June 6, 2025
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.
Thanks for listening to the Infectious Science Podcast . Be sure to visit infectiousscience.org to join the conversation, access the show notes, and don’t forget to sign up for our newsletter to receive our free materials.
We hope you enjoyed this new episode of Infectious Science, and if you did, please leave us a review on Apple Podcasts and Spotify. Please share this episode with others who may be interested in this topic!
Also, please don’t hesitate to ask questions or tell us which topics you want us to cover in future episodes. To get in touch, drop us a line in the comment section or send us a message on social media.
Instagram
@Infectscipod
Facebook
Infectious Science Podcast
See you next time for a new episode!
Thanks for listening to the Infectious Science Podcast. Be sure to visit infectiousscience.org to join the conversation, access the show notes, and don’t forget to sign up for our newsletter to receive our free materials.
We hope you enjoyed this new episode of Infectious Science, and if you did, please leave us a review on Apple Podcasts and Spotify. Please share this episode with others who may be interested in this topic!
Also, please don’t hesitate to ask questions or tell us which topics you want us to cover in future episodes. To get in touch, drop us a line in the comment section or send us a message on social media.
Twitter @Infectious_Sci
Instagram @tick_virus
Facebook Infectious Science Podcast
See you next time for a new episode!
00:00 - Introducing One Health & Dr. Kysak
04:28 - Understanding Hantaviruses
07:17 - The Four Corners Outbreak Story
11:09 - Rodent Reservoirs & Human Spillover
18:21 - Hantavirus Pathophysiology & Detection
30:06 - Recent Cases & Exposure Prevention
34:41 - SARS Discovery & Pandemic Response
WEBVTT
00:00:09.230 --> 00:00:16.730
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.
00:00:17.201 --> 00:00:21.091
Coming to you from the University of Texas Medical Branch and the Galveston National Laboratory.
00:00:21.420 --> 00:00:22.923
This is Infectious Science.
00:00:22.923 --> 00:00:24.768
Where enthusiasm for science?
00:00:25.370 --> 00:00:26.032
is contagious.
00:00:30.640 --> 00:00:33.207
Welcome back to the Infectious Science podcast.
00:00:33.207 --> 00:00:35.533
I'm here today with Dr Camille Ledoux.
00:00:35.533 --> 00:00:36.783
How's it going, camille?
00:00:36.783 --> 00:00:38.268
When are you moving Next week?
00:00:38.268 --> 00:00:40.686
Oh, okay, are you excited?
00:00:40.686 --> 00:00:41.549
Yes, I'm very excited.
00:00:41.549 --> 00:00:44.006
Nice, has it sunk in yet to be?
00:00:44.085 --> 00:00:44.527
a doctor.
00:00:44.527 --> 00:00:44.927
It's weird.
00:00:44.927 --> 00:00:46.191
Yeah, it's getting there.
00:00:46.191 --> 00:00:48.921
I feel like it's not old, it hasn't gotten old?
00:00:49.883 --> 00:00:51.786
All right, we're missing Christina today.
00:00:51.786 --> 00:00:56.311
Yes, we are, but we're compensating with a special guest, alex Alvarado.
00:00:56.311 --> 00:00:57.753
Alex, how are you?
00:00:57.753 --> 00:01:00.823
I'm doing all right, how are you?
00:01:01.124 --> 00:01:15.882
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.
00:01:16.343 --> 00:01:20.272
Okay, so hopefully we'll see or hear more of you on the podcast.
00:01:20.272 --> 00:01:21.260
I certainly hope so.
00:01:21.260 --> 00:01:23.204
All right, welcome.
00:01:23.204 --> 00:01:27.873
And then we have a very special guest today and I'm super excited.
00:01:27.873 --> 00:01:30.849
I wanted to record this episode for probably two years now.
00:01:31.500 --> 00:01:38.274
Today's guest is a true giant in the field of infectious disease research and global outbreak response.
00:01:38.274 --> 00:01:54.349
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.
00:01:54.349 --> 00:02:12.169
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.
00:02:12.169 --> 00:02:27.639
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.
00:02:27.939 --> 00:02:42.192
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.
00:02:42.192 --> 00:02:43.812
Ultimately retiring as a lieutenant colonel.
00:02:43.812 --> 00:02:46.474
Following his retirement from the military.
00:02:46.474 --> 00:02:56.028
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.
00:02:56.028 --> 00:03:04.645
And here's the kicker With over 300 science publications to his name and more than 45,000 citations, that's incredible.
00:03:04.645 --> 00:03:05.354
That's incredible.
00:03:05.373 --> 00:03:05.840
That's wild.
00:03:07.245 --> 00:03:15.787
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.
00:03:15.787 --> 00:03:29.330
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.
00:03:29.330 --> 00:03:44.593
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.
00:03:44.593 --> 00:03:48.307
Consultant on biosafety and laboratory design for organizations worldwide.
00:03:48.307 --> 00:03:51.459
His legacy is not only in science but also in generations of researchers he has mentored and inspired.
00:03:51.459 --> 00:03:58.322
So we're all very excited to have a pioneer here in virology and a true leader in global health security here.
00:03:58.322 --> 00:03:59.044
Welcome, tom.
00:03:59.044 --> 00:04:00.427
How are you today?
00:04:00.427 --> 00:04:05.790
Good Pleased to be here, all right, excellent, camille, do you want to start us off with some of the questions?
00:04:05.971 --> 00:04:06.712
Absolutely so.
00:04:06.712 --> 00:04:08.558
Again, thank you so much for joining us.
00:04:08.558 --> 00:04:13.480
We're super excited to have you here, because we're talking about something that's really been in the news lately.
00:04:13.480 --> 00:04:22.492
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?
00:04:26.240 --> 00:04:27.322
listeners what hantaviruses are and how they spread.
00:04:27.322 --> 00:04:37.273
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.
00:04:37.273 --> 00:04:44.605
Often the viruses are associated with specific rodents and that's usually regional in nature.
00:04:44.605 --> 00:05:15.987
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.
00:05:16.809 --> 00:05:22.887
And from my understanding hantaviruses weren't found in the United States until the Four Corners outbreak in 1993.
00:05:22.908 --> 00:05:24.071
That's not exactly true.
00:05:24.211 --> 00:05:25.254
Not exactly true, okay.
00:05:25.519 --> 00:05:29.809
No, because we have rats and there's a rat-borne virus called SOUL.
00:05:29.809 --> 00:05:43.629
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.
00:05:44.180 --> 00:05:47.810
Okay, and have we seen outbreaks of that in the United States?
00:05:48.360 --> 00:05:57.428
There are occasional cases, usually associated with laboratory rats or rats that are being maintained for one reason or another.
00:05:57.629 --> 00:06:02.079
Okay, but the first true outbreak, is it correct that it was the Four Corners outbreak in 1993?
00:06:02.139 --> 00:06:04.384
There's another Hanoverse that was known about.
00:06:04.384 --> 00:06:08.612
That occurs in wild rodents in the US, before that associated with voles.
00:06:09.233 --> 00:06:14.579
Okay, but you were instrumental in finding out what was happening during the Four Corners outbreak.
00:06:14.620 --> 00:06:15.805
Yeah, it's an interesting story.
00:06:15.805 --> 00:06:30.646
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.
00:06:30.646 --> 00:07:06.992
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.
00:07:06.992 --> 00:07:08.293
What year was that?
00:07:08.293 --> 00:07:09.944
86 or 87.
00:07:09.944 --> 00:07:10.668
Okay?
00:07:11.060 --> 00:07:13.329
I do want to dive more into the Four Corners outbreak.
00:07:13.329 --> 00:07:16.891
Could you set the scene for what exactly happened that led to it?
00:07:17.160 --> 00:07:20.189
There was a sort of mysterious disease that popped up.
00:07:20.189 --> 00:07:42.865
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.
00:07:42.865 --> 00:07:56.351
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.
00:07:56.351 --> 00:08:03.995
Press articles began to appear, they spread to the national press and CDC became interested in it.
00:08:03.995 --> 00:08:16.283
One reason was that a lot of the cases not strictly but a lot of the cases were occurring on Indian reservations.
00:08:16.283 --> 00:08:21.134
So Indian Health Service is a federal institution and so I think we were contacted CDC at large by them.
00:08:21.899 --> 00:08:27.567
And so, from what I was looking back on documents of this outbreak, finally, this was linked to rodents, right?
00:08:27.567 --> 00:08:28.810
How did that come about?
00:08:29.461 --> 00:08:33.135
We knew the history of other hantaviruses first of all Discovering.
00:08:33.135 --> 00:08:59.860
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.
00:08:59.860 --> 00:09:28.428
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.
00:09:28.428 --> 00:09:31.197
This was really before PCR existed.
00:09:31.197 --> 00:09:40.400
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.
00:09:40.400 --> 00:09:49.145
And so specimens were distributed to a variety of people and we set up for hemorrhagic fevers, the agents that we were responsible for.
00:09:49.667 --> 00:10:31.903
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?
00:10:31.962 --> 00:10:32.283
later.
00:10:32.283 --> 00:10:34.369
Okay, it was just, and there weren't that many.
00:10:34.369 --> 00:10:41.732
There were, you know, five or six cases that we had serum samples, primarily on yeah but enough to be scary for sure.
00:10:41.832 --> 00:10:43.383
I was looking at the old articles from that.
00:10:43.482 --> 00:10:52.268
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.
00:10:52.447 --> 00:10:53.169
Yes, for sure.
00:10:53.169 --> 00:10:54.192
And back to the rodents.
00:10:54.192 --> 00:11:03.034
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.
00:11:03.034 --> 00:11:09.114
So why do we see that it's not really necessarily harming rodent hosts the way it's harming a human host?
00:11:09.902 --> 00:11:27.523
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.
00:11:27.523 --> 00:11:37.316
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.
00:11:37.316 --> 00:12:13.701
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.
00:12:13.701 --> 00:12:25.933
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.
00:12:26.419 --> 00:12:33.573
So was this strictly weather or climate related, or was this some anthropogenic influence that humans had modified the environment?
00:12:33.573 --> 00:12:34.519
I don't think this was anthropogenic.
00:12:35.000 --> 00:12:49.884
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.
00:12:51.086 --> 00:12:53.394
There are a couple reasons why humans are involved.
00:12:53.394 --> 00:12:58.937
The rodent host this is what's called the deer mouse or Pyramiscus maniculatus.
00:12:58.937 --> 00:13:21.178
It's a generalist and it may actually prefer things like human.
00:13:21.178 --> 00:13:36.684
They have were thought to be particularly accommodating towards the rodent host, so the rodents could be out there and be infected infected.
00:13:36.684 --> 00:13:49.525
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.
00:13:49.908 --> 00:13:57.376
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?
00:13:58.466 --> 00:14:05.739
The name Four Corners comes from the fact that four states intersect in the region in which the outbreak was occurring.
00:14:06.004 --> 00:14:16.658
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?
00:14:17.504 --> 00:14:26.179
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.
00:14:26.179 --> 00:14:37.225
There have been a couple of instances where in particular a virus called Andes has had some secondary transmission from patients that are infected.
00:14:37.225 --> 00:14:45.148
But it's not a population where it gets into the community and there's human-to-human transmission Largely care of patients.
00:14:45.148 --> 00:14:52.596
That's true of a lot of hemorrhagic fevers where they're not being transmitted in the general community but only by close contact.
00:14:52.596 --> 00:14:57.515
You see it infected and Andes is probably the only one that's really noted.
00:14:58.216 --> 00:14:58.418
Yeah.
00:14:58.418 --> 00:15:04.264
So, Tom, you mentioned that before CDC got involved it was already in the popular press, right?
00:15:04.264 --> 00:15:06.133
You mentioned that there was this unknown disease.
00:15:06.133 --> 00:15:10.419
Did they have a name for that disease, Because sometimes the popular press likes to come up with?
00:15:10.500 --> 00:15:11.065
names right.
00:15:11.065 --> 00:15:16.692
Yeah, I think they were calling it Navajo something or another, and the Navajo Nation didn't like that.
00:15:17.013 --> 00:15:17.755
No, of course not.
00:15:17.755 --> 00:15:20.087
Navajo flu, I think Interesting.
00:15:20.087 --> 00:15:24.003
And then the virus ended up with the name Sinombre, right?
00:15:24.023 --> 00:15:27.674
So no name there's a fairly large story behind that.
00:15:27.674 --> 00:15:37.014
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.
00:15:37.014 --> 00:15:45.791
But arboviruses traditionally have been named after the location where the first isolate was made, so that could be a river.
00:15:45.791 --> 00:15:47.635
Ebola was named after a river.
00:15:47.635 --> 00:16:16.078
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.
00:16:16.078 --> 00:16:24.216
Sinombre is no name, no name, but there are actually locations you can find on maps called Sinombre.
00:16:24.216 --> 00:16:33.519
So that was our approach to naming it without really giving a specific location oh, interesting Okay.
00:16:34.528 --> 00:16:36.034
And that one at least stuck.
00:16:36.034 --> 00:16:38.566
Nobody seemed to raise an objection to it.
00:16:38.566 --> 00:16:48.634
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.
00:16:49.054 --> 00:16:49.615
Gotcha.
00:16:49.716 --> 00:17:00.936
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.
00:17:01.586 --> 00:17:07.267
Oh, okay, can you tell us how Sinombre causes hantavirus cardiopulmonary syndrome, because that's unique.
00:17:07.267 --> 00:17:10.395
As you were saying, most hantaviruses is like a renal thing and this was different.
00:17:10.924 --> 00:17:29.565
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.
00:17:29.565 --> 00:17:51.915
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.
00:17:51.915 --> 00:18:03.659
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.
00:18:04.266 --> 00:18:07.093
Yeah, like extracorporeal oxygenation.
00:18:07.093 --> 00:18:08.836
Yeah, I know what you mean.
00:18:10.424 --> 00:18:22.800
ECMO extracorporeal membrane oxygenation yes, it's a salvage technique, essentially that if you let these diseases progress, eventually you get better.
00:18:22.800 --> 00:18:26.836
But if your kidneys quit functioning you may be in big trouble.
00:18:26.836 --> 00:18:39.212
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?
00:18:39.314 --> 00:18:43.412
And then it's usually an exposure to mouse urine and mouse feces, correct, that gets aerosolized.
00:18:44.535 --> 00:18:58.298
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.
00:18:58.298 --> 00:19:20.076
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.
00:19:20.076 --> 00:19:24.682
It's probably not feces actually, it's actually the urine where it's being excreted.
00:19:24.682 --> 00:19:27.088
Gotcha, okay, they often.
00:19:27.088 --> 00:19:30.837
If they defecate, they'll often urinate at the same time.
00:19:30.837 --> 00:19:35.317
It may appear to be feces, but it's probably the urine.
00:19:36.005 --> 00:19:39.255
So as virologists bunia virus virologist I'm curious.
00:19:39.255 --> 00:19:52.356
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.
00:19:52.416 --> 00:20:02.954
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.
00:20:02.954 --> 00:20:03.576
Gotcha.
00:20:04.317 --> 00:20:08.496
So could you tell us what other hantaviruses are present in the United States?
00:20:09.819 --> 00:20:12.589
Prior to this, again these rat-borne viruses were present.
00:20:12.589 --> 00:20:17.185
And then this vole virus that was found in the northeastern US.
00:20:17.185 --> 00:20:23.058
No diseases have ever been associated with it yet, but it does occur in the vole populations.
00:20:23.058 --> 00:20:32.853
And then after this outbreak in other regions we actually discovered cases that were associated with other Sigma dantian rodents here in the US.
00:20:32.853 --> 00:20:42.913
So one in upstate New York was associated with a close relative of Peromyscus species, but not the same one.
00:20:42.913 --> 00:20:45.138
Leucopus is the name of that species.
00:20:45.138 --> 00:20:58.218
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.
00:20:58.218 --> 00:21:00.353
You have to actually think about it.
00:21:00.353 --> 00:21:06.738
Pyramiscus maniculatus is probably the most common and the largest population of rodents in the US.
00:21:06.738 --> 00:21:13.198
So one of the mysteries about this is why was this disease only discovered in 1993?
00:21:13.239 --> 00:21:13.578
Yeah, indeed.
00:21:13.785 --> 00:21:15.030
Because this rodent's been there.
00:21:15.030 --> 00:21:16.771
This is not a new phenomenon.
00:21:16.771 --> 00:21:26.314
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.
00:21:26.314 --> 00:21:38.487
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.
00:21:38.487 --> 00:21:44.267
Somebody had recognized oh, we saw a case like this going back again, I think, to the 60s.
00:21:44.467 --> 00:21:48.718
Yeah, wow, and so do you think without the federal government getting involved?
00:21:48.718 --> 00:21:52.465
You said this was like the Indian Health Service and the CDC, and these are like people that are coming together.
00:21:52.465 --> 00:21:54.834
Would they have found the causative agent of this?
00:21:55.134 --> 00:21:58.846
Well, you know, the hantavarsas weren't something people thought about here.
00:21:58.846 --> 00:22:07.494
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.
00:22:07.555 --> 00:22:22.490
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.
00:22:22.490 --> 00:22:32.836
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.
00:22:32.836 --> 00:22:38.179
Unfortunately, right now it ain't looking real good for the maintenance of a lot of this stuff.
00:22:38.239 --> 00:22:39.179
Yeah, yeah.
00:22:39.179 --> 00:22:52.894
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.
00:22:52.894 --> 00:23:02.554
And going back looking through these museum specimens, it seems like a possible concern would then be, even now, possible underreporting of hantavirus cases.
00:23:02.554 --> 00:23:08.346
Do you think that there's still a need for increased surveillance in the US or in other parts of the world?
00:23:08.788 --> 00:23:18.809
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.
00:23:18.809 --> 00:23:27.362
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.
00:23:27.362 --> 00:23:50.968
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.
00:23:50.968 --> 00:24:03.852
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.
00:24:03.852 --> 00:24:11.886
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.
00:24:12.361 --> 00:24:29.614
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?
00:24:29.614 --> 00:24:30.234
We actually?
00:24:30.315 --> 00:24:31.737
spent a fair amount of effort.
00:24:31.737 --> 00:24:45.537
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.
00:24:45.537 --> 00:24:48.142
We made a number of attempts with modeling.
00:24:48.142 --> 00:24:52.772
We could always fit it pretty well, but we couldn't necessarily predict it.
00:24:55.641 --> 00:25:21.319
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.
00:25:21.319 --> 00:25:30.884
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?
00:25:30.923 --> 00:25:31.346
of activities.
00:25:31.346 --> 00:25:47.307
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.
00:25:47.307 --> 00:25:52.034
Was actually won some sort of award for public health communication.
00:25:52.355 --> 00:25:53.195
We'd love to hear it.
00:25:53.641 --> 00:25:53.983
Are you in?
00:25:54.065 --> 00:25:54.185
it.
00:25:54.185 --> 00:25:55.598
Tom, Are you starring in it?
00:25:55.598 --> 00:25:58.567
I was part of the process of producing it.
00:25:58.567 --> 00:25:59.790
I don't think I was in it.
00:25:59.790 --> 00:26:03.308
They had talking heads and I wasn't one of them.
00:26:03.308 --> 00:26:04.560
They had talking heads and I wasn't one of them.
00:26:04.560 --> 00:26:06.602
So there are approaches.
00:26:06.602 --> 00:26:09.183
I mean, you can't eradicate the rodents.
00:26:09.183 --> 00:26:13.586
One of the efforts was to rodent-proof dwellings, for instance.
00:26:13.646 --> 00:26:14.326
Yeah, of course.
00:26:14.647 --> 00:26:26.035
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.
00:26:26.035 --> 00:26:29.397
Some of the first cases occurred in mobile homes.
00:26:29.397 --> 00:26:39.306
That was a very repeatable phenomenon during the outbreak and since, for that matter.
00:26:39.306 --> 00:26:43.433
So there have been outbreaks at other national parks having to do with cabins as well.
00:26:43.921 --> 00:27:07.464
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.
00:27:07.464 --> 00:27:15.782
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.
00:27:15.782 --> 00:27:28.549
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?
00:27:29.140 --> 00:27:32.106
There actually have been vaccines created not here in the US.
00:27:32.106 --> 00:27:40.580
There have been work towards that ends, and there are pharmaceuticals that, if you're talking about hantaviruses in general, are successful.
00:27:40.580 --> 00:28:12.411
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.
00:28:12.411 --> 00:28:17.372
And again, it's a matter of you have to treat early in order to be effective.
00:28:17.372 --> 00:28:35.477
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.
00:28:35.941 --> 00:28:45.839
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.
00:28:45.839 --> 00:28:51.173
Have there been studies on suppressing the immune system as a treatment option at that stage?
00:28:51.560 --> 00:29:00.566
It's really thought that I wouldn't say immune response, but maybe the primary immune response has something to do with cytokine storms.
00:29:00.566 --> 00:29:12.819
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.
00:29:12.819 --> 00:29:18.231
It's looked at but I think again having a direct effect on that.
00:29:18.231 --> 00:29:22.951
Steroids have been used for many things to help reduce inflammation.
00:29:22.951 --> 00:29:23.893
I think they were tried.
00:29:23.893 --> 00:29:28.365
I don't think there was great success in the instances when it was supplied.
00:29:28.365 --> 00:29:36.210
In this instance People knew about ribavirin and there was created sort of an emergency NDA to try ribavirin.
00:29:36.210 --> 00:29:48.165
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.
00:00:09.230 --> 00:00:16.730
00:00:17.201 --> 00:00:21.091
00:00:21.420 --> 00:00:22.923
00:00:22.923 --> 00:00:24.768
00:00:25.370 --> 00:00:26.032
00:00:30.640 --> 00:00:33.207
00:00:33.207 --> 00:00:35.533
00:00:35.533 --> 00:00:36.783
00:00:36.783 --> 00:00:38.268
00:00:38.268 --> 00:00:40.686
00:00:40.686 --> 00:00:41.549
00:00:41.549 --> 00:00:44.006
00:00:44.085 --> 00:00:44.527
00:00:44.527 --> 00:00:44.927
00:00:44.927 --> 00:00:46.191
00:00:46.191 --> 00:00:48.921
00:00:49.883 --> 00:00:51.786
00:00:51.786 --> 00:00:56.311
00:00:56.311 --> 00:00:57.753
00:00:57.753 --> 00:01:00.823
00:01:01.124 --> 00:01:15.882
00:01:16.343 --> 00:01:20.272
00:01:20.272 --> 00:01:21.260
00:01:21.260 --> 00:01:23.204
00:01:23.204 --> 00:01:27.873
00:01:27.873 --> 00:01:30.849
00:01:31.500 --> 00:01:38.274
00:01:38.274 --> 00:01:54.349
00:01:54.349 --> 00:02:12.169
00:02:12.169 --> 00:02:27.639
00:02:27.939 --> 00:02:42.192
00:02:42.192 --> 00:02:43.812
00:02:43.812 --> 00:02:46.474
00:02:46.474 --> 00:02:56.028
00:02:56.028 --> 00:03:04.645
00:03:04.645 --> 00:03:05.354
00:03:05.373 --> 00:03:05.840
00:03:07.245 --> 00:03:15.787
00:03:15.787 --> 00:03:29.330
00:03:29.330 --> 00:03:44.593
00:03:44.593 --> 00:03:48.307
00:03:48.307 --> 00:03:51.459
00:03:51.459 --> 00:03:58.322
00:03:58.322 --> 00:03:59.044
00:03:59.044 --> 00:04:00.427
00:04:00.427 --> 00:04:05.790
00:04:05.971 --> 00:04:06.712
00:04:06.712 --> 00:04:08.558
00:04:08.558 --> 00:04:13.480
00:04:13.480 --> 00:04:22.492
00:04:26.240 --> 00:04:27.322
00:04:27.322 --> 00:04:37.273
00:04:37.273 --> 00:04:44.605
00:04:44.605 --> 00:05:15.987
00:05:16.809 --> 00:05:22.887
00:05:22.908 --> 00:05:24.071
00:05:24.211 --> 00:05:25.254
00:05:25.519 --> 00:05:29.809
00:05:29.809 --> 00:05:43.629
00:05:44.180 --> 00:05:47.810
00:05:48.360 --> 00:05:57.428
00:05:57.629 --> 00:06:02.079
00:06:02.139 --> 00:06:04.384
00:06:04.384 --> 00:06:08.612
00:06:09.233 --> 00:06:14.579
00:06:14.620 --> 00:06:15.805
00:06:15.805 --> 00:06:30.646
00:06:30.646 --> 00:07:06.992
00:07:06.992 --> 00:07:08.293
00:07:08.293 --> 00:07:09.944
00:07:09.944 --> 00:07:10.668
00:07:11.060 --> 00:07:13.329
00:07:13.329 --> 00:07:16.891
00:07:17.160 --> 00:07:20.189
00:07:20.189 --> 00:07:42.865
00:07:42.865 --> 00:07:56.351
00:07:56.351 --> 00:08:03.995
00:08:03.995 --> 00:08:16.283
00:08:16.283 --> 00:08:21.134
00:08:21.899 --> 00:08:27.567
00:08:27.567 --> 00:08:28.810
00:08:29.461 --> 00:08:33.135
00:08:33.135 --> 00:08:59.860
00:08:59.860 --> 00:09:28.428
00:09:28.428 --> 00:09:31.197
00:09:31.197 --> 00:09:40.400
00:09:40.400 --> 00:09:49.145
00:09:49.667 --> 00:10:31.903
00:10:31.962 --> 00:10:32.283
00:10:32.283 --> 00:10:34.369
00:10:34.369 --> 00:10:41.732
00:10:41.832 --> 00:10:43.383
00:10:43.482 --> 00:10:52.268
00:10:52.447 --> 00:10:53.169
00:10:53.169 --> 00:10:54.192
00:10:54.192 --> 00:11:03.034
00:11:03.034 --> 00:11:09.114
00:11:09.902 --> 00:11:27.523
00:11:27.523 --> 00:11:37.316
00:11:37.316 --> 00:12:13.701
00:12:13.701 --> 00:12:25.933
00:12:26.419 --> 00:12:33.573
00:12:33.573 --> 00:12:34.519
00:12:35.000 --> 00:12:49.884
00:12:51.086 --> 00:12:53.394
00:12:53.394 --> 00:12:58.937
00:12:58.937 --> 00:13:21.178
00:13:21.178 --> 00:13:36.684
00:13:36.684 --> 00:13:49.525
00:13:49.908 --> 00:13:57.376
00:13:58.466 --> 00:14:05.739
00:14:06.004 --> 00:14:16.658
00:14:17.504 --> 00:14:26.179
00:14:26.179 --> 00:14:37.225
00:14:37.225 --> 00:14:45.148
00:14:45.148 --> 00:14:52.596
00:14:52.596 --> 00:14:57.515
00:14:58.216 --> 00:14:58.418
00:14:58.418 --> 00:15:04.264
00:15:04.264 --> 00:15:06.133
00:15:06.133 --> 00:15:10.419
00:15:10.500 --> 00:15:11.065
00:15:11.065 --> 00:15:16.692
00:15:17.013 --> 00:15:17.755
00:15:17.755 --> 00:15:20.087
00:15:20.087 --> 00:15:24.003
00:15:24.023 --> 00:15:27.674
00:15:27.674 --> 00:15:37.014
00:15:37.014 --> 00:15:45.791
00:15:45.791 --> 00:15:47.635
00:15:47.635 --> 00:16:16.078
00:16:16.078 --> 00:16:24.216
00:16:24.216 --> 00:16:33.519
00:16:34.528 --> 00:16:36.034
00:16:36.034 --> 00:16:38.566
00:16:38.566 --> 00:16:48.634
00:16:49.054 --> 00:16:49.615
00:16:49.716 --> 00:17:00.936
00:17:01.586 --> 00:17:07.267
00:17:07.267 --> 00:17:10.395
00:17:10.924 --> 00:17:29.565
00:17:29.565 --> 00:17:51.915
00:17:51.915 --> 00:18:03.659
00:18:04.266 --> 00:18:07.093
00:18:07.093 --> 00:18:08.836
00:18:10.424 --> 00:18:22.800
00:18:22.800 --> 00:18:26.836
00:18:26.836 --> 00:18:39.212
00:18:39.314 --> 00:18:43.412
00:18:44.535 --> 00:18:58.298
00:18:58.298 --> 00:19:20.076
00:19:20.076 --> 00:19:24.682
00:19:24.682 --> 00:19:27.088
00:19:27.088 --> 00:19:30.837
00:19:30.837 --> 00:19:35.317
00:19:36.005 --> 00:19:39.255
00:19:39.255 --> 00:19:52.356
00:19:52.416 --> 00:20:02.954
00:20:02.954 --> 00:20:03.576
00:20:04.317 --> 00:20:08.496
00:20:09.819 --> 00:20:12.589
00:20:12.589 --> 00:20:17.185
00:20:17.185 --> 00:20:23.058
00:20:23.058 --> 00:20:32.853
00:20:32.853 --> 00:20:42.913
00:20:42.913 --> 00:20:45.138
00:20:45.138 --> 00:20:58.218
00:20:58.218 --> 00:21:00.353
00:21:00.353 --> 00:21:06.738
00:21:06.738 --> 00:21:13.198
00:21:13.239 --> 00:21:13.578
00:21:13.785 --> 00:21:15.030
00:21:15.030 --> 00:21:16.771
00:21:16.771 --> 00:21:26.314
00:21:26.314 --> 00:21:38.487
00:21:38.487 --> 00:21:44.267
00:21:44.467 --> 00:21:48.718
00:21:48.718 --> 00:21:52.465
00:21:52.465 --> 00:21:54.834
00:21:55.134 --> 00:21:58.846
00:21:58.846 --> 00:22:07.494
00:22:07.555 --> 00:22:22.490
00:22:22.490 --> 00:22:32.836
00:22:32.836 --> 00:22:38.179
00:22:38.239 --> 00:22:39.179
00:22:39.179 --> 00:22:52.894
00:22:52.894 --> 00:23:02.554
00:23:02.554 --> 00:23:08.346
00:23:08.788 --> 00:23:18.809
00:23:18.809 --> 00:23:27.362
00:23:27.362 --> 00:23:50.968
00:23:50.968 --> 00:24:03.852
00:24:03.852 --> 00:24:11.886
00:24:12.361 --> 00:24:29.614
00:24:29.614 --> 00:24:30.234
00:24:30.315 --> 00:24:31.737
00:24:31.737 --> 00:24:45.537
00:24:45.537 --> 00:24:48.142
00:24:48.142 --> 00:24:52.772
00:24:55.641 --> 00:25:21.319
00:25:21.319 --> 00:25:30.884
00:25:30.923 --> 00:25:31.346
00:25:31.346 --> 00:25:47.307
00:25:47.307 --> 00:25:52.034
00:25:52.355 --> 00:25:53.195
00:25:53.641 --> 00:25:53.983
00:25:54.065 --> 00:25:54.185
00:25:54.185 --> 00:25:55.598
00:25:55.598 --> 00:25:58.567
00:25:58.567 --> 00:25:59.790
00:25:59.790 --> 00:26:03.308
00:26:03.308 --> 00:26:04.560
00:26:04.560 --> 00:26:06.602
00:26:06.602 --> 00:26:09.183
00:26:09.183 --> 00:26:13.586
00:26:13.646 --> 00:26:14.326
00:26:14.647 --> 00:26:26.035
00:26:26.035 --> 00:26:29.397
00:26:29.397 --> 00:26:39.306
00:26:39.306 --> 00:26:43.433
00:26:43.921 --> 00:27:07.464
00:27:07.464 --> 00:27:15.782
00:27:15.782 --> 00:27:28.549
00:27:29.140 --> 00:27:32.106
00:27:32.106 --> 00:27:40.580
00:27:40.580 --> 00:28:12.411
00:28:12.411 --> 00:28:17.372
00:28:17.372 --> 00:28:35.477
00:28:35.941 --> 00:28:45.839
00:28:45.839 --> 00:28:51.173
00:28:51.560 --> 00:29:00.566
00:29:00.566 --> 00:29:12.819
00:29:12.819 --> 00:29:18.231
00:29:18.231 --> 00:29:22.951
00:29:22.951 --> 00:29:23.893
00:29:23.893 --> 00:29:28.365
00:29:28.365 --> 00:29:36.210
00:29:36.210 --> 00:29:48.165