Publications

Predicting which pathogen will confer the highest global catastrophic biological risk (GCBR) of a pandemic is a difficult task. Many approaches are retrospective and premised on prior pandemics; however, such an approach may fail to appreciate novel threats that do not have exact historical precedent. In this paper, based on a study and project we undertook, a new paradigm for pandemic preparedness is presented. This paradigm seeks to root pandemic risk in actual attributes possessed by specific classes of microbial organisms and leads to specific recommendations to augment preparedness activities.

This year marks the 165th anniversary of the Broad Street cholera outbreak, which resulted in more than 500 deaths in the Soho neighborhood of London. This outbreak marked a critical turning point in both public and academic perception of disease transmission when it became known that cholera was being transmitted through a specific water pump. John Snow, a medical doctor, created a simple spot map to identify the Broad Street pump as the most likely source of the outbreak. Thus, spatial/temporal modeling became foundational in epidemiology and continues to be vital to modern outbreak investigations. Since 1854, mapping techniques and data imaging have greatly evolved in complexity, accessibility, and flexibility, such that they may be applied to a wide range of public health issues.

Research with animals presents a wide array of hazards, some of which overlap those in the in vitro research laboratory. The challenge for environmental health and safety professionals when making their recommendations and performing the risk assessment is to balance worker safety with animal safety/welfare. The care and husbandry of animals require procedures and tasks that create aerosols and involve metabolized chemicals and a variety of physical hazards that must be assessed in addition to the research related risks, all while balancing the biosecurity of the facility and NIH animal care requirements. Detailed communication between health and safety, research, and animal care teams is essential to understand how to mitigate the risks that are present and if modifications need to be made as the experiments and processes progress and change over time. Additionally, the backgrounds and education levels of the persons involved in animal research and husbandry can be quite broad; the training programs created need to reflect this. Active learning and hands-on training are extremely beneficial for all staff involved in this field. Certain areas of research, such as infectious disease research in high- and maximum-containment (biosafety level 3 and 4) facilities, present challenges that are not seen in lower containment or chemical exposure experiments. This paper reviews potential hazards and mitigation strategies and discusses unique challenges for safety at all biosafety levels.

Testing of 14 patients with acute flaccid myelitis, or AFM, showed they had antibodies against enteroviruses, especially EV-D68, in their cerebrospinal fluid at a significantly higher rate than controls, supporting “the plausibility of a link” between enterovirus infection and AFM, researchers reported in mBio.

On July 16, the Johns Hopkins Center for Health Security and Ginkgo Bioworks convened a meeting in Washington, DC, to solicit stakeholder input on specific ways that national policy can strengthen the US bioeconomy. For the purposes of this meeting, the bioeconomy was defined broadly as the economy built on biotechnology. There currently is no consensus on a definition of bioeconomy, but most accept that it encompasses parts of the energy, agriculture, medical, industrial, and defense sectors. The aims of the meeting were to consider the benefits to the US if its bioeconomy were to be expanded; examine the current health of the US bioeconomy; discuss existing US government programs, policies, and initiatives related to the bioeconomy; and identify priorities for strengthening the US bioeconomy.

This paper considers approaches to risk and benefit assessment that could be applied to advances in the life sciences with possible “dual-use” implications for bioweapons development. The paper describes the components of scientific risk assessment and outlines existing risk assessment tools of particular relevance to the Biological Weapons Convention, including those developed by the U.S. National Science Advisory Board for Biosecurity (NSABB), Jonathan B. Tucker, and the U.S. National Academy of Sciences. Finally, it highlights additional risk management tools and discusses approaches to weighing benefits.

Since the 2014–2016 West Africa Ebola epidemic, the concept of measuring health security capacity has become increasingly important within the broader context of health systems-strengthening, enhancing responses to public health emergencies, and reducing global catastrophic biological risks. Efforts to regularly and sustainably track the evolution of health security capabilities and capacities over time – while also accounting for political, social, and environmental risks – could help countries progress toward eliminating sources of health insecurity. We sought to aggregate evidence-based principles that capture a country’s baseline public health and healthcare capabilities, its health security system performance before and during infectious disease crises, and its broader social, political, security, and ecological risk environments.

Infectious disease modeling has played a prominent role in recent outbreaks, yet integrating these analyses into public health decision-making has been challenging. We recommend establishing ‘outbreak science’ as an inter-disciplinary field to improve applied epidemic modeling.

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such has hospital acquired infection (HAI) prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of infectious diseases, threatening the future of the ID workforce. This paper examines compensation data for ID physicians compared to their value in population and public health settings and suggests policy recommendations to address the pay disparities between cognitive and procedural specialties which prevents more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees.

Measurement is a community endeavor that can enhance the ability to anticipate, withstand, and recover from a disaster, as well as foster learning and adaptation. This project’s purpose was to develop a self-assessment toolkit—manifesting a bottom-up, participatory approach—that enables people to envision community resilience as a concrete, desirable, and obtainable goal; organize a cross-sector effort to evaluate and enhance factors that influence resilience; and spur adoption of interventions that, in a disaster, would lessen impacts, preserve community functioning, and prompt a more rapid recovery. In 2016–2018, we engaged in a process of literature review, instrument development, stakeholder engagement, and local field-testing, to produce a self-assessment toolkit (or “rubric”) built on the Composite of Post-Event Well-being (COPEWELL) model that predicts post-disaster community functioning and resilience. Co-developing the rubric with community-based users, we generated self-assessment instruments and process guides that localities can more readily absorb and adapt. Applied in three field tests, the Social Capital and Cohesion materials equip users to assess this domain at different geo-scales. Chronicling the rubric’s implementation, this account sheds further light on tensions between community resilience assessment research and practice, and potential reasons why few of the many current measurement systems have been applied

Among the myriad infectious disease threats humans face from bacteria, prions, parasites, protozoa, fungi, ectoparasites, and viruses, it is viral infections that arguably constitute the biggest pandemic threat in the modern era. The replication rates and transmissibility of viruses are two major factors that underlie this threat. However, at least one additional factor plays an essential role: the lack of ‘broad-spectrum’ antiviral agents. Indeed, while bacteria can still cause substantial epidemics in parts of the world where access to clean water and/or antimicrobials is limited, the pandemic threats posed by bacteria, such as from the plague-causing Yersinia pestis, has been substantially diminished in the antibiotic era [1]. For viruses that pose epidemic risks, on the other hand, current therapeutic options are more limited.

In February 2019, the Johns Hopkins Center for Health Security (“the Center”) hosted a dialogue on biosecurity between senior experts and leaders from the United States and the Republic of India. The purposes of this dialogue are to increase knowledge of prevention and response efforts for natural, deliberate, and accidental biological threats in India and the United States; to look for new synergies and share best practices and innovations; to examine opportunities for partnership and collaboration; to develop and deepen relationships between dialogue participants; and to identify issues that may warrant being brought to the attention of the Indian or US government.

The life sciences now interface broadly with information technology (IT) and cybersecurity. This convergence is a key driver in the explosion of biotechnology research and its industrial applications in health care, agriculture, manufacturing, automation, artificial intelligence, and synthetic biology. As the information and handling mechanisms for biological materials have become increasingly digitized, many market sectors are now vulnerable to threats at the digital interface. This growing landscape will be addressed by cyberbiosecurity, the emerging field at the convergence of both the life sciences and IT disciplines. This manuscript summarizes the current cyberbiosecurity landscape, identifies existing vulnerabilities, and calls for formalized collaboration across a swath of disciplines to develop frameworks for early response systems to anticipate, identify, and mitigate threats in this emerging domain.

A mass drug administration, or MDA, of azithromycin remained effective at reducing child mortality in the 3rd year of its implementation in Niger, according to a cluster-randomized trial published in The New England Journal of Medicine.

A strategic multilateral dialogue related to biosecurity risks in Southeast Asia, established in 2014, now includes participants from Singapore, Malaysia, Indonesia, Thailand, Philippines, and the United States. This dialogue is conducted at the nonministerial level, enabling participants to engage without the constraints of operating in their official capacities. Participants reflect on mechanisms to detect, mitigate, and respond to biosecurity risks and highlight biosecurity issues for national leadership. Participants have also identified factors to improve regional and global biosecurity, including improved engagement and collaboration across relevant ministries and agencies, sustainable funding for biosecurity programs, enhanced information sharing for communicable diseases, and increased engagement in international biosecurity forums.

The Joint External Evaluation Process (JEE), developed in response to the 2014 Global Health Security Agenda (GHSA), is a voluntary, independent process conducted by a team of external evaluators to assess a country’s public health preparedness capabilities under the 2005 International Health Regulations (IHR) revision. Feedback from the JEE process is intended to aid in the development of national action plans by elucidating weaknesses in current preparedness and response capabilities.

To date, the pharmaceutical response to emerging infectious diseases and bioterrorism has been characterized by a “one bug, one drug” approach, where specific medical countermeasures—effective vaccines and therapeutics—are developed, manufactured, and deployed. However, over the past several years, platform technologies have been developed that could make it possible for multiple vaccines to be more rapidly produced from a single system.

The global burden of infectious diseases and the increased attention to natural, accidental, and deliberate biological threats has resulted in significant investment in infectious disease research. Translating the results of these studies to inform prevention, detection, and response efforts often can be challenging, especially if prior relationships and communications have not been established with decision-makers. Whatever scientific information is shared with decision-makers before, during, and after public health emergencies is highly dependent on the individuals or organizations who are communicating with policy-makers. This article briefly describes the landscape of stakeholders involved in information-sharing before and during emergencies. We identify critical gaps in translation of scientific expertise and results, and biosafety and biosecurity measures to public health policy and practice with a focus on One Health and zoonotic diseases. Finally, we conclude by exploring ways of improving communication and funding, both of which help to address the identified gaps. By leveraging existing scientific information (from both the natural and social sciences) in the public health decision-making process, large-scale outbreaks may be averted even in low-income countries.

The presence of bottlenecks in the transmission cycle of many RNA viruses leads to a severe reduction of number of virus particles and this occurs multiple times throughout the viral transmission cycle. Viral replication is then necessary for regeneration of a diverse mutant swarm. It is now understood that any perturbation of the mutation frequency either by increasing or decreasing the accumulation of mutations in an RNA virus results in attenuation of the virus. To determine if altering the rate at which a virus accumulates mutations decreases the probability of a successful virus infection due to issues traversing host bottlenecks, a series of mutations in the RNA-dependent RNA polymerase of Venezuelan equine encephalitis virus (VEEV), strain 68U201, were tested for mutation rate changes. All RdRp mutants were attenuated in both the mosquito and vertebrate hosts, while showing no attenuation during in vitro infections. The rescued viruses containing these mutations showed some evidence of change in fidelity, but the phenotype was not sustained following passaging. However, these mutants did exhibit changes in the frequency of specific types of mutations. Using a model of mutation production, these changes were shown to decrease the number of stop codons generated during virus replication. This suggests that the observed mutant attenuation in vivo may be due to an increase in the number of unfit genomes, which may be normally selected against by the accumulation of stop codons. Lastly, the ability of these attenuated viruses to transition through a bottleneck in vivo was measured using marked virus clones. The attenuated viruses showed an overall reduction in the number of marked clones for both the mosquito and vertebrate hosts, as well as a reduced ability to overcome the known bottlenecks in the mosquito. This study demonstrates that any perturbation of the optimal mutation frequency whether through changes in fidelity or by alterations in the mutation frequency of specific nucleotides, has significant deleterious effects on the virus, especially in the presence of host bottlenecks.

This chapter provides an overview of the scientific, policy, and operational issues involved in environmental remediation of a biological weapons attack, with a significant focus on US programs and policies. The chapter introduces the topic of biological remediation by defining the process and exploring biological agents of concern and their persistence in the environment. Past biological remediation examples are briefly discussed, followed by a review of past and current remediation policies and practices, as well as knowledge gaps and future research direction.