Have we gotten Lyme disease all wrong?

Speakers
Faith Dawson, editorial director, Tulane Communications and Marketing
Monica Embers, associate professor of microbiology and immunology, Tulane National Primate Research Center

 

Dawson
Welcome to On Good Authority, a podcast featuring Tulane University experts. I'm your host, Faith Dawson. Unlike many bacterial infections, antibiotic treatment for Lyme disease often fails. And the people who suffer from long-term or post-treatment Lyme disease may be frustrated that they don't get better. But they don't always feel heard. Physicians might tell them their symptoms are too vague or nonspecific to still be considered Lyme disease. After all, the bacteria may be present, or not, in a patient who complains of symptoms. And the tick that transmits the disease is so tiny that you may not even see it until it's burrowed into your skin. More research may be coming out in support of long-term Lyme disease patients, though, proving that, put simply, it's not all in their heads. And some of this research is coming from Tulane labs. We're talking today with Monica Embers, a scientist at Tulane whose research is challenging long-held assumptions about Lyme disease. Her findings may hold the key to solving a medical mystery. Why do some still have debilitating symptoms long after they've been treated? She's also one of the first to document how long-term Lyme affects the brain. Embers is associate professor of microbiology and immunology at the Tulane National Primate Research Center. Welcome to On Good Authority.

Embers
Thanks for having me. It's a pleasure to be here.

Dawson
A recent study found 14% of people across the world have had Lyme disease. How can a tick the size of a sesame seed cause such havoc?

Embers
Yeah, it's very interesting. This is becoming more and more prevalent. And in the United States, we're looking at at least half a million cases per year alone and over 800,000 cases per year in Europe. So it is definitely a big problem. And the size of the tick is a contributing factor, along with the prevalence of the tick. We’re seeing these ticks that spread Lyme disease growing in terms of their amount, the quantity, and also their geographic distribution.

Dawson
Now to be clear, we are not talking about just any tick. We are talking specifically about the deer tick, which is, as of right now, most heavily concentrated in the northeast part of, at least, of North America, but may be on the move.

Embers
Oh, absolutely. One one way to track it is with surveillance studies. And we've seen the ticks, the prevalence of the ticks migrating southward. So we're seeing a lot more cases in Virginia, in North Carolina, and then even in Northern California.

Dawson
So you've been studying this bacterium that the tick transmits for a while. Why is the disease caused by the bacterium so hard to diagnose?

Embers
That's a really great question, Faith. So the classical case definition for Lyme disease is the development of erythema migrans, or bull’s-eye rash, at the site of the tick bite. But we know that people vary in terms of what kind of rashes they develop, how they develop, you know, how big the rash is, how easy it is to see on different skin colors, things like that. And not everybody develops a rash. So that's one factor. The other factor is that we know these bacteria are able to suppress the immune response. And we're using antibodies, which are the immune response to the infection, to diagnose. So sometimes people can be what we call seronegative, even though they have the infection, and it's short-lived in the blood. So once the tick bites, it spreads throughout the body and into the tissue. So it's really hard to pick up the actual bacteria, or remnants of the bacteria, in the blood.

Dawson
So this bacteria is really determined to survive, you know. It’s trying to turn off the signals, am I right?

Embers
Absolutely. And that's what got me into this field. My my interest in microbiology and immunology was based on host, how, how bacteria or viruses can evade host immune responses and persist. And borrelia burgdorferi, the agent of Lyme disease, basically does everything they can to hide and persist in the host.

Dawson
Why is it so difficult to treat, especially in the long term? As a patient progresses from active disease to post-treatment Lyme disease, do the symptoms evolve or change?

Embers
They do, to some extent. I like to liken it to cancer, in that the earlier you you treat the infection, the more likely you are to cure the infection. And that's because what we think is happening is that the bacteria become tolerant to the antibiotic because they start to grow very slowly. And they become dormant and hide out in these tissues. And so, the antibiotics that we use aren't actually killing the bacteria. They're only acting on actively dividing bacteria and relying on the immune system clear to clear the infection. So, patients usually have three main organ systems affected, which can be the the joints, which which would involve arthritis; the heart, which would involve carditis, or cardiomyopathy; and then the brain, or the central nervous system. But it's also what we consider a systemic infection. So these spirochete bacteria travel throughout the body and can wreak havoc in all different types of organ systems. And most people who have what we call post-treatment Lyme disease complain of cognitive difficulties and fatigue most often.

Dawson
Well, I have one more question about diagnosis for you. Assuming a person knows that they have been bitten by a tick, why would a physician not be able to accurately diagnose or treat post-treatment Lyme disease? Like if we, if we knew that they had Lyme disease, if the patient had Lyme disease in the beginning, wouldn't it stand to reason that it would be easier to diagnose that they have the post-treatment variety?

Embers
You would think so, yes, but there is no test for cure. So once patients have been treated, a large group of physicians called the Infectious Disease Society stand by their treatment guidelines, in that they've been given the antibiotic, and whatever is lingering is possibly autoimmune instead of a persistent infection. And so, the research that we're doing is determining whether or not the antibiotics are curative, and how the persistent infection can cause disease, or long-term sequelae, or long-term disease.

Dawson
Okay, that's a great segue. What does your research show and why is it significant?

Embers
Well, I, I am the queen of persistence, I guess. That's kind of my motto. We study, we study persistence. And so, so what are these bacteria doing to persist in the host, if they're not being cleared by the antibiotic treatment? And so, the work that we have done in non-human primates has shown that doxycycline, which is the most commonly prescribed antibiotic for Lyme disease, is unable to cure the infection, especially when the subjects are treated later in the infection. What we call post-dissemination. So that was something that we showed several times in non-human primates, including their invasion of the of the brain after doxycycline treatment. And then, most recently, we we've been looking at human autopsy specimens from patients who have had Lyme disease. And we had one case report of a woman who was treated early with a bull's-eye rash, continued to have symptoms over a two-year span, was treated even more aggressively, even with intravenous antibiotics, and later went on to develop Lewy body dementia.

Dawson
Lewy body dementia, it is it is a neurocognitive decline disease, similar to Alzheimer's in some ways. Is that correct?

Embers
Exactly. There are some differences in terms of the pathophysiology. And oftentimes, you know, the motor skills are affected as well. So we were given her, we were given specimens from her brain and spinal cord. And we were able to find persistent borrelia in those tissues, thus showing that the treatment she received did not clear the infection, and it probably contributed to her neurological disease. So this study of the patient autopsy really showed that the Lyme disease spirochete can persist despite aggressive antibiotic therapy. And I know, you know, our lab has also been working on improving diagnostics. So we have a diagnostic test that we're we're working on.

Dawson
Were you surprised by that discovery? Or were you kind of expecting that that's what you would, what you would see?

Embers
I was surprised in the amount that we saw. Initially, we only saw a few, but as we continue to look deeper in the tissue, we saw a lot more. And so that surprised me, but given what we had shown in non-human primates, I was I was not surprised. And I think, you know, now our efforts are geared towards finding the right type of treatment for all patients at all phases of disease.

Dawson
You were appointed to the Health and Human Services Federal Tick-Borne Disease Working Group (TBDWG), which provides a report every two years. What is your role within this group, and what topics will the 2022 report address?

Embers
This tick-borne disease working group was established under the 21st Century Cures Act, which was passed at the end of the Obama administration. And so, it's been in progress for six years now. So there are both federal and nonfederal members. And I'm considered a special government employee for the purpose of this working group. And we basically have chaired subcommittees focused on specific topics related to tick-borne disease. And I've been involved in, I chaired this subcommittee on diagnostics, because we do a lot of work on diagnostics for Lyme, and also contributed to the treatment and patient-care-type reports. And once, once we have all written the chapters for the for the report, it will go to Health and Human Services in Congress with recommendations for new research. So we're covering diagnostics, we're covering treatment, we're covering patient care, and we're covering all tick-borne diseases, not just Lyme. It's interesting, and it might be fun to point out that the canine Lyme disease test, called the C6 test, was developed and patented here at Tulane University by my predecessor and mentor, Dr. Mario Philipp. And at one point, it was the highest revenue-earning patent for Tulane, it might still be, but but that's, that's been a fairly successful diagnostic test. But we are building on that to make it even better. So that we can, we can diagnose patients throughout the course of infection. And we're also testing vaccines. So how can we prevent the infection, with the quality of vaccine?

Dawson
We all love our four-legged friends, but the the treatment for canine Lyme disease is not the same. It doesn't translate to humans.

Embers
Dogs develop a little bit different disease. They have more of a pyelonephritis. So the kidneys are affected. They don't often show the same signs throughout the same disease course, like arthritis, that humans do. So they don't make a perfect model, like like non-human primates do, for human infection. But they can definitely, they're highly susceptible, and they're good sentinels for the presence of of Lyme disease in a given geographic area. But they're treated with antibiotics like humans.

Dawson
There is no vaccine available, at least not for humans, though Lyme disease was first identified in the late ’70s. While we still wait for an effective vaccine, can you tell us how treatment has changed since that time?

Embers
Well, that's why I'm here. Treatment has not changed. And that's the problem. I believe, and this is based on a great deal of research, that borrelia burgdorferi is a lot like mycobacterium tuberculosis. And when someone gets tuberculosis, there can be a be a period of dormancy, it's a slow-growing bacteria. And we have to treat it with a combination of antibiotics. No one simple antibiotic will cure the infection. And so, we're taking that same approach with the Lyme disease spirochete. And I'm hopeful that, you know, once we get some of our research published, it'll go into clinical trials, so that we can test this on humans and be able to prevent post-treatment Lyme disease.

Dawson
Environmental concerns may increase the amount of Lyme cases we see. Forest loss has been linked to rise in Lyme disease, as have warmer winters. What else do you wish more people knew about Lyme and other tick-borne infections?

Embers
Well, it's true. The incidence is definitely increasing with climate change. We know that there, when there’s warmer temperatures, the questing cycle, or the period of questing where the ticks are out looking for blood, is longer. We have fewer predators for the primary reservoir host, which is the black, the white-footed mouse.

Dawson
And also opossums. Don't opossums eat ticks?

Embers
Opossums do eat ticks, so be nice to opossums.

Dawson
Be nice to opossums. I’m a big fan of the opossum.

Embers
Yeah, and I always I always like to tell people that if you find a tick feeding on you, you should pull that tick off just with, just with tweezers as close as you can to the skin. Don't worry about parts of it staying in your skin or any of those things. Just pull it out and save it, because we can tell by the type of tick what pathogens it could be transmitting. And now there are actually services where you can send your tick off and have it tested to see if it has the Lyme disease bacteria.

Dawson
Wow. Because not everyone will develop the rash. Everyone assumes that they're going to see the bull’s-eye rash, but like you were saying skin tone, and so on so forth, may prevent you from seeing the rash or seeing it clearly.

Embers
Exactly. And yeah, like I said, the tick testing services will help you and help your physician diagnose it.

Dawson
Do you ever hear from from patients with Lyme disease? What do they tell you?

Embers
Oh, Faith, I hear from patients all the time. I almost always, you know, within a week's time, will have an email or two from patients. Now we're beginning to study Bartonella, which is also an infection, systemic infection, very similar to Lyme disease. And we're hearing, I'm hearing from those patients. I think, you know, having the ability to meet with patients when I go to conferences, hearing from them by email, I always try to respond. I can't, you know, sometimes it takes me a while, but I, I always try to respond. It motivates me, it motivates me like nothing else. Because I know that especially, you know, moms who are at a loss for what to do to help their children, breaks my heart. And several of the foundations that have funded my research were started by angry moms who couldn't get help for their kids. And finally, you know, after we published the autopsy report, I've had people who are so sick that they want to donate their tissues to my lab. And that also breaks my heart. And, you know, I tell them, I really want you to get better. I don't want I don't want your tissues. That's that's my goal is to prevent that from happening.

Dawson
What's happening in the vaccine market right now? Are we, are we at all close to seeing something come to market?

Embers
I think we are. There was a, there's a company in Europe called Valneva, that developed a new version of the Lyme disease vaccine. And Pfizer has now purchased that from, or in conjunction with Valneva, and they're running clinical trials to test this. So stay tuned. It's not a perfect vaccine. It's neat in the sense that it blocks transmission. So it's one of these vaccines that will need several boosters. And we definitely have research interest in improving the human vaccines for Lyme disease, too, at Tulane so.

Dawson
Is there anything else that you wish that people knew about Lyme disease treatment or the potential for vaccine?

Embers
Well, I'm I'm very troubled by a recent estimate that came out on post-treatment Lyme disease syndrome. I've been very interested in studying this problem, but I didn't make up the problem. I'm just trying to figure out what's causing it and how we can prevent it. And, you know, this study reported that if we have 10 to 20% of patients who are treated for Lyme disease go on to develop post-treatment Lyme disease syndrome, in the year 2020, we would have had a cumulative number of over 2 million people in our country suffering from chronic illness related to Lyme disease. And so, I think it's very important that we identify all the causes, all the potential causes of post-treatment Lyme disease, and and make sure that we're giving clinicians what they need in order to treat these patients.

Dawson
Is there anything that I've asked, that I haven't asked you, that you would like to address?

Embers
Yeah, I think we can go back to research funding and the purpose of the tick-borne disease working group. Based on the recommendations of prior tick-borne disease working groups, the recommendations have been to increase research funding, because to this point, it hasn't even been close to on par with the number of cases or the public health burden. And so, there will be further recommendations to increase research funding for Lyme disease. And I know that this is really starting to happen at NIH and the Department of Defense. So that's a good sign. I'm I'm pretty optimistic.

Dawson
That's a good sign, you're right. And I'm hopeful that we will get closer to our goal. Dr. Embers thank you for being a guest on our podcast today.

Embers
Thank you for having me on On Good Authority.

Dawson
Thank you again for listening to On Good Authority. I'm your host, Faith Dawson. For more information on this and other episodes, please visit tulane.edu/on-good-authority.