More than an Itchy Bite! Diagnosing Mosquito-Borne Diseases

Mosquito season is here…and so are the diagnostic challenges. 

Dr. Elitza Theel of the Mayo Clinic joins us to discuss how clinicians and laboratories approach mosquito-borne diseases, with insights on symptom overlap, test selection, timing, and key pathogens seen in North America. 

Transcript

SPEAKER_02 0:10

Hello and welcome to Diagnostics Decoded. Each month we'll be pulling back the curtain on the science, the technology, and the people shaping the diagnostic industry. We are your hosts. I am Richard Keach, Business Development Manager at ZeptoMetrics.

SPEAKER_00 0:24

And I am Jessica Schweitz, market development specialist at ZeptoMetrics. So grab your caffeine of choice, get comfy, and let's have some fun. Enjoy the episode. Hello, and welcome to today's episode of Diagnostics Decoded. Today we're exploring mosquito-borne diseases in North America. Tis the season, from overlapping symptoms that complicate diagnoses to shifting epidemiology and emerging threats. Mosquito-borne illnesses present such unique challenges to both clinicians and laboratories. We are truly honored to be joined by Dr. Alitza Thiel, Director of the Infectious Diseases Serology Department and co-director of the Vector-Borne Diseases Service line at Mayo Clinic. Dr. Thiel, thank you so much for joining us today. We're so excited to learn from your expertise.

SPEAKER_01 1:14

Thank you so much for having me. It's great to be here, and I look forward to chatting about one of my favorite things. I know this is a recording, but um on my ceiling I have a giant mosquito that's whittled out of a big tree trunk. It's one of my favorite things to talk about, mosquito-borne diseases.

SPEAKER_02 1:35

If our listeners could could see what we are seeing, there's a massive mosquito subsidiary. So obviously, she's got a strong bond with mosquitoes.

SPEAKER_01 1:46

Yeah, yes, I do.

SPEAKER_02 1:48

So so, Dr. Thiel, I just want to echo what Jess said. It's a pleasure to have you. Thank you so much for joining us. Um I will jump right in and just get the QA started by talking about some of the issues at in North America today. But maybe a general intro before we get into the QA. Just if you can just give a quick intro on yourself, your background, where you studied, how you got to where you are today, what keeped your interest in mosquitoes, and kind of a story behind your background. Please give us a little overview on yourself.

SPEAKER_01 2:22

Sure. So I um let's see, how far back does one go? So I completed my PhD in microbiology and immunology at the University of Wisconsin in Madison, and then I was super duper lucky and got accepted to to do a clinical microbiology fellowship at Mayo Clinic for two years, and I have been on staff since I completed that fellowship way back long ago in 2012. So I've been a lab director overseeing the ID serology lab for 14 years now. And you know, my I come from a family of academics and professors in academic institutions, and I realized at an early age that I cannot do that. I don't want to do that, which is what kind of pushed me in the clinical field. And uh what got me interested in mosquito-borne diseases in particular is my brother actually got diagnosed with Lyme disease when he was a kid, and for the longest time I thought that was a mosquito-borne thing. Boy, was I surprised when it when I found out, you know, that it was not. Uh that it was tick transmitted. I don't know, that kind of started me down the vector-borne diseases route. So I have an interest in both mosquito and tick-borne diseases, really, thanks to my brother.

SPEAKER_00 3:42

That's incredible. Wow.

SPEAKER_01 3:44

Yeah, talk about a learning moment. Yeah.

SPEAKER_02 3:49

So maybe talk a little bit uh about your titles and and what encompasses those titles because I know you have multiple different hats.

SPEAKER_01 3:59

My laboratory really is focused on detecting antibodies against and antigens from most of the infectious diseases that we that we worry about, from bacterial to fungal to viral to parasitic. Uh, that is kind of what's done in my laboratory. And then Dr. Bobby Pritt and I also run and oversee, if you will, our vector-borne diseases service line. So Dr. Pritt oversees the molecular testing for all of the tick-borne, mosquito-borne pathogens. I oversee the antibody and antigen detection components for those infectious diseases and so kind of consider ourselves kind of a center of excellence in a way for those particular pathogens. So that's when we started the vector-borne diseases service line as a side gig. I also oversee uh all of our testing for sexually transmitted infections here at Mayo. I'm also the fellowship director for our uh clinical microbiology PhD fellowship program. I'm sure there's some other things, but that's enough for now.

SPEAKER_00 5:04

That is a lot. Yeah, I was gonna say that is quite a bit. So you're busy.

SPEAKER_02 5:08

So uh just to add to your full story, one more question before we get into the actual technical questions. What do you do for fun?

SPEAKER_01 5:16

Oh my gosh. My favorite thing in the world to do is read. Okay. Um my kids don't let me do that though. So my second favorite thing to do in the world is drive them and watch their basketball games, their dance competitions, whatever else they make me take them to. Yep. So currently very much in mom mode of a teenager and a middle schooler. And and then there's my husband and my dog.

SPEAKER_02 5:46

That sounds fantastic. We we we have families as well, and that's probably if you asked us our our uh exact answer, driving and escorting to whatever event there is. So we we and dogs, yeah. I applaud you for that. Um but but so to get into the technical QA part here. Um, I guess we can start with North America, and uh, can you tell us what are the most prominent mosquito transmitter disease that that you are seeing and and that we see as a culture here in America?

SPEAKER_01 6:19

By far the most common mosquito-borne illness in North America that we worry about is West Nile virus. That really was first observed in the late 1990s, but really has since established itself in North America and is uh I'd say the most common mosquito-borne illness that that we see. But then there's there's others that are perhaps less common, but can have severe consequences, like Eastern equine encephalitis virus. We see that one more in the Northeast. It comes up every almost every year or every other year, we'll have small outbreaks, really devastating illness uh leading to high morbidity and mortality. Other ones that we see, St. Louis encephalitis virus, kind of in Midwest area, is a common one as well. You know, the ones we hear about, like the dengue, dengue virus, chic and gunia virus, those we don't really see as commonly. There are a few cases, smattering of cases every year, I'd say in um Florida, in Texas, but really for North America, our biggest most common virus that we see is definitely Westnell virus.

SPEAKER_02 7:34

And then I I know we're gonna talk mostly about North America today, but you did mention some other viruses that are seen elsewhere. So maybe touch on the rest of the world while we're at it, and then we can focus on what you're seeing a minute.

SPEAKER_01 7:46

So Westnell virus is also pretty common worldwide, but the most common mosquito-borne virus worldwide is is dengue virus, found throughout South America, Africa, Asia. It's it's very common. And then yeah, we all know about Zika virus, the outbreak that happened in 2016 into 2017. Interestingly, we don't see too much uh Zika virus these days. Another one that is more prominent internationally is chicken gunia virus, also known as breakbone fever because of the severe pain in the joints and bones and muscles that it causes. So those I'd say are kind of the dengue chicken gunia virus are the more common kind of international viruses that we think about.

SPEAKER_02 8:36

Excellent, thank you. Um so back to maybe what you're seeing most at Mayo and the North American viruses that you see. So look in terms of symptoms with the mosquito-borne illnesses in America, um, maybe talk about symptoms. I know you're just talking about uh, but um, what what kind of symptoms do these North American viruses cause? And is there any overlap with symptoms from one to the other?

SPEAKER_01 9:01

Yep. Um so it's interesting for a number of the viruses, uh, West Nile in particular, most people that get infected are actually asymptomatic. Of those that develop symptoms, just kind of systemic symptoms are typically fairly nonspecific kind of influenza or flu-like symptoms, fever, chills, fatigue, malaise, headache, you can have some joint pain as well. RASH is not as common, but the key is that amongst the symptomatic individuals, the symptoms for the arboviruses are actually quite similar and very overlapping. So even though for a few viruses, some symptoms may be more suggestive. For example, severe joint pain, you would be concerned perhaps more with chicken gunia virus. If you have severe headaches or retroorbital pain, we see that more commonly with dengue virus. But for the most part, aside from that, symptoms are quite overlapping. And then for some viruses, like Eastern equine encephalitis virus and Westnell virus as well, a small, very small percentage of individuals can go on to develop neurologic infections and neurologic symptoms as well, encephalitis, meningitis type presentations. But again, those are very, very small percentage of individuals develop those symptoms, and it's typically our immunocompromised or our elderly population that are at higher risk for those particular manifestations.

SPEAKER_00 10:39

So, how would you take into a patient's exposure history when ordering tests?

SPEAKER_01 10:44

Yeah, so that's really key. Even though the symptoms are highly overlapping, a key part of the clinician's role is to consider the exposure history for the patient. So where have they been recently? For example, if the patient has not left North America, probably don't need to be testing for chicken gunia virus.

SPEAKER_00 11:08

Right.

SPEAKER_01 11:09

Unless they have been in, let's say, Florida, where there have been documented cases of dengue virus, probably don't need to test for dengue virus if the patient has not, again, left the country. A lot of the patient exposure history is key. Similarly, within the United States, if the patient we typically see, for example, Eastern equine encephalitis virus is more in kind of the East Coast, Northeast area. If the patient is from California and has not been in that part of the country, triple E virus is probably lower on the differential. So really important to consider where the patient has been. Number one. Also the time of year. So in North America, if your patient is from, I don't know, Minnesota and it is December, probably not going to be thinking about mosquito-borne illnesses.

SPEAKER_00 12:02

Yes.

SPEAKER_01 12:03

So timing in temperate climates as well as exposure history are really important to kind of help guide what should be on the patient's differential.

SPEAKER_00 12:12

And then when they're ordering the test, how do they take into consideration symptom durations? And does that affect the test that's being ordered?

SPEAKER_01 12:22

Absolutely. There are a number of different methods that we can use to detect mosito-borne illnesses. There's the molecular assays, your PCR assays that will detect nucleic acid, ribosomal RNA for a lot of these viruses. And then we also have serologic assays that are detecting a humoral immune response to the infection. And it's really important to know when to order what test. So the problem with arboviruses is that their viremia is fairly low and also transient. It really peaks within the first, let's say, two to four days after symptom onset. After that, viral floats really drop off fairly dramatically. So if you have a patient presenting like eight, nine days after that symptom onset, PCR is not going to be the way to go. They'll most likely be negative. So we recommend molecular testing for arboviruses within the first, I'd say ideally four to six-ish days after symptom onset. After that, we really rely on detecting IgM class antibodies against the virus specifically. Those typically start to become detectable four to six days after symptom onset and then peak within two to three weeks thereafter. IgG, a lot of laboratories also offer detection of IgG class antibodies. Those are maybe not as helpful because, for example, for West Nile virus, if you've previously been infected and recovered, you will have IgG for quite some time. So if you have an IgG only response, you can't tell, you can't rely on that to indicate an acute infraction. We really just want to look at the IgM. Sure. Bottom line though, first few days after symptom onset, molecular testing is the way to go. After that, it's a serial looking for a serologic response.

SPEAKER_00 14:27

Okay. And what type of specimens are collected from the patient to perform that testing?

SPEAKER_01 14:33

Great question. So for serology, pretty straightforward, typically serum. A lot of laboratories have also validated spinal fluid for patients with neurologic symptoms. We can also perform serologic testing on spinal fluid for a lot of these viruses. For molecular testing, whole blood as well as CSF have been validated. Interestingly, there's more and more data coming out that urine is a good source for molecular testing because we have found that the nucleic acid remains in urine, fragments of it likely remain in urine longer than in blood. So we, for a lot of our testing, have validated blood, spinal fluid, as well as urine. So you have a few more options for molecular.

SPEAKER_00 15:21

Interesting. So are you only using spinal fluid when there is a neuropresenting patient, or is there any other that's obviously very intrusive, right? Yes.

SPEAKER_01 15:33

Yep. But it's it's a good, it's a good specimen source for patients presenting with neurologic symptoms. The ideal scenario, right, is you detect this organism in blood. Like we don't want to be jumping to doing a lumbar puncture, but if there's any concern that maybe you know you have a serology positive in in serum in the blood, but you're not convinced perhaps that it's that particular pathogen and you're collecting um CSF fluid for something else, it would be helpful test that uh source as well for antibodies and potentially nucleic acid.

SPEAKER_00 16:09

Is there or how do you work with the physicians to educate them on the type of test to order?

SPEAKER_01 16:15

Well, it starts at medical school. So we try to start early. Yeah, right. But also we have a couple of things we've done. We have an algorithm that we've put together that takes into account exposure history as well as timing of disease, you know, onset from when the sample is collected. And then that algorithm, it's actually available to anybody online, but we also link it in the ordering system for those that are that are you know willing and interested in clicking the link to see what test orders there are. I don't think we have any like pop-ups or anything like that at this point, but uh yeah, we do try. I know actually in a couple of locations when tick and mosquito season comes up, there's you know, um, some clinicians that kind of send out a reminder or a refresher on what testing is available and what testing to order when. So they too, on the clinical side, help to maintain that that education amongst themselves.

SPEAKER_00 17:21

Yeah, yeah, makes sense.

SPEAKER_02 17:23

So just to kind of switch gears on the actual tests and uh test development trends and the actual tests that you're you're running there. So I guess just to talk about the test that you're running, out of curiosity, and PCR and serology lab, are these FDA-approved tests, RUO, lab-developed tests, or is it all a little bit of everything?

SPEAKER_01 17:46

It's a little bit of everything. Westnow virus tests because it is such a common infection. A lot of, you know, those are FDA cleared. Dengue virus as well has some FDA cleared assays, but some of the less common ones are not FDA cleared, or in serology they might be FDA cleared for serum, but they're not FDA cleared for CSF. Um, so for the laboratorian, I think it's really important to make sure you know what your assay is cleared for, not only the method, but also source. So it's a it's really a combination of FDA cleared RUOs that you have to validate as a laboratory developed test. Yeah, and and source for I, you know, I don't know that any of the urine as a source. I don't believe that's FDA cleared for any of the PCR assays, so all of the urine tests right now are essentially laboratory developed tests.

SPEAKER_02 18:41

And what what kind of triggers you and your team to develop a new test?

SPEAKER_01 18:47

As soon as we hear the word outbreak, that's a great word.

SPEAKER_02 18:50

That makes sense.

SPEAKER_01 18:52

But you know, we try to keep track of things before they become an outbreak, so we really kind of rely on our colleagues in public health who are monitoring upticks in diseases. For example, the most recent one that we considered developing in assay for was Oropush virus when there was that out in South America. The the challenge with developing, particularly for serology, developing these for you know current outbreaks is getting specimens, getting well-characterized specimens that you know have antibodies to whatever that particular pathogen is for in order to validate an assay. You know, I can't I can't spike antibodies to validate. So it can be pretty challenging to validate serologic assays for some of these pathogens. But back to your question, again, relying on public health news reports about emerging viruses and new cases is really what we kind of try to keep a pulse on all the time so that we're not caught by surprise.

SPEAKER_02 19:55

That was my next question is what's kind of driving these shifts and patterns and who's monitoring them that you you answered them.

SPEAKER_01 20:04

Well, it's it's interesting, you know, for Westnow virus, for example, it's not like we see massive outbreaks every year. I think the last it's kind of every three to five years we see a huge outbreak. And so what what is driving that? Why is it happening? I think it's right, it's kind of an interplay of a couple of things. One, weather patterns, as we know that those are kind of changing a bit. Uh weather patterns, also kind of the uh immunity um amongst the population. You know, if you don't have a lot of Westnell virus cases, immunity kind of tapers off a little bit, people are more susceptible, and then you kind of get a spike, immunity stays, starts decreasing, you get another spike in cases. So I think it's a combination of weather patterns and susceptibility amongst the population that drives some of the spikes we see. You know, Westnow is one that we kind of see a cyclical nature in. More recently, was it 2025 or 2024? I don't know, the years kind of meld together, but we had that huge outbreak in chicken gunia virus cases, I think over 400,000 in South America that had to do again with kind of changes in in weather patterns, having a much more kind of wet year leading to a lot more mosquito breeding areas becoming available. Also uh in that particular area of the world, kind of going, you know, having the population disrupt more of rainforests and in and environments kind of disrupting the cycle as well. So I think there's a number of things that can lead to outbreaks occurring and manifesting.

SPEAKER_00 21:52

So when you guys at the Mayo Clinic are looking at bringing on or creating a new test, are you looking also at what's happening in South? America, or is it primarily just kind of what's going on?

SPEAKER_01 22:04

We try to keep an eye on things worldwide. Sure. Because you know, mosquitoes know no borders. Our we love to travel all over the world, so people are constantly bringing things back. So we try to kind of keep the pulse on what's going on everywhere as much as possible. You don't want to start developing something just because there were two cases, right?

SPEAKER_00 22:27

Right.

SPEAKER_01 22:28

So you kind of have to have some threshold above which you will really gear up and start developing something. And we now, I think all laboratories have experience with that. You know, influenza, Zika, um uh SARS, COVID, uh, you know, COVID-19. We are well practiced in kind of knowing where that threshold is before we have to jump on and start plugging away at new test development.

SPEAKER_00 22:59

Sure. So I'm gonna switch gears to talk a little bit about the outreach work that you do in Belize. And this specifically caught my eye, not to be a creeper, but when I was looking at your bio on the Mayo Clinic website, and I thought it was really interesting and it tied in really nicely to the work that you do. So could you walk our listeners through a little bit about the outreach work that you've done in Belize? Kind of how you got started and yeah.

SPEAKER_01 23:25

Absolutely. What really got us started in Belize was the Zika outbreak, interestingly enough, when we were looking at kind of cases in you know, Central and South America, all of the countries were reporting Zika cases except this one country, Belize. It was like nothing. Um and uh it turned out it just did not have the capacity really to do the testing and uh kind of monitor um cases. And so that got me thinking. I then reached out to one of our infectious diseases clinicians here at Mayo Clinic who does a lot of outreach and talked to him about that because he had some work in Central America and other areas. And then he happened to know a group from the University of Notre Dame, which is where I'm a graduate, this infectious disease clinician is a graduate of. That group had been working in Belize for over 20 years, and so they were able to connect us to the Central Medical Laboratory in Belize, and we started talking about you know, what are you able to do? Do you have interest in bringing in additional testing and monitoring for Zika at the time? Um, and they did. They were, you know, kind of welcoming with open arms, we'd love to learn from you, that sort of thing. So that's kind of how it really started. This really nice collaboration between the clinical laboratory and ID at Mayo Clinic, an epidemiology group at Notre Dame, and then the clinical laboratory in in Belize. So that's how it started, and we were lucky enough to get external kind of philanthropic funding to support the study, and we've been kind of working with them on and off. COVID was a rough couple of years there. Yeah. But we've been working with them ever since. So it's been a good collaboration.

SPEAKER_00 25:18

Awesome. So when you first arrived, what did their testing capabilities first look like?

SPEAKER_01 25:23

Yeah, so they had molecular testing, but it was very specific. They had a test for uh dengue virus, not surprisingly. Their serologic uh cape testing menu was was much more limited. No Zika, no chicken gunia, no West Nile virus. The group was very eager though to bring on additional testing. So we worked with them on developing like validation plans, kind of coming up with you know what they need to do to confirm the performance characteristics of an assay before they implement it. So we helped them implement a number of assays, including Zika virus serologic testing, as well as a panel, dengue, chic and gunia, and zika for molecular testing as well. We brought in chicken gunia serologic testing and it and then some additional dengue serologic markers by the end of it all. I mean, this took some time, obviously. And then we really focused on kind of optimizing their quality control and quality assurance practices, making sure that once you implement an assay, you are continuing to monitor its performance characteristics. And they were really able to take that and apply it throughout their laboratory, which was really, really nice to see because the goal for us anyway is not to stay there forever, but to empower the laboratory to maintain and uh sustain themselves without external assistance. And I think we've really achieved that.

SPEAKER_00 27:00

Congratulations, that's awesome.

SPEAKER_01 27:02

Yeah, we're pretty, pretty happy.

SPEAKER_00 27:04

Yeah. So how did you justify, or how did you even know what to start or what tests to bring on? There was no data to show what Zika cases were like. How were you able to justify? Okay, let's do tests for this, this, and this, or yeah.

SPEAKER_01 27:20

No, this was uh a great, great point. Probably should have started with this. So because there was really limited knowledge about what was circulating and endemic in the country, we first did, I guess, a somewhat rudimentary assessment of what is circulating. And to do that, we collected over 1,500 just residual blood donor serum samples from throughout all of the districts in the country. And we screened them for just antibodies to all of the mosquito borne and all of the tick-borne assays that we had available in my laboratory up in Rochester, Minnesota. As you can imagine, a lot of um seropositivity for the flaviborne viruses, so dengue, Zika, and West Nile. Happy to report Belize does not have any Lyme disease. They had a little Babesia, a little anaplasma, but you know, nothing really exciting. But we did see that about a quarter of the samples we tested were seropositive for antibodies to Rickettsia riquetsiae, which is the causative agent of Rocky Mountain spotted fever transmitted by ticks. That was an un essentially an unknown before we did this study. So we started out deciding what tests to bring to help them bring in based on the low-hanging fruit, which at that time was uh arbovirus testing. Um, you know, you can't really treat arboviruses, but if you are diagnosed with an arbovirus, you could stop empiric antibacterial right treatment. So a lot of patients we knew were getting just empiric treatment, so it would be nice to kind of stop that. So that's how we rationalize bringing in some of these additional arboviral tests. And then the plan was to bring in PETSEO, serologic testing for Rocky Mountain spotted fever. Fortunately, COVID happened, there was some turnover in the leadership, uh, and we just have not been able to work on bringing that in as of yet. But it's it's a future goal.

SPEAKER_00 29:44

Yeah, yeah. No, thanks for sharing a little bit about that. It sounds like it was both challenging and rewarding. Um and ultimately you were imagine the impact that you guys made on the broader public health, right? Yeah, yeah. Just being able to bring awareness. Yeah.

SPEAKER_01 30:00

Absolutely. We um did a couple of kind of educational tours, I guess, around uh in the northern part of the country where we'd visit uh local areas and kind of do some presentations on what arboviral diseases are and provide education on how to prevent infections, which can be challenging given uh where some of the people are living, but um it was it was beneficial, I think.

SPEAKER_00 30:26

Yeah. So it sounds like you shared quite a bit of education with them from your lab. What did you learn from your outreach or your time and beliefs that you implemented in your lab?

SPEAKER_01 30:39

Yeah, so that's a tough question. Uh but one thing, you know, we have a lot of resources at Mayo, and I think sometimes I, I'll say I and not we, we I take them for granted. And we go above and beyond sometimes for our validations or verifications or the way we do quality control. And you know, given the limited resources in in Belize, I actually took some time to think about well, do we really need to be doing all of this extra work which leads to extra cost? So definitely a bit more cost conscious in the laboratory.

SPEAKER_00 31:31

No, it's quite an interesting like viewpoint to bring back with you. Um makes total sense. Yeah. So full circle, if there is one thing that clinicians or laboratorians should think about differently when it comes to mosquito-borne diseases, what would it be?

SPEAKER_01 31:47

Well, I I guess a couple of things. Maybe not just one. Continue to always consider exposure history. A lot of times what we see is just all of the mosquito-borne serologic tests being ordered. When, you know, I I've gone into medical records a couple of times and see zero travel history. And so, do we really need to do that chicken gunia test? Because you know, low pretest probability leads to false positive results. So just continuing to consider that exposure history component. And then the other thing is again knowing which test to order when relative to duration of symptoms at the time of sample collection, and not being surprised if your PCR is negative but your serology is positive in a patient's with 10 days of symptoms or or vice versa. So again, timing of testing and then relying on that exposure history component, I think, really um will help with test stewardship, which is something we're all focused on optimizing.

SPEAKER_00 32:54

Absolutely.

SPEAKER_02 32:56

So we just want to wrap up here our QA with Dr. Thiel from the Mayo Clinic. We just want to thank her so much for joining us. It has been super informative. We've learned a lot, and I know our listeners have as well. So again, uh, we want to thank Dr. Thiel. That's a wrap for Diagnostic Decoded.

SPEAKER_00 33:13

And if you would like to learn more about clinical microbiology, Dr. Thiel co-hosts an incredibly educational podcast. It is Editors in Conversation through the American Society of Microbiology, or ASM. So please go check it out. Dr. Thiel, thank you so much for joining us today. We really appreciate your time and you sharing your expertise with us and all of our listeners.

SPEAKER_01 33:34

Thank you so much.

SPEAKER_00 33:35

This was this was a blast. Thank you for joining us for today's episode of Diagnostics Decoded. We'll be back each month with new conversations diving into the science, challenges, and innovations shaping diagnostics.

SPEAKER_02 33:51

If you'd like to learn more about Zeptimetrics and the resources we offer, visit us at www.zeptometrics.com. Until next time, thank you so much for listening. Toodles.