FY2019 Health Security Funding Outlook: Quick Take Based on President's Budget Request

By Crystal Watson, Tara Kirk Sell, and Matt Watson

With the release of the President’s Budget Request this week, we now have a glimpse into White House priorities and recommendations for major health security programs. While a detailed analysis will be forthcoming in our annual health security funding article, here is what we know so far:

Centers for Disease Control and Prevention (CDC): There should be a big change at CDC as the Strategic National Stockpile program is moved from its long-time home in the Office of Public Health Preparedness and Response (OPHPR) over to the Assistant Secretary for Preparedness and Response (ASPR). The Public Health Emergency Preparedness (PHEP) Cooperative Agreement program at CDC would receive a $5 million increase above the estimated FY2018 Continuing Resolution (CR) level, while CDC Preparedness and Response would be cut by $20 million, Influenza Planning would get a slight boost, and Emerging and Zoonotic Infectious Diseases programs would be cut by $60 million.

  FY2017 FY2018 FY2019
  (actual) (estimated CR) (budget)
Centers for Disease Control and Prevention (CDC)      
Public Health Emergency Preparedness (PHEP) Cooperative Agreements 658.5 655.5 660.0
CDC Preparedness and Response Capability (includes BioSense) 161.5 160.7 140.0
Strategic National Stockpile (SNS) 573.9 571.1 ---
Influenza Planning and Response 187.2 171.4 180.0
Emerging and Zoonotic Infectious Diseases 575.7 568.3 508.3

Office of the Assistant Secretary for Preparedness and Response (ASPR): As the new home for the SNS, ASPR’s budget would increase by over $575 million in FY2019. Other programs in ASPR would remain relatively flat, with the Hospital Preparedness Program (HPP) at $255 million (compared to $253 million estimated for FY2018), BARDA receiving about $2 million more than FY2018, and BioShield getting a $3 million increase. Pandemic influenza funding (split between ASPR and the Office of Global Affairs) would increase to a total of $250 million (almost $50 million more than in FY2018).

  FY2017 FY2018 FY2019
  (actual) (estimated CR) (budget)
Assistant Secretary for Emergency Preparedness and Response (ASPR)      
Medical Reserve Corps 6.0 6.0 4.0
Operations 30.9 30.9 31.0
Biomedical Advanced Research and Development Authority (BARDA) 510.0 508.0 512.0
Project BioShield 509.0 507.0 510.0
Strategic National Stockpile (SNS) --- --- 575.0
Preparedness and Emergency Operations 25.0 24.0 27.0
National Disaster Medical System (NDMS) 50.0 50.0 50.0
Hospital Preparedness (HPP) Grants (includes ESAR-VHP) 254.0 253.0 255.0
Policy and Planning 15.0 15.0 15.0
Pandemic Influenza (funded between ASPR and OGA) 72.0 112.0 250.0

Department of Homeland Security (DHS): The major development at DHS is creation of the new Countering Weapons of Mass Destruction (CWMD) Office and reorganization of health-security related programs from across the Department into CWMD. This office was created in December 2017 with the purpose of elevating the CWMD mission within the Department, and providing a centralized office for WMD-related programs. This Office will encompass programs and operations from a number of other parts of the Department, including the Domestic Nuclear Detection Office (DNDO), which will transfer all of its functions to the new CWMD Office; the Office of Health Affairs, which will transfer all of its functions; and the Science and Technology Directorate, which will transfer some of its functions to CWMD. A deeper dive into these budgets will be helpful in understanding what programs were moved, defunded, or kept in place. On initial review, here is what we know:

In total, CWMD’s proposed budget is $429.3 million in FY2019, including:

  • $209.3 million for Mission Support and Capability and Operations Support
    • Of which, $51.8 million will be for Biological Support, primarily for bio-detection (BioWatch)
  • $74.9 million for Procurement, Construction, and Improvements (primarily for radiological detection equipment)
  • $80.4 million for Research and Development (primarily for RN detection)
  • $64.7 million for federal assistance to federal, state, local, tribal, and territorial partners

For the Science and Technology Directorate, there is a proposed cost-sharing agreement for the National Bioforensic Analysis Center (NBFAC) within National Biodefense Analysis and Countermeasures Center (NBACC), where the FBI would assume operational costs for NBFAC (which is about 40% of NBACC’s total operational costs). In addition, S&T is proposing to transfer responsibility of the National Bio and Agro-Defense Facility (NBAF) Operations in its entirety to the US Department of Agriculture (USDA).

Global Health Security Agenda: Funding for the Global Health Security Agenda in the FY2019 budget would include $59 million designated GHSA funding out of a $109 million budget in the Global Disease Detection line at CDC, and $72.5 million in repurposed Ebola supplemental funds at US Agency for International Development (USAID). GHSA funds for CDC would be on top of any unexpended Ebola supplemental funding at CDC, which expires in FY2019 for that agency.

More to come in our comprehensive Federal Funding for Health Security analysis, published annually in Health Security.

The problem of horsepox synthesis: new approaches needed for oversight and publication review for research posing population-level risks

By Tom Inglesby

In summer 2017, a team of Canadian scientists revealed that they had synthesized the horsepox virus in a lab at the University of Alberta, and planned to publish their research. I and others expressed strong concern about the work at that time, and we have opposed its publication. 

Today, the science journal PLOS ONE published this research online, so it is now globally available. The horsepox researchers acknowledged that this work may lower the bar for other scientists interested in synthesizing smallpox. Before its eradication from nature in 1980, smallpox was humanity’s greatest infectious disease killer. Almost none of the global population in 2018 has effective immunity, and smallpox vaccine supplies are available only to protect a small fraction of the world. There are only two declared smallpox repositories, one in the United States and one in Russia. Any research that reduces the challenges of synthesizing smallpox de novo outside these repositories—as this work does—should be off limits unless, perhaps, there were to be extraordinary benefits that make the risks worth taking.

This work does not carry such extraordinary benefits. As Greg Koblenz has articulated in his paper on this issue, there is not a compelling case that governments will need or use this virus to develop a new and improved smallpox vaccine. Another justification made by the horsepox researchers was that it is important to demonstrate the feasibility of synthesizing smallpox de novo. But creating a new extraordinary risk (i.e., instructions for how to simplify smallpox synthesis) to show that the risk is legitimate is a dangerous path. In any event, relevant members of the science community have widely agreed that smallpox synthesis has been technically feasible for many years now. What this new research does is show the global scientific community how to synthesize orthopox viruses in an efficient way, to overcome technical challenges, and to employ techniques developed by one of the leading orthopox labs in the world.

Now, with this research published and accessible to the world, those of us who are deeply concerned about it should consider what is needed to prevent future events with such potential harmful impact. This horsepox synthesis research work has exposed serious flaws in how governments oversee research that has profound potential population-level adverse consequences. The University of Alberta research team admitted that regulatory authorities “may not have fully appreciated the significance of, or potential need for, regulation or approval of” their work. Clearly, fundamental changes need to be made. 

The most important locus of control should be whether specific research is approved and funded in the first place. When scientists are considering the pursuit of research that has the potential to increase highly consequential national population-level risks, national authorities and leading technical experts on those issues should be part of the approval process. When there are highly consequential international population-level implications, international public health leaders should also be involved. When researchers put forth claims about potential benefits of this work to justify extraordinary risks, those claims ought not be accepted without discussion; those claims should instead be examined by disinterested experts with the expertise to validate or refute them.

If research posing potential population-level risks does get performed without such high level national or international scrutiny, or without a disinterested examination of the benefits, publishers should have clear guidance from governments and a process for engaging with governments in the decision-making process regarding publication. That kind of system is not in place in the United States or elsewhere. Journals are now often on their own, in some cases with the help of a dual-use research committee that is comprised of individual scientists who may or may not have full understanding of the potential risks or the claims of benefits of the underlying research being published.   

We need to turn what we’ve learned from this damaging situation into actionable policies aimed at strengthening preparedness and global health security. The first step is changing the oversight and approval process for experiments that have potential to create highly consequential population-level risks. We also need a coinciding publication review system for such research with the scientific and government input necessary to avoid publishing research that increases risks to global populations.   

Is Captain America a Biological Weapon?

capt-am.png

As part of my trip to attend the 2017 Meeting of States Parties to the Biological and Toxin Weapons Convention (BWC), I attended a pre-meeting workshop hosted by the Malaysian and American Permanent Missions to the United Nations. This workshop provided a forum to discuss relevant bioweapons nonproliferation, preparedness and response efforts for deliberate and naturally occurring outbreaks and epidemics, international collaboration mechanisms, and the future of the Biological and Toxin Weapons Convention (BWC) leading up to the Meeting of States Parties. During one presentation on the security considerations for advances in genome editing, an interesting question was posed that reframed my perspective on the BWC:

Does the BWC adequately address genetic modification of higher order organisms?

Article I of the BWC states (emphasis added):

Each State Party to this Convention undertakes never in any circumstances to develop, produce, stockpile or otherwise acquire or retain:

(1)  microbial or other biological agents, or toxins whatever their origin or method of production, of types and in quantities that have no justification for prophylactic, protective or other peaceful purposes;

(2)  weapons, equipment or means of delivery designed to use such agents or toxins for hostile purposes or in armed conflict.

Written in the early 1970s, the BWC text is intentionally vague, providing it the flexibility to address emerging and unforeseen threats (eg, prions), but this vagueness leads to questions regarding its scope, especially in the context of higher order organisms—ie, complex organisms such as plants, animals, and humans.

Until this workshop, essentially the entirety of the several years during which I have been paying attention to the BWC, Article I seemed fairly straightforward to me. Beyond toxins (which the BWC explicitly states that it covers), I had always assumed that Article I covered bacteria, viruses, and fungi. Seems pretty obvious, right? Basically, just the things that can intentionally infect humans, animals, or plants in order to directly or indirectly cause harm to target populations.

But what if there is no infection, per se? What if the “biological agent” isn’t a pathogen at all, but rather, a human, animal, or plant? What if the affected individuals are volunteers rather than victims?

Using a fictional example to illustrate these issues, let’s look at the classic superhero Captain America. Captain America underwent some form of human enhancement as part of a US military program that transformed him from tiny weakling Steve Rogers into, well, Chris Evans for the sole purpose of battling Nazis in World War II. Under Article I, normal, naturally occurring pathogens would fall under “microbial or other biological agents,” so it would follow that modified versions of these pathogens would also qualify. But normal humans, animals, and plants do not seem to count as “other biological agents” in the context of the BWC, but what about enhanced or modified versions like Captain America or, perish the thought, the accidentally enhanced Teenage Mutant Ninja Turtles? Have we been unwittingly cheering for bioweapons this whole time?

The two principal tenants of Article I are that (1) the BWC specifically addresses biological organisms (as opposed to chemical or nuclear) AND (2) that the organism is used for purposes other than peaceful or protective (ie, for offensive or hostile purposes). The second part is pretty easy; if you have ever read a Captain America comic book or seen a Captain America/Avengers movie, it should be obvious that Captain America was designed for and utilized in an offensive capacity in combat. The first tenant, however, is a little less straightforward. Captain America is certainly a biological organism, but there is no explicit text in Article I that differentiates him from a normal human. Normal humans have been employed in military combat and other forms of violence for the entirety of our existence, but surely, they would not be regulated under the BWC. On the other hand, Captain America clearly is not a normal human, posing the question:

Does the deliberate modification of a human genome change this distinction in the context of the BWC?

The Captain America scenario raises a number of other questions with respect to how a bioweapon might be employed. In this case, Steve Rogers enthusiastically volunteered to be enhanced. Traditional bioweapons scenarios likely involve the victim population being harmed through direct infection or via secondary effects of infecting their animals and/or food sources rather than the attacker voluntarily being “infected” him/herself and posing no risk of infection to the target population. And speaking of “infected,” Captain America wasn’t ever really infected with a biological agent in the traditional sense; his biological makeup was simply modified through some targeted biological/radiological process, but there was no pathogen involved (to my knowledge, anyway; I’m not a superhero expert).

Would this biological/radiological process be regulated under the BWC, and if so, would Captain America then be considered to be a “[weapon], equipment or other means of delivery”? Additionally, there are numerous mechanisms available to enhance higher order organisms, ranging from improving performance through drugs or supplements to deliberate modification of the genome. Some infections can also potentially alter biological traits of higher order organisms, further blurring the line between infection and modification. In one timely example, mosquitoes infected with naturally occurring Wolbachia bacteria exhibit poorer transmission of vectorborne diseases like dengue and Zika.

The tools required to modify the biological traits of higher order organisms, to varying degrees, are rapidly increasing in number, capability, and availability. Considering the potential for these tools, and the resulting organisms, to be utilized for offensive purposes, explicit discussions are needed to ensure that all States Parties have a common understanding of the BWC’s scope and, in turn, adhere to the same norms with respect to the use of advanced biology and biotechnology and genetically modified organisms of all kinds.

The incredible pace of advancement in biology and biotechnology and its impact on the ability to deliberately modify the genomes of higher order organisms necessitates that these types of questions be addressed proactively rather than reactively. The ability to utilize tools such as CRISPR-Cas9 to treat genetic diseases seems to be just over the horizon. In fact, the US FDA recently approved the first directly applied gene therapy to treat blindness caused by an inherited genetic mutation. Scientists have also produced animals with excessive muscle mass using these types of tools, research that could potentially lead to treatments genetic disorders such as muscular dystrophy. If these techniques were utilized to enhance similar properties in normal, healthy humans—or other properties that could provide an advantage in combat—it could essentially result in the creation of super-soldiers, real-life versions of Captain America. In another example, genetically modified mosquitoes have already been employed to reduce local mosquito populations and, therefore, incidence of vectorborne diseases such as Zika and chikungunya. A release of modified bees or other insects in an agricultural area could result in substantial risk to food and economic security in the affected country or region due to the release of a genetically modified higher order organism.

The 2017 BWC Meeting of States Parties succeeded in its mandate to agree upon a program of work for the remainder of the intersessional period before the next Review Conference in 2021. The agreed-upon agenda includes an annual Meeting of Experts that provides for 8 days each year dedicated to substantive discussion about technical and policy issues surrounding:

  • International cooperation and assistance in the context of BWC Article X (2 days)
  • Review of developments in science and technology potentially relevant to the BWC (2 days)
  • Strengthening national implementation of the BWC (1 day)
  • Requesting and providing international assistance, response, and preparedness for deliberate biological incidents in the context of BWC Article VII (2 days)
  • Institutional strengthening the of the BWC—eg, legally binding verification mechanisms (1 day

The two days of discussion about emerging science and technology will be critical to ensuring that the BWC adequately addresses the potential risks posed by a broad range of dual-use science capabilities, but discussion at this level (ie, national delegations) is not sufficient to fully address the risks potentially posed by this kind of research.  As these capabilities become more prolific, it is increasingly likely that they will be utilized—for public health purposes (eg, vector control), military purposes (eg, human enhancement), or otherwise.  Explicit discussion is required in fora such as the BWC to ensure that all States Parties understand and agree on the extent to which these techniques and/or the resulting organisms are regulated by the BWC so that all States Parties adhere to the same established norms, particularly when the issue at hand is technology with potential military applications.

Course of Conversation: Infectious Disease Threats to Global Health Security

Jennifer Nuzzo, DrPH, a senior scholar at the Johns Hopkins Center for Health Security, teaches the Infectious Disease Threats to Global Health Security elective as visiting faculty in the department of environmental health and engineering at the Johns Hopkins Bloomberg School of Public Health. The course will be offered for the first time in spring 2018.

In the following Q&A, Jennifer explains what students should expect from her course and why the material is so valuable to future public health leaders.

What are the learning objectives of your Infectious Disease Threats to Global Health Security course?

Jennifer Nuzzo, DrPH

Jennifer Nuzzo, DrPH

My goal for this course is to help students understand why infectious disease threats pose a risk to the security of nations. As we have seen in recent years with events like the Zika epidemic, the Ebola epidemic in west Africa, and prior to that SARS and MERS, emerging infectious diseases keep popping up and causing harm to public health as well as to economies. We want to explore what the specific impacts of these events are, and what public health practitioners can do to ensure that nations are ready to prevent them—or, if they can’t prevent them, to mitigate them when they occur.

We think this is relevant because we’ve seen an increase in the frequency of emerging infectious disease events. Unfortunately, that means public health professionals will likely be involved in one of these events at some point in their career. It’s valuable for public health students to understand the consequences not only so they can improve response, but also so they can convey to political leadership in a convincing way the importance of preparedness and appropriate resource allocation.

Who should take the course?

Every public health student should take this class. One of the themes of the class we’re going to explore is that increasingly we’re seeing that all public health is global health, so anyone who’s interested in US public health has to recognize that disease threats can start abroad and have impacts at home.

Folks who want to focus on improving public health globally, even if you’re interested in routine public health conditions like HIV or TB, or non-communicable diseases, that work can be jeopardized if a large-scale epidemic emerges.

How do infectious diseases threaten global health security?

Emerging infectious diseases threaten global health security in myriad ways. They have the immediate effect of impacting health, causing illness and potentially death, but there are secondary and tertiary effects on societies, on the ability of people to be able to work and provide for their families, and threats to economies—particularly when measures are taken like closing boarders or shutting down travel and trade.

There are also political effects. How a society responds to these threats, whether that response is effective, can impact public confidence in government.

Subject matter aside, what’s unique about this course?

We’re going to spend some time talking about the broader themes and political dimensions of public health events, more than students experience in their other classes. The foundation public health education gives students the methods to describe infectious disease events and the tools to respond to them. This is essential, obviously. I hope to build on those themes with a multi-faceted approach to the infectious disease problem: you need to know what strategies work and what strategies don’t; you need to know the consequences of making the wrong decisions and what the wrong decisions are; and you need to know how to interface with political leadership so policymakers are supportive of what needs to be done and don’t undermine the overall response.

In addition, I want the class to be highly relevant to the world that we’re living in. I’m committed to tailoring the material in the course to the events that we are witnessing in the world. As new events occur, we will incorporate that into our class and encourage students to interpret the world around them as it’s currently happening.

What’s the most important key takeaway for students?

Understanding how health is important for broader societal goals like improving economies and strengthening the defense of countries. Public health professionals have a role to play in the security of nations and protecting economies, and I want to help them understand what that role is so they can then make stronger arguments for the value of investing in public health.

What got you interested in work on the prevention of infectious diseases?

When I graduated with a Master of Public Health in 2001, I took a job in New York City as an epidemiologist. Shortly after the attacks of Sept. 11, what had previously been a small component of my job—maintaining a surveillance system that had a potential application to bioterrorism—became a large part of the focus of my job. It was that event that particularly underscored for me the interdependency between health and security.

Since then, my colleagues and I at the Johns Hopkins Center of Health Security have worked every day to demonstrate to political leaders that health is a vital component of national security.

***

Jennifer Nuzzo can be reached by email at jnuzzo1@jhu.edu and on Twitter at @JenniferNuzzo.

Course of Conversation: Biotechnology and Health Security

Gigi Kwik Gronvall, PhD, a senior associate at the Johns Hopkins Center for Health Security, teaches the Biotechnology and Health Security elective as visiting faculty in the department of environmental health and engineering at the Johns Hopkins Bloomberg School of Public Health. The course will be offered for the first time in spring 2018.

In the following Q&A, Gigi explains what students should expect from her course and why the material is so valuable to the public health curriculum.

What are the learning objectives of your Biotechnology and Health Security course?

Gigi Kwik Gronvall, PhD

Gigi Kwik Gronvall, PhD

The goal is to introduce public health students to the advances in synthetic biology and biotechnology (e.g., CRISPR, DNA synthesis technologies) to give them a preview of the tools they might have as public health professionals in the future. I also want to expose them to some of the downsides of biotech—some of the things they’ll have to deal with in a negative way.

We’ll address what’s called the “dual use dilemma,” the idea that some things could be beneficial for medical research but could, if misused, lower barriers to biological weapons development. I’ll also encourage students to consider policy options to reduce biosecurity vulnerabilities and expand norms against biological weapons.

I’m hoping to bring in a number of guest speakers to address these issues, including some in government who are setting policies for this field.

Who should take the course?

Students who are intrigued by policy will find this class interesting. Public health and biotechnology touch more than the people who are in those fields. The material won’t be overly scientific and the readings will not be overly technical.

I’m really looking forward to hearing from the students—their ideas on what we should be doing for policies to help shape emerging technologies. Gene drives won’t get developed without funding, safety considerations won’t be put into place without leadership. So, it’s not just the technologies themselves, it’s also the environment that they’re in. I’m interested in exploring that with students and hearing what seems most important to them.

How will including an historical look at biological weapons use benefit students?

Many people don’t realize that biology could be used as a weapon because it hasn’t happened in their lifetime, or it has but only in small terrorism cases. Biology was once considered to be a legitimate form of warfare and the major nations of the world had expansive biological weapons programs. Students should certainly be aware that this was part of the human experience and humans could go there again, and we need to do what we can to prevent that.

Why is it valuable for public health students to learn about biotechnology?

A comprehensive look at how biotechnology can affect public health is not currently part of the conventional public health curriculum. I wouldn’t be doing this if I wasn’t certain it was vitally important.

Biotechnology innovations will happen no matter what, so students need to know how to take advantage of the positive aspects for public health. These technologies aren’t developed in a vacuum. If the next generation of public health professionals wants biotech to be in the public interest, in the public health interest, then they need to know about it and help shape its future.

Take synthetic biology (bioengineering that makes biology more useful). There are opportunities for public health that were definitely not possible until recently. For example, the use of gene drives to eliminate disease like dengue or malaria by going after mosquitos, or being able to treat inherited diseases. There are options that we can see now and there will be so much more in the future.

Subject matter aside, what’s unique about this course?

I’m committed to making written assignments useful, so I’m exploring ways for students to write about the material and improve their professional communication skills at the same time. Whether these students pursue careers in government, academia, or otherwise, it’s critical for them to communicate in a concise, persuasive way.

What’s the most important key takeaway for students?

The lessons about new technologies and how they affect health are broader than just this class. We’ve seen many advances in biotechnology recently that affect public health and those advances are not going to stop. This class will provide a grounding for students as they absorb news on new scientific developments so they are able to analyze where technologies are going and think about ways technologies can be properly incorporated, regulated, or controlled.

This goes beyond biology. With nanotechnology in other fields, with artificial intelligence, you have groups of scientists working in one direction and in the other you have governments considering how to limit misuse and promote public interest.

What got you interested in biotechnology and health security policy?

I was working at a leading cancer treatment and research institution as a laboratory technician before I got my PhD. My job was to create oligos (short pieces of DNA), and it occurred to me that somebody could make something that they’re not supposed to make—for example, a virus. I brought this up to my supervisor, and he said, “Don’t worry. If that happens—if someone were to come up with a scary virus—we’ll just get a whole bunch of smart people together to think about it and do something.” I looked around and thought, how can top people at this visionary organization fail to recognize that some problems that could cause a lot of damage are too difficult and too complex for a group of smart people to solve?

At that moment I realized there was a compelling need for real policy work in the biotechnology space. And I wanted to be on the forefront of it.

***

Gigi Gronvall is the author of Synthetic Biology: Safety, Security, and Promise. She can be reached by email at ggronvall@jhu.edu and on Twitter at @ggronvall. 

Watercooler chat transcript: Plague in Madagascar

Excerpts from semi-organic conversations among Johns Hopkins Center for Health Security staff in their Slack #biosecurity channel (inspired by 538’s Slack Chats).

cmrivers (Caitlin Rivers): Today we’re discussing the outbreak of plague in Madagascar, which has been ongoing since August. First a little background. As of Oct 26 there have been 1,309 cases and 93 deaths. Two thirds of cases have been pneumonic (spread person to person). The case fatality rate is reported at 7%, which ProMed notes is quite low. Two cases were imported to Seychelles, both of which resulted in no secondary transmission [Update: the suspected cases in the Seychelles ultimately tested negative upon confirmatory testing]. A number of control measures have been implemented beyond the usual steps of contact tracing and isolation. The World Health Organization has released $1.5M in emergency funds, and eight specialized health centers have been opened. Public schools are closed and public gatherings are forbidden.

cmrivers: So, what do you make of this outbreak and how worried are you?

sanjana (Sanjana Ravi): My initial reaction -- I'm not super worried that this will escalate into an Ebola-level crisis, since, as an island, Madagascar is somewhat more geographically isolated and doesn't appear to have the same problem with porous borders that we saw with Guinea, Sierra Leone, and Liberia. I am a bit concerned that little has been said about vector control.

tara (Tara Kirk Sell): I don't think that this is another Ebola. Plague is endemic there (and I'm wondering if that may have a role in the low case fatality rate). It’s not good that it's in the cities but I just don't think that it's going to be as explosive.

cmrivers: I see the endemicity as a problem, actually. There's a whole dimension in the sylvatic cycle that we didn't have to deal with during Ebola.

tara: Well, I think that the endemicity means that the threat will never really go away but I also think that it means that it's not a rare event we are dealing with.

watson (Matt Watson): That said though, Ebola did show what can happen when a previously "rural" neglected tropical disease gets into cities. I don't think we know nearly enough about transmission dynamics and how to effectively intervene in those settings.

crystal (Crystal Watson): It seems to be behaving similarly to the outbreak in India in 1994. Like India, it is in a highly densely populated area with a mix of bubonic and pneumonic plague. Also, I think the close proximity of those who are infected is a huge driver. A lot of these pneumonic outbreaks occur in mine workers where they are close together in confined spaces.

cmrivers: Any guesses why this outbreak is unusually large compared to Madagascar's usual outbreaks? Is anything about the epidemiology here unusual?

crystal: I do wonder if there are plague superspreaders.

cmrivers: There are! The index case of this outbreak infected 30-some people, if memory serves.

meyerda (Diane Meyer): According to our Outbreak Observatory post, this outbreak has entered an urban and non-endemic area...perhaps that is why it is larger than normal.

michael (Michael Snyder): Also, there's a higher proportion of the more transmissible pneumonic plague variant than bubonic.

crystal: Also burials!

tara: Good point - burials are often a huge problem.

watson: Then there’s this story on families seizing plague victims’ bodies… If true, it may indicate a lack of trust in the government and international response.

cmrivers: That’s troubling. Rumors on that topic abound. One says that a “local tradition of dancing with dead bodies” is fueling transmission? Could this be true?

crystal: That would aerosolize bacteria for sure.

cmrivers: Y. pestis is non-spore forming, so I think that rumor is salacious and unfounded.

crystal: I think we chronically underestimate how long pathogens can persist in the environment. The literature suggests that it can survive for years in soil and on other surfaces.

nalexopulos (Nick Alexopulos, Communications Director): Aren’t there reindeer frozen in Siberian ice that carry transmissible plague?

cmrivers: That’s anthrax, which is spore-forming and very persistent in the environment.

nalexopulos: [goes back to writing tweets]

crystal: Plague seems to go dormant though.

cmrivers: But is it possible for transmission to happen years after death?

crystal: It says here that “a growing body of evidence suggests that Y. pestis can survive without a host for extended periods under certain environmental conditions while, in many cases, retaining infectivity.”

crystal: I wonder what the mechanism is for plague to make the switch from bubonic to pneumonic though? Is it always that superspreader?

cmrivers: One way to get at your question is to look at chains of transmission and see how many generations they last.

crystal: The superspreading issue I think needs a lot more attention. There are so many examples of this now. It seems to be a major driver of a number of outbreaks.

cmrivers: I think so too. It was a major feature in SARS and Ebola. I think this is a place where better outbreak science would be helpful. There's not much real-time effort to reconstruct transmission chains, in part because it’s hard. But it does reveal a lot about the transmission dynamics.

crystal: Definitely. If we really committed resources to understanding transmission dynamics, it would reduce a lot of uncertainty.

tara: Like Crystal said, we should understand more about why someone gets bubonic vs pneumonic plague.

michael: It’s true -- given their different transmission pathways, it's almost like having to manage two separate (but related) disease outbreaks at the same time.

sanajana: So according to WHO, human-to-human bubonic plague transmission is very rare. It's almost always the result of a flea bite. The fact that there are so many cases suggests that most are of the pneumonic variety, OR that the vector control situation is really bad.

tara: I wonder if animals are common in the home, or if it is more pest control that is the vector control issue.

michael: The WHO has cited the poor environmental and sanitation conditions as a driving factor, so I imagine vector control is playing a big role for bubonic plague transmission.

watson: There’s often talk of plague “foci” where it persists as a zoonosis, for example, this paper.

tara: So based on that paper, are climatic conditions right for this year’s Rattus rattus explosion?

cmrivers: Well three-quarters of cases are pneumonic, so I think that speaks to Michael's point about two different but related outbreaks. Even without zoonotic cases there's still a major outbreak.

crystal: I think they are synergistic.

cmrivers: What should they be doing beyond vector control?

watson: [WHO has] moved in a small stockpile of antibiotics - that's good. And actually, at 1.2 million doses, it's not all that small.

cmrivers: That is pretty sizable. Contacts need 7 days of post-exposure prophylaxis though so...it adds up.

crystal: Also, probably a lot of supportive care is needed for pneumonic cases and isolation precautions.

michael: I think Crystal’s comparison to the 1994 plague outbreak in Surat, India, is interesting. That one had about 50 case fatalities but caused an estimated 500,000 refugees.

crystal: Yes. I wonder if that slowed the epidemic in India actually? People got out of town as soon as there was a confirmed case.

cmrivers: The refugees is an interesting twist. Can you say more about that?

crystal: People got out of town as soon as there was a confirmed case. Plague is historically very scary.

michael: Panic. Made only more fascinating by the fact that they never confirmed it was plague until about 6 years later.

cmrivers: Did they take any cases with them, spreading the disease?

crystal: They did, but not hugely. Plague is less transmissible than some people think, even pneumonic. [Our founder] DA Henderson always said that.

cmrivers: That brings us back to “why is this happening now in Madagascar?”

tara: I wonder if genetic analysis at a later date will tell us if this is all one introduction or many. My money is on many. It also brings us back to my question about climate conditions! Is there a global warming component?

cmrivers: There has been some work on predicting plague emergence, e.g. here.

crystal: It's the end of dry season in Madagascar. The rodents may be hungry and are venturing into the cities to eat, whereas normally they would eat in the wild. I wonder if the condition of the soil also makes a difference?

meyerda: This article states that warmer/wetter conditions cause rodent numbers to drop, sending fleas looking elsewhere for food.

cmrivers: I think from a public health perspective it's more prudent to focus on the rat-human interface...like keeping rats out of human homes. Climate is not a modifiable risk factor, but habitation conditions are.

tara: But rats aren’t the only animal that can maintain a flea infestation, which speaks to the importance of pets [as risk factors].

cmrivers: Ok back to our roots. As a tier 1 select agent, Y pestis is considered a candidate pathogen for biocrimes. Is there anything we should be learning either from this outbreak or the response that applies to biosecurity?

crystal: It's really hard to limit accessibility of Y pestis. It's everywhere. Here is a sign from the field near my parents’ house.

Plague 2.png

nalexopulos: And that "etc." in the parens does some HEAVY lifting.

watson: Yet more evidence to support my thesis that everything in the American West is trying to kill you.

cmrivers: We have most of the tickborne diseases out East. I feel pretty negatively about that. So Crystal, what are the implications here? Stop regulating research?

crystal: Research should still be regulated, but it will never be possible to stop access if someone really wants to collect Y pestis.

watson: From a violent non-state actor perspective, ISIS or other groups haven't yet gotten people all worked up about a "plague weapon" like they did w/ Ebola. (In fairness, they've got other things on their minds...).

sanjana: There's something to be said about how we need to get better at integrating/coupling microbial forensics with biosurveillance/early detection systems. Just thinking about connections between this outbreak and the 1994 Surat outbreak. To my knowledge, the origin of the Surat outbreak was never identified, although the outbreak itself was eventually curbed through extensive vector/rodent management and public health measures.

watson: To that point, from the article I linked to above... "Finally, the discontinuation of plague surveillance since 2006 (due to financial shortages) has contributed to the reappearance of plague in the capital's suburbs six years after the last reported case." Right there is why the world needs the Global Health Security Agenda (GHSA).

sanjana: I’m wondering if there is a way to integrate forensics into routine public health/epidemiological investigations to enhance our ability to ID biocrimes.

cmrivers: All good points. Any final thoughts?

michael: Just that there's a lot more to this story -- unanswered questions that will hopefully come to light. Seems odd that a country with so much experience with plague wasn't able to control this one - not like Ebola where it was a totally unexpected disease in West Africa!

cmrivers: l agree. I think at this point I'm past being surprised about the...tenacity of outbreaks though. Even diseases we think we know all about are full of surprises.

cmrivers: Thanks, all!

Examining HHS’s Public Health Preparedness for and Response to the 2017 Hurricane Season

This year’s Atlantic hurricane season has been unusually devastating. Throughout September and early October, Hurricanes Harvey, Irma, Jose, and Maria tore through vulnerable communities in Texas, Florida, Puerto Rico, and the U.S. Virgin Islands, leaving trails of destruction in their wake and dealing severe blows to the health, safety, and livelihoods of the affected populations. Despite the severity of the storms and their aftermath, the U.S. federal response has proven to be uneven and ineffective, particularly for Puerto Rico and the Virgin Islands. As of this writing, for instance, many Puerto Ricans still lack electricity and access to healthcare; much of the island also suffers from food and water insecurity.

On October 24, the U.S. House Committee on Energy and Commerce hosted a hearing, “Examining HHS’s Public Health Preparedness for and Response to the 2017 Hurricane Season,” to brief lawmakers on the efforts of four agencies within the Department of Health and Human Services (HHS) – the Food & Drug Administration (FDA), the Office of the Assistant Secretary for Preparedness and Response (ASPR), the Centers for Disease Control & Prevention (CDC), and the Centers for Medicare and Medicaid Services (CMS) – around hurricane response and recovery. Witnesses included Dr. Scott Gottlieb (Commissioner, FDA), Dr. Robert P. Kadlec (ASPR), Dr. Stephen Redd (CDC), and Ms. Kimberly Brandt (CMS).

The following are a few highlights from the witnesses’ testimony:

  • HHS has sent 439 tons of medical equipment and supplies. ASPR has deployed 2,500 personnel through NDMS, who have cared for more than 15,000 patients in Puerto Rico, Texas, Florida, and the Virgin Islands. More than 200 dialysis patients have been evacuated from the Virgin Islands.
  • CDC has activated its Emergency Operations Center, currently has about 500 staff coordinating the agency’s hurricane response efforts, and has deployed 70 staff (including 30 to Puerto Rico) to aid with response and recovery, as well as federal medical stations to serve as temporary, non-acute facilities.
  • CDC is using syndromic surveillance to monitor Puerto Rico for disease outbreaks, and CDC has arranged for clinical specimens to be transported to Atlanta to be tested for priority diseases (e.g., leptospirosis, TB, rabies, influenza, and salmonella) because much of the island’s laboratory infrastructure has been destroyed.
  • Puerto Rico is the manufacturing site for many medical products, including more than 1,000 medical devices and 15 sole-source drugs (i.e., drugs not produced anywhere else). FDA is working to help these companies get their power restored, as many are currently functioning at low capacity using temporary generators. The Committee members expressed concern about the potential implications of grid insecurity for medical supply shortages, both in Puerto Rico and on the U.S. mainland.
  • Nearly 50% of Puerto Rico is covered through a CMS program. CMS is working closely with ASPR to monitor the healthcare needs of vulnerable patients (especially dialysis patients), as well as track available supplies of fuel and water. CMS has also waived and/or modified certain rules that facilitate both Medicare enrollment and patient transportation between hospitals in the affected locations.

Notably, Congressman Raul Ruiz, MD (D-CA), who recently visited Puerto Rico, offered the witnesses a series of recommendations (see below; lightly edited for clarity) for leveraging U.S. federal response capabilities more effectively to meet the needs of hurricane victims, particularly those living in remote, underserved areas:

  • Establish a clear chain of command and clarify the roles and responsibilities of the responding agencies. Is FEMA running the show? Or is it HHS, the Department of Defense, or the Puerto Rican government? Command posts should be established on the ground to facilitate decision-making and resource allocation.
  • It is crucial to get into the remotest areas affected by the hurricanes and talk to people; we will not get the full picture by staying in San Juan.
  • There appears to be a lack of clarity in the metrics being used to assess the effectiveness of the federal response. We should be discussing capacities for ensuring food, water, and grid security in relation to the overall need of residents on the island.

We will continue to track and report on federal response and recovery efforts in the weeks and months to come.

Mass Casualty Incidents and the Overlap Between Trauma Systems and Hospital Disaster Preparedness

The horrific mass shooting in Las Vegas on October 1, 2017 has resulted in nearly 60 deaths and more than 500 injuries at the time of this writing. The injured have been transported to a number of hospitals around Las Vegas and have overwhelmed some of the hospitals closest to the scene. A number of the injured are in critical condition and hence the death toll is likely to rise. Among other issues, this tragedy illustrates the overlap between trauma systems and hospital disaster preparedness.

A single patient with a gunshot wound (GSW) to a vital body part (e.g., head, chest, abdomen, or major artery) will stress a typical community hospital. Most community hospitals do not routinely treat these kinds of patients because trauma systems have been organized across the country over the last 50-60 years. Trauma systems consist of hospitals that have been certified as having varying levels of expertise and resources for treating trauma victims. Level I trauma centers are held to the highest standard, Level III to the lowest. University Medical Center is the only Level I trauma center in Nevada, and reports indicate that at least 30 critical patients were treated in its trauma center and more than 100 non-critical patients in the emergency department. Sunrise Hospital, a Level II trauma center and the closest trauma center to the shooting, reports having treated 180 patients and operated on approximately 30.

Today, Emergency Medical Services (EMS) ambulances will usually transport severely injured patients to accredited trauma centers, which are typically part of large academic medical centers. As a result, community hospitals rarely treat gunshot wounds anymore except for the occasional “walk-in” minor gunshot victim. Before the creation of trauma centers in the 1960s and 70s the situation was different: patients with severe traumatic injuries, including GSWs, would be taken to the closest hospital where general surgeons with varying degrees of trauma training and experience would treat them. The patient outcomes were often less than optimal.

Level 1 trauma centers have round-the-clock in-house coverage by specially trained trauma surgeons, surgical subspecialists (e.g., thoracic, cardiovascular, neuro), and anesthesiologists. In addition, they have specialized equipment—such as cardiac bypass—not often found in community hospitals. With the advent of the specialized trauma centers, patient outcomes have greatly improved but this progress has come at a price: community hospitals’ trauma capabilities have atrophied because they no longer routinely see severe trauma patients. A severe trauma patient who does somehow present to a community hospital emergency department these days is typically stabilized and transferred to a trauma center as quickly as possible. On a routine day-to-day basis, this benefits the patients, but in a large-scale trauma disaster like a mass shooting this centralization of trauma care limits a community’s surge capacity for trauma in a disaster.

While all hospitals must have disaster plans and practice them twice a year, no hospital can handle a large-scale disaster on its own—especially a complex mass casualty event. Because of this challenge, hospital disaster preparedness and response is increasingly organized around collaboration among different hospitals and between hospital and EMS, emergency management, and public health agencies. This has given rise to healthcare coalitions across the country.

Complex mass casually events of all types (e.g., chemical, biological, radiological) require highly specialized care that is only found in large academic medical centers—the same hospitals that are the Level 1 trauma centers. For the most part, community hospitals do not have the resources, depth of staff, or expertise needed for these types of events. But even the largest trauma centers can be overwhelmed by a very large-scale mass disaster. It is therefore important that trauma centers be integrated with the other hospitals in the community in a well-coordinated system that delivers the right care to the right patient in the right place—the more severe injuries to the trauma centers and the less severe to other facilities. For this to work well, it must be planned and practiced. In my view, this is best done through the emerging healthcare coalitions. As the disaster preparedness and response system continues to develop in the United States, it should be integrated with the existing trauma system with large academic medical centers being at the hub of both systems.  

A New Framework for Considering Security Risks Posed by Synthetic Biology

The ongoing biotechnology revolution – particularly in the fields of genome sequencing, editing, and synthesis – has led to advancements and applications in the fields of medicine, agriculture, and environmental science. Naturally, the potential use of these technologies by those with malicious intent has brought up many questions and concerns. To begin to provide some answers and clarity, the US Department of Defense (DoD) asked the National Academies of Science, Engineering, and Medicine (NAS) to conduct a study regarding the potential concerns related to advances in synthetic biology. On Aug. 25, 2017, they published their initial report, “A Proposed Framework for Identifying Potential Biodefense Vulnerabilities Posed by Synthetic Biology.”

Synthetic biology is the use of biotechnology to predictably modify or create organisms or biological components. Synthetic biology is being used to design microbes that will seek and destroy tumors, build organisms to consume toxic chemicals in water or soil, and synthesize biofuels that would reduce our dependency on fossil fuels. However, in this golden age of biotechnology, the dual-use threat of synthetic biology has raised questions such as: what are the synthetic biology threats, their time frames, and options for mitigation? Some of these issues have been explored by our colleague Dr. Gigi Gronvall in her recent book, Synthetic Biology: Safety, Security, and Promise. Dr. Gronvall is also a contributor to the NAS report under consideration.

The NAS committee created a framework that seeks to answer these questions. It is important to note that the authors limited their analysis to threats that could potentially be used to directly target either human health or prevent military personnel from executing their missions. Modification of plants, animals, their associated pathogens, and organisms with an environmental effect (e.g., undermine agricultural productivity) were beyond the scope of their report. It would be interesting to see a future study that applies the guidelines in this report to synthetic biology threats that target the biosphere at large such as engineered insects, modification of bacterial and fungal species to produce chemicals on demand, and gene drives.

Proposed Framework

The framework breaks down synthetic biology technologies and applications into several broad categories. Within these categories various questions will be asked regarding specific technologies, potential actors who may use them, the feasibility of creating biological weapons, and options for mitigation.

Each synthetic biology technology and application was categorized in terms of the ways in which they enable the Design-Build-Test (DBT) cycle – which is an iterative design strategy that demonstrates the cyclical nature of practical synthetic biology from the designing of a prototype, to the building of said prototype, and finally testing to evaluate and improve its design.

Approaching synthetic biology in this manner allows the guiding principles of the framework to be applicable to not only the technology of today but of those in the future. However, some technologies may enable multiple aspects of the DBT cycle, and those will be of particular interest to the NAS committee during the second phase of this project. Additionally, the committee will examine the complex interplay that advancement in other fields may have on increased use or ease of access to synthetic biology technology.

The committee’s final report will further refine their initial framework with the input of those in the synthetic biology research community and provide insight as to what biosecurity concerns are most warranted and what the DoD can do to address the areas of greatest concern.

Important questions global health and science leaders should be asking in the wake of horsepox synthesis

The publication of the experimental work that synthesized horsepox is imminent, according to multiple reports. Horsepox no longer exists in nature, so this was the creation of an extinct virus in the same genus as smallpox. It doesn’t infect people, but causes pox disease in horses. Researchers have cited several objectives for the work, including the intention to develop it as a smallpox vaccine, the intention to develop it as a virus-based cancer treatment, and the intention to show that synthesizing smallpox de novo is possible.

The work raises a number of serious questions and concerns, partly about the specifics of the work and partly about what this says about biosecurity and biosafety considerations related to a circumscribed set of experiments.

The first question is whether experimental work should be performed for the purpose of demonstrating something potentially dangerous and destructive could be made using biology. In this case, horsepox was created in the laboratory, at least in part to show that synthesis de novo of smallpox virus is feasible. In this specific case, leading virologists have agreed for many years that de novo smallpox synthesis was scientifically feasible, and there has been no serious counterargument that it was not feasible. But the important decision going forward is whether research with high biosafety or biosecurity risks should be pursued with a justification of demonstrating that something dangerous is now possible. I don’t think it should. Creating new risks to show that these risks are real is the wrong path. At the very least, it’s a serious issue needing serious discussion.  

A second question that is more relevant to this experiment is how much new detail will be provided in the forthcoming publication regarding how to construct an orthopox virus. It is one thing to create the virus; it’s another thing altogether to publish prescriptive information that would substantially lower the bar for creating smallpox by others. The University of Alberta lab where the horsepox construction took place is one of the leading orthopox laboratories in the world. They were technically able to navigate challenges and inherent safety risks during synthesis. Will labs that were not previously capable of this technical challenge find it easier to make smallpox after the experiment methodology is published? 

A third question relates to the approval process for experimental work with implications for international biosecurity or international biosafety. The researchers who did this work are reported to have gone through all appropriate national regulatory authorities. Researchers who created horsepox have said that the regulatory authorities “may not have fully appreciated the significance of, or potential need for, regulation or approval of” this work. So while work like this has potential international implications – it would be a bad development for all global citizens if smallpox synthesis becomes easier because of what is learned in this publication – the work is reviewed by national regulatory authorities without international norms or guidelines that direct them. This means that work considered very high risk and therefore rejected by one country may be approved by others. 

In the case of the horsepox experiment in Canada, the Advisory Committee on Variola Virus Research at WHO was briefed on the work after it was completed. Moreover, the primary charge of that committee is actual smallpox research itself (as opposed to horsepox). Beyond that, this WHO committee is unique. WHO does not have special disease by disease committees that review work on a case by case basis for other pathogens.

I think the new P3CO policy published by the White House in January 2017 could be a good step forward in the US regarding future policy development for experiments involving potential pandemic pathogens. Whether and how that policy will be implemented remains to be seen since it is guidance for federal agencies but does not require their action. Importantly in this case, even if this policy had been implemented in the US, it doesn’t seem that the policy would have had bearing on the horsepox research had that been proposed in the US. So even as the US has spent a substantial amount of time considering these kinds of issues, it still doesn’t have policy (or high-level review committees) that directly considers experiments like this. Beyond that, there is no international component to P3CO. There clearly needs to be an international component to these policies. We need agreed upon norms that will help guide countries and their scientists regarding work that falls into this category, and high-level dialogue regarding the necessary role of scientific review, guidance, and regulation for work that falls into special categories of highest concern. It is not clear that these considerations are now even being discussed internationally.   

The rapid advance of biology in the world overall will continue to have enormous health and economic benefits for society. The entrepreneurial and unpredictable nature of biological research, now coupled with powerful global markets, is overwhelmingly positive for the world. But this case of horsepox synthesis shows us that there are also specific and serious challenges that require special attention now.  

Tom Inglesby, MD, is the director of the Johns Hopkins Center for Health Security