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.