Episode 51: In Search of Outbreaks

Karie Dozer [00:00:04] If West Nile virus has a season, this is it. Welcome to TGen Talks. I'm Karie Dozer. The end of summer in Arizona, as in many places, is hot and humid, and it's the perfect environment for the spread of West Nile virus. On this episode of TGen Talks, we meet a new member of the research team whose specialty includes the study of West Nile and the mosquitoes that carry it. At the same time, this researcher is tracking COVID 19 and its spread through our communities using wastewater samples and some pretty unique methodology. For this episode of TGen Talks. We are at TGen North in Flagstaff, Arizona, and we're meeting a fairly new member of the research team here, Dr. Crystal Hepp. Tell me a little bit about your background and how it is that you came to work for teaching.

Dr. Crystal Hepp [00:00:56] So my background is really in understanding how different pathogens move over time in space and through different populations. And we've really focused the past few years, or since about 2015, heavily in RNA viruses, so West Nile virus, more recently coronaviruses, but also Saint Louis encephalitis virus. And I suppose the reason that I came to TGen is just because there is such a translational component to the research that I've already been working on in the past few years, that it really made sense for me to work with this team who's already doing so many other translational things.

Karie Dozer [00:01:29] So you've been a big part of TGen’s COVID research, but from a slightly different perspective. Tell me what it is that you study. 

Dr. Crystal Hepp [00:01:36] Well, a few different things. We have we have several different projects going on. And one of them is looking for COVID in students in different school districts, as well as individuals in long term care facilities to try to help those agencies, institutions monitor their situational awareness of COVID over time and space. But then also, we've been working on wastewater studies since March of 2020, and we already had several partnerships in place to allow us to access different wastewater sites. And so since the very beginning, we've been looking for COVID and providing information to our county partners, local partners, state partners.

Karie Dozer [00:02:14] How do you conduct that research? You obviously lab based and wastewater is not in the lab. How does that research take place?

Dr. Crystal Hepp [00:02:21] Yeah, we have several different partners and I suppose I'll focus on the first partners which have been the city of Flagstaff. We actually have a wastewater dashboard that's a collaboration between the city of Flagstaff, Coconino County Health Services and TGen. So with the city, what we do is we go out to the wastewater treatment plants once weekly and they provide us samples from their influent, and then we bring those samples back to the lab and test them here, but with the different sites. So for example, congregate living settings and different locations where you have a lot of people. We actually access the wastewater through different manholes and we've been using a more swab technique which in the past has been using a big strips of gauze that have been wound up together and secured by fishing line and angled into the wastewater flow.

Karie Dozer [00:03:10] So it's really low tech.

Dr. Crystal Hepp [00:03:11] All right. But we instead we didn't want to have to be bundling a bunch of gauze together. And so we use ultra-sized tampons and dangle that in the wastewater flow for 24 to 48 hours. Pull those samples out, bring those samples back to the lab. And so that's a really low-cost way for us to provide some important situational awareness to our community.

Karie Dozer [00:03:31] You probably never thought you'd be doing that.

Dr. Crystal Hepp [00:03:33] Never. Well, when it happened, especially with the wastewater, these different composite samplers that you can buy, they're $5,000 apiece. And we were sampling at so many different sites that it was not feasible at the time because different agencies were worried about budgets. There wasn't a lot of money available. So we really quickly had to think of what is a low cost way that we can still provide all this information.

Karie Dozer [00:03:58] Who came up with that?

Dr. Crystal Hepp [00:04:00] So actually back during the time of typhoid and it's I think the first publication was back in late 1930s, early 1940s, researchers would go out and instead of taking grab samples from the wastewater, which is just going out and grabbing a cup of the wastewater as it flows through, they wanted to get a more composite sample. And so having something that was sitting in the wastewater over time, picking up the sample like gauze was better than just these grab samples. And so and then we thought that we were the first to come up with the using tampons for collecting.

Karie Dozer [00:04:36] You got the bad news that someone else had thought.

Dr. Crystal Hepp [00:04:38] Somebody from the CDC, I think in the late eighties in Indonesia had used tampons to sample wastewater. So it had been done one other time, but it wasn't something that was widely used. But since we started doing it, there have been several institutions that we passed our protocols on to it. It's become a pretty widely used I wouldn't want to say technology, but technique.

Karie Dozer [00:05:02] What do you learn about COVID from wastewater? Why would it be important to study that virus after it's infected an individual?

Dr. Crystal Hepp [00:05:10] So we don't we're not really focusing on the individual level. It's more on the population level. So what we're not just getting presence absence. When we look at wastewater samples, we're actually getting a quantitative value. So an estimate of how much virus is circulating in the wastewater at any given point in time. And what we've seen is that this signal in wastewater really mirrors what we see in the number of human cases, sometimes several days and even weeks in advance of a surge, COVID surge. And so it can either give you such situational awareness at that exact time of what's going on in the population or even a week or two in advance so it can help our public health agencies prepare. Also, if you think about the transition that we've undergone, so we really, really were doing a lot of PCR testing, but a lot of people have transitioned to rapid testing and rapid testing is very useful for individuals to know if they're positive and make their own individual decisions. But it's harder to get a community level sort of situational awareness and wastewater doesn't care. 

Karie Dozer [00:06:14] Doesn't discriminate.

Dr. Crystal Hepp [00:06:15] It does important. 

Karie Dozer [00:06:16] For you.

Dr. Crystal Hepp [00:06:16] Your reports for you. So it's pretty unbiased and that's what we're reporting out.

Karie Dozer [00:06:21] What is your research showing you about wastewater after it's been treated? Is it safe? Is it clean of COVID and other viruses?

Dr. Crystal Hepp [00:06:29] Yeah, so well, especially of COVID and other RNA viruses, because they tend to be very sensitive. And these quality control process processes that the different wastewater treatment plants have in place, they really do completely remove the virus from from the wastewater. We can't detect any RNA after the wastewater treatment process. 

Karie Dozer [00:06:48] Like most researchers at teach and you don't just do one thing so you're not just looking at COVID in wastewater, what else is on your plate?

Dr. Crystal Hepp [00:06:56] So our other big project that we have going on, we do have another one that's kind of gearing up right now. But the other big project that we have going on right now and that started back in 2016 has to do with West Nile virus. So we've been working with several different vector control agency is primarily and starting with Maricopa County Vector Control. But now we are also working with agencies in Yuma, different parts of California and Nevada, Utah, to really understand how West Nile virus is circulating over time in space. And if there are hotspots, regional hotspots, local hotspots, because if you can understand where hotspots are, then you can apply different interventions to try to drive down the virus before it spills over into humans.

Karie Dozer [00:07:40] How do you study that incidence? It's so seasonal. Does West Nile occur anywhere else? Is it purely mosquito borne and therefore fairly seasonal?

Dr. Crystal Hepp [00:07:48] Yeah, it's it definitely exists primarily in it this enzymatic cycle. And what that is in this case is circulation primarily between birds and mosquitoes. So birds, they develop a really high level of virus in their in their bloodstream, so that if an infected bird was to get bit by and an infected mosquito, then the mosquito could become infected. And so it keeps that cycle going. But occasionally they're an infected mosquito or bite a human. That human doesn't develop a super high level of viremia, even though they might get really sick. So an uninfected mosquito could not come in and get infected from a human. It has to be from a bird or another animal that would develop really high levels of viremia.

Karie Dozer [00:08:32] This is the first time I've ever it's ever occurred to me that a mosquito bites a bird. I just thought of mosquitoes that humans do. Kilos bite all animals.

Dr. Crystal Hepp [00:08:40] They do bite a lot of animals. But the culex mosquitoes in Maricopa County, especially, that transmit West Nile virus, they definitely prefer birds. So different mosquitoes have preferences for different blood meal types. Aedes aegypti, the one the mosquitoes that transmit Zika, dengue, yellow fever, they have a preference for human blood, whereas the mosquitoes in Maricopa County that we're worried about with West Nile, they have a strong preference for bird blood.

Karie Dozer [00:09:08] How many different kinds of mosquitoes are there? 

Dr. Crystal Hepp [00:09:10] No, I know. I know about the ones that we're working with. But, you know, globally, there are just so many different types of mosquitoes. You know, you've got mosquitoes, Anopheles, Gambia, that are transmitting malaria. You've got Aedes aegypti, and it is albopictus that are going to be transmitting Zika, dengue and those things. And then typically the Culex family. So in Maricopa County is culex chrysalis and Culex quinquefasciatus.

Karie Dozer [00:09:33] And it's quite a name.

Dr. Crystal Hepp [00:09:34] For a mosquito. Sure is. But those are the ones we really focus on in the Southwest.

Karie Dozer [00:09:39] What's the hope with West Nile? Obviously, you want to see trends and you want people to prevent the bite. Is that the best hope or is there do you have hopes that your research will lead to a better prevention or a better cure? 

Dr. Crystal Hepp [00:09:54] So prevention is really the game that we're in. And just focusing again on Maricopa County, where we've had our sort of longest standing study, we found that in Maricopa County, the endemic population of West Nile virus, there is the longing longest standing population of West Nile virus in any county in the United States. So. Right, yeah, it's a really important place. But also what we're seeing from previous years is that there's a lot of spillover from West Nile of West Nile in Maricopa County to different counties in the southwestern United States. So that means that the West Nile virus in Maricopa County is not just important for the public health of Arizona citizens, but also for many other places in the Southwest. And what we're trying to do is I. Identify hot spot locations where you could go in, for example, where our vector control agency partners might be able to go in, apply early season interventions like Larvicide to drive down that mosquito population in these hotspot areas before it before it spills over into humans.

Karie Dozer [00:10:58] You just recently were the first author of a paper on West Nile. What was the finding and what was the research that led up to it?

Dr. Crystal Hepp [00:11:06] So that study was the big takeaway from that study is that Maricopa County does not continuously have importations of West Nile virus from other locations in the United States. It does occasionally, but those tend to fizzle out. What we really found is that for a long period of time and now it's for the past decade we have had a single importation that happened about a decade ago that keeps reemerging every year. And so in Maricopa County then, it's not typically a matter of if, it's a matter of when the reemergence is going to happen. So that was a big finding for us. It helps you think about, okay, so we're not we're not worry so, so worried about importation from other locations. But we really need to think about how to handle our own environment because we know that it's there and it's probably going to keep reemerging year after year.

Karie Dozer [00:11:56] When you talk about an importation of West Nile, you're talking about a different strain of the same virus.

Dr. Crystal Hepp [00:12:01] Well, so yes, so different strain of the same virus. West Nile entered the United States probably in 1998 and was first detected in 1999 and came across the Atlantic.

Karie Dozer [00:12:12] So it's relatively new.

Dr. Crystal Hepp [00:12:13] It's relatively new, yeah. So it was first detected in New York back in 1999, and within four or five years, for about five years, it made its way all the way across the United States to every single state because of the presence of these culex mosquitoes that were already in place. But then with Maricopa County, what we found is that it's stuck. It is not it's not dying out every year because of the permissive environment.

Karie Dozer [00:12:41] So just like a lot of people who moved to Maricopa County, they liked it and they stayed.

Dr. Crystal Hepp [00:12:45] Yet people like Maricopa County. 

Karie Dozer [00:12:46] It's a friendly West Nile environment.

Dr. Crystal Hepp [00:12:48] It is. 

Karie Dozer [00:12:50] So what next? Do you continue your research along that same set of questions? Do you move on to another set of questions? What's next.

Dr. Crystal Hepp [00:12:58] For you? Yeah. So what we're what we're starting at now is we are trying to do more real time genomic surveillance, because what we find is with the West Nile virus genomes, the diversity that accumulates in the virus, it accumulates faster than mosquitoes get infected or than human cases occur. So it happens before. So we think that we're getting about four weeks where we're seeing the virus, the virus population increase in size, four weeks before we see an increase in mosquito counts or human cases. And so understanding when the virus is increasing, the environment can give you an estimate of risk of spillover, which can allow for triggering the public to. Okay, you need to be taking these steps to prevent yourself from getting bit, to make your backyard a little less friendly to these different mosquitoes, to try to prevent the spillover of human cases. It gives us time to implement interventions.

Karie Dozer [00:13:58] What have I missed? I've asked you about two big areas of study. Is there anything else you're looking into or plan to or want to? You're a teacher.

Dr. Crystal Hepp [00:14:06] Yeah. So we have one study that we are planning out with a large group of folks to look for coronaviruses in different animal populations. It's important for us to understand which populations might be able to be reservoir species so that we can expect so that we can try to start estimating when we might see spillover back into humans or if there would even be spillover back into humans. But first we have to identify those reservoir species. And so we have a study plans that that we're going to kick off here pretty soon.

Karie Dozer [00:14:39] It sounds like you've done about three years of work and you've only been here for six weeks. Yeah. Is the pace of work at T Gen that the way it is?

Dr. Crystal Hepp [00:14:46] That is the way that my group has always existed. So, yeah, we've. We keep busy 

Karie Dozer [00:14:52] All right. If I could give you more hours in the day, I would. It sounds like you're on to some exciting stuff. Thanks for taking the time, considering how busy you are, I think shared it.

Dr. Crystal Hepp [00:15:00] Thanks.

Karie Dozer [00:15:01] 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.