From Four Corners to Hollywood: Tracing Hantavirus's Deadly Path

A hidden killer lurks in the humble dust of forgotten cabins and outbuildings across America. World-renowned virologist Dr. Thomas Ksiazek takes us behind the scenes of the landmark 1993 Four Corners outbreak, where hantavirus first emerged on the national stage, claiming lives with a swift and devastating pulmonary syndrome unlike anything seen before in North America.

With over four decades on the frontlines of viral discovery and outbreak response, Dr. Ksiazek shares the detective story of how his team at the CDC identified Sin Nombre ("no name") virus by drawing on their unique expertise with Asian hantaviruses. He explains the ecological cascade that triggers cyclical rodent population explosions, creating perfect conditions for spillover into human communities.

The conversation turns chillingly relevant as we discuss recent high-profile cases, including the tragic February 2024 death of Betsy Arakawa Hackman, and a cluster of deaths in Mammoth Lakes, California. Dr. Ksiazek explains why spring cleaning poses a particular risk when disturbing rodent-contaminated areas, and why conventional treatments often prove ineffective against the rapid progression of hantavirus pulmonary syndrome.

As both a co-discoverer of the original SARS coronavirus and a veteran of countless global outbreaks, Dr. Ksiazek offers profound wisdom on what makes outbreak responses succeed or fail. His insights on the critical importance of early detection and international cooperation carry urgent lessons for our pandemic-weary world. Whether you're a scientist, healthcare worker, or simply someone who might one day clean out a dusty cabin, this episode delivers potentially life-saving knowledge about a persistent threat hiding in plain sight.

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Transcript

Introducing One Health & Dr. Ksiazek

Speaker 2 0:09

This is a podcast about One Health the idea that the health of humans, animals, plants and the environment that we all share are intrinsically linked.

Speaker 3 0:17

Coming to you from the University of Texas Medical Branch and the Galveston National Laboratory.

Speaker 2 0:21

This is Infectious Science. Where enthusiasm for science?

Speaker 3 0:25

is contagious.

Speaker 4 0:30

Welcome back to the Infectious Science podcast. I'm here today with Dr Camille Ledoux. How's it going, camille? When are you moving Next week? Oh, okay, are you excited? Yes, I'm very excited. Nice, has it sunk in yet to be?

Speaker 5 0:44

a doctor. It's weird. Yeah, it's getting there. I feel like it's not old, it hasn't gotten old?

Speaker 4 0:49

All right, we're missing Christina today. Yes, we are, but we're compensating with a special guest, alex Alvarado. Alex, how are you? I'm doing all right, how are you?

Speaker 1 1:01

Yes, so I'm a second year microbiology and immunology graduate student in the lab of Tom Geisbert and my project is currently working on developing a recombinant vesicular stomatitis virus vectored vaccine for guanarito virus which causes Venezuelan hemorrhagic fever.

Speaker 4 1:16

Okay, so hopefully we'll see or hear more of you on the podcast. I certainly hope so. All right, welcome. And then we have a very special guest today and I'm super excited. I wanted to record this episode for probably two years now.

Speaker 4 1:31

Today's guest is a true giant in the field of infectious disease research and global outbreak response. Dr Thomas Kysak is a world-renowned virologist, veterinarian and epidemiologist currently serving as the director of high containment laboratory operations here at the Galveston National Lab at the University of Medical Branch, where we are here in our podcast closet. Over a remarkable career spanning more than four decades, dr Kaysik has been on the front lines of some of the world's most significant viral outbreaks, including Ebola, marburg, nipah, rift Valley Fever, sars and the topic of today's session, hantaviruses. He's been credited to be one of the co-discoverers of SARS coronavirus in 2003 during the outbreak back then, and Dr Kaysack's expertise is rooted in a unique blend of veterinary medicine, military service and laboratory science.

Speaker 4 2:27

After earning his DVM from Kansas State University, he embarked on a distinguished 21-year military career with the US Air Force and Army, working in research stations around the world, ultimately retiring as a lieutenant colonel. Ultimately retiring as a lieutenant colonel. Following his retirement from the military. He joined the Centers for Disease Control and Prevention, where he was part of the leadership team of the Special Pathogens Branch and coordinated international responses to emerging viral threats. And here's the kicker With over 300 science publications to his name and more than 45,000 citations, that's incredible. That's incredible.

Speaker 5 3:05

That's wild.

Speaker 4 3:07

Dr Kaysack's work has shaped our understanding of hemorrhagic fever and arthropod-borne viral diseases, and his rapid diagnostic innovations have saved countless lives. He's obviously the recipient of multiple honors, including three Secretary of Health and Human Service Awards, a Lifetime Achievement Award for Filovirus Science and the Distinguished Alumnus Award from Kansas State. Very exciting to me, dr Kayser's career is taking him to outbreak zones in Asia, africa, south America and the Middle East, and he continues to serve as a consultant on biosafety and laboratory design for organizations worldwide. Consultant on biosafety and laboratory design for organizations worldwide. His legacy is not only in science but also in generations of researchers he has mentored and inspired. So we're all very excited to have a pioneer here in virology and a true leader in global health security here. Welcome, tom. How are you today? Good Pleased to be here, all right, excellent, camille, do you want to start us off with some of the questions?

Speaker 5 4:05

Absolutely so. Again, thank you so much for joining us. We're super excited to have you here, because we're talking about something that's really been in the news lately. We've wanted to do this episode for a while, but since you are really the expert in the room on this topic, could you define for our listeners what hantaviruses are and how they spread?

Understanding Hantaviruses

Speaker 6 4:26

listeners what hantaviruses are and how they spread. Well, hantaviruses are a rodent-borne zoonotic disease that really depend on rodent reservoirs that are chronically infected with the virus and they're pretty much worldwide in distribution. Often the viruses are associated with specific rodents and that's usually regional in nature. Probably the Western medicine's most familiar with it because of what happened during the Korean War, which was that HFRS hemorrhagic fever, renal syndrome became a problem for UN troops in the Korean War in the 50s, discovered more recently than that that there were other hantaviruses in other regions, again usually associated with specific rodent species, that can become seasonal issues of some importance.

Speaker 5 5:16

And from my understanding hantaviruses weren't found in the United States until the Four Corners outbreak in 1993.

Speaker 6 5:22

That's not exactly true.

Speaker 5 5:24

Not exactly true, okay.

Speaker 6 5:25

No, because we have rats and there's a rat-borne virus called SOUL. That's associated with the Rattus norwegica, which is worldwide distribution, and along with the rats, the virus was distributed from, whatever its original origin, which is thought to be Asia original.

Speaker 5 5:44

Okay, and have we seen outbreaks of that in the United States?

Speaker 6 5:48

There are occasional cases, usually associated with laboratory rats or rats that are being maintained for one reason or another.

Speaker 5 5:57

Okay, but the first true outbreak, is it correct that it was the Four Corners outbreak in 1993?

Speaker 6 6:02

There's another Hanoverse that was known about. That occurs in wild rodents in the US, before that associated with voles.

Speaker 5 6:09

Okay, but you were instrumental in finding out what was happening during the Four Corners outbreak.

Speaker 6 6:14

Yeah, it's an interesting story. I was a part of discovering what it is and the basis for that was I had been in the military at Fort Dedrickrick and we were interested in Korean hemorrhagic fever because we have troops there and there were outbreaks. For instance, in 87, I believe it was I responded to Okinawa after a large outbreak in an exercise that had occurred there involving the third Marines that had deployed from Okinawa to Korea, and then, as they began to deploy back to Okinawa, there were cases occurring both at Korea and then when they returned to Okinawa and I and a couple of epidemiologists and a couple of lab people who worked for me went and set up a lab in Okinawa to diagnose that. What year was that? 86 or 87. Okay?

Speaker 5 7:11

I do want to dive more into the Four Corners outbreak. Could you set the scene for what exactly happened that led to it?

Speaker 6 7:17

There was a sort of mysterious disease that popped up. I found out about it I had given an awards lecture at CDC and went up afterwards to tip a beer and somebody one of the leaders in the Division of Viral and Rickettsial Diseases approached a group of us and started talking about this outbreak that occurred and it was in the popular press already. I think there was an article in People magazine about cases occurring and a few deaths that occurred by that time and generally it began to be frightening for the local population. Press articles began to appear, they spread to the national press and CDC became interested in it. One reason was that a lot of the cases not strictly but a lot of the cases were occurring on Indian reservations. So Indian Health Service is a federal institution and so I think we were contacted CDC at large by them.

Speaker 5 8:21

And so, from what I was looking back on documents of this outbreak, finally, this was linked to rodents, right? How did that come about?

Speaker 6 8:29

We knew the history of other hantaviruses first of all Discovering. It was a hantavirus, and one of the things that was unique about this particular outbreak was that it was primarily a pulmonary syndrome, not a kidney disease, which the previous hantaviruses largely were associated with hemorrhagic fever, with renal syndrome that being one of the prominent names for the syndromes, for the diseases that occurred in Asia, and there was not a lot of thought about hantaviruses. And then, when CDC was contacted, eventually some specimens came and CDC put a full court press on testing for a lot of different agents, and so I think we were probably one of the ones that received the material, because we operated a variety of high containment laboratories, and so the specimens often came and we distributed those to other laboratories that did a variety of testing. This was really before PCR existed. It does play a role in this, but it wasn't a widely used assay with commercial sorts of kits and stuff available at the time. And so specimens were distributed to a variety of people and we set up for hemorrhagic fevers, the agents that we were responsible for.

Speaker 6 9:49

Flu was one of the initial thoughts, and so the flu branch and a few other bacterial diseases all of them were doing testing, and what happened is that I had been involved in drug trials for treating Korean hemorrhagic fever that were occurring in China, and so we had developed some newer tests by that time, and so those tests we had brought myself and Dr Peters, having moved from USAMRA to CDC some of that testing technology with us, and we applied that to this particular outbreak, and we got hits with hana viruses so, tom, the specimens that you mentioned, were they those human specimens or were they, did they know at that time, to look for the roads came?

Speaker 6 10:31

later. Okay, it was just, and there weren't that many. There were, you know, five or six cases that we had serum samples, primarily on yeah but enough to be scary for sure.

Speaker 5 10:41

I was looking at the old articles from that.

Speaker 6 10:43

People were afraid were afraid I don't think the people in the lab were necessarily afraid to deal with it, the public was developing some angst over this.

Rodent Reservoirs & Human Spillover

Speaker 5 10:52

Yes, for sure. And back to the rodents. Something I read was that when rodents in the region were eventually tested, up to 30% of them were carrying a hantavirus, but they weren't necessarily dying. So why do we see that it's not really necessarily harming rodent hosts the way it's harming a human host?

Speaker 6 11:09

The general thought about different sorts of reservoir hosts for a variety of pathogens are that there's a sort of a mutualism that develops with a pathogen that depends on its survival for a rodent host, so that these rodents become chronically infected. It's not that it doesn't have any effect on a variety of metabolic or other courses, but it doesn't kill them and it spreads in the population. The other important part of this is it's probably not present at the prevalence rates that you just mentioned 30% but there had been an event people call it a cascade of events that created a very high density in populations because of natural resources being available to the rodents higher than normal and denser than normal, and therefore transmission among a denser population of the particular rodent host that's involved in this was higher and led to those high prevalences. And that's cyclical because the natural resources the rodents depend on are dependent on the resources that go up and down with climatic or weather conditions.

Speaker 4 12:26

So was this strictly weather or climate related, or was this some anthropogenic influence that humans had modified the environment? I don't think this was anthropogenic.

Speaker 6 12:35

It's masting and conifers, I think, was what a lot of people felt was responsible, so that pine nuts, for instance, was one of the things that's often made Got you and so those kind of that cascade is probably why we saw the spillover into humans then.

Speaker 6 12:51

There are a couple reasons why humans are involved. The rodent host this is what's called the deer mouse or Pyramiscus maniculatus. It's a generalist and it may actually prefer things like human. They have were thought to be particularly accommodating towards the rodent host, so the rodents could be out there and be infected infected. But it's really that they bring themselves into close association with humans, or that humans are injecting themselves into circumstances where the rodent contact can occur, and that's where the fact that the rodents are found in these human habitations plays a role in this.

Speaker 5 13:49

And I want to make sure we're talking about the Four Corners outbreak, but that geography might not be widely known, so can you talk more about what exactly we're talking about with these four states?

Speaker 6 13:58

The name Four Corners comes from the fact that four states intersect in the region in which the outbreak was occurring.

Speaker 5 14:06

So to pivot from the geography of this and what might have caused that original spillover, why do we see something like rodents infecting humans but we don't have any human transmission of that particular hantavirus?

Speaker 6 14:17

Yeah, through the sort of medical history of hantaviruses as we knew them at the time, human-to-human transmission is just not part of the story. There have been a couple of instances where in particular a virus called Andes has had some secondary transmission from patients that are infected. But it's not a population where it gets into the community and there's human-to-human transmission Largely care of patients. That's true of a lot of hemorrhagic fevers where they're not being transmitted in the general community but only by close contact. You see it infected and Andes is probably the only one that's really noted.

Speaker 4 14:58

Yeah. So, Tom, you mentioned that before CDC got involved it was already in the popular press, right? You mentioned that there was this unknown disease. Did they have a name for that disease, Because sometimes the popular press likes to come up with?

Speaker 6 15:10

names right. Yeah, I think they were calling it Navajo something or another, and the Navajo Nation didn't like that.

Speaker 4 15:17

No, of course not. Navajo flu, I think Interesting. And then the virus ended up with the name Sinombre, right?

Speaker 6 15:24

So no name there's a fairly large story behind that. Generally, I was trained in arbovirology and the people I worked with were largely arbovirologists, some of who had strayed over into the hemorrhagic fever arena. But arboviruses traditionally have been named after the location where the first isolate was made, so that could be a river. Ebola was named after a river. It could be a town or it could be a forest or something like that, and the Four Corners was one of the first names proposed, I think another name which we who are working with it were somewhat attracted to was one of the locations, was a place called Muerto Canyon, and I'm trying to think of another one, but Sonombre, it turns out, was a tongue-in-che, cheek approach because there was controversy about giving this a name. Sinombre is no name, no name, but there are actually locations you can find on maps called Sinombre. So that was our approach to naming it without really giving a specific location oh, interesting Okay.

Speaker 6 16:34

And that one at least stuck. Nobody seemed to raise an objection to it. There are mountains and ski resorts and street names called Sanombre, but we weren't targeting a specific place in the way it's traditionally done.

Speaker 5 16:49

Gotcha.

Speaker 6 16:49

So again, it was a tongue-in-cheek approach to dealing with the objection to using a name associated with an area or something that the Chamber of Commerce didn't like.

Speaker 5 17:01

Oh, okay, can you tell us how Sinombre causes hantavirus cardiopulmonary syndrome, because that's unique. As you were saying, most hantaviruses is like a renal thing and this was different.

Speaker 6 17:10

Yeah, the pathogenesis is probably pretty similar in terms of the disease and the organ system involved, but this one seemed to be more in the tissues of the lungs and the way it creates a problem is that the capillaries in particular are affected by the virus. It's not a particularly lytic virus, but it upsets the ability to keep fluids in one compartment or the other, and so you get this capillary leak syndrome and eventually what happens is you fill the alveoli of the lung with fluids and therefore you lose the ability to respirate. One of the solutions initially they probably put you on oxygen, but another solution, which is last ditch measure, was to put them on, essentially, a heart lung machine.

Speaker 4 18:04

Yeah, like extracorporeal oxygenation. Yeah, I know what you mean.

Hantavirus Pathophysiology & Detection

Speaker 6 18:10

ECMO extracorporeal membrane oxygenation yes, it's a salvage technique, essentially that if you let these diseases progress, eventually you get better. But if your kidneys quit functioning you may be in big trouble. But if you can get them through it, by doing dialysis, for instance or, in this instance, using ECMO- Okay, so once people were exposed whether these mice were coming into their dwellings, what was the incubation time?

Speaker 5 18:39

And then it's usually an exposure to mouse urine and mouse feces, correct, that gets aerosolized.

Speaker 6 18:44

Yeah, the thought is probably that there's dust, people have been exposed I think there's instances where they had wounds and it may have been a percutaneous exposure but primarily the excreta of the rodents. And a common scenario I think you're going to bring up a recent outbreak is that people, in the spring in particular, will go into a seasonal dwelling, a cabin or something like that, and then clean it up and the rodents have, during the wintertime, taken residence and they've contaminated it with their excreta and then clean it up and the rodents have, during the wintertime, taken residence and they've contaminated it with their excreta. It's probably not feces actually, it's actually the urine where it's being excreted. Gotcha, okay, they often. If they defecate, they'll often urinate at the same time. It may appear to be feces, but it's probably the urine.

Speaker 4 19:36

So as virologists bunia virus virologist I'm curious. Bunia viruses are typically not very stable, but in a protein-rich matrix, like maybe urine or feces mixed with urine, they are stable for a long period of time and can form aerosols.

Speaker 6 19:52

Drying helps to create the aerosol, and then the human activity of trying to clean it up is probably what gets the dust up in the air that may infect people. Gotcha.

Speaker 5 20:04

So could you tell us what other hantaviruses are present in the United States?

Speaker 6 20:09

Prior to this, again these rat-borne viruses were present. And then this vole virus that was found in the northeastern US. No diseases have ever been associated with it yet, but it does occur in the vole populations. And then after this outbreak in other regions we actually discovered cases that were associated with other Sigma dantian rodents here in the US. So one in upstate New York was associated with a close relative of Peromyscus species, but not the same one. Leucopus is the name of that species. And then we found down in the southeast a couple of other sigmadontine rodents that also are infected with similar but distinct viruses that cause cases Not as common. You have to actually think about it. Pyramiscus maniculatus is probably the most common and the largest population of rodents in the US. So one of the mysteries about this is why was this disease only discovered in 1993?

Speaker 1 21:13

Yeah, indeed.

Speaker 6 21:13

Because this rodent's been there. This is not a new phenomenon. One of the things that we did do in the midst of this was we got museum specimens and looked back at rodents and you could find the presence of the rodents. I think the specimens were back into the 60s and I think we actually found a couple of cases of Hanna-Weir's pulmonary syndrome by looking at fixed tissues that had been preserved. Somebody had recognized oh, we saw a case like this going back again, I think, to the 60s.

Speaker 5 21:44

Yeah, wow, and so do you think without the federal government getting involved? You said this was like the Indian Health Service and the CDC, and these are like people that are coming together. Would they have found the causative agent of this?

Speaker 6 21:55

Well, you know, the hantavarsas weren't something people thought about here. So one of the reasons I think that our group was successful is that I'd been in a group where hantavarsas were very much what we had done.

Speaker 6 22:07

I had developed some new diagnostic techniques, largely to deal with some of the drug trials that we were doing in China at the time to deal with some of the drug trials that we were doing in China at the time, and so that was a good combination, but those weren't things that universities in general were involved in. So, yeah, having a central national public health laboratory that deals in exotic things that's part of the mission, of why they're created is very important. Unfortunately, right now it ain't looking real good for the maintenance of a lot of this stuff.

Speaker 1 22:38

Yeah, yeah. So I had some questions for you, building off of what you were discussing earlier about the isolation of some of these samples containing viruses that would cause HPS in fixed tissues. And going back looking through these museum specimens, it seems like a possible concern would then be, even now, possible underreporting of hantavirus cases. Do you think that there's still a need for increased surveillance in the US or in other parts of the world?

Speaker 6 23:08

If you think about the outbreak in particular, it was very pretty dense in the population, particularly on the Indian reservations, but in the general population not so much. There are cases we're going to talk about some, I think, in a little bit but there are cases every year and it does go up and down. If you look at their publications about the cyclical occurrence of Hanovaris, you'll see that there is a cyclical thing that's based again on this cycle in the rodents and how many of them and the prevalence of infection, so that in years when there aren't particularly dense populations of the rodents and the Hanoover's prevalence in the rodents isn't high, you don't tend to get so many infections. And 93 just happened to be one of the years in which this was particularly high and it emerged in a specific population that had pretty high potential for exposure. And it did and it made the press and that's probably what led to its discovery, if that's the right term to use.

Speaker 4 24:12

And so antiviruses, like other viruses too, are linked to the weather phenomenon El Niño or La Niña, right, and is science good enough to predict when we have another La Niña coming up, or is the transmission cycle and the reservoir activity too complex to predict when we have another La Nina coming up, or is the transmission cycle and the reservoir activity too complex to predict? We actually?

Speaker 6 24:30

spent a fair amount of effort. You can correlate the prevalence in the rodents or the amount of infection in the rodents to human cases I mean they are co-joined but trying to predict that in some very finite way. We made a number of attempts with modeling. We could always fit it pretty well, but we couldn't necessarily predict it.

Speaker 1 24:55

Something I was also wondering about, especially in light of what you've mentioned about some of these cyclical peaks and valleys, if you will, in terms of the epidemiological trends with hantavirus, is every year we see a number of reports in the news of hantavirus cases among, say, hikers or among individuals who you know, given, as you mentioned the somewhat peridomestic nature of deer mice, that cases that might come up during the course of spring cleaning, right. So what are some of the best strategies you think that Americans should be aware of and should take in order to reduce the prospect of this rodent-human transmission as they go about these sorts?

Speaker 6 25:30

of activities. There was an effort to try and look at communicating the ways of modifying human behavior by ways to clean out a cabin, for instance, particularly in the regions where this was really important, and I think we made a film video about that. Was actually won some sort of award for public health communication.

Speaker 5 25:52

We'd love to hear it.

Speaker 4 25:53

Are you in?

Speaker 6 25:54

it. Tom, Are you starring in it? I was part of the process of producing it. I don't think I was in it. They had talking heads and I wasn't one of them. They had talking heads and I wasn't one of them. So there are approaches. I mean, you can't eradicate the rodents. One of the efforts was to rodent-proof dwellings, for instance.

Speaker 1 26:13

Yeah, of course.

Speaker 6 26:14

The hogans are a traditional type of dwelling on the Indian Reservation, so we made efforts to try and help them deal with excluding rodents with that environment. Some of the first cases occurred in mobile homes. That was a very repeatable phenomenon during the outbreak and since, for that matter. So there have been outbreaks at other national parks having to do with cabins as well.

Speaker 1 26:43

So it's really a matter of trying to keep the rodents where they belong, in their natural habitats, versus now taking up residence in human-created environments that they like Certainly something to be aware of, going forward when it comes to, say, cleaning out these sorts of cabins or making sure that they're in a position that is really fit for human habitation. You know, something that also has been a point of concern, of course, is that there are no vaccines for any of these new world hantaviruses that have received clinical approval. But are there any vaccine or medical countermeasure candidates that have seen promising results thus far, and what aspects of hantavirus transmission or hantavirus biology lend themselves to being areas of interest when it comes to countermeasure development?

Speaker 6 27:29

There actually have been vaccines created not here in the US. There have been work towards that ends, and there are pharmaceuticals that, if you're talking about hantaviruses in general, are successful. One of the issues with this particular outbreak, sanombre virus, is that the progression of the disease, from the first prodromal occurrences, that is, maybe fever, to a very serious syndrome of pulmonary insufficiency, is so rapid that when we tried a drug trial with ribavirin one of the compounds was the subject of some of the drug trials we were involved in China was showing that ribavirin was effective for HFRS. And again, it's a matter of you have to treat early in order to be effective. If you wait, it don't work so well, and with this one, the time from the first clinical signs appearing until being a whiteout on an X-ray is clear that it doesn't appear that ribavirin had a great chance of success.

Speaker 4 28:35

So, tom, you mentioned that the effects of the pulmonary symptomology is driven by the immune system, right, that the immune system is creating this influx of fluids, and so on. Have there been studies on suppressing the immune system as a treatment option at that stage?

Speaker 6 28:51

It's really thought that I wouldn't say immune response, but maybe the primary immune response has something to do with cytokine storms. Cytokines that when the cells are infected forms cytokines, that when the cells are infected they then create this permeability of the barriers that keep fluids on one side of the blood barrier. It's looked at but I think again having a direct effect on that. Steroids have been used for many things to help reduce inflammation. I think they were tried. I don't think there was great success in the instances when it was supplied. In this instance People knew about ribavirin and there was created sort of an emergency NDA to try ribavirin. But again, the problem is that the time from onset to a very serious disease doesn't allow time for the antiviral to really have much effect on reducing the effects of the virus.

Speaker 5 29:48

Yeah, and I think that's something we come across pretty consistently in the public health and infectious disease sphere is that prevention is so much more effective than us trying to have a cure or something that can really reduce kind of this morbidity and mortality that we see that these diseases cause once somebody has been infected.

Recent Cases & Exposure Prevention

Speaker 4 30:05

Antiviruses have been in the news lately. Right, most of us have seen the surprising news of the hackmans in New Mexico. Tom, can you give us a summary of the case, of what happened?

Speaker 6 30:16

I don't know anything more that you can read in the newspaper and it's been covered. I think now, a month or further after the incident occurred, that the wife who was the one infected with Hanna virus Hackman himself was not was looking on the Internet for not necessarily for Hanna virus, whether she had Hanna virus, just a respiratory syndrome that was precipitated.

Speaker 5 30:39

Like COVID and flu.

Speaker 6 30:40

As I understand the scenario, he was incapacitated with Alzheimer's an Alzheimer's-like syndrome and depended for his care on his wife, and then she went down and that eventually led, it would appear, to his demise.

Speaker 5 30:59

Yes, it was Betsy Arcara Hackman. She was a businesswoman, a really well-known classical pianist, and she was married to Hackman and then eventually recently passed, in February, from hantavirus and they're still not quite sure what the exposure was, because rodents weren't found in the home. And could you talk to us a bit about how might people be contracting hantavirus if not through what we would normally consider exposure, if there's that exposure to urine or things like that of rodents?

Speaker 4 31:24

I think one bit of information that I saw come out just a couple of days ago is, I think, that they were trapping rodents on the premises, and I think there were quite a few.

Speaker 1 31:33

Yes, I believe I saw some reports that they would trap some in some of the outbuildings In the outbuildings, yeah.

Speaker 6 31:37

Outbuildings are often part of the story as well that you might go to an outbuilding and do something there I don't know whether they had horses or other animals and cleaning up again might raise generally, somehow being exposed to an environment that the rodents have been in with some frequency I mean just walking down a trail where a Pyramiscus is jobbed across the trail is not going to get you. That's good to know.

Speaker 5 32:05

That's good to know. That's good to know. I was actually out hiking the other day in Galveston. I was with a friend and we saw these massive Galveston rats and my immediate thought was hantavirus.

Speaker 6 32:15

That was my immediate thought.

Speaker 5 32:16

I don't even know if there's hantavirus here in Galveston, but like I saw the rat and I was immediately like no, I don't want to be anywhere near it. But yes, good to know that that's not exposure.

Speaker 6 32:26

Well, in an outdoor space I mean if it's an aerosol infection the concentration of the particles is much higher in an area that's closed off, no ventilation. Oh yeah, so that's part of the story, we believe.

Speaker 4 32:40

Yeah, yeah, I was just looking at the timeline of events the other day and how rapid the progression was of her demise. Right, I think in the morning she was still like Googling oxygen tanks on Amazon and things like that and was still seen at a store. And then I think the next day I don't know what they used I guess her like phone activity or like her computer activity or something like that, or like phone activity or like a computer activity or something like that.

Speaker 6 33:06

I should mention it was a video presentation on a site called we Were there that CDC runs and it was I think the 20th anniversary of the occurrence of this outbreak, and so there's a variety of things presented.

Speaker 6 33:20

Jay Butler presented sort of the clinical aspects of this and some of the early epidemiologic parts. I talked about the laboratory diagnosis and then Jamie Child talked about the follow-up with the rodents and absolutely demonstrating what the rodent reservoir was and how that played out during this epidemic. So if you're really interested you should visit that site. You guys can somehow link it in the show notes. We'll put it in the show notes.

Speaker 4 33:48

Yeah.

Speaker 5 33:49

And I was wondering another case that I don't think has been as widely picked up by the media, but there's been three hantavirus-linked deaths in the news from Mammoth Lakes, california. So it's a town that they do often see a case or two in the spring, as you mentioned, but three deaths this early in the spring is pretty surprising for them. Just for our listeners, we're recording this at the end of April in 2025. And so right now these deaths aren't linked to activities that are usually associated with exposure. There's not been instances where they were necessarily cleaning out a cabin or something like that If it's not through a normal exposure I know you mentioned that there can be kind of exposure through like wounds or something like that Is there any other way that people would become exposed to hantavirus? Not that?

Speaker 3 34:30

I know of, not that you know of.

SARS Discovery & Pandemic Response

Speaker 5 34:31

Okay, this has been a brilliant overview on hantaviruses. I have learned so much. Thank you so much for answering all of our questions. I do have one more question, if that's all right, and it's not related to hantaviruses viruses but I didn't realize that you were one of the co-discoverers of SARS, which is really wild, and I think that's probably, as you know, an infectious disease. Geek, I feel like SARS is probably one of the things that originally got me interested in infectious diseases, because it was that perfect example of you know. You have something and our health is so globally interconnected. Now, what was that like to be there as that was coming out? Because I think in the news, all the articles that I've ever seen from that time were very fear-mongering and people were very afraid. So what was that like?

Speaker 6 35:10

Again, this one did involve community.

Speaker 5 35:14

Yes.

Speaker 6 35:15

The original part of the story was that we at CDC knew there was something going on in China, in southern China, knew there was something going on in China, in southern China, and I think that the assumption at the time was this was H5N1, which goes back to 97. We're now talking about, for us, the spring of 2003, that there's something bubbling up and there were efforts made to try and figure out what that was, to help the Chinese, which weren't working terribly well Right now. This week, who has announced that there's a new set of pandemic preparedness regulations that are finally, I guess, finalized, that will be presented to the World Health Assembly, and part of this is to make sure that if there's something bubbling up that has pandemic or real epidemic potential, that you report it to central authorities so that international efforts to keep it localized or from becoming a pandemic can occur. And what happened in 2003 was that again, the notion that there was something happening in southern China was already apparent. We made an attempt to help in some way.

Speaker 6 36:33

So somebody from the flu branch at CDC was actually sent to China and I don't think I'm going to offend China at the moment, but he was stonewalled. He went and sat and essentially was offered no ability to talk to anybody or review any data. And shortly after that, something was starting in Hong Kong or actually in Vietnam was the story, but it emanated from a physician from Guangdong province having traveled to Hong Kong for his daughter's wedding and staying up in a hospital that then began to infect other patients and that was reported by a WHO epidemiologist working there. The epidemiologist himself became infected. He then traveled to Bangkok and we obtained because we had some HIV folks present in Thailand specimens from him that were sent to Atlanta, and those were the specimens that I believe were the actual earliest determination of the etiology of this as being coronaviruses, interesting Coronavirus.

Speaker 4 38:03

Yeah, yeah, tom, you brought up the pandemic agreement. Right, that's finally, after three years, been finalized. But do you think countries will stick to that agreement and will Well after SARS?

Speaker 6 38:14

you have to realize that they strengthen the world health regulations and part of that was to strengthen reporting. But in this instance and part of that was to strengthen reporting, but in this instance once again, things didn't happen the way they were. I would say first of all that SARS was bad, but once it was discovered what it was, there was follow-up and the natural sort of reservoir and probably the means of that becoming a human transmitted disease was pretty well worked out. If everybody wants to recall the circumstances, I would say, once the virus got to Wuhan at least as far as I can tell, the Wuhan Institute of Virology, whose name is MUD right now, probably unjustifiably actually contacted people from the outside and revealed the sequence of the virus and that it was another virus. Part of, unfortunately, the political environment was that the Chinese Communist Party clamped down on the dissemination of information and have also suppressed other investigations, including by international bodies such as WHO, and that's the part that sticks in everybody's craw.

Speaker 5 39:38

So if I can ask, because you've been present for many outbreaks, you've helped work on them, you've really contributed and helped keep people safe from a public health perspective, to you, what do you think makes or breaks an effective outbreak response, whether that's hantaviruses, whether that's SARS? What does that look like?

Speaker 6 39:56

Figuring out what it is early and then figuring out whether there are countermeasures or social things that can be done to diminish transmission is probably the most important.

Speaker 6 40:08

I would use an example Ebola and the West African outbreak.

Speaker 6 40:13

So what happened in that outbreak is that outbreak probably began in 2013 and essentially became disseminated to three countries before it was ever identified as Ebola.

Speaker 6 40:29

And holding up that same example, we had been involved at CDC and special pathogens in particular, in an outbreak that occurred in 2000 in Uganda in Gulu, and a lot of lessons were learned from that. Part of it was that we had a permanent presence special pathogens in a PEPBAR CDC unit at the National Institute of Virology in Uganda, and there's a paper published about a number of outbreaks of both Marburg and Ebola Sudan that occurred in Uganda and that laboratory presence had allowed the very early identification and we had trained up people how to respond early and how to isolate cases of Ebola so that they're being taken care of by people who are wearing appropriate PPE, so that there's not transmission to other people who aren't nursing and using appropriate protective equipment. And that's the key with Ebola, it's not something that circulates in the community. It's circulated by patients that become infected, have high loads of virus and people that are intimately exposing themselves to them, then get it, and that chain goes on.

Speaker 4 41:51

Yeah, it's a caretaker's disease, like Paul Farmer always says. Yeah, all right.

Speaker 5 41:57

Thank you so much. This was brilliant. I've learned so much. Again, we cannot thank you enough for taking the time to come speak with us. It's really rare and exciting to get such a well-versed expert on the podcast. So thank you for taking the time, Dr Kysak Really appreciate it.

Speaker 6 42:10

You're welcome, my pleasure, thank you. Thank you.

Speaker 5 42:13

All right, and thanks for joining us for this episode of Infectious Science. As always, let us know what you want to hear, and thanks for listening.

Speaker 3 42:19

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Speaker 2 42:30

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Speaker 3 42:38

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Speaker 2 42:48

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Speaker 3 43:03

Thank you.