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  • What I'm going to talk about here are the characteristics and traits of pandemic pathogens.

  • You just heard my colleague Crystal's talk where she introduced the concept of GCBR.

  • I'm going to try and delve very deep into that concept, to try to understand what is

  • it about certain pathogens that allows them to cause a GCBR?

  • And I think the theme of this conference is to be curious, and that's really what motivated

  • this project, was to be very curious about what goes on there.

  • I have a picture of my blog there, Tracking Zebra, if you're interested in infectious

  • disease, I do write a lot about that, and that's my Twitter handle.

  • The aim of this project was really to develop a whole new framework around the traits of

  • naturally occurring pandemic pathogens that could constitute a GCBR in order to change

  • preparedness activities.

  • In the past, I'm going to talk about this a little bit later, we've really focused on

  • list based approaches, that are largely derived from the former Soviet Union's biological

  • weapons program.

  • There hadn't been a lot of fresh thinking.

  • It was very static.

  • I think that's what we tried to do in this project.

  • So a couple of basic definitions, just because I don't know if everybody has a biological

  • background.

  • Pandemics are infectious disease outbreaks that occur over a wide area and affect a large

  • proportion of the population.

  • It doesn't necessarily have to be severe; 2009 H1N1 was a mild pandemic, but it was

  • still a pandemic.

  • An epidemic is an infectious disease outbreak that occurs over a large number of individuals

  • within a population.

  • So, the SARS outbreak in 2003 would be an epidemic.

  • An endemic is something that occurs regularly within a population.

  • For example, the common cold is endemic in the human population.

  • Those are just things to keep in mind.

  • What we're talking about are specific types of pandemics that are very severe for the

  • GCBR, to meet GCBR criteria.

  • I'm not going to spend much time on this definition because Crystal really went into some great

  • detail, but what I'm going to do is really expand on what is it about those biological

  • agents?

  • What types of biological agents can cause GCBRs?

  • Everybody is very focused on viruses, some people are focused on bacteria, some people

  • on other things, that's what I'm trying to understand is what traits does a biological

  • agent have to have in order to be able to cause something this severe, to cause this

  • massive catastrophic loss of life, disruption of society, that type of analysis.

  • I just want to draw a distinction, because what I'm talking about here are pathogens

  • of pandemic potential, versus what's this distinction that was made in Mike Osterholm's

  • recent book about pathogens of critical regional importance.

  • When you have an outbreak like Middle East Respiratory Syndrome, that doesn't mean...

  • just because it's not a GCBR doesn't mean it's not important or that it's not going

  • to be very disruptive to people's lives and to societies and to governments.

  • But what we're talking about in the GCBR is something that's going to be global, like

  • the 1918 flu.

  • Something that's a lot different in scale than even Middle East Respiratory Syndrome

  • or SARS.

  • Something much different.

  • There's lots of pathogens of critical regional importance.

  • Even the Ebola outbreak in 2014 in West Africa falls under this type of criteria, versus

  • this type of criteria.

  • The specific aim with this project was really to, like I said, move away from this list-based

  • historical approach.

  • People had really just taken the Soviet Union Biological Weapons program and added a couple

  • things here and there, but really hadn't thought much about why were these things on there?

  • Challenge the assumptions that put them on there, and really try to understand what was

  • it that made smallpox so scary?

  • What was it that makes pandemic flu so scary?

  • We really try to go into an inductive manner, trying to make a whole new paradigm, looking

  • at the actual attributes.

  • We tried to do this by being totally microbignostic.

  • What I say microbignostic, that means we didn't go into this project saying, "This has to

  • be a virus.

  • This has to be a bacteria".

  • We said it could be anything.

  • It could be a parasite, a protozoa, it could be a prion.

  • So that was something that was totally new.

  • We really wanted to challenge thinking and then take this paradigm, and hopefully use

  • it to move forward when we think about preparedness and try and think of new infectious disease

  • outbreaks with this new paradigm in mind, to get better at being prepared because we're

  • constantly surprised, which I'll get to later in the talk.

  • What are the essential traits?

  • The next slide is a little busy.

  • I'm going to walk through it one by one.

  • Thinking about what does it have to have?

  • Talking to people and doing a lot of literature review, there's a whole bunch of different

  • things that make up the alchemy of a pandemic pathogen.

  • I'm going try and explain what this equation means and all of this as best I can.

  • The first thing you need to do, is you have to have a pathogen that can efficiently transmit

  • from human to human.

  • You can have a disease that can be really bad like Tetanus.

  • That doesn't transmit between humans, so it can't be a pandemic pathogen.

  • When you're talking about a pandemic pathogen, it has to be able to get from people to people,

  • so that's number one.

  • It has to have a moderate fatality rate.

  • It doesn't have to be really, really horrible like a 90% fatality rate or 100% like rabies.

  • It has to be something that's kind of in a sweet spot that it allows enough death to

  • occur that it causes disruption in the society.

  • Remember that the 1918 Influenza pandemic, which killed 50 to 100 million people, only

  • had a fatality rate of two percent.

  • But because it was so widespread, it led to disruption.

  • Contagious during incubation period.

  • I have bolded this because in multiple modeling studies, and in experience, and Crystal alluded

  • to this earlier when she talked about smallpox, if a disease is contagious during the incubation

  • period, when you're not sick, it's very, very hard to control.

  • That's why the H1N1 pandemic had spread everywhere before anybody even knew about it because

  • people were contagious one day before symptoms.

  • If a disease is contagious in that period, it becomes very, very difficult for public

  • health interventions to have any impact.

  • The same goes with mild illnesses with contagiousness.

  • When you have the flu or the common cold and you're out shopping, doing your normal daily

  • life, you spread that to other people.

  • It's very hard to stop that, versus something like Ebola, when you're sick and highly contagious

  • you are in bed and you can't really move, and move about in society.

  • So this is another key factor.

  • An immunologically naïve population.

  • Again, reflecting back on Crystal's talk when she showed the map of the indigenous populations

  • in the Americas, in the pre-Columbian area in 1492.

  • That was an immunologically naïve population to smallpox, which allowed smallpox to spread

  • very rapidly through that population.

  • That's what a pandemic pathogen would require.

  • No vaccine or treatment.

  • You don't have any way to stop this.

  • That's another thing that fits into this.

  • Correct atmospheric and environmental context.

  • Infectious diseases happen in a context.

  • Is it happening during World War I like the pandemic flu did in 1918?

  • Is it happening where there's been societal disruption?

  • Like, for example, Yemen right now and the Cholera outbreaks?

  • All of that's going to play a major role in how prolific an infectious disease outbreak

  • is.

  • There's a lot of biology that has to go into this too.

  • Not every pathogen can infect every type of human.

  • You have to have a proper receptor.

  • So you've got to have some receptor that lots of humans have that this virus or this bacteria

  • can actually cling onto.

  • It's also going to explain which organs it affects, because obviously some organs are

  • more important.

  • If it affects your brain, your kidney, your liver, your lungs, those are what you really

  • see with these pandemic pathogens.

  • And then it has to be able to evade the host immune response.

  • It has to be something that is not easy for the immune system to mount an effective response

  • against.

  • This is a fancy equation that showed up.

  • The point of this equation is not to memorize it or to think about it, it's just that you

  • can take all of these things and give them values, and come up with pandemic potential

  • of a pathogen.

  • You can look and vary them.

  • If you look at some other things, for example, the more host types a pathogen has, the more

  • chance it is to emerge.

  • That's another thing that comes up, that these things can infect more than one type of species.

  • That's where the concept of zoonosis comes about, where something comes from an animal

  • species into humans.

  • But the more hosts something has, the more likely it is to be able to infect humans and

  • cause a problem.

  • Thinking deeper about this.

  • We have that recipe there.

  • When you think deeper, there's a couple of things that come out of this.

  • When you look at the way these things transmit, the most likely way to cause a pandemic is

  • for it to be done through the respiratory or the airborne route.

  • There's much, much less you can do to stop an airborne virus or a respiratory droplet

  • spread virus.

  • If I had measles right now, you would all be exposed.

  • It's very, very hard to do that.

  • But if it was something that was spread through, for example, fecal/oral, like Hepatitis A

  • or Cholera, you can really delimit that with sanitation.

  • Remember, there was a couple of cases of Cholera in Mexico about five years ago, and everybody

  • panicked.

  • But there was just even a modicum of sanitation - stopped Cholera.

  • It did not spread in Mexico.

  • You can't do that with respiratory viruses and airborne viruses.

  • It's much, much harder through the respiratory or airborne bacteria.

  • A vector borne transmission, so that means through mosquitoes, through ticks, that's

  • something that's very interesting and it is something that I think we struggle with trying

  • to figure out exactly how bad a vector borne outbreak can get.

  • They are, in general, limited by the vector range.

  • For example, mosquitoes frolic in places that are going to be much more conducive to their

  • habitat, so it's going to be very hard for them to live in a temperate climate.

  • I live in Pennsylvania, we don't have mosquitoes year round there.

  • But there are parts of the world that mosquitoes thrive in all year round.

  • That's why I talked about specifically aedes mosquitoes, which are the mosquito that's

  • responsible for spreading Dengue, Chikungunya, Zika, Yellow Fever.

  • They are basically covering half the population of the globe.

  • That is something that's a little bit different with vector borne.

  • In general, we don't think vector borne could do this because the host range, the range

  • of the vector, is kind of limited.

  • The other thing to think about is, talking about global catastrophic biological risk,

  • we talk about deaths, but is fatality everything?

  • This is a question to pose to yourself.

  • There's two purposes for an organism.

  • To survive and to reproduce.

  • What if you had a disease like Zika?

  • It was much more widespread.

  • Or Rubella?

  • Pre-vaccine.

  • If you decrease the reproductive fitness of a species, could that lead to a GCBR?

  • I think the answer is yes.

  • I don't think that Zika or Rubella really make that criteria, and maybe if we were talking

  • about this, if Rubella occurred now, maybe it would fit in the GCBR.

  • But back in the 1960s, people coped with Rubella, but it is one way to think about a GCBR that

  • doesn't end up killing everybody.

  • The other thing is, there's another virus, HTLV, which as been in the headlines a lot

  • in the last couple of weeks because of some studies that have come out of Australia.

  • HTLV is the most carcinogenic virus.

  • It causes human t-cell leukemia.

  • This was the first human retrovirus that was discovered.

  • What if an infectious agent causes cancer in everybody?

  • Would that lead to a GCBR?

  • That's something just to think about, that it's not always going to necessarily be death.

  • I think you have to be very broad and active minded about this.

  • There's also something I wanted to talk about called sapronotic disease.

  • That's a term that we found from the plant world and the animal world, where you have

  • this idea that if an infectious agent is killing everybody that it's infected, it's not very

  • good because it's going to run out of people to infect.

  • But what if it doesn't care?

  • What if that's a secondary source?

  • What if it's an amoeba that eats things in pond scum, but only intermittently infects

  • humans?

  • Like the brain-eating amoebas that always grab headlines?

  • How does that fit into this?

  • If it doesn't necessarily need to be in humans to thrive.

  • That it has other things.

  • It could eat dead bark on a tree, or it can eat stuff on the bottom of the forest floor.

  • That's another way to think about a pandemic pathogen, I think is really interesting that

  • came out of this talk.

  • The first set of conclusions we drew from this project were, the traits that are most

  • likely to be possessed are going to be respiratory droplet transmission, fecal/oral much less

  • likely.

  • The aedes vector-borne agents, those mosquitoes, have a special status because there's widespread

  • mosquito prevalence and there are certain viruses that get very high levels in your

  • blood that these mosquitoes can just kind of pick off.

  • That's why we've seen explosive outbreaks of Dengue, Chikungunya, Zika, why we've seen

  • Yellow Fever resurface.

  • So they are a special category.

  • They probably don't fall as high as respiratory/droplet, but that's something to keep in mind, that

  • these could possibly do that.

  • So then the next thing we try to do is think about, okay, we've said respiratory/droplet

  • transmission.

  • So we have to make a choice, we have to think: is it gonna be virus, bacteria, fungi, parasite?

  • So I say there's no agnostics in a foxhole.

  • We had to push people that we talked to in this thing, and push ourselves to think, what

  • would it really be?

  • So I think that viruses are very formidable in this realm.

  • They mutate much, much more rapidly than bacteria.

  • The transmission and replication cycle in a human is much faster than in bacteria.

  • And you heard this earlier today, that there's no real broad spectrum antiviral agent.

  • I have a picture there, this is from Epcot Center, for penicillin.