Publications

The Johns Hopkins Center for Health Security is working to analyze and deepen scientific dialogue regarding potential global catastrophic biological risks (GCBRs), in a continuation of its mission to reduce the consequences of epidemics and disasters. Because GCBRs constitute an emerging policy concern and area of practice, we have developed a framework to guide our work. We invited experts from a variety of disciplines to engage with our underlying concepts and assumptions to refine collective thinking on GCBRs and thus advance protections against them.

Due to increasing rates of antimicrobial-resistant infections and the current inadequacy of the antibiotic pipeline, there is increasing interest in nontraditional approaches to antibacterial therapies. We define “traditional” agents as small-molecule agents that directly target bacterial components to exert a bacteriostatic or bactericidal effect, and “nontraditional approaches” as antimicrobial therapeutics that work through other means (ie, not a small molecule and/or utilizes a nontraditional target). Due to their atypical features, such therapies may be less susceptible to the emergence of resistance than traditional antibiotics. They include approaches such as monoclonal antibodies, virulence disruptors, immunomodulators, phage therapies, microbiome-based therapies, antibiotic potentiators, and antisense approaches. This article discusses both the developmental and regulatory advantages and challenges associated with each of these technologies. By identifying existing regulatory and developmental gaps, we hope to provide a sense of where focusing resources may provide the greatest impact on successful product development.

A severe influenza pandemic could overwhelm hospitals but planning guidance that accounts for the dynamic interrelationships between planning elements is lacking. We developed a methodology to calculate pandemic supply needs based on operational considerations in hospitals and then tested the methodology at Mayo Clinic in Rochester, MN.

Mosquito-borne infectious diseases such as dengue, chikungunya, and now Zika, pose a public health threat to the US, particularly Florida, the Gulf Coast states, and Hawaii. Recent autochthonous transmission of dengue and chikungunya in Florida, the recent dengue outbreak in Hawaii, and the potential for future local spread of Zika in the US, has led to the consideration of novel approaches to mosquito management. One such novel approach, the release of sterile genetically modified mosquitoes, has been proposed as a possible intervention, and a trial release of GM mosquitoes is being considered in one Florida community. However, this proposal has been controversial. The objective of this research was to increase understanding of community knowledge, attitudes, and beliefs regarding mosquito control and GM mosquitoes.

Recent developments in the ongoing West African Ebola outbreak have, according to the media, prompted doctors to “tear up” everything they know. The events in question are the “relapse” of Scottish nurse Pauline Cafferkey, Dr. Ian Crozier's battle with an Ebola-caused eye infection, and the possibility of sexual transmission of the virus long after recovery.

While these phenomena are important and perhaps not widely known, they are not unprecedented and are fully consistent with known pathophysiological principles of disease. The key to understanding why these events occur—and could have been anticipated—is the concept of “sanctuary sites.”

Increasingly frequent and costly disasters in the US have prompted the need for greater collaboration at the local level among healthcare facilities, public health agencies, emergency medical services, and emergency management agencies. We conducted a multiphase, mixed-method, qualitative study to uncover the extent and quality of existing collaborations, identify what factors impede or facilitate the integration of the preparedness community, and propose measures to strengthen collaboration. Our study involved a comprehensive literature review, 55 semistructured key-informant interviews, and a working group meeting. Using thematic analysis, we identified 6 key findings that will inform the development of tools to help coalitions better assess and improve their own preparedness community integration.

Leading experts have declared that the end of the age of antibiotics is imminent and that this development could undermine the foundation of much of modern medicine and public health., Since antibiotics were first introduced into clinical practice some 80 years ago, microbes have been evolving ways to resist these drugs, but in recent years this problem of antimicrobial resistance (AMR) has been rapidly getting worse.

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.

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).

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.

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.

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 current outbreak of Ebola in West Africa—a region that has been largely devoid of visitations from this virus—has sparked many news stories and fueled speculation about how such outbreaks are started, sustained, and eventually controlled. However, with some important caveats, this outbreak displays many of the characteristics of prior outbreaks, the first of which occurred in 1976.

From October 22 to 31, 2012, Hurricane Sandy affected 14 US states and Washington, DC, causing particularly severe damage in New York and New Jersey. It was the second costliest hurricane in US history and caused 43 deaths in New York City and tens of thousands of injuries. When Sandy hit New York City on October 29, 2012, the flooding and power outages led to the evacuation of residents, hospitals, nursing homes, and assisted living facilities. New York City hospitals and various government agencies evacuated approximately 6,300 patients from 37 health care facilities. . . . Despite robust preparedness efforts, the severity of Sandy caught New York City hospitals by surprise because major hospital evacuations were not anticipated. Widespread power outages forced hospitals to rely on backup generators, which subsequently failed because of flooding. When health care facilities evacuated, neighboring institutions received the displaced patients. . . . We sought to use a structured, narrative-based approach to describe the effect Hurricane Sandy hospital evacuees had on hospitals and the strategies that facilitated their response.

During past influenza seasons, the principal quandary individuals faced was whether or not to get a flu vaccination. However, this flu season we have the additional decision of choosing among several different vaccine options. The fact that these options exist is a testament to the investments made to improve flu vaccine in the face of looming pandemics.

To better respond to influenza pandemics, vaccines have been sought that offer broader protection, can be delivered in novel ways, have greater immunogenicity, are antigen sparing (that is, contain less of the active ingredient), do not require eggs for manufacture, and harness recombinant technology. This year, for the first time, each of these advances is represented in one or more of the vaccine options.

In 2009 the state of Florida confirmed that native transmission of dengue fever was occurring—something that had not happened for decades. An astute clinician in New York made the diagnosis in a patient who had just returned from Key West. In the years prior to that outbreak, local transmission of dengue fever had occurred in both Texas and Hawaii.

That such a scenario occurred in 21st-century America, where other mosquito scourges such as yellow fever and malaria are historical curiosities, reinforces the fact that so long as mosquitoes capable of spreading disease inhabit a country, that country will harbor some risk of an outbreak of a mosquito-borne disease occurring.

Not only do dengue outbreaks have the potential to cause significant morbidity in the populace, but the identification of the presence of dengue in a region can also have a negative impact on the local economy in decreased tourism and added expenses for augmented vector control activities.

Diagnostic tests are critical for diagnosing diseases in US troops, for domestic and in­ternational early disease detection and bio­surveillance, and for improving global health.¹ Advances in diagnostics could improve clinical management of a range of diseases in the US healthcare system. The ability to rapidly di­agnose infectious disease has been identified as a strategic priority by the White House,^2,3 the US Department of Health and Human Ser­vices (HHS),⁴ the National Institutes of Health (NIH),⁵ the US Centers for Disease Control and Prevention (CDC),⁶ and the US Department of Defense (DoD).⁷

It has been suggested that the true case fatality rate of human H5N1 influenza infection is appreciably less than the figure of approximately 60% that is based on official WHO confirmed case reports because asymptomatic cases may have been missed. A number of sero-epidemiological studies have been conducted in an attempt to identify such missed cases.

The Center for Biosecurity of UPMC conducted this study to provide leaders in the US Department of Defense (DOD) with an expert assessment of the technical feasibility and strategic implications of next-generation monoclonal antibodies (mAbs) as medical countermeasures (MCMs) for DOD personnel. Our assessment includes identification of potentially appropriate DOD investments in mAb technologies.