes, tires, and specialized chemicals that formerly required the use of petrochemicals.

The US government has made sustained biodefense-related investments in basic and applied R&D aimed at producing anti-Ebola MCMs for more than a decade. Investments made by the National Institute of Allergy and Infectious Diseases (NIAID), through Biodefense and Emerging Infectious Diseases Program funding, and by the Department of Defense (DoD) Defense Threat Reduction Agency (DTRA), through the Chemical and Biological Defense Program (CBDP), have led to the development of a majority of the countermeasures in the pipeline. In addition, biodefense investments in building advanced development capabilities at the Biomedical Advanced Research and Development Authority (BARDA) and in building mechanisms for emergency clinical testing and emergency regulatory approval at the Food and Drug Administration (FDA) are now proving critical to current efforts to rapidly confirm safety and efficacy and ramp up production of countermeasures.

This article describes adoption by local health departments (LHDs) of federally recommended participatory approaches to public health emergency preparedness and LHD organizational characteristics associated with more intense community engagement in emergency preparedness, a top priority for US national health security.

Smallpox was one of the worst diseases that ever plagued humankind. From the time of the pharaohs until the 20^th century, it was a continuous scourge, killing 30 percent of those who were infected, and disfiguring most of the afflicted. The ability to vaccinate against it, and to use vaccine to diminish its spread, culminated in the eradication of smallpox. In 1980, the World Health Organization (WHO) declared that smallpox was no longer causing infections and that vaccinations could cease.

The UPMC Center for Health Security is grateful for the opportunity to provide comments on the ethical issues related to public health emergency response that have arisen as a result of the Ebola Virus epidemic in West Africa. The following comments reflect the collective views of several staff members of our organization but do not necessarily represent the views of all our staff and do not necessarily represent the official views of UPMC. We address each of the 7 issues posed in the Request for Comment.

Singapore is a critical security partner to the US in Southeast Asia. The US and Singapore share longstanding military relations, with American forces making use of Singapore’s Naval Base facilities, contributing to peace and stabilizing efforts throughout the region, offering humanitarian assistance, and acting as a deterrent to potential security threats.1 US-Singaporean security cooperation also extends to bilateral exercises, joint military training activities, and cargo screening efforts. The importance of Singapore to biosecurity in Southeast Asia continues to grow, due to its rapid biotechnology growth, its leadership in biosafety training within the region, its experience in containing the pandemic of severe acute respiratory syndrome (SARS), as well as ongoing preparedness efforts related to new, emerging diseases. 

Research on highly pathogenic organisms is crucial for medicine and public health, and we strongly support it. This work creates a foundation of new knowledge that provides critical insights around the world’s most deadly infectious diseases, and it can lay groundwork for the future development of new diagnostics, medicines, and vaccines. Almost all such research can be performed in ways that pose negligible or no risk of epidemic or global spread of a novel pathogen. However, research that aims to create new potential pandemic pathogens (PPP) (1)—novel microbes that combine likely human virulence with likely efficient transmission in humans—is an exception to that rule. While this research represents a tiny portion of the experimental work done in infectious disease research, it poses extraordinary potential risks to the public.

Half of the US population lives in close proximity to the nation’s 65 nuclear power plants. The safety of the communities living in the Emergency Planning Zones (EPZs) encircling these nuclear power plants has long been the subject of debate. For example, the size of an EPZ and the scope of emergency planning around nuclear power plants are challenged (Thomas et al. 2011; Government Accountability Office 2013). This debate intensified after the nuclear disaster in Fukushima stressed the framework for nuclear disaster response, leading some to recommend an evaluation of planning in the US (UPMC Center for Health Security 2012; U.S. Nuclear Agency 2013).

Cases of Ebola that have turned up in Dallas and New York City have prompted calls for a travel ban to prohibit travelers from Sierra Leone, Liberia, and Guinea from entering the US during the ongoing Ebola outbreak. But travel bans have not worked in past epidemics and will not stop Ebola from spreading. Banning travel would slow the movement of people and goods to those countries, harm the international response to the outbreak in West Africa, and increase the prospect of ongoing global spread of Ebola. In addition, travel bans could lead to complete isolation of those 3 countries and would further worsen the economic and humanitarian toll of this crisis.

Managing any contagious infectious disease outbreak involves breaking the chain of transmission from those who are infected with the pathogen to those who are not. Not all pathogens, however, are equal in their contagiousness, and considerable variation exists.

The viral disease measles, for example, is considered to be one of the most contagious human diseases. Its high rate of contagion is driven by 2 attributes: the ability to spread through the air via small particles (ie, airborne transmission) and the fact that one of the symptoms of measles is coughing, an effective means of expelling those particles. On average, a person infected with measles can infect 15 other people through the course of his or her illness. Diseases like tetanus and anthrax, on the other hand, are not contagious at all because they lack the ability to spread between humans. In between these 2 extremes lie all the other infectious diseases.

In considering how to weigh the risks and benefits of synthetic biology, Kaebnick, Gusmano, and Murray pose the question of whether there is scientific research that should not be funded or performed or if there are potentially dangerous results that should not be widely disseminated.¹ Such questions, they propose, require a new set of rules and norms for knowledge generation—an “ethics of knowledge.”² They identify two examples of research that might fall into a nonpermissible category, including “research that is aimed at producing and disseminating knowledge of . . . how to produce more dangerous forms of H5N1 and smallpox.” There are already rules and norms to guide the funding and generation of scientific knowledge, however, including research on influenza and smallpox. Even if more rules and guidance were added to the practice of science, potentially problematic, “dual-use” research would still occur, and as a practical matter, it is unlikely that results from those studies can be contained, particularly if the research is of wide interest.

Contemporary cost estimates of dengue fever are difficult to attain in many countries in which the disease is endemic. By applying publicly available health care costs and wage data to recently available country-level estimates of dengue incidence, we estimate the total cost of dengue to be nearly 40 billion dollars in 2011.

Since December 2013, an outbreak of Ebola virus disease in the West African nation of Guinea has rapidly evolved into a humanitarian crisis of unforeseen proportions, overwhelming vulnerable communities in Liberia, Sierra Leone, Nigeria, and Senegal. While previous outbreaks of Ebola cumulatively resulted in 2,486 cases and 1,590 deaths, the current Ebola epidemic has so far resulted in 8,376 infections and claimed 4,024 lives (as of October 10, 2014), prompting the World Health Organization (WHO) to designate it as a public health emergency of international concern.1,2 Officials from the US Centers for Disease Control and Prevention (CDC) estimate that, in the absence of public health interventions, Liberia and Sierra Leone could experience as many as 550,000 cases (or 1.4 million after correcting for underreporting) by January 2015.

The size of the world’s largest Ebola outbreak now ongoing in West Africa makes clear that further exportation of Ebola virus disease to other parts of the world will remain a real possibility for the indefinite future. Clinicians outside of West Africa, particularly those who work in emergency medicine, critical care, infectious diseases, and infection control, should be familiar with the fundamentals of Ebola virus disease, including its diagnosis, treatment, and control. In this article we provide basic information on the Ebola virus and its epidemiology and microbiology. We also describe previous outbreaks and draw comparisons to the current outbreak with a focus on the public health measures that have controlled past outbreaks. We review the pathophysiology and clinical features of the disease, highlighting diagnosis, treatment, and hospital infection control issues that are relevant to practicing clinicians. We reference official guidance and point out where important uncertainty or controversy exists.

The objectives of the Global Health Security Agenda (GHSA) will require not only a “One Health” approach to counter natural disease threats against humans, animals, and the environment, but also a security focus to counter deliberate threats to human, animal, and agricultural health and to nations' economies. We have termed this merged approach “One Health Security.” It will require the integration of professionals with expertise in security, law enforcement, and intelligence to join the veterinary, agricultural, environmental, and human health experts essential to One Health and the GHSA. Working across such different professions, which occasionally have conflicting aims and different professional cultures, poses multiple challenges, but a multidisciplinary and multisectoral approach is necessary to prevent disease threats; detect them as early as possible (when responses are likely to be most effective); and, in the case of deliberate threats, find who may be responsible. This article describes 2 project areas that exemplify One Health Security that were presented at a workshop in January 2014: the US government and private industry efforts to reduce vulnerabilities to foreign animal diseases, especially foot-and-mouth disease; and AniBioThreat, an EU project to counter deliberate threats to agriculture by raising awareness and implementing prevention and response policies and practices.

The Global Health Security Agenda (GHSA) was launched in February 2014 by the US government in partnership with more than 25 other governments, the World Health Organization (WHO), the World Organisation for Animal Health, and the Food and Agriculture Organization of the United Nations. The GHSA aims to accelerate progress toward a world prepared to counter major infectious disease threats and to focus greater political attention on the need to promote global health security as an international priority.