Bobbi Pritt, M.D. (00:04):

Hello, I'm Dr. Bobbi Pritt, a clinical microbiologist and laboratory leader at Mayo Clinic and your host for today's episode. I'm excited to be here today with Mayo Clinic Laboratories' CEO and president Dr. Bill Morice, to discuss some trending topics. Then my colleague, Dr. Elli Theel, will be joining me for a deep dive into vector-borne diseases as we head into the summer. So Bill, it's wonderful to have you as always.

William Morice II, M.D., Ph.D. (00:29):

Oh, wonderful to be here as always. It feels like it's been a while.

Bobbi Pritt, M.D. (00:33):

I agree it does feel that way. And I know we have a lot to talk about. You've been busy traveling. You've been to Becker's Healthcare Annual Meeting, and then of course, there's all the infectious diseases in the news, one of my favorite topics. Why don't we start with some updates of what you've been taking away from some of your recent travels. Let's start with Becker's.

William Morice II, M.D., Ph.D. (00:52):

Sure. And it's funny because there is a sign of an intersection between travel and the infectious diseases that are out there, right? There's a travel theme throughout. This is our travel episode.

Bobbi Pritt, M.D. (01:03):

Yeah. You weren't on the cruise ship anytime soon?

William Morice II, M.D., Ph.D. (01:06):

No, I was not, nor in Central Africa. I was actually in Chicago. I've been in the domestic United States here for the Becker's Healthcare Conference, which is hosted by Becker’s. They do a newsletter, they look more on kind of the financial side of healthcare, financial and operational side, and public policy, and those things. And so, I was on a panel around CEO game plans for AI and tech kind of things. And then, just taking in the rhythm of the meeting. There's a lot of overlap between my particular session and the meeting itself. One of the things that really stood out to me, first of all, that main meeting has continued to grow, which means that there's more continued, growing interest I should say, in the business of healthcare in this country and how it's going to be sustainable. People really sharing a lot of different stories, and it's really interesting to be at that meeting, understanding what kind of large integrated delivery networks are facing, urban hospitals versus rural hospitals, all those sorts of things.

 But there was one theme that really stood out was AI. Just the propagation of AI in healthcare in so many different ways, really a lot on the operational side. We know in the area of revenue cycle management, or RCM, that's where claims are adjudicated, there's a ton of AI there. You now have AI from payers talking to AI from hospitals and from labs, so that's a lot of it. The other though is, and it's something you and I have talked about, is that yes, there's this big AI upskilling, if you will and driving efficiency in healthcare. But the panel I was on, two of the other CEO and leaders were from small rural hospitals. One of which I think was critical access. One was in the Dakotas. I can't recall where the other was. Just that the kind of resources that are available to a Mayo Clinic in this space are just so much different than what they are. Everyone's trying to use it, every company that was there. It's like, yeah, I don't think you can have a company now in healthcare and not have AI some place in the name, but the reality is that there's big differences in access to the resources needed, right? And many hospitals, especially now with some of the changes that are happening at the federal level are really struggling just to make ends meet. And so on the one hand you can say, "Well boy, AI would be a lifeline for those sorts of healthcare delivery systems because it introduces efficiencies in these things." But the reality is, they're just trying to keep the lights on.

Bobbi Pritt, M.D. (03:26):

The startup costs of buying the equipment, the license and the validation even. I know of a lot of smaller healthcare institutions, like laboratories at least, they stay away from laboratory developed tests. And you know, a lot of these solutions aren't FDA approved yet.

William Morice II, M.D., Ph.D. (03:41):

Yeah. And that's the other thing that's happening, of course for us, particularly in the lab side, is there's a lot of changes and hope that maybe we'll get to another episode on the federal level about payment. PAMA collection is just happening, right? Who's going to pay for these things? So, that's a whole another thing, and there's a clear modernization bill that was just introduced around that. So, lots of stuff for us to talk about the next time I come on.

Bobbi Pritt, M.D. (04:04):

Yeah, absolutely. That it has to be feasible for all of us, you know, so important. Well, I think let's table that for the next talk then, and just briefly cover all the infectious diseases that have been in the news. There's been hantavirus, Ebola, also another virus. And it got me really reflecting on just the importance the laboratory makes in diagnosing and controlling these outbreaks. Really, you need the laboratory to first confirm that you have an outbreak, to sequence the organism to see where it might have come from for your epidemiological investigation, trying to find out if your current treatments and your vaccines are going to work, but then also following up patients, doing contact tracing. So even though the laboratory isn't necessarily always on the front cover of these outbreaks, it plays such an essential role.

William Morice II, M.D., Ph.D. (04:54):

Yeah. You know, they do, right? And I can't even help but be struck by the irony when I see these stories coming out, like the cruise ships and going back to COVID. It was just sort of like something we'd all kind of like to put out of our collective memory because there was a lot of challenges with it. But the reality was, you know, there was this great cry for testing, and it was difficult to get testing because there just was an underinvestment in the diagnostic infrastructure. And I know you and I and many of us in laboratory medicine leadership thought, "Boy, this is the time. Now, we won't face this again." And yet now, we are back to trying to remind people that testing is really the key to keeping us safe, collectively and as well as individuals. And we don't know in the world that we live in, we had talked back then with climate change, with more travel, with all these things, we're just going to continue to see outbreaks of these infectious diseases. And so, I would just make a pitch that there probably will be legislation introduced to address the PAMA, which would be cutting, you know, reimbursement to laboratories from the federal government. So, just stay engaged with your professional societies. We both are engaged with them because this is critically important and that's honestly what kind of rattles around in my head when I see these things.

Bobbi Pritt, M.D. (06:10):

That's a good point. What better example do you have to just present and say, "Look, this is laboratory testing keeping us all safe." So, what better example to show why it's important, why we need to be reimbursed so laboratories can keep testing so that they can stay open and perform testing for our patients.

William Morice II, M.D., Ph.D. (06:30):

Exactly.

Bobbi Pritt, M.D. (06:31):

Well Bill, always a lot to talk about and always great to touch base with you. I can't wait to talk about our next topics.

William Morice II, M.D., Ph.D. (06:38):

Yeah, I always look forward to it. So it's great to see you too, Bobbi. Take care.

Bobbi Pritt, M.D. (06:41):

Yeah, thanks Bill. Bye.

Bobbi Pritt, M.D. (06:48):

Welcome to the deep dive where we go beyond the headlines to explore topics in laboratory medicine and diagnostics. Today, I'm excited to be joined by Dr. Elli Theel to talk about one of my favorite topics and her's, vector-borne diseases. Dr. Theel is a clinical microbiologist specializing in infectious disease serologic testing. She's also the director of the Infectious Diseases Serology Laboratory. And together, we co-direct the Vector-Borne Diseases Testing Service. Thank you as always for joining us today, Elli.

Elli Theel, Ph.D. (07:20):

I am happy to be here, as always.

Bobbi Pritt, M.D. (07:23):

So, I figured we could start by setting the scene about vector-borne diseases and this is the time we're starting to get the mosquitoes and the ticks out. So, let's talk a little bit about the growing prevalence of vector-borne diseases and why they're important. Can you speak to that a little bit?

Elli Theel, Ph.D. (07:40):

Yeah, so both of our labs see quite a bit of vector-borne disease test ordered every year. And it increases annually and I think we're seeing just a general increase in the number of vector-borne diseases, both tick-borne and mosquito-borne throughout the United States, and North America really. And part of that, or it's due both I think to just increased awareness in clinicians but also increased infection rates. One of the reasons being that these vectors are really expanding in the areas that they cover. Part of that due to changes in climate obviously, but also just humanity, I think, encroachment into areas where both the vectors as well as the reservoirs for some of these pathogens reside. So multiple reasons that we're seeing increased numbers in vector-borne diseases throughout North America.

Bobbi Pritt, M.D. (08:43):

Yeah, well said. For sure, it's multifactorial, and you and I just wrote a review paper on it. So I'm going to quote some of the figures from that paper. So, ticks transmit more than 75% of all vector-borne diseases. So, I think we're going to focus on ticks for this talk today, and that's the cases that are reported to the CDC. Of course, we know there probably is underreporting, but that greatly outnumbers cases transmitted by mosquitoes, fleas, other arthropods. And June and July, that we're coming up to, are the months with the highest occurrence of tick-borne diseases in the U.S. And as you mentioned, the incidents, so how many new cases of tick-borne diseases continues to rise. Reported cases more than doubled since 2004, and the actual numbers are probably much greater. So, for Lyme disease, this is definitely a focus, the cases are estimated to be eight to 12 times higher than actually reported. So, that corrected estimate places Lyme disease as the third most common nationally notifiable infectious disease in the U.S.

Elli Theel, Ph.D. (09:51):

I think that's just astounding, really.

Bobbi Pritt, M.D. (09:54):

Exactly. So let's talk about Lyme disease, and I'm going to turn it over to you because really serology is the backbone and still gold standard for laboratory diagnosis of Lyme.

Elli Theel, Ph.D. (10:06):

Yeah, so Lyme disease is an interesting one. Infection obviously after that initial tick attachment and transmission of Borrelia burgdorferi in most cases in North America. After that transmission, which takes at least 36 hours of tick attachment for the spirochetes to be effectively transmitted. In most cases, patients will go on to develop an erythema migraines rash, about 70 to 80% of cases will present with that rash. And in those patients, testing is not needed. It's a fairly path …

Bobbi Pritt, M.D. (10:44):

nomonic.

Elli Theel, Ph.D. (10:45):

Thank you. It's a fairly pathognomonic rash and can be diagnosed by a clinician with treatment started immediately. After that initial stage, patients can go on to present kind of non-specific symptoms, in which case serology is really preferred because the organism doesn't really reach a very high level of bacteremia in the blood. So molecular testing is not very sensitive, which is why we rely on detecting that immune response, which takes anywhere from seven to 10, in some cases 14 days to develop. And so we look for that immune response to infection as the reference standard method to diagnose Lyme disease. And then kind of later stages of Lyme, which really in North America are associated with a joint infection. Again, serology will detect all of those cases, but should synovial fluid be collected, molecular testing is actually quite sensitive in that specimen source as well. So there's a place for molecular testing, but it's not the typical assay that's ordered.

Bobbi Pritt, M.D. (11:54):

Right. It's not really the frontline. And you mentioned molecular, that's the area that I oversee, and I'll be the first to note that we really need to look to serology, our clinical signs and symptoms, the suspicion of a tickborne infection for the first line diagnostics. But we do have a PCR that detects Borrelia burgdorferi and the related genome species in that group. It's really good for synovial fluid and fresh tissue if you're taking it from an erythema migraines rash, but not very sensitive in CSF and in blood. The one exception I will mention though is the second recognized cause of Lyme disease in the United States. It's called Borrelia mayonii, and we were part of the team that detected it here and named it after the Mayo brothers who founded Mayo Clinic. And that is actually an instance where the level of the spirochetes, the bacteria that caused Lyme disease, Borrelia mayonii Lyme disease, actually reach high enough levels in the blood that PCR would be useful. And we detected that in 2016 now, so 10 years ago.

Elli Theel, Ph.D. (13:00):

It's been a decade. Along those lines though, the serology assays are really targeting Borrelia burgdorferi and depending on the assay design, it may not pick up antibodies to Borrelia mayonii. So, I think molecular testing really does play a key role for detecting that particular line causing Borrelia. So that's something to keep in mind. Serology may not detect it.

Bobbi Pritt, M.D. (13:27):

Yeah, that's a good point. So sometimes it would be helpful to do a molecular test. Now of course, it's not just Lyme disease. So the most common tick-borne diseases in North America are Lyme disease, but also anaplasmosis, ehrlichiosis, babesiosis, Rocky Mountain spotted fever and the spotted fever rickettsioses and then tick-borne relapsing fever and tularemia. But we know the past two decades we've witnessed the emergence of five additional bacterial pathogens that includes Borrelia mayonii, and another one we detected here at Mayo Clinic, Ehrlichia muris eauclairensis, and then three human viral pathogens. And then we've also had a few that have been detected through our collaboration with the CDC that look like they are probable pathogens, but we need more data to support that. So, it really looks like the landscape is changing.

Elli Theel, Ph.D. (14:23):

That's right. Kind of makes me fearful to go outside and walk in the forest.

Bobbi Pritt, M.D. (14:26):

I know. Well, we'll get to how to protect yourself because we don't want people to just sit inside. Although I agree, I'm sometimes tempted, but maybe you could talk a little bit about the algorithmic approach that we use, Elli, since there are all these pathogens. It's not just Lyme disease.

Elli Theel, Ph.D. (14:44):

Right? So, you listed quite a number, but I think it's important to remember that we don't see all of these pathogens all throughout the United States. So we, you and I, have put together an algorithm like you mentioned, and it really starts by asking the question, "Where has the individual been?" Kind of what region in the country, which based on that, can kind of help clinicians better tailor appropriate test ordering. So for the Midwest, we are concerned about Lyme disease, but also other tick-borne pathogens that are transmitted by the same vector that transmits Lyme disease like anaplasma and babesia. So we kind of go through and recommend what testing to order for those particular pathogens. So once we've identified the region that the patient has been in, we look at the duration of symptoms. So in the vast majority of cases, patients with acute symptoms within the first seven to 10 days, we would recommend clinicians really order molecular testing to detect your anaplasmas, babesias ehrlichias in addition to a baseline serology test for Lyme disease. For patients that present with a longer duration of symptoms and if they're immunocompetent, oftentimes they will have resolved that bacteremia or parasitemia and molecular testing may not be as sensitive, in which case we recommend going, or I should say ordering, serologic testing for those same pathogens. Importantly, we do indicate that for patients with a, you know, for who anaplasma, or are pretty high on the differential, to start treatment while waiting for those results to come back so as to not delay effective therapy for those individuals. And then the algorithm available online really for anyone also outlines how to interpret the results that you get and kind of what we would recommend as next steps or additional testing.

Bobbi Pritt, M.D. (16:48):

Yeah, those are really great points, Elli. And as you mentioned, the algorithm is freely available online and we can include a note or a link to it in the show notes. So I think what you mentioned though is an algorithmic approach. You don't need to order every single test on the testing menu because it could be quite a lot. Having said that, we do continue to innovate and in addition to detecting new pathogens, we've developed new tests. So, there are sometimes times where you would want to order a test that might not be part of the first line of your algorithmic approach. One that you've developed that I think is very useful is the Lyme antibody index. Do you want to just say a brief word about that?

Elli Theel, Ph.D. (17:29):

Yes. So the Lyme antibody index test is really indicated for individuals who present with neurologic symptoms who are seropositive for Lyme disease, have had appropriate exposure and are presenting with various signs and symptoms that would be suggestive of neuroborreliosis. Bell's palsy is one that really comes to mind immediately. And so the Lyme antibody index essentially looks for intrathecally synthesized antibodies specific to Borrelia burgdorferi. And without going into too much detail, the test will detect Lyme specific antibodies in CSF and in serum and then normalize those levels to total IgG and albumin in both specimen sources. So, we're really able to tell clinicians whether Lyme antibodies that we detect in spinal fluid are there due to a true neuro invasive infection versus just passive diffusion across a more permeable blood brain barrier. The Lyme antibody index is actually in both the European and the IDSA guidelines for diagnosis of neuro invasive Lyme disease.

Elli Theel, Ph.D. (18:37):

So, we are one of the few laboratories that offer that test. It's really interesting looking at the positivity rates for that test actually. We see a peak every single August. We go up to about 5% positivity of all of the testing submitted, and that declines down to about 0.5% positivity in the winter months. So, we clearly do see spikes every summer. I think Lyme neuroborreliosis in North America is actually something that's underappreciated. We typically think of neuro invasive Lyme disease associated with Borrelia garinii, which is more common in Europe, but we have quite a bit, I would say, neuro invasive Lyme disease here in North America. And we're happy to offer a test that can detect that easily and effectively.

Bobbi Pritt, M.D. (19:23):

That's great. Yeah, that's great that you offer that. And those are really interesting statistics. And of course we said our tick-borne diseases really peak in June and July, and I wonder if people are getting infected then and then presenting with this later form of disease in August.

Elli Theel, Ph.D. (19:38):

I think that is exactly what's happening.

Bobbi Pritt, M.D. (19:41):

All right, so maybe we should close on how to guide people in protecting themselves from ticks so that they're not sitting inside all summer long, but that they're safe. So, I like to refer to the ABCs of tick-bite prevention. So A, avoid the areas where ticks are found. So, you know, if you're hiking on a trail, staying in the middle of the trail is usually safer. Avoiding the tall grasses on either side, going out into the woods, you're more likely to get bitten by a tick or get exposed to ticks. B is bug spray. And we have the EPA, the Environmental Protection Agency, that has a really nice list of all of the different types of bug spray, how long they're effective for, and whether they're effective against ticks and mosquitoes or just one of the two. And then C would be coverup, wearing protective clothing, tucking your pants into your socks, and of course you can treat your gear and your clothing with permethrin, which gets back to bug spray. So we actually, Dr. Theel and I, for our listeners created an A through Z of ticks, and we're going to include a link to that in the show notes so you can see that as well.

Elli Theel, Ph.D. (20:54):

Bobbi, can I add a D to your ABCs?

Bobbi Pritt, M.D. (20:58):

Oh, please.

Elli Theel, Ph.D. (20:59):

So D is for dogs.

Bobbi Pritt, M.D. (21:01):

Oh, yes.

Elli Theel, Ph.D. (21:02):

A lot of cases of Lyme disease come through patients that have their dogs go on walks with them and then ticks are transferred from the dog to the individual. So kind of just making sure that your dogs are getting tick preventive treatment. There's also a Lyme vaccine for dogs if individuals are interested. So add a D.

Bobbi Pritt, M.D. (21:28):

I like that. Well, especially because the dogs are probably not following the ABCs as well as we would be. They're not avoiding those tall grasses. They want to go right into those tall grasses. I love it. So yes, check out our ABCs, all the way through Z, and maybe learn a little bit more about ticks. Well, Dr. Theel, as always, it was fabulous to have you on our podcast today.

Elli Theel, Ph.D. (21:52):

Happy to be here. Thank you.

Bobbi Pritt, M.D. (21:59):

Let's wrap up with the top takeaways and how to learn even more on the topics we discussed. In the summary of the news today, Dr. Morice reflected on insights from a recent healthcare conference he attended, and we discussed hanta and Ebola virus, two outbreaks, and the importance of laboratory testing in recognizing and tracking and giving us appropriate information about outbreaks. And then in our deep dive summary, Dr. Theel joined me for a conversation about vector-borne diseases and diagnostic solutions helping clinicians as these diseases expand with climate change. We've included links in the show notes to information on vector-borne disease prevalence by geographic region and testing options. You'll also find a link to the full ABCs of tick bite prevention to help protect you as you head outdoors for this summer. Thank you for joining us today. If you haven't already, make sure to subscribe so you never miss an episode. For our next episode, Dr. Anne Moyer and I will explore how clinical testing is improving cancer treatments. I hope you can join us.