Episode 50: The World of Pathogens

Karie Dozer [00:00:04] I'm Karie Dozer, and this is TGen Talks. When you hear the word detective, you probably think of a crime scene officer searching for clues and ultimately an answer to the question, what happened here? But when the mystery is something physical, something medical, signs and symptoms of a little-known disease teach. And scientists are hard at work. They're like disease detectives. They study the sometimes strange and often little-known ailments that plague those who live in the desert southwest. This episode of TGen Talks brings us to TGen North. It sure is a nice time of year to be up here. And we're talking with Dave Engelthaler. He's the director of the Pathogen and Microbiome Division up here in Flagstaff. Thanks again for joining us. You're a regular guest. I appreciate it.

Dr. David Engelthaler [00:00:53] Yeah, it's good to see you again, Karie.

Karie Dozer [00:00:55] For people who are listening, who don't know that TGen has a TGen North location, tell me a little bit about who works here, how big you are and what you're looking into in general.

Dr. David Engelthaler [00:01:03] Sure. TGen North is essentially our division of infectious diseases, what we call the pathogen and microbiome division. So we do all the same great science that the rest of TGen does, except we're looking at the genomics of pathogens, including bacteria, viruses, fungus. And so the group up here is really focused on infectious diseases and supporting public health, as well as supporting health care and our doctors and nurses to try to take care of patients.

Karie Dozer [00:01:32] Do most of your staff members, your researchers, do they work on more than one thing at a time?

Dr. David Engelthaler [00:01:37] As you can imagine, in when we work in infectious diseases, we work on pretty much everything that that is important. We jumped in, as we all know, and did a lot of work during COVID. But prior to that, you know, we'd been working on valley fever and tuberculosis and hospital acquired infections, other viruses that may be shared in the environment, mosquito borne diseases and the like. So there's no one specialty up here. We do work on a wide variety of pathogens.

Karie Dozer [00:02:07] Let's talk Valley fever. It's something that I feel like everyone in Arizona is aware of. They've heard of it. They know somebody who had Valley fever with a poor outcome. It's tough. What are you looking into at TGen North? What kind of data do you gather and what do you do with it?

Dr. David Engelthaler [00:02:23] Well, so first of all, obviously, Valley fever is critically important for Arizona and much of the southwest. We see it as Arizona's disease. That's why we spend so much time on it. So actually, one of the first things that we started working on 15 years ago when we opened TGen North, but we really try to apply all the different tools and technologies from a variety of areas, develop better diagnostic tools, help develop new treatments. We've worked on that in the past, develop ways to understand how the fungus survives in the environment, how it moves around, and now, more importantly, how are people getting infected? That's an area that we've been focused on a lot.

Karie Dozer [00:03:02] It seems like there's not a lot of treatment options. It doesn't people have a hard time being diagnosed with valley fever and once they're diagnosed, they don't know what to do about it. Does the research that you're doing here help to that end?

Dr. David Engelthaler [00:03:15] Yeah, that valley fever being caused by a fungus that survives in the environment that people breathe in makes it harder to actually treat. In the end, all fungal diseases are more difficult with valley fever. There are a few decent treatment options, but those treatments are a bit toxic to people. Humans genomically are more related to fungus than we are to say bacteria and other things that we can kill with really good antibiotics. So the treatments we have are not perfect. And we have helped in the past to try to improve those. Look at different small molecules and chemical compounds that actually are really good at killing the fungus. We don't have a large active program in that right now, but we're working with a number of groups that do.

Karie Dozer [00:04:03] You mentioned a term earlier called Cox's Watch.

Dr. David Engelthaler [00:04:06] Yeah, Cox Watches is based off of actually something that we have referred to as Bio Watch, which is really the use of air filters to monitor, to look for, you know, potential pathogens that may be airborne. Well, valley fever, probably the most important airborne pathogen that we have. And in Arizona. And what we've been wanting to do is try to understand how much fungus is actually floating around in the air and are there times of the year that it's more important or are there weather patterns that will make it a higher risk for individuals? So we are looking at dozens of air filters collected on a daily basis throughout over cross multiple years and doing all of that analysis, tying it to weather data, tying it to human case data, tying it to cases in dogs. Try to understand if we can develop a predictive model that could be essentially like an early warning system to let people know. Yeah. We also know when we have high. Pollution in the air. Right. We should know. When do we have high amounts of the toxic fungus in the air?

Karie Dozer [00:05:08] Does Valley Fever have a season?

Dr. David Engelthaler [00:05:11] Valley fever is known to be seasonal. But what we've also seen is that there are cases throughout the year. It's not strictly relegated to one time of the year. But our monsoon time is thought of as an important early environmental indicator. When we might start seeing cases, we get more rainfall that probably increases fungal growth to the point that you can actually get more fungal spores getting up into the air and spreading. But we haven't proven that yet because no one has ever looked in the air for this fungus, strangely enough. That's what we're doing now with Cox's watch. 

Karie Dozer [00:05:48] What else are you looking into that affects us here in the Southwest Desert?

Dr. David Engelthaler [00:05:52] We're, you know, we do try to be international and think about the important infectious diseases. But we absolutely have to be thinking about our backyard. And what is going on in Arizona. Valley Fevers is we consider Arizona's disease. One of the other ones that we think about, obviously, is West Nile virus. We just brought on a great faculty member to TGen North in Dr. Crystal Hepp, and her team is focused on that. We are working with our different tribal nations. We're working with the hospitals to understand what is most important to them and how can we apply the tools to support their specific needs. Rural Arizona has vastly different concerns and problems than, say, more urban Phenix in Tucson areas.

Karie Dozer [00:06:41] When we run down the list of things that TGen North is looking into, Cryptococcus comes up. That just sounds scary. What is it and how prevalent is it?

Dr. David Engelthaler [00:06:49] Cryptococcus is another one of these fungal diseases. It's a fungus that we knew for a long time survive primarily in the tropics and could get in the air and infect people. But mostly it's just living in the environment and not affecting people. But then we've also seen that there's a type a strain of this cryptococcus ah that got up into the Pacific Northwest, which is very not tropical and so seem to be inhabiting a different area and then started causing a significant number of deaths up in Vancouver and in Washington, even in Oregon. So that was an area that we spent a lot of time working with CDC to understand what was going on with this fungus. How did it change? Why is it up there? And now, just in the past couple of years, we've been seeing cases of Cryptococcus locally here in Arizona that had no travel to either Brazil or to the Pacific Northwest. And we've just recently identified that this is this new strain is certainly here in Arizona. We don't know exactly where we've seen it in southern Arizona, but we're studying it really closely. So it's this is all kind of emerging infectious disease work that we're hot on the trail.

Karie Dozer [00:07:58] Most people wouldn't know that that's what they have. And I imagine most doctors don't haven't ever seen it. How do you find it when you say you've discovered cases? Where do they come from? 

Dr. David Engelthaler [00:08:07] Yeah, the technology to look for different pathogens has really increased in our in our hospitals and the clinical laboratories that they use. But they don't know exactly what strain of something they can they're looking at so they can identify cryptococcus. It's a fungal disease. It's typically causing a respiratory illness sometimes can cause a neurologic disease, but they can grow a fungus out of a patient sample. Those are the samples that have been sent to us because they know that we're we have a lot of expertise in this area and we've identified there's clearly a strain that is seems to be specific to Arizona or the Southwest. And we're only talking about a handful of cases. So not to be alarmist on this, we don't know how widespread it is or how hard it is to get, but it is certainly emerging in our understanding.

Karie Dozer [00:08:54] It makes your team sound like a little bit like detectives. A doctor sees something they don't know what to call, what to name, and eventually it rises to the level of TJ and North who finally gives it a name? Is that how it works?

Dr. David Engelthaler [00:09:07] Yeah. Well, we're not naming these, per se. We do work with the international community when a new pathogen is identified. But, yeah, your point about being detectives is absolutely the case. That's what an epidemiologist is, is a disease detective. We're essentially genomic based detectives. We can apply all this technology to help understand on a level that we've never been able to before. So that's how we're able to determine. Yeah, there's a brand new what some people are calling a brand new species. We don't know if it's a brand new species, but it certainly is distinct from all other cryptococcus that we're seeing and we're trying to understand where does it live? How quickly does it change so that it can adapt to an environment like the Southwest, who's at risk from being infected? All of these questions we don't know yet, but we're certainly put on our detective caps right now.

Karie Dozer [00:09:59] Does the international research community have a top ten list like a. FBI most wanted. I mean, does that exist?

Dr. David Engelthaler [00:10:06] Well, it does exist in some cases. I mean, the W.H.O. certainly has its top urgent threats. Infectious disease threats around the world. And in this is not on it. But actually, there's another type of cryptococcus that's commonly found in Africa where there's a lot of HIV cases and tuberculosis cases. And the combination of those three is one of the most important health conditions in the world. So it's not an unknown fungus to us. It's just was previously unknown to be here in Arizona.

Karie Dozer [00:10:36] You mentioned tuberculosis, which I think most listeners think of as a little passé. What is the incidence of tuberculosis and what is it that you're looking into, T.J.?

Dr. David Engelthaler [00:10:47] Yeah. Aside from this past two years of COVID. Tuberculosis is the number one infectious disease killer in the world and has been for a while. I mean, essentially, somebody dies every 20 seconds from tuberculosis. Really? Yeah. It is that important and it's that prevalent. We think about one third of the world's population is infected with tuberculosis. Now, most of these people are getting sick from it. Are they carrying around what we call a latent stage in their lungs? And it's kind of walled off. But if you get, you know, immune suppressed somehow or going through some disease condition, tuberculosis could also break out in you have a really, really bad infection, but it is mostly seen everywhere. But here we do have cases in Arizona. It is important when we see it so that it doesn't become drug resistant and doesn't become untreatable like it has in some parts of the world. We're seeing some countries see what we call extremely drug resistant. So it's resistant to most drugs that are out there and even pan drug resistant. It's resistant to every drug out there. And those people have to be essentially locked away in isolation because there's no way to treat them. We can't have them infecting other individuals. So it's a it is a really bad disease that we're still battling. But what TGen is doing is applying technology that allows us to have an essentially an early warning system for when drug resistance is starting to develop. So then you could switch the drug combination and give the doctors that ability to actually treat and cure their patients before they become resistant.

Karie Dozer [00:12:21] It sounds like with all of these scary sounding things that you look into at T Gen North that none of your team would go outside. How do you all look at these pathogens? Because you know so much about them. Are you more or less aware? And I would say scared is the wrong word. Are you more or less frightened by them?

Dr. David Engelthaler [00:12:41] Yeah, I you know, I think it would be tough to work here if you were a germaphobe. And some people are naturally. And that is and if you have that fear it, we'd have to get past it, because we do have to work with some of the more dangerous microbes out there. But we also are really public health minded and understand this on a population level and understand what the risks are. And so, you know, that is the that gives us the mission of the importance of this work that we're trying to do. So that helps overcome, you know, maybe some fears that people may have because we're doing such amazing work to support the overall population. We work with doctors and help them with individual patients, but we're also thinking about the whole population. And so that sense of mission gives that kind of sense of duty, which is, you know, makes it I think it makes it a lot easier to work here.

Karie Dozer [00:13:37] To that end, you you're very involved in an effort called the Pathogen Intelligence Center, something you're creating. Tell me what it is, how the regular person could access it and what they might find.

Dr. David Engelthaler [00:13:49] Yeah. So pathogen intelligence is a is a phrase that we came up with to really understand what it is that we're trying to do. We're trying to gain intel on these pathogens, and the best intel we can get is in their genetic material. So a lot of that means sequencing DNA or RNA of these organisms. And we can understand who's more related to who. We can understand when outbreaks are occurring, where outbreaks are occurring. We can see if something is drug resistant or may have a virulence gene that makes it more dangerous. All of this information comes out of the genomics. A lot of things we just had to guess about before. We can do that now. And for us, it's important to make this data available to our public health partners, to our health care partners, as well as to the general public. During COVID, everybody was tracking numbers. We were we were tracking the variants across the state since the beginning of the pandemic and making all that information publicly available. So there is a certain sense of power that individuals have when they have knowledge, they know more about it. They know what the better, what the risks are, what we should and shouldn't do when we get this information. So we're trying to make that information more accessible in a. Bailable. It's not this very complex genomic data, but bringing it to the point where it's we can visualize it and make it relevant to individuals. So we do have a website Pathogen Dash Intelligence Board where we're posting a lot of this, but we're also making some parts of that is early warning reports so that the local health officials can actually see what is happening today with some of these pathogens in our state.

Karie Dozer [00:15:30] How far away do you think we are from having something like a high pollution advisory that goes out to the general public? We get dust storm warnings. We get monsoon warnings on our phones. How are we close to that? Will that will that day come?

Dr. David Engelthaler [00:15:44] Yeah, no, I think it will. You know, so like, for instance, the Cox's watch, the Valley Fever Alert system, that's not available yet because we're still learning about what is important and what is actually predictive of a higher risk. But we do know that, like when with wastewater testing, where we were able to identify the SARS-CoV-2 virus in wastewater before cases were showing up. And so we know that that provides maybe a week to two weeks early warning that this is in our community. And so that is something that we are making, trying to make it available as real time as possible. So we have these dashboards that show this information. We're starting to look at other viruses in the wastewater. We'll probably be looking at other stuff in the air or what we're finding in our health care system and trying to make that is closer to real time available as possible so that it is kind of that warning system like you were talking about.

Karie Dozer [00:16:36] Awesome. Good information. Thanks so much again for your time.

Dr. David Engelthaler [00:16:39] Yeah, thank you, Karie.

Karie Dozer [00:16:41] For more on TGen’s research, go to TGen dot org, slash news. The Translational Genomics Research Institute, part of City of Hope, is an Arizona based nonprofit medical research institution dedicated to conducting groundbreaking research with life changing results. You can find more of these podcasts at TGen dot org, slash TGen Talks, Apple and Spotify and most podcast platforms. For TGen Talks, I'm Karie Dozer.