60. Lyme persistence and combination antibiotic research with Monica Embers

Advancing research in Lyme and Bartonella infections.

Episode 60 with Dr. Monica Embers on Looking at Lyme with Sofia Osborne and Catherine Kinsella.

In this podcast, we’re excited to speak with Dr. Monica Embers, associate professor in the division of immunology, director of vector borne disease research, and director of the education and training program at the Tulane Primate Research Center.

Dr. Embers’ research is focused on the detection of persistent Lyme disease in human autopsy tissues, identifying treatments to eradicate Borrelia infection and immunodiagnosis of Borrelia burgdorferi infection and cure. Her team is also developing research models for Bartonella infection.

Researching pathogens that evade the immune system

Dr. Embers became interested in researching Lyme disease while studying other pathogens that evade and suppress the immune system. While living in Pennsylvania, she knew people who were affected by Lyme disease. After reading a research paper describing how the Lyme bacteria Borrelia burgdorferi could evade the immune system, Dr. Embers reached out to an investigator at Tulane University and has been working there ever since. 

“It’s almost like a needle in a haystack. So, we don’t always find persistent infection, but when we do, it’s really striking and it’s really troubling because we know that those patients have been treated extensively with antibiotics in some cases.”

Monica Embers, PhD

Lyme bacteria detected after antibiotic treatment

Dr. Embers discusses the progression of research in persistence of the Borrelia burgdorferi. Following studies by Dr. Barthold that looked at persistence in mouse models, her team wanted to see if persistence occurred in non-human primates. They placed uninfected ticks on primates who had received standard treatment for Lyme disease. Borrelia was found in the previously uninfected ticks, demonstrating that the bacteria persisted after treatment.1

Lyme spirochetes can evade the immune system

Even though her research demonstrates persistent infection, Dr. Embers explains that limitations in testing for Lyme disease make it difficult to know exactly what is causing symptoms after treatment. She discusses several of the mechanisms that Borrelia employs to alter the immune response and evade our immune systems, emphasizing that antibiotic resistance and antibiotic tolerance are not the same. Antibiotic tolerance occurs when a pathogen is able to survive by transforming itself when in threatening environments. For example, when Borrelia detects the antibiotic doxycycline, it can become dormant until that threat has diminished.

“The Lyme disease spirochetes are hiding. They’re in, deep in tissues. They’re hiding…They’re hard to find, and it really takes a lot of effort to find these bacteria in infected animals and in humans. You know, even when they’ve been treated with antibiotics, we can find them.”

Monica Embers, PhD

Antibiotic combination therapy

Some infections, such as mycobacterium tuberculosis, require a combination of antibiotics that act in a variety of ways to combat infections. Dr. Embers’ team has applied this strategy and studied the effectiveness of various antibiotic combinations in eradicating Borrelia. She notes that a variety of combinations have been effective in mouse models, and they are now being tested in non-human primates before going on the human trials.2

“The way that we treat tuberculosis is with a combination of different antibiotics that target the bacteria through different mechanisms. So it might inhibit the translation. It might target…something in the cell membrane, something that will kill the persisters. And that’s the approach that I think we need to take with treating Lyme disease as well.”

Monica Embers, PhD

Addressing ongoing symptoms: we need better tests

Dr. Embers also points out that patients can continue to have symptoms after early treatment for Lyme disease, and that many more remain ill if treatment is delayed. In order to better understand persistence, she reiterates that we need better testing. Her lab is currently doing research in that area as well.

The importance of ongoing learning for patients, healthcare providers, friends and family

Information about Lyme disease can be confusing and overwhelming. Dr. Embers encourages listeners to learn as much as they can, and to be cautious about “not so good” information as well. She points out that it’s challenging for physicians to stay up to date with the latest research for different diseases and encourages patients to bring peer reviewed research to their physician.

“Patients rely on clinicians to know what’s happening in the research area, and I think it’s important to emphasize physician education. I think if you…find different publications and you know that they’re in respectable journals, that they’ve been peer reviewed, bring them to your doctor…They have to understand all these different things. And so expecting them to know all the research and all the data on any particular disease is pretty daunting. And so I think it’s I think it’s a great idea to bring forward some of the latest research, to your physicians and, certainly, educate your friends.”

Monica Embers, PhD

Bartonella and the impact of concurrent infections

Dr. Embers and her team are also studying Bartonella infections. She notes that although the pathogen can be transmitted by ticks, there are other ways it can be transmitted, making it ubiquitous in our environment. Historically, this infection drew attention during the Aids epidemic when immunosuppressed patients tested positive for Bartonella. Dr. Embers’ team is looking at the impact of having multiple infections at the same time and reiterates that better testing is needed to study these diseases. She explains that Bartonella can lead to neurological problems, psychological manifestations and mental health issues, and that, as with Lyme disease, problems with testing can make Bartonella challenging to diagnose.

“I learned so much about bartonella and how it can go undetected…the bacteria are ubiquitous in the environment. They’re ubiquitous in our daily living, and the question that I came up with is if you have a borrelia infection, if you have Lyme disease, does Bartonella become a problem? And, you know, it was first identified…during the AIDS epidemic. And so patients who were immunosuppressed with HIV were coming up positive for Bartonella. And so we’ve been engaging in studies looking at how the coinfection can affect the disease, and I think that’s a pretty darn good hypothesis that, you know, being preinfected either with Bartonella or Borrelia makes you more susceptible to disease.”

Monica Embers, PhD

Ongoing and potential research opportunities

Alongside their research in persistence and exploring new testing modalities, Dr. Embers discusses some of the other research happening in her lab at Tulane. She also touches on the possibility of better understanding maternal fetal transmission by studying it in non-human primates. Thank you Dr. Embers for all of the important research you and your team are doing!

Canadian Lyme Disease Foundation, 20th Anniversary.

Transcript

Catherine Kinsella: Welcome to Looking at Lyme, an educational podcast of the Canadian Lyme Disease Foundation designed to increase awareness, empower listeners with expert knowledge, and explore solutions. I’m Catherine Kinsella.

Sofia Osborne: And I’m Sofia Osborne.

Catherine Kinsella: In this podcast, we’re speaking with Dr. Monica Embers. Dr. Embers is an associate professor in the division of immunology, director of vector borne disease research, and director of the education and training program at the Tulane Primate Research Center.

Her research is focused on the detection of persistent Lyme disease in human autopsy tissues, identifying treatments to eradicate Borrelia infection and immunodiagnosis of Borrelia burgdorferi infection and cure. Her team is also developing research models for Bartonella infection.

Sofia Osborne: Welcome to the podcast, Dr. Embers.

Dr. Embers: Thank you for having me.

Sofia Osborne: So what prompted you to specialize in researching Borrelia, Lyme disease, and Bartonella infections?

Dr. Embers: Well, as a graduate student in Pennsylvania, I began to learn about how different pathogens are able to evade and suppress host immune responses in order to persist. And my doctorate is in microbiology and immunology. And so this was one of the aspects that I found really to be the most intriguing of all microbiology and immunology. And it just so happens that I was studying papillomaviruses, looking at different antibody responses. This was the time when we were starting to develop, you know, the papillomavirus vaccine.

I was looking for different immune responses to parts of the virus, and I started reading about Borrelia burgdorferi because I knew people in Pennsylvania who were affected by Lyme disease. And I came across this article showing a really unique way that the Lyme disease spirochete could evade the host immune response. And it just so happens that this paper came out of the lab that I’m sitting in right now at Tulane. And I emailed the principal investigator, and I asked him if he had any openings for a post doctoral fellowship. And one thing led to another, and he found a way to get me to Tulane, and I’ve been here ever since.

Catherine Kinsella: That’s amazing. Now since you’ve been there, you’ve done a lot of research on persistent Borrelia. Can you touch on the different kinds of research that’s being done regarding persistence and what we’ve learned so far?

Dr. Embers: Yeah. So I started to think about, you know, the model that we work with, which is the nonhuman primate, and how we could best utilize it to answer the biggest questions. And I was really fascinated by knowing all these patients who had been treated with the standard course of antibiotics and still were not cured, physically cured. And so I applied for a pilot grant just to do a small study. And in doing so, we were able to identify persistent spirochetes in nonhuman primates that had been treated with doxycycline, which is the standard of care.

And it was very, very hard to do. The way that we found this was by feeding uninfected ticks on monkeys that had been infected and treated, And those uninfected ticks, when they fed, took up the spirochetes that were still in the bodies of those infected animals after antibiotic treatment. And so I had been reading papers from the Barthold Lab at UC Davis, which is University of California, Davis. And I would say this,Steven Barthold was one of my heroes. Growing up in the Lyme disease field, he was someone that I really looked up to.

He was a veterinary pathologist. And I think he’s retired now, but I think, you know, he’s very well known for characterizing the mouse model of Lyme disease. And he had done a number of studies looking at persistence in that model. And, you know, there are always these critiques. You know?

It’s not reflective of human. Like, what can we do? And I I started to think, you know, what can we do in a nonhuman primate that would help to really answer this question of whether or not the antibiotics we’re using are curative. And so that’s what led me into the studies with nonhuman primates.

Catherine Kinsella: Yeah. Thank you so much for doing that research because it’s just so fundamental in understanding why patients are having ongoing symptoms.

Dr. Embers: Yeah. Thank you. I mean, it’s yeah. It’s a challenge because I think it’s really hard to see. That’s one of the challenges of of Lyme disease is that when patients are infected, there’s no way to actually see the infection.

Like, if we have a urinary tract infection, you can culture the bacteria from the urine. If you have a skin infection, you can culture the bacteria, blood infection, etcetera. Whereas the Lyme disease spirochetes are hiding. They’re in, deep in tissues. They’re hiding.

They’re hard to find, and it really takes a lot of effort to find these bacteria in infected animals and in humans. You know, even when they’ve been treated with antibiotics, we can find them. And you mentioned the autopsy specimens that we’ve been looking at, and I can tell you that it’s almost like a needle in a haystack. So we don’t always find persistent infection, but when we do, it’s really striking and it’s really troubling because we know that those patients have been treated extensively with antibiotics in some cases.

Catherine Kinsella: What are some of the mechanisms that Borrelia uses to evade the immune system? You mentioned about going into tissues. What are some of the other mechanisms that it employs to avoid our immune systems?

Dr. Embers: Yeah. That’s a really good question. There are a number of tricks that the spirochetes play on our immune systems. They have ways of actively suppressing the immune response. They induce the production of interleukin 10, which is a cytokine produced by immune cells, which is suppressive. It suppresses the rest of the responses and the recruitment of other immune cells.

They change the way they look over time, so they have this protein called VlsE which is an antigen that is on the outside of the, on the surface of the bacteria. And as the antibody responses start to develop, the structure, the components of that protein change over time. So the antibody response has to keep up with it. We also know that they change their outer surface in terms of just the mix of lipoproteins on the surface that could be recognized by the immune response. There’s also a system of blood proteins called complement, which help to identify microorganisms, and there are proteins on the surface of the spirochetes that will bind the complement so it can’t be targeted as foreign by our immune response.

It’s just really anything and everything they could do, they do it. It’s really fascinating.

Sofia Osborne: Wow. And what are some of the possible reasons that initial treatments for Lyme disease fail, and what research is being done to tease out those different causes?

Dr. Embers: You know, this is something that has been studied by microbiologists for many years, and Borrelia is not necessarily different. Bacteria have the capability to engage in what is called antibiotic tolerance. We think about antibiotic resistance, and we hear about that a lot. This is different. So antibiotic resistant bacteria have something in them genetically that prevents the antibiotic from working on them, whereas tolerance is a bit different.

And what we know from Borrelia is that these spirochete bacteria are able to enter a slow growing or dormant phase. And like, doxycycline, for example, is an antibiotic that inhibits translation of proteins. And so what that means is that, you know, DNA is used to make RNA, is used to make proteins, and it interrupts that cycle. So when the bacteria are actively growing, the doxycycline will stop them from actively growing. But if they’re just sitting there dormant, that antibiotic will not directly kill them.

So if they’re in a very slow growing state or a dormant state, they can live and persist as long as the antibiotic is, even when the antibiotic is there. And once it’s removed, we’ve shown in vitro, which in the test tube, once it’s removed, those bacteria can regrow. And so what we really need to start thinking about is ways that we can directly kill the bacteria. And I like to use the analogy of mycobacterium tuberculosis. Now this is, we all know this is a dormant, slow growing bacteria that, you know, it can form granulomas in the lung and persist for long periods of time without really causing disease.

And the way that we treat tuberculosis is with a combination of different antibiotics that target the bacteria through different mechanisms. So it might inhibit the translation. It might target, you know, something in the cell membrane, we have another antibiotic that targets something in the cell membrane, something that will kill the persisters. And that’s the approach that I think we need to take with treating Lyme disease as well.

Catherine Kinsella: I know you’ve done a lot of research comparing single antibiotics and combination therapy in nonhuman primates. What have you learned so far, and what are the next steps in that research?

Dr. Embers: Yeah. That’s a really good question. We recently published a study in mice showing that we could get eradication of the bacteria using dual and triple combinations of antibiotics. But whenever we used a single antibiotic, we could not clear the infection. The next step is really to test these combinations in nonhuman primates, which we haven’t completed those studies yet.

We’ve done some, but we haven’t completed them and published them yet. And that’s really, that’s really important, what we call preclinical studies, because we all know that it’s a lot easier to cure certain diseases in mice than to cure them in humans. And because rhesus macaques are so much more similar to humans, if we think we can find a treatment regimen that works in nonhuman primates, I think there’s a good chance that it’s going to work in humans. And so that would pave the way for clinical trials, which, you know, I hate to, a lot of patients will you know, email me and say, you know, what combinations of antibiotics should I use for my Lyme disease? And I really don’t wanna give that advice because if you wanna know what’s gonna work, you really need to do the clinical trials.

And those are not cheap, but they really need to be done. And for all the cancer drugs, for all the new antibiotics that are on the market, all the new drugs that are on the market, they’ve all been through some kind of human clinical trial to determine if they will work.

Catherine Kinsella: This just kind of makes me wonder about the research that you are doing with nonhuman primates and the effectiveness of standard antibiotic treatment. And do you have percentages of the animals that do have persistent infection or persistent symptoms? I guess, I don’t know how you would tell if they have symptoms or not. But, I’m curious to know because we have some numbers for humans, but curious to know if they’re similar with the nonhuman primates.

Dr. Embers: Yeah. It’s definitely a challenge to determine if they have symptoms. So what I can say is that the probability that you’re going to have persistent symptoms increases with the delay in treatment. So we know that from humans. We know that from mice.

In nonhuman primates, the studies that we have done have been exclusively focused on disseminated infection, which means that we waited several months after the infection before we treated them because we wanted to see if the recommended antibiotics for disseminated infection were, in fact, efficacious in nonhuman primates. So we haven’t done those early treatment studies. But if you treat earlier, there’s a good chance that you’ll have, you’ll be able to clear the infection, a much better chance. So in terms of percentages, I don’t have really good statistics for you because we have so few animals that have been involved in these studies, and and it’s pricey to do this kind of research because, you know, we spend a lot of money taking care of them and making sure that everything is done well. It’s very different than rodent studies.

But I think with humans, what we’ve seen is anything from around 14% of patients. I think John Aucott’s shown this. Around 14% of patients treated early go on to develop post treatment Lyme disease. And so if that increases as you, you know, lengthen the duration between onset of infection and treatment, then that, you know, climbs up to 30, 40, 50%. And so it’s really important to have a good diagnostic, which we can venture into next if you want, and to get that early treatment because it will be much more likely to cure the infection.

Catherine Kinsella: So, yeah, if you could go ahead and talk a little bit more about good diagnostics, what you’re seeing coming up in the research now.

Dr. Embers: Yeah. So I think for Lyme disease, the holy grail appears to be a direct detection test or an early detection test. And what we have now is called the 2 tier test, at least in the United States, this is what’s most commonly used, and it’s only about 50% sensitive, meaning half of the people who get tested may be positive, and it won’t be detected. And that’s because it takes a while for antibodies to develop after the tick bite, and this is an antibody based test. And so there are a couple of different approaches that you can take.

One that we have taken is to to look at how antibodies develop over time and to try to target those very early responses, which are which are IgM immunoglobulin, on the early antibodies or IgM, those can persist in Lyme disease, which is which is odd, and also IgG which are later developed antibodies. So, when you combine those, then you have a better chance of diagnosing patients throughout the course of infection. So this is something that our lab has been very interested in studying and working to develop a better test. The other option is to directly detect the bacteria, and you can do that by detecting their DNA, their RNA, or their protein. And the challenge with that is that once the tick feeds, the bacteria are regurgitated into the bloodstream, and they exit the bloodstream fairly rapidly and start to enter the tissue.

So the length of time that Borrelia is bloodborne is a fairly narrow window. And so you have to have a method that is highly, highly, highly sensitive in order to detect the bacteria early in infection. And so there have been a lot of really novel strategies at doing this. There are some  good potential tests. And then the challenge, you know, for scientists is, okay, we’ve invented this test.

We’ve used it on animal specimens. We’ve used it on human specimens. We know it works pretty well. Now what? Right?

We need investment from commercial entities, from investors, big pharma, somebody to invest in it in order for it to get to market. And so, that’s one of the big challenges, and this is no longer a small market. Right? We have in the United States alone, we have almost half a million cases and over 3 million tests between 3 and 4 million diagnostic tests run per year. So, hopefully, we can get some more investment from industry on this.

Catherine Kinsella: There’s hope on that front. That’s for sure.

Dr. Embers: And the government, at least the US government, has been investing in Lyme disease diagnostics as well.

Catherine Kinsella: How do patients or listeners better understand what the research means? Different levels of research?

Dr. Embers: I think that’s I think, you know, that’s a really good question because patients rely on clinicians to know what’s happening in the research area, and I think it’s important to emphasize physician education. I think if you, you know, find different publications and you know that they’re in respectable journals, that they’ve been peer reviewed, bring them to your doctor. Why not? You know? They don’t have to listen, but, you know, I don’t envy clinicians because they don’t have to just understand one disease like I do.

They have to understand all these different things. And so expecting them to know all the research and all the data on any particular disease is pretty daunting. And so I think it’s I think it’s a great idea to bring forward some of the latest research, to your physicians and, certainly, educate your friends. There are different websites out there and, you know, groups and some, you know, you have to be careful about, you know there is some not so good science out there, and there is some not so good information out there.

And so it’s important to get the right kind of information to patients, friends, advocates, and physicians.

Sofia Osborne: Absolutely. And your team is also studying Bartonella infection. Have you started to look at persistence there as well?

Dr. Embers: Oh, Bartonella. Yes. So what has really interested me about Bartonella is that it’s kind of, it’s a lot like Lyme disease in the sense that it can be very difficult to diagnose and also very difficult to treat. I wouldn’t even be looking at Bartonella if it weren’t for a physician named Neil Spector, and I don’t know if you know who he is. But I began working with him on a project several years ago focused on trying to develop live imaging diagnostics for Borrelia.

And he said, well, we should look at Bartonella too. Can you just develop a mouse model so we can do this? And I said, oh, okay. Sure. And then I started to read, and well, that was a very difficult task. 

I’ll just say that. But it made me realize I learned so much about bartonella and how it can go undetected. It’s you know, the bacteria are ubiquitous in the environment. They’re ubiquitous in our daily living, and the question that I came up with is if you have a borrelia infection, if you have Lyme disease, does Bartonella become a problem?

And, you know, it was first identified really, you know, became prominent during the AIDS epidemic. And so patients who were immunosuppressed with HIV were coming up positive for Bartonella. And so we’ve been engaging in studies looking at how the coinfection can affect the disease, and I think that’s a pretty darn good hypothesis that, you know, being preinfected either with Bartonella or Borrelia makes you more susceptible to disease. And, you know, there’s some controversy about whether or not ticks transmit Bartonella. What do I think about that?

Well, I think ticks can definitely, they can, transmit it. We’ve shown it in the lab. But how frequently they do it is not on par with how frequently ticks transmit the Lyme disease bacteria because I think there are much different mechanisms. And I just think, like, a lot of people probably have subclinical Bartonella infections or, you know, they’re sick with Lyme, and they acquire Bartonella, and then they become, then they test positive. And it’s really important to focus on direct detection for Bartonella because a lot of us have been exposed and will probably have antibodies.

So it doesn’t mean that you have an active infection. But, yeah, Bartonella has become very fascinating to me, especially because of the neurological complications that can come with bartonella, especially when it comes to psychoses and mental health. The studies that are coming out that are linking Bartonella with psychological disorders and mental health problems is really, really troubling. So we’re obviously looking for bartonella in our autopsy specimens as well.

Catherine Kinsella: As you’re learning more about it, what can you tell us just about the testing that we have right now for Bartonella? And would it be similar in nonhuman primates and humans? And are there any challenges with that testing?

Dr. Embers: Yeah. So the testing is really not that good right now. If you go to your physician and say, I think I have bartonella, they’re probably going to order an antibody test. And, you know, you might get lucky and see an IgM positive, but most likely, it’s gonna be an IgG test, and it doesn’t necessarily indicate an active infection, like I said. So there are only some specialty labs that do really good bartonella testing.

And what this requires, and I’m thinking of one in particular, and what they do is they take large quantities of blood. They culture it in a special growth media for bartonella, and then they use a sensitive detection method to pick up the DNA. And that’s really the way you have to do it. And so this is not something that’s standard and on the market right now, but there are specialty labs who run these tests. And in terms of the animal models, I’d love to say that the nonhuman, there’s a nonhuman primate model for Bartonella, but we really don’t have one.

We know that Bartonella quintana is found in a lot of rhesus populations, rhesus macaque populations, and they’re a natural reservoir host. So they don’t really get sick with it. So, you know, a lot of rodents like, if you do surveys of rodents out in the environment, you’ll see lots of different kinds of Bartonella. Doesn’t mean they’re sick with it. Right?

So finding the right animal model that becomes ill with the specific bartonella species is a challenge. And a lot of times, it requires some immune suppression to see that manifest.

Sofia Osborne: Is there any other research happening right now that you’re excited about?

Dr. Embers: I’m excited about a lot of different things that we’re doing. We’re looking at tick saliva and how tick feeding affects the characteristics of the bacteria and thinking of ways that we can use tick saliva to improve diagnostics and therapeutics to bring the spirochetes out of hiding in the body. We’re also looking at immune therapies. So what we know is that patients who are treated with doxycycline, for example, and don’t get better, it’s because they don’t generate good immune responses. So what we wanna do is, you know, we’re working on finding ways to to look at the the phenotype or the characteristics of the bacteria after treatment with doxycycline and use those characteristics to develop antibodies or, you know, to make synthetic immune responses for patients who don’t make their own good antibodies, and how could we use those therapeutically as well?

So we’re interested in antibody based therapeutics. We’re working on our diagnostic tests. We’re working on tick saliva. We’re working on Bartonella animal models. We’re interested in testing combination therapy for Bartonella too because there is no regimen that’s known to be effective for treating all species of Bartonella.

And so that’s another black box. Yeah. We’re we’re we’re very busy over here at Tulane.

Catherine Kinsella: Thankfully. So I had a question about maternal fetal transmission of Borrelia and just wondering if nonhuman primate model is a good model to learn more about that mode of transmission.

Dr. Embers: Thank you for that question, Catherine. And I think, obviously, I think it is. The physiology of humans and nonhuman primates is very similar when it comes to, for example, the placenta. So mice give birth to multiple pups. We typically give birth to 1 or hopefully, 1, sometimes 2 or more, but the the physiology is such that it would be an excellent model to test not only transmission of the Borrelia spirochetes across the placenta but also any inflammatory disease that occurs with a Borrelia infection during pregnancy.

And so this area of research, we’ve seen studies in animals and case reports in humans to indicate both that it can happen and sometimes it doesn’t happen. So we really need to get to the bottom of this and figure out, you know, one aspect that I think is really important is what is the immune response of the fetus, of the newborn, compared to someone who acquires the bacteria by a tick bite? Because we know that the characteristics of the bacteria coming from a tick are different when they’re, when it’s transmitted from one host to another. And so, do we need to modify our tests to be able to detect infection in the offspring?

Catherine Kinsella: Thanks for joining us today, Dr. Embers.

Sofia Osborne: Thank you so much. Was there anything else you wanted to add or talk about?

Dr. Embers: No. I just wanna thank you for the opportunity to speak on your podcast and let you know that Canada is on our mind as well. I know that cases are rising there and migrating throughout Canada. And so keep up the education.

Sofia Osborne: We will. Thank you so much. That was such an interesting interview with Dr. Embers and just the amount of research that her lab is doing into all of these different issues related to Borrelia and Bartonella, and it was really inspiring, and she’s just so knowledgeable.

Catherine Kinsella: Yeah. Her research regarding persistence of infection has been so fundamental in helping us understand what’s going on with patients after treatment. And also just kind of looking at the different mechanisms that these bacteria use to escape antibiotic treatment and to adapt to different environments and then reemerge when they’re in a safe environment. It’s just so important to understand that when considering what’s happening with the patient as well. Definitely.

Sofia Osborne: And make sure to tune in next time as we engage with more experts from Canada and around the world.

References

  1.  Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding
  2. Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease

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