Toxins and early heart damage; why bees matter; fighting the dengue virus: Upstate Medical University's HealthLInk on Air for Sunday, Sept. 10, 2023

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," a public health researcher shares a study linking early heart damage in children to toxins in the environment.

Brooks Gump, PhD: ... It's not so much "if" we're exposed, it's how much and how much is enough to actually find detrimental effects. ...

Host Amber Smith: A sustainability manager talks about bees and other pollinators.

Paul Corsi: ... If we lose pollinators or pollinator populations decline, we're talking a huge impact on agriculture, on our ecosystems. And that has a huge impact on public health. ...

Host Amber Smith: And an infectious disease expert provides an overview of the threat of dengue virus.

Stephen Thomas, MD: ... What happens is you get someone who's sick with dengue, and they've got the virus replicating in their blood, and then the mosquito feeds on them. They get infected, and then they go feed on somebody else. And then they infect that person. ...

Host Amber Smith: All that, plus a visit from the Healing Muse, right after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith.

On this week's show, we'll hear about efforts to support bees and other pollinators. Then, we'll get an overview of dengue virus and research taking place in Syracuse. But first, a researcher found that children exposed to environmental toxins develop cardiac damage at an early age.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

High levels of toxic chemicals in children who are exposed to lead and arsenic leads to early cardiovascular disease, according to research conducted in Syracuse. My guest today is Brooks Gump, a professor from SU who led the study.

He's from the department of public health in the Falk College at Syracuse University.

Welcome back to "HealthLink on Air," Dr. Gump.

Brooks Gump, PhD: Thanks, Amber. Good morning. Thanks for having me.

Host Amber Smith: What made you want to investigate what toxic chemicals are doing to children in our community?

Brooks Gump, PhD: We've been doing this research for over 20 years. We started in Oswego. Actually, my background is in just general cardiovascular disease risks in children. When I first arrived at Oswego, they were doing work on PCBs (polychlorinated biphenyls, a group of chemicals banned since 1979), and so we looked at their cohort, the Oswego cohort, and looked at lead levels and saw some differences in the way the kids were reacting to stress.

We found that in Oswego. And then, the arsenic was an offshoot of a bigger study that we did in Syracuse more recently, where we were looking again at lead and how children react to stress. But we also had arsenic levels that we had collected. So we looked at the same kind of outcomes, cardiovascular disease risks in children, but in this case, with arsenic.

Host Amber Smith: So how did you structure your study?

Brooks Gump, PhD: It was designed to be half African American, half Anglo-American (white) children, in Syracuse city, so we selected ZIP codes that had elevated levels of lead. Also, relatively equal numbers of racial distribution, and so that ended up somewhat in the South Side and some of the ZIP code areas in that. We ended up actually expanding because we had such a difficult time with recruitment.

So we got more Syracuse urban area in general, and we also, in terms of what else, other selection, was 9- to 11-year-old children. The reason for that is because most of our research in the past has been that it's an age group where they're able to do the testing that we want, but they're generally prepubertal so that we're not looking at some of the other, more complex, changes that can happen after puberty.

So, we haven't actually done this kind of work with adults or specifically with toxicants. The outcomes that we looked at, which are reactions to stress, that's kind of a standard approach to looking at that risk factor in adults and children. So, we took some basic procedures that are pretty common in the field, in the cardiovascular field, but not common in the toxicology field, and we applied it to the toxicology.

So, most of the toxicologists at the time didn't really understand how you could study actual reactions to stress. They were working with rats and whatnot, but there are ethical ways to do the research we do.

Host Amber Smith: And this was conducted long term, over several years. Is that right?

Brooks Gump, PhD: No, actually, in this case, it was a cross-sectional study, so we were engaged in recruitment for five years, but those children were all recruited, 9-, 10- and 11-year-olds, throughout those five years. It essentially spans a number of specific ages, but a number of years.

We haven't followed them up yet. It's all been cross-sectional so far. Which does raise all the issues that you need to consider when you do see associations in a cross-sectional study. But we are trying to recruit, re-enroll, I should say, those children that helped us out so much in the past, in new studies as they age.

But no, so far, we have not yet completed a longitudinal part.

Host Amber Smith: So what was the commitment from the families and the children who participated in this? What did they do?

Brooks Gump, PhD: Well, it was a lot, and we really appreciate what they did. The children had a venipuncture. So for a 9-, 10-, 11-year-old, that's a big deal. So these are children that were willing to do that.

And then also collected a number of testing measures in our lab for a couple hours. Then they also went to a local cardiologist, Dr. Nader Atallah-Yunes. a pediatric cardiologist in Syracuse, and he did echocardiograms for all these children.

In addition to that, we had another lab on campus. Dr. (Kevin) Heffernan runs an exercise physiology lab, and he did some of the measures of thevasculature (blood vessels) and how the vasculature in the body is changing.

Host Amber Smith: You said "venipuncture." That's like a blood draw, taking blood samples, right?

Brooks Gump, PhD: Right. It's not the finger stick that sometimes you see with lead because we needed to, well, we wanted to, look at a number of chemicals. So, although it wasn't, (in) quantity, very much blood, we had about eight or nine tubes of blood for all different exposures.

Host Amber Smith: So what did you think you might find, and what did you find?

Brooks Gump, PhD: Well, we've been exploring, and we have a new paper coming out in a couple of months on it. What we're exploring is how to classify these toxicants in general as cardiovascular disrupters. Just as there's endocrine disrupters that you hear about in the (medical) literature and the press, we think that also some classes of chemicals fall more into the cardiovascular disrupter category.

So the neuroendocrine system, the stress response system, involves both the endocrine and catecholamines, the adrenaline, noradrenaline, things like that, that you react to, but it also involves all the cardiovascular side to things in the vasculature -- constricting, increasing your blood pressure, all those things.

And those are intertwined, those two systems, but we think some of these toxicants are essentially targeting the cardiovascular side to that system, increasing vascular resistance and things like that. So, we think lead for sure is a cardiovascular disrupter. We're looking at perfluoro chemicals, PFAS (per- and polyfluoroalkyl substances), and looking at that as a cardiovascular disrupter. And arsenic is another that's been shown in the past.

But most associations are these overall associations with disease in adults. What we're trying to find is how these chemicals affect the reactions and the underlying processes that lead to that disease way down the line, so children that don't have disease per se, but they're reacting more to stress in their cardiovascular system, which is damaging to that system and ultimately could lead to heart disease.

Host Amber Smith: Well, in addition to the cardiovascular, what did you find with sleep disorders and behavioral issues?

Brooks Gump, PhD: Some of those were with other chemicals, so arsenic wasn't associated with those. We did find some behavioral disorders, and this has been shown before with lead, so, conduct disorders. We also, in the past, in the Oswego cohort we found impulsivity related to the PFAS, which are the toxicants that are in things like Teflon and Gore-Tex and Stainmaster carpets and wrappers on fast food, things like that, and those seem to increase impulsivity.

And the idea is all of this work showing these different things like sleep, we did with activity, actographs -- so, the children wore these kind of watches around for a week, so we could look at how much activity they had, but also how much they slept, and we looked at some of the effects of that sleep on their outcomes, cardiovascular disease.

So that study had nothing to do per se with toxicants actually, but it was just looking at what are the outcomes of poor sleep quality in terms of the cardiovascular system?

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith.

I'm talking with public health professor Brooks Gump from Syracuse University.

Let's talk about how kids are exposed to begin with and how common these chemical exposures are. How are kids exposed to lead and arsenic and mercury?

Brooks Gump, PhD:

There's a whole, essentially separate, field in the science where you look at the sources. So, most of our work to date has been looking at the effects. So we say, essentially, regardless of where they're getting it from, what effect does it have on the cardiovascular system?

But with the new study in Syracuse, we actually added Dr. Lynn Brann, who's a nutritionist, and so we're looking at all the foods they consume. We have another researcher at Upstate, actually he's a postdoc now, Dr. Dustin Hill. And he does some of the geographic mapping that we've looked at, to try to see, what's the distribution, to see if we can identify the sources.

So these chemicals, one of the facts you see is that the chemicals are widespread. So all of these children have PFAS. We looked at about 10 different types of PFAS chemicals, and some 100% of the kids had it in detectable levels. So, there's probably 50 to 100, at least, chemicals that are man-made that are circulating in most children and adults.

It's not so much "if" we're exposed, it's how much and how much is enough to actually find detrimental effects. So these these thresholds are critical, even though they're probably not hard thresholds, probably it just progressively get worse as you get more and more exposure.

So, zero is certainly nice, but that's unrealistic, so they establish thresholds that are more realistic. Like our work with lead, they cited that when they lowered the threshold for children from 10 micrograms per deciliter down to 5. They cited our findings showing that kids are reacting more to stress, even at very, very low levels of lead.

So that resulted in that reduction, which results in all kinds of remediation and other efforts to try to deal with it. So what you do is you essentially lower the threshold, and you create, in quotes, a "public health problem," which needs to then be addressed. If you have the threshold up higher, then everyone will say, "Oh, I'm fine," when in reality, they're not, they're just getting exposed at lower levels and smaller effects.

Host Amber Smith: So, what about the future for these kids who were in your study who already have cardiac damage? Are they having symptoms?

Brooks Gump, PhD: So, they don't have any clinical disease, meaning there are no symptoms.

And the thing with cardiovascular disease is, it develops very slowly. So, toddlers that are given autopsies because of accidental deaths, you can already see cardiovascular atherosclerosis, the disease process has already started even in the toddlers. And then they did some studies with casualties in Vietnam, and those young men and women had cardiovascular disease indicators as well, when you do the autopsy.

So, anyone who's prone to this disease, either genetically or because of their situation, is going to develop it very slowly from a very young age, so this is just one of those kind of pushes on that. So, if they're eating poor food, they're not exercising, those are also risk factors for eventual cardiovascular disease.

So, this is another in that line. What we found is just subtle changes, in their vascular thickness and some of the other things, and they're not irreversible. With healthy diet and healthy exercise -- there's some work by (widely published researcher) Dean Ornish looking at interventions -- I think the general consensus is that you can reverse some of these subclinical (hard to detect) indicators, subclinical changes, through other healthy behaviors or, of course, removing the problem, to the extent you can remove it, but it's difficult in this context, because we're not even sure where they're exactly getting the arsenic, for example. We believe right now it's in the soil. One hypothesis, we don't really know, one hypothesis is there's a lot of orchards in that area and there's lead arsenate, (which) would elevate both lead and arsenic in that soil in that area.

So, if you look at old maps of Syracuse and that South Side, in addition to the salt flats, there was also some orchards in that area, apple orchards, so that's another possible. It's kind of like forensics toxicology. We really don't know yet exactly where it's coming from. We do have some ongoing soil studies looking at old soil samples, and hopefully, that will give us some clues as to where it's coming from.

Host Amber Smith: Why is there arsenic in apple orchards?

Brooks Gump, PhD: It's a pesticide, so lead arsenate was sprayed on them to prevent this specific moth that was eating them. And I have pictures of these sprayings, without any protection. I mean, they heavily sprayed this lead arsenate.

Host Amber Smith: Well, what additional research would you like to do on this subject?

Brooks Gump, PhD: The one I'm most interested in right now is kind of a "food is medicine" approach. There's a colleague at SU, Sudha Raj, who does some work on food as medicine and Ayurvedic (traditional medicine of India) methods for reducing toxicants. I'd like to see if there's something that's natural and not harmful, so it doesn't have side effects, because their current methods for chelating and pulling out metals and toxicants frequently have side effects attached to them as well, so you're getting one substance replacing another.

So, if there's some natural dietary changes, even something as simple as drinking more water during the day, and we can start to look to see if there's something that people can do daily. Just as they're daily probably exposed to these toxicants, maybe they can be daily exposed to some foods that will remove the toxicants, is where we're hoping to head.

Host Amber Smith: You mentioned that you might want to do some more work involving the kids that were in this original study. What is that about? And where does that stand?

Brooks Gump, PhD: We recently got a grant, internal grant, from Syracuse University to try to reconnect with these children, or now young adults, so they'll be 18, 19, 20, and we're hoping that with their generosity, they might participate again, as we can do some more studies, more questions, kind of follow up, see where they're at, what they're doing, how they're feeling.

And so, if they want to contact me, that's at: [email protected]. I'm happy to receive emails and direct you to the research team and for any of those children or parents, because the parents also did a lot for our study. I should mention, I'm sorry, that parents were also bringing the children, filling out many, many questionnaires, things like that, so we're really grateful for all their work.

Host Amber Smith: Well, thank you for making time for this interview, Dr. Gump.

Brooks Gump, PhD: You're welcome, Amber. Thank you for having me.

Host Amber Smith: My guest has been Dr. Brooks Gump. He's a professor in public health at Syracuse University's Falk College.

I'm Amber Smith for Upstate's "HealthLink on Air."

Next on "HealthLink on Air," learn why and how to support bees and other pollinators.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Upstate's campus was designated a "Bee Campus USA" affiliate, but there's more to becoming part of this nationwide program than helping to conserve native pollinators. I'll talk about this with my guest, Paul Corsi, who is Upstate's sustainability manager.

Welcome to "HealthLink on Air," Mr. Corsi.

Paul Corsi: Thank you for having me.

Host Amber Smith: So Upstate committed to working to conserve bees by making the campus a better place for pollinators. What's involved in that?

Paul Corsi: There's three main strategies that we're approaching those with. The first is, we don't use any chemical pest or weed control on any of our properties. That's a really big thing that can harm, particularly, a lot of insects.

And then secondly, we're also looking at planting pollinator-friendly plants. A key is that, especially in a lot of manicured, landscaped areas by buildings, there can sometimes be a lack of habitat for particularly a lot of native pollinators. So, trying to find native plants, pollinator-friendly plants, that we can plant there, to provide that habitat and provide that food.

And finally, just doing a lot more education and outreach and volunteer opportunities for faculty, staff, students, the community. The more I learn about pollinators, it's harder to overemphasize how important they are for our health, our well-being, the stability of our ecosystem, the environment, et cetera.

Host Amber Smith: So what is the purpose of this Bee Campus USA?

Paul Corsi: Yeah. I want to clarify, too. I know that sometimes there's confusion. It's B E E. It's not the letter B, right? Some people ask me why we aren't an A campus, and I say, "No, it's the insect, right?" It's bee-focused, but it's really just about pollinators in general.

But the idea is that there's a lot of habitat loss. There's a lot of stress on these populations, andour food system, our environment, is heavily dependent on pollinators. So it's important, particularly for Upstate as an academic medical center, as a health care institution, that we protect these pollinators. Something like one out of every three vegetables or produce that we eat relies on pollinators. That percentage is a lot higher when we're talking about wildlife. So, if we lose pollinators or pollinator populations decline, we're talking a huge impact on agriculture, on our ecosystems. And that has a huge impact on public health.

Host Amber Smith: Do you know if our academic neighbors -- Syracuse University or SUNY College of Environmental Science and Forestry -- are they involved in anything like this as well?

Paul Corsi: Yeah. They're also both certified as "bee" campuses. In fact, they helped us a little bit with the application process, and I lean on some folks at ESF for the more technical details when it comes to what pollinators and what plants we're looking to plant here.

Host Amber Smith: Now you mentioned pollinators. The only one I know of are bees. What are other pollinators?

Paul Corsi: There's a ton. I mean a lot of birds, hummingbirds can be pollinators. Bats are pollinators. Sometimes small mammals are pollinators. And then, just within insects in general, I know when we're just talking about native bees, I think in New York State, there's something like 450 different native bee species. So there's an incredible diversity of pollinators out there.

And I think that's really the key. When we're talking about creating habitats that are pollinator friendly, it's all about diversity. There's no one plant or habitat or whatever that can be attractive or provide habitat or food to every type of species. So, it's about creating this diversity, this rich patchwork of different plants, animals, habitat spaces that can attract that diversity.

Host Amber Smith: And you're having to do that in, really, an urban environment. So what are the things, can you name anything specifically that attracts pollinators or something specifically that scares them away?

Paul Corsi: Sure. I think the big thing is, particularly for native bees, is a lot of folks don't realize that I think some 70% of native bee species are actually ground nesting. So they'll actually burrow and dig in the ground. So, having patches of dirt that you don't, like, till or mess around with all that much -- hugely important.

Another large segment of native bees really like to live in, like, dead wood. So, if you think, like, a standing dead tree, or even, like, a pile of branches on the ground or something. That's something that can be really attractive. So, a lot of it, we talk about like, this benign neglect. I like to think of it as just, like, a more creative landscaping. That's not about, or it's about acknowledging that sometimes these areas that we think of as, like, kind of messy, or, like, a dead branch on the ground or something like that, we think, like, "Oh, it's an eyesore." But it can really be a really beautiful and important part of the environment if we kind of let it be and leave it as a place for these pollinators to live.

Host Amber Smith: So, do the bees just find us, or do you have to go find a hive and try to move it onto the campus?

Paul Corsi: Oh, no. I mean, they're here. They're everywhere. They're pretty ubiquitous. So it's just about supporting the population that's already here. And also, as we think about, like, development and building new spaces and parking lots and all these other things, that we're kind of offsetting some of that development with some places that they can continue to live on.

Host Amber Smith: Can humans coexist with the bees without getting stung, though?

Paul Corsi: Oh, sure.

A lot of native bee species are not aggressive, and they don't sting. And then pollinators, generally we're talking about like butterflies and beetles and birds and all these other things. So, I can totally understand if you're anxious about being stung, maybe you can if you think about, like, making your own backyard a bit more pollinator friendly. Focus on birds or, like, butterfly-friendly plants if you're a little nervous about bees. But for the most part, a lot of native bees are perfectly safe and are not interested in you at all.

Host Amber Smith: So, with all of these bees here, will there be honey? Because bees naturally make honey, right?

Paul Corsi: Yeah. So, some bees. This is another really interesting point, too, that I think a lot of folks aren't aware of is that when we think of bees, we think of the honeybee. The honeybee is, really, kind of like a livestock, essentially. You know, it's like an agricultural animal almost. And a lot of native bees don't produce honey. They don't live in hives. They have very different life patterns or ways of being.

So, honeybees are really great. I know SU has some honey beehives, and maybe that's something we'll pursue in the future. But the benefits of having a robust native bee population, particularly when we're talking about pollinating and ecosystem health, are much greater when we're talking about these native bee species over honeybees.

Host Amber Smith: Have you seen bats near campus?

Paul Corsi: I have not. I live in the university neighborhood though, by SU (Syracuse University), and I definitely can see them sometimes around there, especially near, like, Barry Park or Thornden Park. They're around, for sure.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with Upstate's sustainability manager, Paul Corsi.

Now, sustainability is not just about saving bees. Can you talk about Upstate's broader sustainability goals?

Paul Corsi: Sure. Yeah. Sustainability is something that I think the healthcare industry in general has kind of gotten a pass on, particularly in recent years with COVID, right? We've had a lot of our plates. So maybe it's understandable.

But the pitch I always try to make to folks is that sustainability is health care, right? When we look at the great public health crisis of our time, climate change, when we look at pollution, pollution of water, the air quality that we've had, even in Syracuse, Upstate New York, over this past summer has been really bad, right? These are all massive public health issues.

So, sustainability is really about addressing those issues and understanding that if we're going to provide the highest quality care to patients, and if we're going to really protect public health, we need to provide care in a way that's not contributing to climate change or pollution, that we need to be more conscious of how much waste we're producing, where our energy is coming from, how we're generating electricity, things like that. So, it's an increasingly important consideration that the health care industry broadly is taking.

Host Amber Smith: So, it sounds like sustainability means that we take efforts to make sure that we're still able to provide health care in the future, that we're not doing things to our detriment now.

Paul Corsi: Sure. Yeah. Definitely. Yeah. The dictionary definition of sustainability that we sometimes forget when this word gets very politicized or thrown around a lot, it literally just means to sustain. So, sustainability means we're just trying to ensure that the way we're doing things now does not impede our ability to continue to do those things into the future.

Host Amber Smith: What are some examples of sustainability efforts that individuals make at home, in general?

Paul Corsi: I think in general, just being more aware of what you're purchasing. Food is something that has a huge impact on the environment. If you try and consume more locally sourced goods. Try to eat more seasonally, so eating vegetables that are in season now, or that can be sourced locally, is always good.

I would say generally that I think a problem, or maybe a blind spot that a lot of conversation about sustainability has had is that these systems really require a much greater or much broader investment than what any particular individual is capable of, right?

I think when we start talking about individual responsibility, we end up just, like, stressing a lot of people out. Because they're like, "Well, I can't carpool to work," or, "You know, there's no bus route at my house." Like, "How am I going to be sustainable," right?

And we really need to think about how do we expand things like public transportation. Or in health care, you know, if you're relying on an already very busy nurse on hour 10 of their shift to figure out which trash receptacle this particular recyclable thing goes into, or to make those decisions, you're kind of already setting folks up for failure. So, a lot of my work is trying to make sure that sustainability is essentially invisible when it comes down to the individual, that the default thing that you do, the default way you move through the world and do your job and perform your duties is already sustainable before you even have to make, like, a choice or decision to do this thing or that thing.

Host Amber Smith: Well, I want to talk to you about what else is in the works that Upstate tied to sustainability. I've heard of something called "Low Mow Spring." What is that?

Paul Corsi: Low Mow Spring is a part of our Bee Campus affiliation, and essentially it's acknowledging that maintaining a beautiful "golf course" lawn is actually fairly energy intensive. In Upstate New York it's less of a consideration, but in other places, it's very water intensive. And so Low Mow May is just about sort of letting the lawn kind of grow and breathe a little bit, incorporating some other plants, so it's not just what we call a monocultured grass, which is just a big blanket where there's just one plant growing, just grass. right?

And so we've identified a few areas on campus this year, and we're hoping to expand it next year of reducing carbon emissions by not mowing or maintaining those areas. I actually read recently that operating a gas a leaf blower for an hour has the carbon emissions of driving a car somewhere over 1,000 miles. So some of this lawn equipment is actually fairly impactful to the environment. So, taking a little time each spring to let the lawn breathe a little bit and get a little shaggy can have some fairly significant environmental impacts.

In addition to helping native pollinators, I know dandelions aren't like the best thing for pollinators for a handful of reasons, but it always -- I will defend the dandelion because I feel like it's very maligned. You know, as soon as the dandelions start popping up, everyone tries to mow them down as quickly as possible. But they're a very important early spring food source, so a Low Mow May, a Low Mow Spring, is just about allowing those kind of early food sources to survive and just about kind of letting our hair down a little bit when it comes to landscape.

Host Amber Smith: Can you talk about how you're involving students on campus in some of these efforts?

Paul Corsi: I love working with students. They always have some great ideas, and they move through our built environment in a way that's very different from the way I move through it. So they'll let me know when it's a pain to recycle in a certain building, or if they're trying to, for example, we're working now on building a compost collection system in Geneva Tower, which is the student residence hall. So they've been really supportive, and it's really helpful to bounce ideas off them because at the end of the day, they're the ones living there who are going to compost. So they're really passionate about that.

There's a community garden on campus that's mostly student run. So they're in there weeding and watering and harvesting from early spring to late fall. Publicizing things around best practices for recycling. We've done some, like, clean-up days where we go around picking up litter and trash. We're planning some things in the future where we're going to build some nest boxes for pollinators, which I'm really excited about. So, yeah, there's a lot of opportunities as a student to be involved for sure.

Host Amber Smith: Well, I appreciate you making time for this interview, Mr. Corsi. Thank you.

Paul Corsi: Thank you so much for having me. This was great. I appreciate it.

Host Amber Smith: My guest has been Paul Corsi, who is Upstate's sustainability manager. I'm Amber Smith for Upstate's "HealthLink on Air."

The growing threat of dengue virus and efforts to create a vaccine -- next on Upstate's "HealthLink on Air."

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Researchers from Upstate's global health and translational sciences department have long been involved with investigations of dengue, and they're hosting infectious disease experts from around the world in Syracuse for a conference that imagines a world where dengue is under control.

To understand more about this disease, I'm talking with Dr. Stephen Thomas. He's the director of the department.

Welcome back to "HealthLink on Air," Dr. Thomas.

Stephen Thomas, MD: Thanks for having me, Amber.

Host Amber Smith: Researchers at Upstate were collaborating with the U.S. Army to develop an experimental dengue human infection model that was meant to help drug makers create a safe and effective vaccine against the dengue virus.

Is that model completed?

Stephen Thomas, MD: Human infection models: I'll probably take a moment to describe what those are. This is when we take weakened forms of bacteria or viruses or parasites, and we intentionally infect healthy volunteers. And the goal of trying to do that is to mimic a mild form of the disease that we're studying. And there are multiple models out there -- for influenza, for malaria, the one we work on, which is dengue. There are some cholera, for example. There's lots of different models, and they have been very instrumental in advancing our understanding of these hard-to-study diseases. And before you can even progress to doing these types of experiments, you have to fulfill a number of very strict criteria that basically lead you to the conclusion that there really is no other way you can do the type of research that needs to be done and that the risk is minimal and manageable and that there will be benefit on a very large scale.

So, with that as the background, yes, experimental human infections with dengue, they've been doing those experiments since the early 1900s. One of the researchers that did some of the seminal experiments was Albert Sabin, when he was in the Army. So, of polio vaccine fame, he did a number of experiments on dengue. And as we hit about 75 years of trying to, but unsuccessfully, develop a dengue vaccine, this was something that folks in the military said, "Well, geez, we really need to kind of brush this model off and try again." So, we've been working with the Army for about 10 years now, in terms of an Upstate/Army collaboration. And University of Maryland joined our consortium, and it's been a very productive collaboration. And we've done a number of studies, and there are a number of vaccine and drug developers who are collaborating with us now because the model works. It's safe, and it's reproducible, and it works. It works quite well.

Host Amber Smith: And so there are some Central New Yorkers who can be proud that they were part of this. They helped you. They were your volunteers, right?

Stephen Thomas, MD: That is absolutely correct. Yes, we enroll younger, so, from 18 to mid-40s, mid-50s people, they have to be extremely healthy, have very few, if any, medical problems. They have to take very few, if any, medications. And these are small studies, so these might be five to 10 people, and the intensive portion is about a month long, and we're seeing them every day or every other day for that entire month. We become quite close to the volunteers (laughs), as you can imagine.

If you count all the recent studies that we've done, and the studies that were done with the military since about 2000, I mean, geez, we've had about a dozen studies so far. And the models have worked quite well, and we're excited about it.

Host Amber Smith: What is unique about the dengue virus that makes creating a vaccine such a challenge?

Stephen Thomas, MD: That's a great question. Dengue is the disease, and when people develop dengue, they have fever. They have headache. They have muscle aches. They have fatigue. They can have pain kind of with moving their eyes. They have bone pain. They can get a rash. That clinical situation is caused by infection with one of four different dengue viruses. And they're named -- (laughs) not creative -- they're named dengue 1, 2, 3 and 4, and they're transmitted by mosquitoes. And the dengue viruses are in the same family as some other viruses, which people may be familiar with, such as Zika, yellow fever, Japanese encephalitis, West Nile virus, and then, a new virus, relatively new virus, that we have in the Hudson Valley, in this part of the world, called Powassan, which is transmitted by a tick, but the others are transmitted by mosquitoes. And they're typically found in tropical and subtropical climates, so places where it's hot enough, and there's enough moisture, that mosquito populations can thrive and live. And so what happens is you get someone who's sick with dengue, and they've got the virus replicating in their blood, and then the mosquito feeds on them. They get infected, and then they go feed on somebody else, and then they infect that person, and that cycle keeps going.

But what we've been seeing, because of changes in temperature and changes in moisture in different parts of the planet, we're starting to see dengue being transmitted in more temperate climates. So, we've seen dengue transmitted in Texas and in Hawaii. We had a large outbreak in Key West, in Florida. We've had cases in Miami, Dade County. They've had cases in Europe as well. So, people are concerned that as the temperatures on the planet change that these mosquitoes are going to find more and more places where they can live year-round, and with travel being the way that it is that there's going to be a lot more opportunity for viruses to be introduced into places where they have the mosquito, and they have people who are susceptible. So, four different viruses means you've got to develop a vaccine against each virus, and then you have to combine them all successfully. And that's been very, very challenging.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith.

I'm talking with Dr. Stephen Thomas. He's the medical director of the Upstate global health and translational sciences department. And we're talking about dengue virus.

So, are doctors in the U.S. seeing more cases of dengue that were contracted in the continental U.S.?

Stephen Thomas, MD: It's not a frequent occurrence when it has happened. So, I mentioned, in Key West, there was a large outbreak a number of years ago. There have been large outbreaks in Hawaii. And then there have been sort of sporadic cases that have occurred on the Texas/Mexican border. So it doesn't happen often that we have large outbreaks, but the potential is certainly there.

But what they do see is they see a lot of travelers who come back. So, Puerto Rico has a lot of dengue. The Caribbean can have a great deal of dengue. People who go to Southeast Asia; there's a ton of dengue in Southeast Asia. Central and South America, so Brazil, for example; there's a big outbreak in Peru right now.

The problem is, most people, when you get that first infection, most children who get a first infection, don't even know they've been infected. Adults, they have a higher frequency of developing the type of illness that I mentioned before. But what happens is when you get a second infection with a different type of virus than you had the first time, so let's say your first infection is with dengue 1, and then a couple of years later, you get a dengue 2 infection, then there is this increased risk of getting severe disease and potentially dying. And, in places where they don't know how to take care of people with severe dengue, the mortality rate can be up to 20%, which is extremely high.

And unfortunately, in many of these places, the burden of that severe disease is on kids, so anywhere between 5,000 and 40,000 people a year die of dengue, and unfortunately, most of them are children.

They do think, though, that about 400 million people are infected every year, and about 100 million people get sick. And so what you have is places that don't have a lot of health care resources, the resources are getting consumed by people experiencing dengue, which is why we're trying to make vaccines, to sort of lower that burden and at the same time, protect travelers, protect expatriates and protect military personnel deployed to these areas.

Host Amber Smith: So, if most people who are infected don't get sick, or very sick, with this, is it our immune system that is able to typically fight it off? At least the first time?

Stephen Thomas, MD: Yes, the first time. So, you get exposed, and then your body has sort of a nonspecific reaction to that particular virus, which is an antivirus-type reaction, like we've experienced with lots of other viruses that we become in contact with. And we believe that for multiple decades, you will be protected against getting severely ill if you get infected again with that same type of virus.

The problem is that in about 5% of people who get a second infection with a different type, the immune system is not our friend. And what happens is that immunity that exists from that first infection actually helps this second virus to infect more cells to replicate more aggressively and to then have all sorts of problems where we get leaky blood vessels, we can get fluid in our lungs, fluid in our belly, we can have problems with our coagulation system, and we can have bleeding into our gut, and people develop very low blood pressure and shock, and their organs start to shut down, and it can happen very, very quickly.

And it's another reason why it's been difficult to make a vaccine, because you don't want to create an immune response with a vaccine that could potentially place somebody at increased risk for severe disease when they get that first natural infection, so it's been another reason why it's been so difficult to make a vaccine against this disease.

Host Amber Smith: Well, are there any medications that are used to treat dengue if someone gets infected?

Stephen Thomas, MD: In places that are very, very experienced with treating dengue infections, and severe dengue infections, the case fatality rate can be extremely low, so it can be less than half a percent. So you have dengue, even severe dengue, and you get to one of these hospitals, like the hospitals in Bangkok, Thailand, which is where we do a lot of our research, then they treat you with IV fluid replacement to keep your blood pressure up. They treat you with acetaminophen, which is the ingredient in Tylenol, or paracetamol overseas, to help with your aches and pains and fever. On rare occasions, they may need to transfuse blood, but most of the time, just Tylenol and fluids, and people will do quite well.

But we do not have anything that is specific for the virus. And people have tried, and companies have tried, and academic groups have tried, but it's been sort of one failure after another, unfortunately.

And then there are some groups, including Upstate, that are looking at whether or not it produced antibodies, so kind of like an immune system in a jar, much like we did for COVID, these monoclonal antibodies.

There are groups that are looking at that, and that holds some promise. Groups have looked at whether or not they could impact the immune response that seems to damage people's organs, like using steroids, for example, right, to try to suppress inflammation, but that hasn't shown to be highly effective, either, so right now there is no specific drug that is available to treat dengue.

Host Amber Smith: Is there progress on a vaccine?

Stephen Thomas, MD: As we discussed, I mean, people have been trying to make dengue vaccines for over 75 years, close to 90 years, and it's been very, very difficult, and there has been one vaccine, which was licensed a couple of years ago, to include licensed in the United States. The problem is that it does not protect, in a balanced way, against infection and disease caused by all four types, first of all.

Second of all, there is a concern about the safety of the vaccine in people who get vaccinated that have never been exposed to dengue before. So, if you've been exposed to dengue before, and you get this vaccine, it seems to boost your immune system very nicely and offers you lots of protection, and it's highly safe. If you've never been exposed to dengue before, and you get this vaccine, we have seen an increased risk in people who then subsequently get infected, and we think it's that phenomenon that I was talking about earlier, about these second infections kind of resulting in more severe disease.

So, the vaccine is licensed in lots of countries, but it is only to be used in people who have been previously infected, which makes it very complicated to use, and it has really reduced the uptake of that vaccine.

So now there's a second vaccine -- that first vaccine was made by Sanofi Pasteur -- the second vaccine, which has just started to get licensed in different countries, is made by a company called Takeda.

And that vaccine is similar to the Sanofi vaccine in the sense that there is an imbalance in how well it protects against the four different types, but it's an improvement upon the Sanofi vaccine because it appears to be safe in people, whether they've been previously infected or whether they have not been previously infected. And so, they've been licensed in the EU (European Union) and Brazil and Thailand and Indonesia. And I'm assuming that there's going to be more licenses to come in the near future, but not in the U.S. The U.S. has one vaccine. It's the Sanofi vaccine, and it's only for people 9 to 16 years of age and only people who have been previously infected, so I don't think it gets used that much.

Host Amber Smith: Now, for the summit that you're hosting at Upstate, you'll explore the historical challenges associated with dengue control. Can you explain what those are?

Stephen Thomas, MD: This is a summit that's being sponsored by the Institute for Global Health and Translational Sciences. It's been largely coordinated by Tina Lupone and Dr. Adam Waickman, who is one of the basic scientists in microbiology and immunology and a dengue expert. And we have, you know, geez, about 100 people that are coming from all over the world, Brazil, Singapore, Puerto Rico, Thailand, and they're going to represent academia, industry, government, military, ministries of public health, and they're going to talk about how difficult it has been in these countries where the disease is endemic, so, meaning there's always virus, it's always being transmitted. And it's a constant battle for these folks, and they're going to talk about what the challenges have been in trying to reduce the burden of this disease on their populations without having highly effective vaccines available, without having treatments available and the types of things that they have been trying to do, whether it's spraying to try to reduce mosquito populations or education or a combination of all the above.

So that's going to be one part of the conversation, is sort of, "This is what's going on, on the ground, frontline, right now, in the world, in these places." And it's very interesting because we're going to have U.S. territory: Puerto Rico. We'll talk about their experience, and then we're going to have a highly resourced country like Singapore talk about their experience, and then we're going to have Brazil and Thailand, which are developed and developing economies, kind of talk about their experience. So the comparisons and contrast, I think, are going to be really quite interesting.

And then we're going to have people that talk about the tools that they are trying to develop, whether it's drugs or antibodies or monoclonal antibodies or vaccines, whether it's new ways to make diagnoses, whether it's new ways to address mosquito populations, we're going to talk about all the tools that folks are trying to develop and the tools that are currently available.

And then we'll end the two-day summit by kind of taking all of that in and saying, "OK, well, where do we go from here? What are the questions that are not being asked? How could we do better, and how do we prepare these countries for when vaccines and drugs and antibodies actually start to roll out in a highly scaled way."

So, I'm very excited. I'm excited to have all these people coming to our little old Central New York (laughs).

Host Amber Smith: Different countries will be able to learn from each other, maybe.

Stephen Thomas, MD: Absolutely. Absolutely. They all have unique elements of their experience. But in addition, they all share a lot of common themes, that being that dengue infects a lot of people, dengue causes a lot of pain and suffering in communities, and dengue consumes a ton of resources to try and manage in places that don't have lots of resources, in places that they would prefer to use the resources for nutrition or other vaccine-preventable diseases or education -- you name it -- things other than trying to keep people out of the hospital or keep people from dying from this disease.

Host Amber Smith: Well, Dr. Thomas, thank you so much for making time for this interview.

Stephen Thomas, MD: Well, thanks for having me.

Host Amber Smith: My guest has been Dr. Stephen Thomas, medical director of the Upstate global health and translational sciences department at Upstate. I'm Amber Smith, for Upstate's "HealthLink on Air." Here's some expert advice from urologic oncologist, Dr. Joe Jacob, from Upstate Medical University. What are symptoms of bladder cancer that a man or woman should not ignore?

Joseph Jacob, MD: The main thing that you have to understand is that seeing blood in the urine is not normal. So if you have blood in the urine, you should tell your doctor, and likely you need to see a urologist. Now, sometimes you'll have a bad urinary tract infection with blood, but if you're having what we call asymptomatic blood in the urine -- so you're not having any symptoms, and you're seeing blood in the urine -- then you really, really need to see a urologist. And that's one thing. The other thing is, you have to see your primary care doctor, and your primary care doctor will check your urine and check for microscopic blood as well. So this would be something you may not necessarily see with your own eyes, but they'll see this when they look under the microscope, and if there's blood microscopically, then you need to see a urologist as well.

Host Amber Smith: You've been listening to urologic oncologist Dr. Joe Jacob from Upstate Medical University.

And now, Deirdre Neilen, editor of Upstate Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Eric v.d. Luft, poet, publisher and curator, takes a new look at our notion of the Prodigal Son and creates a stunning portrait of the inevitability of heartbreak in parenthood in his piece "The Prodigal Son's Father."

The father exploring his own emotions

Offends the son

The mother seeking her own truth

Offends the daughter

The son being himself

Breaks his mother's heart

The daughter being herself

Angers her father

The children's complexities

Conflict the parents' simplicities

Talking does no good

When no one wants to talk

Loyalty

The enemy of ethics

Family loyalty

The archenemy

Children kill and burn

For their parents

Parents forgive

Murder and arson

Parents rejecting children

The worst of all crimes

Children rejecting parents

Only to be expected

They'd rather be miserable

In their own world

Than comfortable

In yours

If any healing is done

It will come

From children

Not parents

You don't control or abuse him

You guide him and give him options

He'll still break your heart

He'll find a way

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

Next week on "HealthLink on Air," caring for aging parents.

If you missed any of today's show, or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org.

Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Bill Broeckel.

This is your host, Amber Smith, thanking you for listening