Publications

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.

Synthetic biology and other advanced biotechnologies hold a great deal of promise for medicine, public health, manufacturing, and national economies, but they also have biosafety and biosecurity implications. Using synthetic biology techniques, it is possible for a nefarious actor to acquire a viral pathogen made with chemically synthesized pieces, versus having to acquire samples of pathogens from an environmental source or from another laboratory. It is also possible to test many parallel approaches for designing new functions into existing pathogens, given that the costs of DNA synthesis continue to drop; this has dual-use implications for biodefense. These biosecurity concerns do not replace the existent challenges prior to the advent of synthetic biology but add to them, as early non-synthetic biology paths to biological weapons development are still able to be used to make biological weapons. In addition to biosecurity concerns, there are biosafety implications of synthetic biology, as the techniques are powerful, they may be used outside of traditional biocontainment, and because relative newcomers to biological containment are entering the field.

On December 3, 2018, the Johns Hopkins Center for Health Security convened the first annual Global Forum on Scientific Advances Important to the Biological and Toxin Weapons Convention, coinciding with the 2018 Meeting of States Parties to the Biological and Toxin Weapons Convention (BWC MSP) in Geneva, Switzerland. The forum had 2 purposes: (1) to inform States Parties’ delegations of cutting-edge biological capabilities, including the ability to engineer pathogens or more complex organisms, and (2) to build awareness of and support for international bioweapons nonproliferation norms among the scientific community. Advanced biology, engineered pathogens and other organisms, and accidental biological threats as sources of risk are of great concern to international biological nonproliferation regimes such as the BWC.

In 2017-18, the Johns Hopkins Center for Health Security conducted a multiphase research project to help inform the development of a strategic approach for communicating about global catastrophic biological risks (GCBRs). In brief, we define a GCBR as a biological development that could adversely affect the human species as a whole or radically change the course of human civilization—for instance, a severe pandemic involving a naturally occurring or deliberately engineered pathogen. GCBRs are an emerging concern among a discrete set of scientists and organizations located principally in Europe and the United States. To conceive and implement activities necessary to prevent or respond to biological threats of a global scale will require effective communication of the issue’s importance—internationally—to a range of people with knowledge, influence, and control of resources.

December 2018 marked the fifth anniversary of the start of the worst Ebola epidemic in recorded history. The epidemic spread rapidly from rural villages in Guinea to major cities across West Africa,¹ ultimately resulting in 28,652 cases and 11,325 deaths across 10 countries,² including the first known transmission of Ebola virus infection outside of Africa.³ Despite the declaration of a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in August 2014,⁴ the international response lagged. The epidemic peaked in October 2014,⁵ but another 20 months passed before WHO issued its final declaration of the end of the epidemic in June 2016.⁶ Even before the official end of the epidemic, WHO announced major organizational and operational reforms in response to the challenges faced during the global epidemic response,^7,8 and public health and healthcare organizations around the world, including those that treated Ebola virus disease (EVD) patients, initiated efforts to increase preparedness for Ebola and other high-consequence infectious diseases (HCIDs).

The epidemic of Ebola virus disease in the Democratic Republic of the Congo (DRC) is the second largest in history after the 2014 west African epidemic. A storm of detrimental factors complicates this event: armed conflict, political instability, and mass displacement. WHO, the DRC Government, and non-governmental organisation (NGO) partners have shown remarkable leadership but are badly stretched. The outbreak remains far from controlled, risking a long-term epidemic with regional, perhaps global, impacts.

The 2014–16 West Africa Ebola epidemic was a watershed moment for global health. The outbreak galvanized global action around strengthening infectious disease prevention, detection and response capabilities. We examined the nascent landscape of international programmes, initiatives and institutions established in the aftermath of the 2014–16 Ebola outbreak with the aim of assessing their progress to date to illustrate the current state of the world’s global health security architecture. We also compare these efforts with shortcomings in epidemic management documented during the epidemic, and underscore remaining gaps in regional and global epidemic response capabilities that might benefit from additional programmatic and financial support. Notably, most of the post-Ebola initiatives considered in this analysis have yet to meet their financial goals. Operational progress has also been limited, revealing a need for continued investments to improve outbreak surveillance and detection capabilities specifically. Furthermore, our review highlighted the dominance of the USA and Europe in leading and financing efforts to coordinate long-term recovery efforts in West Africa, strengthen health systems across the continent, and enhance global preparedness for future epidemics, raising important questions about ownership of global health security efforts in non-Western regions of the world. Finally, the lack of transparency and available data on these initiatives’ activities and budgets also complicate efforts to project their impacts on the global health security landscape.

Successful containment of the ongoing Ebola virus disease outbreak in the Democratic Republic of the Congo (DRC) hinges on the return to the region of US Centers for Disease Control and Prevention (CDC) personnel and an immediate ramping up of international financial commitments to the World Health Organization (WHO). The US government ought to make security arrangements that would allow CDC staff to return to the field for as long as the WHO and fellow response agencies deem necessary. The international community should act now, despite the absence of a formal Public Health Emergency of International Concern (PHEIC) declaration. The WHO remains dependent on international support, both technical and financial. Its Contingency Fund for Emergencies—funding for responses to disease and other crises—has received from member states less than a third of its $100 million annual target. The WHO’s response to the DRC Ebola outbreak alone will cost an estimated $44 million.

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.