From Surveillance to Bedside: Tools for the Next Outbreak

By Michael Krug

The recent emergence of the novel Coronavirus (nCoV) hdemonstrates an essential demand for tools to rapidly respond to infectious diseases. These tools range from improved disease surveillance to therapeutics that mitigate infection spread. As new emerging diseases continue challenging global health response, it is imperative that these technologies continue to be developed, tested, and licensed for global use. This session, moderated by Dr. Vineet Menachery of the University of Texas Medical Branch and Dr. Kari Debbink of Bowie State University, touched on cutting edge research for the response to the next emerging infectious disease.

First to present was Dr. Amy Hartman from the University of Pittsburgh. Dr. Hartman’s presentation was titled In Utero: Transmission of Rift Valley Fever Virus: Ramifications for Future Outbreaks. The takeaway of Dr. Hartman’s presentation revolved around the use of animal models to better understand vaccine and therapeutic effectiveness. One of the projects investigating viable models involved using Rift Valley Fever Virus (RVFV), a select agent and priority disease declared by WHO, to test for vertical transmission of the disease in pregnant women. Limited human outbreak data suggest that vertical transmission of RVFV to a developing human fetus can lead to detrimental outcomes. In order to complete this study, a tested and validated animal model was needed, a difficult task to achieve given the human fetal tissue bans. Using immunocompetent Sprague-Dawley rats infected with a pathogenic strain of RVFV, Dr. Hartman’s lab demonstrated direct vertical transmission, which included fetal death. Additionally, the lab used donated placental explants to show RVFV replication in human cells that are typically resistant to viral infection. With the in vivo model and human placental cell evidence, Dr. Hartman’s lab demonstrated RVFV replication in the human placenta cells, as well as vertical transmission of RVFV in a novel animal model. Continue reading “From Surveillance to Bedside: Tools for the Next Outbreak”

Smallpox: Development and Use of the Panoply of Countermeasures in the Armamentarium

By Michael Krug

Smallpox remains one of the most devastating biothreats known to mankind. The reemergence of the variola virus, a member of the orthopoxvirus genus, could result in a catastrophic loss of life worldwide due to high transmissibility and high mortality rates, in combination with a relatively immunologically naive human population. The development of a safer and better tolerated vaccine would greatly ease the threat of a smallpox reemergence. The development of a new medical countermeasure (MCM) is easier said than done. The absence of the disease makes research and development a very difficult task. This session, moderated by BARDA’s Michael Merchlinsky, sought to provide detail into some of the recent breakthroughs throughout the orthopoxvirus field.

The first presenter of this session was Dr. Paul Chaplin of Bavarian Nordic. His presentation, titled The Approval of JYNNEOS, an Attenuated MVA-Based Vaccine for the Prevention of Smallpox and Monkeypox Infections, provided detail on the progression of developing an MCM without the luxury of working with the disease. Due to the harsh complications, especially to high risk individuals, that the traditional smallpox vaccines could cause, the U.S. government sought to develop a safer vaccine. In 2018, after nearly 15 years of public-private partnership efforts between BARDA and Bavarian Nordic, the U.S. FDA approved JYNNEOS for prevention of smallpox and monkeypox. The vaccine is a further attenuated version of the Modified Vaccinia Ankara (MVA) virus. JYNNEOS is unique because it is the first non-replicating smallpox vaccine to hit the market, greatly diminishing potential complications caused by replicating vaccines. When compared to the ACAM 2000, JYNNEOS stimulated an almost two-fold increase in antibody titer. Additionally, with greater than 10,500 clinical subjects, JYNNEOS has been proven to be safe and well tolerated, with no signs of clinical adverse side effects. JYNNEOS’s name was derived from Edward Jenner, the developer of the original smallpox vaccination process, known as scarification, and NEOS meaning new in Latin. Continue reading “Smallpox: Development and Use of the Panoply of Countermeasures in the Armamentarium”

Event Summary: Battling Insecurity, Mistrust, and Disease

By Greg Witt, GMU Biodefense PhD student

Since at least the fifth century BCE, when the Plague of Athens contributed to the outcome of the Peloponnesian War, states have recognized the detrimental effect that infectious diseases can have on their stability and security. In the modern era, as the focus of governments shifted from traditional concerns about national security to encompass new threats to economic prosperity, access to food, and public health – collectively known as “human security” – efforts to combat the risks posed by disease have been given an even higher priority. Nowhere is this connection more central than in the burgeoning field of health security, defined by the World Health Organization as “…the activities required to minimize the danger and impact of acute public health events.” However, just as the burdens imposed on societies by disease pose a threat to the security of states and populations, the inverse is equally true: insecurity tends to exacerbate the harmful effects of disease by displacing vulnerable people, impeding access to medical care, and breeding mistrust against government institutions. This can lead to a vicious cycle in which intrastate conflict reduces the capacity of states to respond to public health crises, which in turn makes it harder to prevent further violence. Continue reading “Event Summary: Battling Insecurity, Mistrust, and Disease”

Innovations in Biothreat Detection

By Joseph DeFranco

On 30 January 2020, Drs. David Walsh  from MIT Lincoln Lab, Timothy M. Reed from the 20th CBRNE CARA Lab, and Phillip M. Mach from the CCDC Chemical Biological Center, presented on their team’s innovations in biological threat agent detection.

Over the past several decades, the United States and the international community have dramatically improved their abilities to identify, respond, mitigate, and manage public health emergencies. Yet, there are demands to strengthen the prevention, protection, and treatment of individuals that may be exposed to dangerous pathogens, such as high-confidence & autonomous biological sensors. These technologies must be able to scan an area or environment, identify specific agents, and quickly inform stakeholders of an event. These sessions examined the recent advancements in rapid, confident, and fieldable biological threat agent – or biothreat – detection.

Dr. Walsh’s team works on biothreat detection research to overcome both the technical challenges (e.g., limits of detection) and operational challenges (e.g., availability of the device). These obstacles are compounded by the real-world environments in which these devices must be deployed versus the more controlled environments often found in hospitals or research institutions. Dr. Walsh’s team strives to create the “ideal” biosensor that would be sensitive to specific species, quick, reliable, and adaptable to environmental parameters. They are currently testing a rapid, autonomous device that performs sample collection, sample preparation, and biological identification.  A microcompactor condenses the surrounding air toward an impaction surface that collects the aerosols in the environment. Then, the device spins the raw sample from the impaction surface into a testable sample. Finally, the purified sample is amplified and analyzed by a relatively new method of detection called Extreme PCR (xPCR). Polymerase chain reaction (PCR) is a technique that scientists use to increase the amount of DNA from a sample, a process that usually takes an hour or longer. PCR requires repetitive heating and cooling to denature the original DNA strands, anneal the primer to the target sequence, and synthesize new DNA strands. xPCR uses state-of-the-art technology to accelerate the heating and cooling aspects of the assay and can detect the presence of DNA within minutes. Continue reading “Innovations in Biothreat Detection”

Symposium on “International Collaboration without Complications and Confusion”

By Madeline Roty

The symposium “International Collaboration without Complications and Confusion” at the ASM Biothreats Conference emphasized the complexity of promoting and protecting biological research and innovation in today’s society. The four speakers featured on the panel discussed what exists now and what still needs to be done to strike a balance between promoting and protecting biotechnology, with attention given specifically to export controls, synthetic biology, the select agent program, and biosecurity.

Kimberly Orr, from the Bureau of Industry and Security in the Department of Commerce opened the symposium with a discussion on “Deemed Exports: Sharing Technology or Material with Foreign Collaborators.” When it comes to biotechnology, how do you know if the Department of Commerce needs to be involved? The 2018 Export Control Reform Act (ECRA), codified by the Export Administration Regulations (EAR) establishes regulations on the export, reexport, or transfer of emerging and foundational technologies, including to foreign nationals located in the United States. Orr defined terms and briefly discussed the provisions of the ECRA. The key takeaway from all of this information was that laboratories and companies need to know the classification and licensing requirements, be aware of their personnel, and establish an export control program. In today’s world of interconnectedness, export control systems are essential for national and global security.

The next panelist, Diane DiEullis from the National Defense University, explored “Synthetic Biology: Industry/Government.” DiEullis has conducted research regarding industry practices in synthetic biology in order to identify opportunities for biosecurity. When it comes to biotechnology, there is always the risk for accidental or intentional misuse, but controlling the bioeconomy, comprised of consumer products, pharma, fuel, agriculture, food, material, and digital sectors, is complicated. It is even appropriate to ask if we should be controlling things that have every day purposes in laboratories. The issue does not just concern the United States because industry is becoming increasingly international. Continue reading “Symposium on “International Collaboration without Complications and Confusion””

Coronavirus Infections: More Than Just A Common Cold

By Joseph DeFranco

On 29 January 2020, Dr. Anthony Fauci, the Director of the National Institute of Allergy and Infectious Disease (NIAID), spoke at the ASM Biothreats meeting about the advent of the 2019 novel coronavirus (2019-nCoV).

Although scientists first characterized the human coronaviruses (CoV) in the 1960s, CoVs rarely received international attention. Then, in 2002, severe acute respiratory syndrome (SARS), a new disease, caused worldwide panic and consternation as the virus spread quickly from China to the rest of the world. Of the 8,098 SARS-infected patients, there were 774 fatalities (9.5% Case Fatality Rate [CFR]), and the pandemic cost the global economy an estimated US$30-100 billion. In the wake of SARS, the World Health Organization (WHO) would implement new International Health Regulations (IHR) to address some of the weaknesses exposed during the 2002 pandemic. Continue reading “Coronavirus Infections: More Than Just A Common Cold”

Lessons from “The Doctors Without Borders Experience: Patients as People and not Biohazards”

By Madeline Roty

Avril Benoit from Médecins Sans Frontières (MSF) opened the ASM Biothreats Conference by taking a step back from the micro level of a cell and focusing on the macro level of global health. Ms. Benoit is the Executive Director of the U.S. Management Team for MSF, more commonly known as Doctors Without Borders. In addition to the work being done by MSF, Benoit discussed the limitations and challenges hindering its mission. She challenged the audience of students, policymakers, scientists, and innovators, to be committed to humanitarianism over political and financial motivations and to promote human engagement before technology.

MSF is a non-profit medical humanitarian organization that primarily provides medical care to the most vulnerable in society, including those experiencing displacement, conflict and violence, or disasters. Because it is an organization primarily funded by private donors, MSF maintains more independence in decision-making. Fueled by the belief  that “every person is deserving of healthcare,” independence means MSF can “take enormous risks” to deploy personnel to regions other organizations cannot, especially in areas of conflict. In addition to providing medical care and supplies, MSF has epidemiologists, media personnel, and a research and development team. Continue reading “Lessons from “The Doctors Without Borders Experience: Patients as People and not Biohazards””

Pandora Report: 1.31.2020

ASM Biothreats
Missed the 2020 ASM Biothreats conference? Next week we’ll have you updated with our coverage across multiple talks, panels, and the highlights of this top conference on all things biological. GMU biodefense graduate students will be providing detailed accounts of these discussions at a pivotal time in international health. “ASM Biothreats is a one-of-a-kind meeting offering professionals in biodefense, biosecurity and biological threats the opportunity to exchange knowledge and ideas that will shape the future of this emerging field. ASM Biothreats offers a unique program that explores the latest developments and emerging technologies in the industry.”

Update: 2019-nCoV
If you have turned on any news channel or navigated to news website, you most certainly encountered a number of discussions about the ongoing coronavirus outbreak originating in Wuhan, China. The WHO was alerted on New Years Eve of this novel pathogen causing pneumonia-like illness and chaos increasingly ensued over the continuing weeks. This mysterious pathogen was identified as a coronavirus (think SARS and MERS) and is currently dubbed “2019-nCoV.” As the disease spreads globally, the WHO is launching a Global 2019-nCoV Clinical Data Platform for Member States to contribute anonymized clinical data that can inform the public health clinical response. On 30 January, the Emergency Committee on the 2019-nCoV under the International Health Regulations (IHR 2005) reconvened to determine if the outbreak constitutes a Public Health Emergency of International Concern (PHEIC), and, if so, what recommendations and actions should be made to manage it. Thursday evening, the Committee announced declaration of a PHEIC for the 2019-nCov outbreak. As of 28 January, there are confirmed cases in China, Nepal, the Republic of Korea, Japan, Sri Lanka, Viet Nam, Thailand, Cambodia, Malaysia, Singapore, United Arab Emirates, Australia, France, Germany, Finland, Canada, and the United States. Within the United States, there are 5 confirmed cases in Washington, California, Arizona, and Illinois as well as an additional 92 suspected cases awaiting diagnostic results. Currently, there are 165 persons located in the US under investigation for 2019-nCoV infection. On Thursday, public health officials reported that the husband of the case identified in Chicago, had tested positive for the disease. This marks a second-generation of cases, or transmission, within the U.S. There are also reports of people running to buy face masks in the U.S., leaving concern for shortages. Experts have been quick though to note that these are not needed as transmission is not widespread within the United States and that hand hygiene is most effective this time of year. GMU Biodefense doctoral alum Saskia Popescu recently spoke to CNN on this, noting that “Wearing a surgical mask helps you prevent sharing your germs if you’re sick,” Saskia Popescu, a hospital epidemiologist and infection prevention expert, told CNN. “Surgical masks do not seal around the face, so while they offer some protection, it’s the N95 mask that offers the most protection.” The CDC released an updated travel warning to its most severe yet – Warning Level 3 – urging travelers to avoid all nonessential travel to China. According to the WHO, the latest figures (30 January) for the outbreak are:

  • 7,818 confirmed cases worldwide
  • 7,736 confirmed cases in China
  • 170 deaths worldwide
  • Global Risk Assessment: High

Experts from the University of Hong Kong estimate the true total number of cases in Wuhan to be about 44,000, and they predict this figure could double by the start of February. The city is already under an unprecedented quarantine and hospitals are overrun as the epidemic intensifies. GMU biodefense graduate program director Dr. Gregory Koblentz recently spoke about the importance of promoting education, not travel bans as coronavirus concerns spread. “Widespread travel bans are ineffective and even counterproductive,” said Koblentz, a professor at George Mason University’s Schar School of Policy and Government and an expert on biodefense and biosecurity. “The idea that you can quarantine the entire population of large cities is just not feasible.” If people want to travel, they will find a way to travel, but they will be secretive about it, said Koblentz. “Then when they do get sick, they will avoid seeking medical attention because they don’t want to get in trouble,” said Koblentz. “A travel ban basically means that people will avoid getting help and notifying public health authorities, and the spread of the virus will continue, undetected.” Instead, Koblentz recommended that health officials work to get the public on their side by communicating with them about the symptoms and when to seek medical care.

Speculation abounds about the zoonotic origin of the virus, but the prevailing theory (at the moment) points toward bats as the culprit. The source location of the outbreak is the Huanan seafood market in Wuhan, which did not sell bat meat, so speculation continues. It is possible that another animal provided the channel to human infection. Previous conjecture that snakes are the origin is under criticism as it remains unclear if coronaviruses can infect snakes. Additionally, experts reject the fringe theory that the outbreak is a consequence of accidental release of biological weapons research samples housed in the Wuhan Institute of Virology. Richard Ebright, a professor of chemical biology at Rutgers University, stated the virus’s genome and properties do not indicate that it is the product of engineering. Stay tuned to the Pandora Report for updates on the progression of the 2019-nCov outbreak.

Of Quarantine and robots: How China and the U.S. Are Working to Combat Coronavirus
GMU Biodefense PhD alum Saskia Popescu recently wrote on the efforts by both the Chinese and the U.S. in responding to and preventing transmission of the 2019-nCoV. From quarantine to travel screenings, Popescu discusses the pros and cons, but also breaks down the opportunities within U.S. response. “The first case of the coronavirus in the United States received wide news coverage, and rightly so. But the Providence Regional Medical Center in Everett, Wash., used some extreme techniques to treat the patient, a man in his 30s who’d travelled to Wuhan. He was taken from an urgent care to the hospital in a negative-pressure transportation device called an ISOPOD that’s more often associated with Ebola care and put into an isolation room, where the hospital used a robot to treat him to reduce health care worker exposure. At this point, though, these extra precautions aren’t required. The Centers for Disease Control and Prevention notes that health care workers caring for patients with coronavirus should protect themselves with a gown, gloves, eye protection, and an N95 mask, which can filter out most airborne particles. If the Everett hospital wanted to use its robot and ISPOD to test its capabilities and protocols, it should have communicated this more clearly–to keep from confusing other health care providers about the advice of federal officials.”

ABSA International – Risk Group Database App
The Association for Biosafety and Biosecurity (ABSA) just released their new International Risk Group Database app, which allows users to work offline and access the ABSA database via their mobile device. The ABSA International Risk Group Database consists of international risk group classifications for bacteria, viruses, fungi, and parasites. In many countries, including the United States, infectious agents are categorized in risk groups based on their relative risk. Depending on the country and/or organization, this classification system might take the following factors into consideration: pathogenicity of the organism; mode of transmission and host range; availability of effective preventive measures (e.g., vaccines); availability of effective treatment (e.g., antibiotics); and other factors.

Doomsday Clock
The Bulletin of the Atomic Scientists released their 2020 Doomsday Clock statement and revealed that the clock is now closer than ever at 100 seconds to midnight. The Doomsday Clock is “universally recognized indicator of the world’s vulnerability to catastrophe from nuclear weapons, climate change, and disruptive technologies in other domains.” This year’s statement highlights two coexisting existential threats to humanity: nuclear war and climate change. Adding insult to injury, these threats are exacerbated by cyber-enabled information warfare, which continues to advance in efficiency and capability. The last year saw the dissolution or undermining of several key arms control treaties aimed at quelling the risk of nuclear war – the Joint Comprehensive Plan of Action (JCPOA) and Intermediate-Range Nuclear Forces (INF) Treaty, for example. Iran, the DPRK, and Russia remain major dangerous players in the nuclear game. On a more positive note, awareness of the adverse effects of climate change swelled over 2019; however, governmental action to counter climate change left much to be desired. The Bulletin implores leaders and citizens to take thoughtful and actionable steps to lessen these threats:

  • US and Russian leaders can return to the negotiating table to reach an agreement on nuclear arms and other arsenals
  • The nations of the world should publicly rededicate themselves to the temperature goal of the Paris climate agreement (limiting warming below 2 degrees Celsius higher than the preindustrial level)
  • US citizens should demand climate action from their government
  • The United States and other signatories of the JCPOA cooperate to curb nuclear proliferation in the Middle East
  • The international community should commence multilateral discussions to create norms of domestic and international behavior that discourage and punish the misuse of science

Alumni Spotlight – NextGen GHSA
A new piece published on the Next Generation Global Health Security Network was co-authored by Anthony Falzarano, Stephen Taylor, Kate Kerr and Jessica Smrekar, graduates of GMU’s MS in Biodefense program (Taylor Winkenfeld is also an author). This Op-Ed, “We Preach Prevention, WHO Practices Response,” chastises the sluggish response of the WHO to the ongoing 2019-nCov outbreak originating in Wuhan, China. China’s President Xi Jinping instituted a mass quarantine of 50 million people, yet the WHO has yet to declare this outbreak a Public Health Emergency of International Concern (PHEIC), which helps mobilize funding and political will toward outbreak response efforts. In fact, the committee that makes such a declaration met on 30 January, weeks after the start of the outbreak. The WHO possesses a history of delayed action, such as with the current Ebola outbreak in the Democratic Republic of Congo. The authors suggest that the delay in PHEIC declaration for the 2019-nCov outbreak is founded in fear of political and economic impacts, especially given the “reach of the Chinese global engine.” This outbreak is yet another example and, hopefully, lesson waiting and watching cannot be the default response to tragic events, especially ones that harm public health, regardless of the political, economic, and social issues that complicate decision-making and action.

The Ethics of Acquiring Disruptive Military Technologies
Technological innovation – especially in human enhancement, artificial intelligence, and cyber tools – continues at an accelerating rate and yield a significant effect on combat by reducing risk to soldiers and civilians, but also broadening the spectrum of actors capable of chasing policy goals through military methods. An article by C. Anthony Pfaff published in the Texas National Security Review expands the discussion about emerging and advancing technologies to include the ethics of disruptive military technologies. Disruptive technologies in a military context are defined as “technologies or sets of technologies applied to a relevant problem in a manner that radically alters the symmetry of military power between competitors, which then immediately outdates the policies, doctrines and organization of all actors.” These technologies necessitate changes in soldier training and identity as well as the relationship between society and soldiers. A technology is considered disruptive based on its attributes’ interactions with a specific community of users in a specific environment. The author outlines a framework to evaluate the moral effect, necessity, and proportionality of technologies to determine if and how they should be developed and deployed. This framework includes consideration for moral autonomy, justice, well-being, transfer of technology, and, of course, the civilian-military relationship. The author recommends eight measures and policies to maintain ethical conditions for developing disruptive technologies ranging from managing the transfer of technologies to greater society to accounting for soldier well-being.  Pfaff’s full article detailing his analysis, framework, and recommendations is available here.

Considering Pediatrics During CBW Preparedness and Response
Often during measures to prepare for a chemical or biological weapons attack, it can be easy to forget about the unique care that children and neonates require. A new article in Physicians New Digest discussed this very critical nuance to CBW preparedness, highlighting the CW attacks in Syria by the Assad regime against civilians, included children, underscoring the need for pediatricians. Often, medical countermeasures require very specific dosages or are contraindicated in children, which poses a very unique challenge for responders. “In chemical attacks, for example, children may be disproportionately affected because they would take in more contaminated air, food and fluids relative to their body weight than adults, said co-author Carl Baum, MD, FACMT, FAAP, a former AAP Council on Environmental Health executive committee member who now serves on the Council on Disaster Preparedness and Recovery executive committee. ‘Children also spend more time closer to the ground, where toxic substances can settle. And they have a relatively larger body-surface area, which makes chemicals that touch the skin more dangerous for them,’ Dr. Baum said.” Children might also have high respiratory rates or present differently, which puts them at an increased risk for both inhalation of a CB agent, but also delays in medical care or diagnostics. The authors highlighted the importance of including pediatricians in preparedness efforts to ensure children have triage and treatment protocols in the event of a CBW attack.

News of the Weird
Sure, the novel coronavirus is in the news a lot right now, but where does beer come into the picture? Unfortunately the whole “corona” portion of the name has been throwing people off. “In the United States, Google Trends calculated that 57% of the people that searched one of those terms searched for “beer virus,’ and the remaining 43% searched for ‘corona beer virus.’ States like Hawaii, New Mexico and Kansas are searching ‘beer virus’ more, whereas states like South Carolina, Colorado and Arizona are searching ‘corona beer virus’ more”

Pandora Report: 1.24.2020

ASM Biothreats Coverage
With this three-day conference just around the corner, you’ll want to make sure not to miss our coverage in the coming weeks. GMU Biodefense has been sending graduate students to attend ASM Biothreats since 2016 and we’re always excited to share their insights into the presentations and discussions. Check out our previous coverage here, which will provide you with detailed accounts of this conference and the timely conversations that will likely take place surrounding the 2019-nCoV outbreak.

The Novel Coronavirus Bubbles Out of China 
As the first case of 2019-nCoV was identified in the United States this week, questions continued to bubble up regarding the transmission mechanisms and if human-to-human transmission will be sustained. On Wednesday, the WHO met to discuss a declaration of a PHEIC (public health emergency of international concern) as cases spilled into Japan, Thailand, and South Korea, and case counts surpassed 830 infections and 17deaths. Interestingly, as the emergency committee was split on the decision, it was pushed to review again on Thursday and just before, China decided that the city of Wuhan would effectively have a cordon sanitaire, or quarantine. Ezhou and Huanggang have bene added to this list as of Thursday. Mid-day on Thursday, the WHO announced that they would not be declaring the outbreak a PHEIC. WHO situation reports can be found here. Moreover, as news of infection in 14 healthcare workers, it’s a reminder of previous coronavirus outbreaks. With the news of the Wuhan closure, it draws similarities to the quarantine efforts tried by Toronto in the SARS-CoV outbreak, which were considered widely ineffective and frustrating to the community. While each outbreak requires unique control measures, it is important to also note that it is challenging to truly know the case facility rate at this point in the outbreak, and that sudden bursts of identified cases are likely a result of surveillance efforts. As this outbreak has evolved in recent days though, the initial statements of “there has not been sustained human-to-human transmission” have been questioned. Beyond the initial worries about information sharing from the Chinese that were reminiscent of SARS-CoV, the role of healthcare and super-spreaders has been re-established. Chinese media has been quick though, to deny superspreading events. In 2003, the spread of SARS-CoV throughout Toronto taught us several lessons about not only importation of cases due to international travel, but also how super-spreaders in the right environments, like a hospital, can cause devastating outcomes. A lesson learned from Toronto too, is that of the importance of enhanced infection prevention measures and the questionable efficacy of quarantine efforts..not to mention the importance of communication, both between healthcare/public health, but also to the public. Flash forward nearly 10 years and a novel coronavirus was again causing problems…this time, beginning in Saudi Arabia. Spreading across 27 countries since it was first identified in 2012, MERS-CoV is another lesson in novel diseases and the role of One Health. MERS-CoV gave us new insights in not only why the WHO won’t declare an outbreak a PHEIC, but also a hard lesson in how hospitals can amplify an outbreak. In particular, the 2015 outbreak in South Korea, where it is estimated that 91-99% of cases were related to healthcare transmission and 83% of transmission events were tied to five superspreaders. Health system components like multiple patients per hospital room, family involvement in care, and hospital shopping, encouraged the spread of disease. In Saudi Arabia, small outbreaks have consistently happened since 2012, with links to not only camels, but also hospitals in which busy emergency departments and delays in isolation helped spread the disease. In fact, since 2013, most of the cases have been in Saudi Arabia and 19.1% have been in healthcare workers. There are many lessons to be learned from these previous outbreaks of novel coronaviruses, but as of now there are several discussions that need to happen – with a lower case fatality rate (CFR), will emergency measures need to be taken? How effective is airport screening, especially for international flights in the middle of respiratory virus season? As this outbreak is quickly unfolding and we learn new components to the virus daily, a few things are certain though – efforts have been swift (sequencing of the virus took only a matter of weeks), and the Chinese have worked to maintain diligent information sharing and outbreak investigations..not to mention to amazing and rapid efforts of international public health workers. Also, when we provide people with information, these efforts might prove to be just as effective as screening measures as the first case of 2019-nCoV within the U.S. was not identified through this route, but rather by some one who alerted to the outbreak and sought medical care, informing their healthcare provider of relevant travel history. Here are some valuable sources – regarding what we know and don’t know,  the implications of the quarantine for people in Wuhan, and fatality details.

Vulnerable Hospitals and Federal Funding Cuts for Biopreparedness
GMU Biodefense doctoral alum and infection preventionist Saskia Popescu discusses the tiered hospital approach to special pathogens and how despite its imperfections, the cut to funding should be taken seriously. Despite the flaws with the existing tiered system for dealing with special pathogens, it’s a more comprehensive and better resourced approach than what was in place before the 2014-2016 Ebola epidemic. As it stands, Congress has funded the 10 advanced treatment facilities and the National Ebola Training and Education Center but not the 60 treatment centers included in the tiered network. (The nearly 5,000 frontline hospitals never got much federal funding for their special pathogen-related efforts.) Trump signed the bill into law in December.

Redefining Neuroweapons: Emerging Capabilities in Neuroscience and Neurotechnology
Joseph DeFranco, a graduate of the GMU Biodefense MS program, recently co-authored an article about the emerging capabilities in neuroscience and neurotechnology that may enable new types of neuroweapons. Neuroscience and neurotechnology – lovingly nicknamed neuroS/T – are interwoven fields with research and development spanning medicine and military uses. Neuroscience is the study of the developmental processes, structures, functions, and of the brain and nervous system. The field is often referred to in the plural as neurosciences because of its cross-disciplinary nature encompassing molecular biology, developmental biology, physiology, anatomy, cytology, chemistry, mathematics, engineering, linguistics, computer science, medicine, and psychology. Neurotechnology produces a variety of tools, outputs, and substances that affect or probe the nervous system. DeFranco, DiEuliis, and Giordano consider the swift timeline for advancement in neuroS/T and the dual-use potential of such advancements in warfare, intelligence, and national security (WINS) applications. Certain neuroS/T advancements such as gene editing methods and nanoparticles can modify the central nervous system, providing significant utility and application for WINS. Existing pitfalls in international biological and chemical weapons conventions include the lack of consideration for existing and emerging neuroS/T outputs. Frankly, the inventions of neuroS/T are the redheaded step-child of these treaties, as none claim to cover it. The growth of “neurodata” is another important issue as biology becomes increasingly digitized. Though these data can prove immensely helpful in medicine and performance, they also have the potential to be used to target or alter specific individuals or groups. These data, as with all data, are vulnerable to cyberattacks or nefarious surveillance. Based on these benefits and risks of emerging neuroS/T, the authors outline a series of recommendations to either rectify existing insufficient oversight and governance or develop strong oversight and governance for the future.

Update: Ebola in the DRC
The current Ebola outbreak in the Democratic Republic of the Congo (DRC) is the second largest of its kind with over 1,600 cases from 2018 to mid-2019. This outbreak is mired in the exacerbating effects of conflict. Beyond the almost natural increase in disease transmission in a warzone, the DRC sees targeted attacks against medical workers there to quell the outbreak. Recent research focuses on the effects of violence on Ebola disease incidence. Mueller and Rebmann assessed the relationship between attacks targeting aid workers and the incidence of Ebola during the 2018-19 DRC outbreak in the North Kivu and Ituri provinces, regions characterized by violence. Findings from the analysis showed that the relationship between targeted violence against aid workers and disease incidence may be explained etiologically and logistically given the harmful impact on operations from the targeting of facilities, supply lines, and personnel. Wannier et al. quantified the effects of conflict on disease transmission using transmission rates between health zones that have versus have not experienced recent conflict events during the EVD outbreak. The mean overall R (reproduction number) of the total outbreak was 1.11, the average R for regions unaffected by recent violence was 0.61-0.86, and the average R for regions affected by recent violence was 1.01-1.07. These results indicate conflict contributes to increased transmission of Ebola in this outbreak. Wells et al. provides a timeline and ethnographic appraisal of the violence and disease in eastern DRC using data and information regarding the period from 30 April 2018 to 23 June 2019. Additionally, the authors constructed a model to quantify the strife prior to a conflict event and its ensuing impact on disease control activities in order to reveal the influence of war on the persistence of an epidemic. The gist of this trio of studies is that the Ebola outbreak is being exacerbated by the ongoing violence in eastern DRC as well as the attacks on the personnel in the field to respond to the outbreak.

Epidemics in Movies and Social Response
Need a break from the constant stream of coronavirus news? In perhaps one of our more favorite articles, a research team looked to the way films illustrate epidemics to the public. The authors note that there are two ways these films affect society – ” fear leading to a breakdown in sociability and fear stimulating preservation of tightly held social norms. The first response is often informed by concern over perceived moral failings within society, the second response by the application of arbitrary or excessive controls from outside the community.” If you’re a fan of outbreak or infectious disease themes in films, this is a great article to read on everything from Dallas Buyers Club to Contagion.

How much Should the Public Be Told About Risky Virus Research?
This is definitely a great way to start a fun dinner discussion with your favorite biodefense folks! Nell Greenfieldboyce recently discussed the NSABB meeting that started on Thursday and will conclude today. The news of a new coronavirus outbreak surely will add to this conversation and the future research that will study this novel disease. The argument regarding research on potential pandemic pathogens and gain-of-function experiments is one that has been going on for years. The conversations don’t just stop at if these experiments should exist and what they look like, but also about the publication of such information and just how much should be shared publicly. A new framework for evaluating potential experiments has already had three proposals – two made it and one is currently under review. “There’s a lot of interest out there in how these reviews get done, notes Wolinetz, but “it’s a little bit tricky, because all of these discussions are happening before funding decisions are made. Under current rules and regulations in the government, those conversations, pre-award conversations, are protected.” That’s to ensure, for example, that someone’s idea for a novel experiment doesn’t get stolen by another researcher. It also lets reviewers be candid in their critiques. What’s more, if a proposed study was deemed too alarming to fund, it might not make sense to make that idea available to all. On the other hand, some biosecurity experts argue that the public needs to know who is evaluating the risks and benefits and exactly what their reasoning is.” Confidence-building measures, like including a range of voices and disciplines into this decision-making process, are all ideas that have been raised during this process. Inclusion of risk-mitigation efforts and communication strategies are also measures that several researchers have emphasized. As Dr. Tom Inglesby noted though, “once we publish the mechanisms for making pathogens more dangerous —potentially ‘pandemic dangerous’ — we can’t take that information back. That information will be out there online for good.”

Patient Proximity to Farms and Increased Risk for C-diff Colonization
Talk about a One Health relationship – imagine living close to a livestock farm and having an increased risk for a diarrheal illness? That’s exactly what a new study is showing. The authors found that “the independent effect of residential distance to livestock farms was substantial; regardless of health care exposure, the probability of colonization more than doubled for those living 1 mile from a livestock farm compared with those living 50 miles from a livestock farm. Specifically, the probability of colonization increased from 6.5% among those living 50 miles from a livestock farm to 15.7% among those with previous hospitalization and from 4% to 10.6% among those without a recent hospitalization.”  Comorbidities played a factor in those patients admitted to a non-hematology/oncology unit, increasing the odds of colonization by more than 4 times.

Genetic Modification Could Protect Soldiers from Chemical Weapons
Despite bans on the development and deployment of chemical weapons, their use in conflict continues. Current treatment options are picky as they must be administered immediately and may not be satisfactorily efficacious; however, US Army researchers recently made a breakthrough in toxicant protection for soldiers. Specifically, the researchers developed a type of gene therapy that allows mice to create their own “nerve agent–busting proteins,” which provide protection against the agents, possibly for months. Though this therapy bears the potential for human use, it is risky. Such risks include the development of an adverse immune response to the introduced protein. Lead biochemist Nageswararao Chilukuri called the experiment of a “proof of principle” study. The long-short of the experiment is the livers of mice were reprogrammed as factories pushing out a “bioscavenger” enzyme that quickly incapacitate nerve agents. The team recently reported that the mice survived nine customarily lethal injections for six weeks, a promising but preliminary result.

USAMRIID 2019 Lab Protocol Failures and Findings 
Last year it was announced that the USAMRIID lab at Fort Detrick was temporarily shut following CDC inspections that found failures in their practices. “The lab itself reported that the shutdown order was due to ongoing infrastructure issues with wastewater decontamination, and the CDC declined to provide the reason for the shutdown due to national security concerns.” Documents that were recently obtained found that those violations initially reported were only a handful, but many were labeled as “serious” including – “The CDC reported that an individual partially entered a room multiple times without the required respiratory protection while other people in that room were performing procedures with a non-human primate on a necropsy table. ‘This deviation from entity procedures resulted in a respiratory occupational exposure to select agent aerosols,’ the CDC wrote.” You can read more here on these findings and the serious observations that were identified, triggering the lab’s temporary closure.

 

Pandora Report: 1.17.2020

Happy Friday! We’re glad to start the weekend with a healthy dose of all things biodefense. Before we get too far down the nCoV-2019 rabbit hole…Senator Dianne Feinstein recently wrote a letter to DHHS regarding steps the department is taking to protect the U.S. against pandemics.

ASM Biothreats 
It’s almost that time of year and if you can’t make the January 28-30 ASM Biothreats conference, don’t worry – we’ll have great coverage. GMU Schar School Biodefense is sending graduate students to the conference to report out on these three days of all things biothreats. Check out previous years of our coverage here, where we provide detailed overviews of the talks and events. “ASM Biothreats is a one-of-a-kind meeting offering professionals in biodefense, biosecurity and biological threats the opportunity to exchange knowledge and ideas that will shape the future of this emerging field. ASM Biothreats offers a unique program that explores the latest developments and emerging technologies in the industry.”

AI Weapons
The end of 2019 and the start of 2020 sees an uptick in discussion regarding artificial intelligence-driven weapons. Three of the world’s biggest plays – the United States, Russia, and China – are all strongly indicating that artificial intelligence (AI), considered a transformative technology, will be dominant in their respective national security strategies. Recent headlines on the topic include terms like “killer robots” and “Terminator-style war.” Indubitably, we are in an era of rapid and momentous technological advancement and discovery; however, the true application of these technologies is fairly narrow and now necessarily nefarious. Larry Lewis, a senior advisor for the State Department in the Obama administration and a member of the US delegation in the UN deliberations on lethal autonomous weapons systems, recently published an article in the Bulletin of the Atomic Scientists about the utility of AI in reducing the collateral damage of war. Lewis spent the last decade working to reduce the civilian casualties in war, and he found that such casualties were largely the result of inaccurate indicators regarding civilian presence or the misclassification of civilians as combatants. Though military applications of AI include autonomous weapons, this technology can also be employed to optimize automated processing to detection and as a decision aid to helping personnel interpret complex or vast sets of data. Though discussion tends toward the risks of AI technology, especially its military applications, Lewis endorses adding a new facet to the discussion that focuses on the benefits of AI technology in minimizing civilian casualties in warfare.

nCOV-2019 and the Wuhan Outbreak
The past few weeks have been busy with the news of this novel coronavirus cluster in Wuhan, China. Following the identification of it as a novel strain and the temporary name of nCoV-2019, public health authorities have been working to better understand the epidemiological aspects of the virus and how we can prevent further transmission. News of a case in Thailand, following travel to the affected region in China, quickly spread as it meant that cases were no longer contained in China. Interestingly, the Chinese woman whose infection was detected after her arrival in Thailand, had no exposure to the market that is considered to be the epicenter of the outbreak. “A new statement from the World Health Organization (WHO) today had several new details, including that the woman had not visited the Wuhan seafood market, which also sold live animals such as chickens, bats, and marmots, where most patients are thought to have been exposed. However, she reported regularly visiting a local fresh market before her symptoms began on Jan 5. That illness onset is later than that of the others infected in the outbreak, which ranged from Dec 8 to Jan 2, according to a Jan 12 update from the WHO. The incubation period for nCoV-2019 isn’t known, and authorities closed the seafood market on Jan 1.” 182 contacts are being monitored related to this case and eight febrile travelers at the Suvarnabhumi Airport have been isolated and tested (all were negative). Japan also confirmed their first case in a 30-year-old man who tested positive following a visit to Wuhan. On Thursday, officials released more information regarding a second family cluster in Wuhan (likely exposed via the same source), as well as findings from environmental testing at the market in Wuhan.

Antibiotic Tolerance Can Affect Combo Treatments, Study Finds
A team of scientists in Israel found evidence that antibiotic resistance in microbes may render combination therapies ineffective, a long-held fear that may now be reality. Combination drug therapy is a commonly used clinical method for treating infections caused by resistant microbes and to prevent the progression of resistance. This team monitored the evolution of Staphylococcus aureus strains in patients undergoing combination treatment and exposed the swift emergence of tolerance mutations trailed by the emergence of resistance. Tolerance mutation in antibiotics is a general term “used to describe the ability, whether inherited or not, of microorganisms to survive transient exposure to high concentrations of an antibiotic without a change in the MIC, which is often achieved by slowing down an essential bacterial process,” whereas antibiotic resistance is “the inherited ability of microorganisms to grow at high concentrations of an antibiotic, irrespective of the duration of treatment, and is quantified by the minimum inhibitory concentration (MIC).” After the discovery of tolerance to combination treatments in the S. aureus case, the scientists were able to expand the finding by measuring bacterial growth in Escherichia coli after drug combinations from four different antibiotic classes. Isolates with tolerance to norfloxacin and ampicillin promoted resistance in some of the combinations for treating E. coli. Therefore, the authors conclude that “rescue of resistance mutations by tolerance is a general phenomenon that may have crucial implications for the evolution of resistance in patients treated with combinations of antimicrobials.” A short article summarizing the study can be found here and the original publication can be found here.

WHO- Urgent Health Challenges for the Next Decade
The World Health Organization has released their list for the new decade – which was “developed with input from our experts around the world, reflects a deep concern that leaders are failing to invest enough resources in core health priorities and systems.” The list does not place challenges by priority, as they are all urgent and includes elevating health in the climate debate, delivering health in conflict and crisis, making healthcare fairer, expanding access to medicines, stopping infectious diseases, and more. Within each challenge, the WHO discusses what it is and what they are doing to help correct it.

Outbreak Dashboard 
While much attention has been to the novel coronavirus outbreak, more Ebola cases have been identified in the DRC. The latest situation report from The Who reports 8 new cases, including 3 in Beni.