Publications

The optimization campaign for a nitrofuran antitubercular hit (N-benzyl-5-nitrofuran-2-carboxamide; JSF-3449) led to the design, synthesis, and biological profiling of a family of analogs. These compounds exhibited potent in vitro antitubercular activity (MIC = 0.019-0.20 μM) against the Mycobacterium tuberculosis H37Rv strain and low in vitro cytotoxicity (CC₅₀ = 40->120 μM) towards Vero cells. Significant improvements in mouse liver microsomal stability and mouse pharmacokinetic profile were realized by introduction of an α, α-dimethylbenzyl moiety. Among these compounds, JSF-4088 is highlighted due to its in vitro antitubercular potency (MIC = 0.019 μM) and Vero cell cytotoxicity (CC₅₀ > 120 μM). The findings suggest a rationale for the continued evolution of this promising series of antitubercular small molecules.

Multi-drug resistant bacterial infections are a serious threat to global public health. Changes in treatment modalities and prudent use of antibiotics can assist in reducing the threat, but new approaches are also required for untreatable cases. The use of predatory bacteria, such as Bdellovibrio bacteriovorus, is among the novel approaches being considered as possible therapeutics for antibiotic resistant and/or unidentified bacterial infections. Previous studies have examined the feasibility of using predatory bacteria to reduce colony-forming units (CFUs) in the lungs of rats exposed to lethal doses of Klebsiella pneumoniae; here we apply the approach to the Tier 1 select agent Yersinia pestis, and show that three doses of B. bacteriovorus introduced every six hours reduces the number of CFUs of Y. pestis in the lungs of inoculated mice by 86% after 24 h of infection. These experiments further demonstrate that predatory bacteria may serve to combat Gram negative bacterial infections, including those considered potential bioweapon agents, in the future.

New clinical practice guidelines from the Infectious Diseases Society of America emphasize the need to test and promptly treat patients at high risk for seasonal influenza-related complications, including pregnant women, young children, patients who are extremely obese and those who have a weakened immune system.

The 2014-16 West Africa Ebola epidemic was the largest Ebola outbreak on record, and thousands of individuals were involved in the response, including local and national governments as well as numerous philanthropies and other non-governmental organizations. A number of after-action reports and other reviews of the global response to the epidemic routinely pointed out key challenges, including gaps in operational research. To determine the extent to which operational research studies were conducted during the 2014-16 West Africa Ebola epidemic, the authors conducted a quantitative analysis of literature published during and immediately after the epidemic.

Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017. This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six species of domestic animals, six species of wildlife, and humans. To forestall adverse consequences in humans, pets, livestock, and wildlife, several critical actions are indicated, including expanded surveillance to determine the evolving distribution of H. longicornis, detection of pathogens that H. longicornis currently harbors, determination of the capacity of H. longicornis to serve as a vector for a range of potential pathogens, and evaluation of effective agents and methods for the control of H. longicornis.

With the advance of biotechnology, biological information, rather than biological materials, is increasingly the object of principal security concern. The authors argue that both in theory and in practice, existing security approaches in biology are poorly suited to manage hazardous biological information, and use the cases of Mousepox, H5N1 gain of function, and Botulinum toxin H to highlight these ongoing challenges. The authors suggest that mitigation of these hazards can be improved if one can: (1) anticipate hazard potential before scientific work is performed; (2) consider how much the new information would likely help both good and bad actors; and (3) aim to disclose information in the manner that maximally disadvantages bad actors versus good ones.

Dr. Robert Redfield, Director of the Centers for Disease Control and Prevention (CDC), joined Dr. Tom Inglesby, Director of the Johns Hopkins Center for Health Security, at a November 5 congressional seminar at the Dirksen Senate Office Building to discuss the latest events in the ongoing Ebola outbreak in the Democratic Republic of Congo (DRC). Dr. Redfield commented on the serious challenges involved and the possible trajectory of the outbreak, how CDC and the US government are involved, and what is needed to control spread of the disease. The goal of this seminar was to provide the Hill community and other stakeholders with the most current information on this outbreak and how the United States is participating in the international response.

This article is the latest in an annual series analyzing federal funding for health security programs. We examine proposed funding in the President's Budget Request for FY2019, provide updated amounts for FY2018, and update actual funding amounts for FY2010 through FY2017. Building health security for the nation is the responsibility of multiple agencies in the US federal government, as well as that of state, tribal, territorial, and local governments and the private sector. This series of articles focuses on the federal government's role in health security by identifying health security–related programs in public health, health care, national security, and defense and reporting funding levels for that ongoing work.

Emergency physicians in every location in the world, in developed and developing countries alike, will undoubtedly be confronted with the possibility of an emerging infectious disease in their career. A subset of these physicians may be faced with a patient who has potentially been exposed to biological weapons. Of the myriad infectious disease emergencies an emergency physician contends with, these 2 possibilities are the gravest and most impactful. In such scenarios, the emergency department (ED) clinician can be the key in recognizing or containing an outbreak. The challenge inherent with emerging infectious diseases presenting in the ED is that such cases can be camouflaged, lurking amongst innumerable infectious disease clinical syndromes, from common colds to viral rashes. This article provides guidance to emergency physicians as to how to approach this challenging problem as well as familiarizing readers with specific microbial threats of high consequence.

In September 2018, the Johns Hopkins Center for Health Security (“the Center”) hosted a dialogue on biosecurity between experts from the United States and the Republic of India. The dialogue, which was held in Washington, DC, was organized in collaboration with the DBT-UNESCO Regional Centre for Biotechnology, an autonomous institute of the Department of Biotechnology (part of the Ministry of Science and Technology, Government of India). This was the fifth meeting of the dialogue, following previous engagements in Washington, DC, in September 2016 and November 2017, as well as meetings in New Delhi, India, in February 2018 and February 2017.This effort is supported by the Project on Advanced Systems and Concepts for Countering WMD (PASCC, which is sponsored by the Defense Threat Reduction Agency, DTRA) of the US Air Force Institute for National Security Studies.

The authors describe a critical care disaster resource allocation framework developed following a state-wide community engagement process in Maryland. It is intended to assist hospitals and public health agencies in their independent and coordinated response to an officially declared catastrophic health emergency in which demand for mechanical ventilators exceeds the capabilities of all surge response efforts and in which there has been an executive order to implement scarce resource allocation procedures. The framework, built on a basic scoring system with modifications for specific considerations, also creates an opportunity for the legal community to review existing laws and liability protections in light of a specific disaster response process.

This report highlights 15 technologies or categories of technologies that, with further scientific attention and investment, as well as attention to accompanying legal, regulatory, ethical, policy, and operational issues, could help make the world better prepared and equipped to prevent future infectious disease outbreaks from becoming catastrophic events.

The experiences of communities that responded to confirmed cases of Ebola virus disease in the United States provide a rare opportunity for collective learning to improve resilience to future high-consequence infectious disease events.

In January 2018, Dr. David Evans from the University of Alberta and his colleagues published a scientific paper describing the synthesis of the horsepox virus de novo. Horsepox doesn’t cause infection in humans, but another related virus—Variola major—causes smallpox. The publication of the horsepox synthesis process lowers technical hurdles for making smallpox de novo. This commentary argues that there are serious potential adverse implications of this work that don’t justify the purported benefits. It also makes the case that there should be a new norm related to experiments that increase pandemic risks and that there should be more transparency and stronger oversight for biological research and science that increases pandemic risks.

On July 10, 2018, in Washington, DC, the Johns Hopkins Center for Health Security hosted a meeting on global health security in South Asia. The goal of the meeting was to discuss health security challenges in South Asia and to identify opportunities for implementation of health security initiatives. The speakers included high-level participants from the government of Pakistan, the World Bank, the US Centers for Disease Control and Prevention, the US Department of Health and Human Services, the US National Academies of Science, and from other academic, nonprofit, and government organizations. The meeting was sponsored by the Project on Advanced Systems and Concepts for Countering WMD (PASCC; sponsored by the Defense Threat Reduction Agency, DTRA) of the US Air Force Institute for National Security Studies. The highly interactive meeting presented an important opportunity to focus on the health security challenges facing South Asia and to identify paths forward, and it emphasized the importance of dialogue in bringing together multiple disciplines, sectors, and countries, extending even beyond the region. As one participant noted, “A health risk anywhere is a health risk everywhere.” This document is a summary report of the meeting discussions.

Rapid medical countermeasure (MCM) dispensing is an important intervention during a public health emergency. In the United States, MCM planning and exercising efforts have largely focused on dispensing therapeutics, with less emphasis on mass vaccination operations that would require additional specialized staff and infrastructure. Difficulties in distributing vaccines during the 2009 H1N1 influenza pandemic highlighted the need for enhanced planning and exercising of plans for conducting mass vaccination campaigns. In Taiwan, seasonal influenza mass vaccination campaigns are conducted annually, which both mitigate the effects of seasonal influenza and serve as functional exercises for mass vaccination operations during a pandemic. To identify lessons that can be applied to mass vaccination planning in the United States and elsewhere, we conducted an in-person observation and data review of Taiwan’s annual seasonal influenza mass vaccination efforts in October 2017.We offer findings and recommendations for enhancing preparedness for seasonal and pandemic influenza and other public health emergencies that would require mass vaccination.

To gather broad input on the forthcoming US Global Health Security Strategy, the Johns Hopkins Center for Health Security convened more than 70 public and private sector global health security stakeholders for a meeting on July 30, 2018, in Washington, DC. The purpose of the meeting was for stakeholders to engage in discussion regarding the US Global Health Security Strategy and provide recommendations to the USG for this strategy. This report on the recommendations is based on participant discussions. This document does not represent consensus of the meeting participants, but rather reflects the Center’s interpretation of what was discussed and our recommendations.

National investments to facilitate prompt access to safe and effective medical countermeasures (MCMs) (ie, products used to diagnose, prevent, protect from, or treat conditions associated with chemical, biological, radiological, or nuclear threats, or emerging infectious diseases) have little merit if people are not willing to take a recommended MCM during an emergency or inadvertently misuse or miss out on a recommended MCM during an emergency. Informed by the Expert Working Group on MCM Emergency Communication, the Johns Hopkins Center for Health Security developed recommendations for achieving desired public health outcomes through improved MCM communication based on a review of model practices in risk communication, crisis communication, and public warnings; detailed analysis of recent health crises involving MCMs; and development of a scenario depicting future MCM communication dilemmas. The public’s topics of concern, emotional requirements, capacity for processing information, and health needs will evolve as an emergency unfolds, from a pre-event period of routine conditions, to a crisis state, to a post-event period of reflection. Thus, MCM communication by public health authorities requires a phased approach that spans from building up a reputation as a trusted steward of MCMs between crises to developing recovery-focused messages about applying newly acquired data about MCM safety, efficacy, and accessibility to improve future situations.

Paper submitted by the United States and presented by Gigi Gronvall at the August 2018 Meeting of Experts on Review of developments in the field of science and technology related to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction. This paper considers several emerging biotechnology capabilities that may have implications for the Biological Weapons Convention (BWC), in view of their “dual use” implications for bioweapons development. It includes sections on: Gene editing; Metabolic pathway engineering; Gene drives; and Gene synthesis. The paper briefly describes some of the legitimate applications and benefits of these technologies, identifies challenges to realizing these benefits, and describes the nature and impact of their potential BW applications, to permit a balanced assessment. It then describes a recently developed framework for evaluating risks of misuse and identifying mitigation options. Finally, the paper highlights the need for greater international collaboration and harmonization of approaches to address potential biosecurity threats that might result from applications of biotechnology.

The Johns Hopkins Center for Health Security conducted a Track II multilateral biosecurity dialogue between Singapore, Malaysia, Indonesia, and the United States—with observers from the Philippines and Thailand—in Nusa Dua, Indonesia on April 18-20, 2018. Dialogue topics included national biosecurity priorities as well as ongoing and emerging biosecurity threats facing Southeast Asia countries, ranging from emerging infectious diseases to advances in biotechnology to bioterrorism. Participants discussed national-level biosecurity programs and shared lessons from their experiences, building on trusted relationships established over several years of this dialogue with the aim of improving national capacity and collaboration across the broad scope of biosecurity issues.