ALL ABOUT KIDS WITH LYME, PANS, MOLD ILLNESS

Ticktective Podcast Transcript

 

In this conversation between Ticktective™ host Dana Parish and Harvard-trained pediatric infectious diseases specialist Charlotte Mao, MD, the discussion focuses on how Dr. Mao gradually moved away from the narrow view of Lyme disease and began to champion understanding and therapeutics for children suffering from persistent Lyme. They explore tick-borne diseases and their connection to other chronic illnesses that are often misunderstood and misdiagnosed by conventional medicine. Note: This transcribed podcast has been edited for clarity.

Dana Parish: Welcome to the Ticktective Podcast, a program of the Bay Area Lyme Foundation, where our mission is to make Lyme disease easy to diagnose, and simple to cure. I’m your guest host today, Dana Parish. I’m the co-author of the book Chronic, and I’m on the advisory board of Bay Area Lyme Foundation. This program offers insightful interviews with clinicians, scientists, patients, and other interesting people. We’re a non-profit foundation based in Silicon Valley, and thanks to a generous grant that covers a hundred percent of our overhead, all of your donations go directly to our research and our prevention programs. For more information about Lyme disease, please visit us at bayarealyme.org.

Dana Parish: Hi I’m so excited to guest host the Ticktective podcast today. I want to introduce you to a very dear friend of mine, one of the most brilliant, curious, interesting, funny, and dearest people. Please welcome Dr. Charlotte Mao. She is a pediatric infectious diseases physician with a special focus on Lyme disease and associated infections. She received her medical degree at Harvard Medical School and did her pediatric and infectious diseases training at Boston Children’s Hospital. The first 25 years of her career were focused primarily on pediatric HIV clinical care and clinical research, serving as a site co-investigator for numerous NIH funded multi-center pediatric HIV clinical trials at Boston Children’s Hospital. She turned her focus to Lyme and associated diseases after gaining extensive clinical experience with pediatric Lyme patients in Boston children’s hospital’s referring ID clinic. Then she joined the Pediatric Infectious Disease Department at Mass General Hospital and Spaulding Rehab Hospital Dean Center for Tick-borne Illness, where she was the pediatric IG specialist in a multidisciplinary clinic for children with complex Lyme disease. She is currently curriculum director for Invisible International. She most recently served on a tick-borne disease working group subcommittee for prevention and treatment and co-organized a Cold Spring Harbor Laboratory Banbury Conference on perinatal transmission of Lyme Disease. She’s also on the Bay Area Lyme Foundation’s Science Committee. Welcome, Charlotte. It’s so great to see you!

Charlotte Mao: Thank you for that lovely introduction.

Dana Parish: So, I really love your story so much about how you transitioned from an ID HIV specialist into learning so much about Lyme disease and its associated infections. Would you share a little bit about that?

Charlotte Mao: As you said in the introduction, I was focused for the first part of my career on HIV and that was when I started seeing lots of patients in a general referral ID clinic at Boston Children’s Hospital clinic where pediatricians refer types of infectious disease problems. And it turns out that this is in Boston, in the northeastern United States where Lyme is highly prevalent. Lyme disease was the single most common reason for kids being referred to this clinic. And it was an enormous learning experience for me. I entered medicine with the standard teaching that I was taught as a medical student and with my pediatric and infectious disease training. And I gradually came to realize this is a narrow view that doesn’t begin to reflect the full complexity of this disease. (My view evolved) over a couple of years, very gradually as I saw many cases. And if you think about it, pediatricians are going to refer a case for specialty evaluation at a children’s hospital. It’s going to be a more atypical case. It’s not going to be the standard presentation or standard response to treatment, because then the pediatrician wouldn’t need to refer it. So, I was seeing cases that at least are considered atypical according to the standard paradigm. But everything in medicine is pattern recognition. I started seeing repeated kinds of presentations and things that weren’t something I was aware of that Lyme disease could present us. I was reading very deeply into the primary literature, both basic science and the clinical literature, and I realized there’s a lot in the primary literature that speaks to a much more complex constellation of symptoms. Then I was hooked and reading everything I could about Lyme disease and really trying to educate myself. And it led me to turn the focus of my career to entering Lyme disease treatment and the care of kids with these complex conditions.

Dana Parish: Was it surprising to you how controversial this is? This topic of chronic Lyme? I speak to a lot of physicians, and I went through my own chronic Lyme illness in 2014 where I was dismissed, like there, there’s no such thing. I saw three infectious disease docs. They said, it doesn’t even exist. It’s a fake disease and all kinds of stuff. And it was so demoralizing to go through that. And as a clinician, when you’re learning certain parameters and guidelines, is it mind blowing to really go down this rabbit hole?

Charlotte Mao: It was, I actually used that word. I felt like I was going down the rabbit hole as I was learning about Lyme disease, because I knew that there was some controversy in the field, but I didn’t know details or the depth of it. I did have this idea that there are these patients who think that they have chronic Lyme and there’s a group of physicians who are sort of ‘alternative’ or even somewhat ‘fringe’ who see these patients. And I think that the attitude that, or the view that physicians are taught is to have anything from skepticism to derision, is how I perceived the view of the patients and the other clinicians that cared for these patients. So, as I started to realize I think that there might be some validity to this other point of view, it was a very eye-opening experience.

Dana Parish: There is so much literature that speaks to and references chronic Lyme, especially from the Infectious Diseases Society of America, the IDSA. There was a huge body of incredibly wonderful research done. And then at some point it sort of stopped. It tapered off and the whole thing changed. I reviewed a Newsweek article recently from the eighties—I’m sure you’ve read it—where it was on the front cover of Newsweek about Lyme, and saying that if it wasn’t for HIV, it would be the biggest and worst disease of our time. And it talked about congenital Lyme, and it talked about how prevalent it was in California and all over the place, and how many people were sick from it. It was this wonderful in-depth article that laid it all out. And now we don’t even acknowledge any of these things as being true anymore. It’s the craziest thing to think about an infectious disease that’s so prevalent all over the world and has been politicized. It’s just so sad for patients. You have been such a gift to the Lyme community because obviously you are Harvard-trained physician scientist and with the most incredible bedside manner and brilliant mind. I’ve heard from many of your patients over the last few years how grateful many of them are that you’ve made better. So, what should parents look for? What are the signs of Lyme or chronic Lyme in children?

Charlotte Mao: Lyme can present in children in the same ways that it can present in adults. So, let’s talk about what are the most commonly recognized manifestations. Of course, there’s the so-called ‘bullseye’ rash that can happen at the site of a tick bite, right? But in fact, it’s often not a bullseye appearance, and that’s important to know. More commonly, it’s homogeneous. So, it’s red throughout instead of that target/bullseye appearance. And  we see that it has an expanding progression of the rash.

Dana Parish: Do people always see the rash?

Charlotte Mao: No. So, that’s another important thing; There’s lots of people who present, without any recollection of having a rash. And the estimates for how common the rash is very widely. It’s said that up to 70-80% of people will have the rash. But when you look at the earliest papers that described Lyme arthritis only 25% of people recalled ever having a rash.

Dana Parish: That’s, that’s a big deal for people to understand. You don’t have to have the rash in order to have Lyme. Are there strains of Lyme that don’t produce a rash? Because I know there are so many strains that we’re dealing with.

Charlotte Mao: Well, that’s something that really needs to be studied more. There are different variants or strains of the Lyme bacteria, which is called Borrelia burgdorferi, and what kinds of symptoms they can manifest with. And that’s something that was studied earlier, and you can find in the historical research literature. But this didn’t get fully fleshed out and didn’t continue to be studied. So, that is something that definitely deserves more research.

Dana Parish: You just made me think about how Lyme’s discovery in children was made because of a cluster of kids who got juvenile rheumatoid arthritis in Lyme, Connecticut. Do you still commonly see that? Do you think that juvenile RA is highly associated with Lyme?

Charlotte Mao: Well, Lyme has been very aptly dubbed the new ‘great imitator’ because it can mimic so many other conditions. Interestingly, the first great imitator was syphilis, which is also a spirochetal disease similar to Lyme disease. It can present in stages with a wide variety of manifestations, multi-symptom, multi-systemic symptoms. But going back to your question about the arthritis, yes, that can be the first manifestation in children just as it can be in adults, that all of a sudden you present with a swollen knee that is often swelling out of proportion to the pain. Lyme arthritis does most commonly affect large joints, often a single joint, but the important thing to know is that yes, that is the most common, but it can in fact present in a whole variety of joints, including small joints. And that was something I was very surprised by when I went to the original papers. When you go back to the historical literature and read the papers that the earliest researchers wrote, there are just beautiful clinical descriptions of Lyme and the heterogeneous symptoms and signs that could be seen. I was so surprised because that’s what pediatricians are always taught about large joint monoarthritis, meaning it affects a single joint, but in the paper, it says that occasionally it could present in the small joints of the hands and feet. And in fact, it was in 30% of patients. That really surprised me when I read that.

Dana Parish: That’s very surprising. And I also feel sometimes when I talk to parents whose kids have ‘growing pains,’ I’m often suspicious that growing pains could be associated with vector-borne diseases like Lyme. Do you think that’s a fair thought to have?

Charlotte Mao: It is. I had growing pains actually growing up and I think it’s a real phenomenon. It’s not just that the kid is complaining of pain without an organic reason as we like to say in medicine. My personal suspicion is that a common co-infection of Lyme called Bartonella, could be a root cause of growing pains. But that’s just my personal suspicion. Very interestingly, Trench Fever in soldiers from World War I is caused by another species of Bartonella. In fact, deep-seated shin pain was something that was described in an article about Trench Fever.

Dana Parish: What is Trench Fever?

Charlotte Mao: It was a febrile illness that was seen in soldiers in World War I when they were in the trenches. And it was similar to Cat Scratch Disease, which is the most common manifestation of Bartonella that doctors generally know about. In the case of Cat Scratch Disease, the cats have fleas. The cats groom themselves and they can get the bacteria on their claws, and then they scratch you. And you get what can be a swollen lymph node in the area that drains the site where you were scratched. If you’re scratched on your arm, you might get a swollen lymph node in your armpit. With Trench Fever the insect factor that transmits it is the body lice that affect the body. You can imagine that soldiers are in cramped quarters in the trenches. That’s a ripe environment for something like body lice to spread.

Dana Parish: That is a horrifying thought. Talk to me about kids and psychiatric issues. What I hear a lot from parents are things like: it was like a lightswitch turned on or turned off in my kid’s brain where they changed overnight, their personalities changed overnight. I hear about this so much. Kids get sudden anxiety, depression, insomnia, OCD; they’re throwing a chair in the classroom where they were the most well-behaved child, or their grades are getting poor, they can’t concentrate. Do you see this a lot? And can you talk a little bit about neuropsychiatric issues?

Charlotte Mao: I think that psychiatric and neuropsychiatric manifestations of Lyme disease and associated infections, including in particular the Bartonella that we were just talking about are very underappreciated manifestations of tick-borne diseases. This was something that I really was not aware of when I started seeing Lyme patients. Again, when you go back to the historical literature, many of the early reports of neurologists who were seeing patients early on, including kids, described psychiatric manifestations. It’s very interesting that, as I mentioned before, that syphilis, another spirochetal disease, can be a great mimic, and can also present with psychiatric manifestations. At the turn of the century, a large proportion of patients were in mental institutions with things like anxiety, depression, etc. Also, you mentioned rage. This anger, aggression, rage is considered to be more characteristic of Bartonella by clinicians. A lot of patients with complex Lyme disease and associated infections present with OCD-type of behavior, obsessive compulsive behavior. There is a constellation of syndromes called PANDAS. Lyme disease and associated co-infections can be a trigger for this. Pediatric PANDAS stands for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Strep. This is the strep bacteria that causes strep throat, and this was first described in the late 1990s by a researcher at the National Institute of Mental Health. At that time, it was initially described as children who presented with sudden onset of OCD behavior as well as motor tics, that’s T. I. C. S., not ticks, the insects. Doctors noticed that this could happen in the setting of a strep infection or a recurrent strep infection. What was postulated is that there was a similarity to this with what is called Sydenham’s Chorea. This is a manifestation of rheumatic fever, also well-known post-streptococcal phenomena. It can present with a constellation of manifestations, for instance, arthritis or carditis inflammation in the heart—valvular involvement being potential manifestations. But Sydenham’s Chorea is a movement disorder, but it also has prominent psychiatric and neuropsychiatric manifestations.

Dana Parish: I didn’t know that. That’s so interesting.

Charlotte Mao: Yes. It’s so interesting. A very famous physician named William Osler who’s considered the father of modern medicine, actually described this in the late 1800’s. He had a manuscript on Chorea. He described these children with Sydenham’s Chorea and the neuropsychiatric manifestations that they had. It’s just striking to read because it really makes you think, “Wow, this sounds very similar to what you see in kids with PANS/PANDAS” and the kinds of neuropsychiatric manifestations that they have. So, yes, there is a very significant manifestation in children, and they can be severely affected where it’s really life-altering symptoms that are extremely distressing both for the child and the family.

Dana Parish: One of my dear, dear friends has a son who has PANS and has been going through it for five or six years. You’ve been so helpful to this family. And it’s just absolutely devastating. It was one of those ‘light switch’ cases—he was just a happy, healthy, go-lucky kid. Then all of a sudden, boom, he just completely changed in every way. He had body pain and nausea and severe OCD and couldn’t sleep anymore. And I’m so glad that we can talk about PANS because so many physicians don’t really know about it at all. I don’t even know that it’s so controversial, more than it’s just not recognized as much as it should be. Where should parents go? How do they even get a diagnosis? What hope is there for them to lead them on the right path and lead them out of this? Because it’s so devastating. I’d love to hear about some of your hopeful cases. I know you’ve helped a lot of kids.

Charlotte Mao: Yes. So, as I learned about this disease, I was so impressed with parents who really trusted their intuition. You know, they knew their kid and they knew there was something more than what they were being told. And they kept at it. And frankly, they educated me. So, I would say, because Lyme disease and these associated infections can present a very confusing constellation of symptoms and signs, and because we aren’t well-taught as physicians about the hugely heterogeneous symptoms, it’s no surprise that doctors won’t necessarily consider Lyme disease or one of these other associated infections.

Dana Parish: I think it’s so underappreciated as you’re talking. It’s blowing my mind how many people that you and I both know personally in common (who have dealt with this), just in our regular old lives, not even in the Lyme world.

Charlotte Mao: I agree with you. I think it is much, much more common than is generally realized by either the public or the medical community. And, frankly, a lot of people do not have symptoms. You can have infection with these organisms and have no symptoms and stay that way for your entire life. And that’s what’s so confusing.

Dana Parish: So, is it a certain strain that causes different manifestations in one person versus another? Is it the host themselves, some type of genetic predisposition? Is it the other co-infections? Is there a tipping point for us humans? Different hits? And I also want to talk to you about latency, because I think that’s a huge issue that is so under-recognized as well, where you get the initial bite or infection, and then you have a long period where you may feel pretty good and then boom (the disease hits), and you don’t connect it back (to the bite/scratch).

Charlotte Mao: Yes. I do think that in many of these patients who present with a more complex and prolonged constellation of symptoms that don’t respond to standard treatment courses, that what you are dealing with are a ‘multiple hits’ model of illness where Burgdorferi— the agent of Lyme disease—is just one hit, one infection. There can be a multitude of co-infections, some of which are also transmissible, through a tick bite. But frankly, other ones that can be infections acquired in other circumstances. For instance, with Bartonella, it’s considered controversial whether it’s actually transmitted by ticks, even though the organism has been documented in ticks and different tick species all over the world, that whether they’re actually efficient vectors to transmit it is not clear. However, it’s transmitted by a multitude of other insects. I mentioned, you know, lice for one, one species of Bartonella fleas for another.

Dana Parish: And spiders,

Charlotte Mao: Oh yes. It could have been a preexisting infection also that was asymptomatic or latent as you mentioned. But then boom, boom, you acquire these multiple hits over time. And one of them can be the straw that breaks the camel’s back. Or the thing that makes your bucket overflow. And finally, you present with symptoms.

Dana Parish: Yes. I feel like I see that. And I have to say in this day and age, I would feel remiss not to mention how often I think I’m seeing it where Covid is activating latent or pretty minimally symptomatic cases of Lyme and Bartonella . I hear from so many Lyme patients who got better and then they relapse after a Covid infection with the same symptoms. They get retreated for their Lyme and Bartonella and they get better. So, it has to be studied, but I feel comfortable saying this. I feel comfortable speculating.

Charlotte Mao: I do too, because of how commonly it gets reported.

Dana Parish: Since we’re touching on Covid, can we talk a little bit about the overlap and symptoms between Bartonella and Covid. I’m going to talk to Dr. Ed Breitschwerdt later today about this as well. I see an overlap, but I’m not the doctor. So, what do you think?

Charlotte Mao: What I do wonder about is exactly what you described. Are these preexisting, asymptomatic, or minimally mildly, moderately symptomatic? It’s the whole spectrum that you can even have intermittent symptoms with. It’s not like the symptoms are continuous. With these illnesses it’s their very nature that they can be relapsing remitting illnesses. And then you get this additional hit that can really trigger the infection to become active. So, yes, in terms of the symptoms—as we mentioned before— we see neuropsychiatric manifestations. I have seen in my patients who have complex Lyme borrelia, that anxiety is a very common symptom. Of course, it’s a common symptom overall, but sometimes it can be almost a physical anxiety in patients. 

Dana Parish: Internal vibrations too. We hear a lot about vibrations.

Charlotte Mao: Yes. That’s an unusual symptom. But one that yes, clinicians who see a lot of these patients think it could be more associated with Bartonella again. 

Dana Parish: And Covid, we’re hearing it so much with Covid. 

Charlotte Mao: Yes! So, could it be Covid be activating Bartonella just as you described before. It’s logical to think that that could be the case. Other infections can do that, so why not Covid?

Dana Parish: Yes. And it’s a weird and unusual symptom to describe. And yet you and I hear it described historically with Lyme and Bartonella, probably more with Bartonella. I had it and I know you’ve had patients with it. And it’s so bizarre. I am part of some Long Covid groups because I did some interviewing for the book about Covid. I’m really interested in the patient experience and what the researchers are learning. They all talk about this internal vibration feeling. And it’s finally being studied and taken seriously. I think it was one of those weird things that nobody knew whether it was real. Clinicians would say, ‘I don’t know. I don’t know what to tell you about that.’

Charlotte Mao: Yes. I do think that that symptom is maybe more reported by adults than children. Why that’s the case, I don’t know. Is it that you have the organism for longer?

Dana Parish: That’s an interesting delineation to hear, that there’s not as much of an overlap with kids with that symptom.

Charlotte Mao: Or do they not have the language to be able to describe that symptom? Because it is such an odd symptom. A lot of times adults don’t want to re report it to their doctors because they think it sounds crazy.

Dana Parish: I would describe it like I was being plugged into an electric socket and there was just a current that would go through my whole body. You couldn’t see it necessarily. But it was there, and I’d wake up with it. It’s a really, really intense sensation and scary because you don’t know if it’s some neurodegenerative thing taking hold. If you’re me and you’re thinking ‘Oh my gosh, I have Parkinson’s.’ It’s really scary. As you know, these are my 3:00 AM panics. So, one of the things that you have taught me so much about is the role of mold in these cases. And just in, I’m not talking exclusively about kids, adults too. It’s so under-recognized in the medical world. Yet I looked online before our conversation just to see, but the CDC acknowledges the severity of mold and there’s so much research on how toxic they are and can cause cancers. They can be used in bio warfare; they can totally poison people like literally to death. And you do hear about this with adults. I can’t speak to kids saying this, but this feeling of being poisoned. I have heard that many, many times. And then people go on sometimes to discover that mold is playing a major role in either their illness or in holding them back from healing. What is your take on all of this?

Charlotte Mao: So, mold and specifically the toxins that the mold produces are called mycotoxins. That’s what we’re talking about here. These can really impact patients with persistent Lyme and Bartonella and other co-infections. It’s something that I actually learned about as I was seeing patients in this clinic for kids with complex Lyme disease. Other physicians had diagnosed one of my early patients with a number of mycotoxins complicating their illness. And it’s interestingly something that doctors really are not taught about in medical school and in their training. So, what we are taught is that mold can cause invasive fungal infections in people who are immunocompromised, for instance, transplant patients and also allergic type disease, for instance, asthma. But the idea that mold toxins could complicate a  chronic persistent infection like Lyme disease or Bartonella, is something that really is not recognized or discussed in standard medical training. We also find there is a lot of interesting literature in the veterinary literature because animals get exposed to these mycotoxins in their animal feed. There’s some mold in their food. It’s just in the food supply. But the other major place is in water-damaged buildings that get contaminated by mold. Again, lots of people are exposed to this, right? So, why are only certain people so dramatically affected? I would say that this is an emerging science and a lot more research needs to be done in the area. But there is a group of clinicians who really have seen many patients with mycotoxin health-related effects and have developed expertise in how to manage these patients. And what I was seeing, what I was taught and what I found in my patients is that if you have a patient with say, persistent Lyme symptoms, or Bartonella symptoms that hasn’t responded well to standard treatment, you need to think, ‘Is there something else? Is that another hit that’s preventing them from being able to respond well to treatment?’ And mold toxins are, I think, something that can be a common hit and that in a subset of patients can have a very negative impact. There can be overlap in symptomatology, but also effects that basically make it difficult for that patient to respond to treatment.

Dana Parish: I found it very interesting to learn about the neurological impacts of certain molds. Can you talk a little bit about that and also the neuropsychiatric impact?

Charlotte Mao: Yes. There are certain mold toxins that have been well delineated to cause nerve, neurologic and psychiatric symptoms including, for instance, there are even ones that are called tremorgens because they cause tremors. It’s unclear what the actual mechanism is in patients with Lyme disease or Bartonella.  How is mold making those or worsening or making manifest those neurologic or psychiatric symptoms. But one thing that I think could be possible is that basically they are worsening the co-infections, the borrelia or the Lyme. And so, making their neuropsychiatric and neurologic manifestations more severe.

Dana Parish: I sent you this episode of a show about a family who was all poisoned, which was a documentary style show, and wasn’t a fictional representation where they all died. The mother, I think she was the first she had gotten sick, or no, the husband got dementia. He was very young.

Charlotte Mao:I remember that.

Dana Parish: It was horrific. And that’s an extreme case, but very common, and very commonly under-recognized. Nobody is talking about this. And I find it extraordinary. I think it’s responsible for so much chronic illness, so much asthma. My friend’s son developed asthma when he was around nine or ten, and she had an inkling that it could have been mold and she had people come over and evaluate the house. She was correct. They remediated mold and her son’s asthma went away. So, I hear these stories and asthma is the tip of the iceberg, as asthma’s the obvious thing, right? The one we think of. But when I think about its role in neurodegenerative diseases like that case, who knows how often that’s happening? We know infections can also cause dementia and neurological and neurodegenerative diseases, but these things just seem so symbiotic to me.

Charlotte Mao: Yes, I agree. They’re, they’re all very common in and of themselves. So having them occur in combination is also something that you can see I think much more commonly than is recognized.

Dana Parish: As I talked to you about all of this, I realize how uncommonly physicians consider root cause.

Charlotte Mao: We aren’t taught about mold and the issue of mycotoxicosis, and it’s even more controversial than Lyme disease. And, and whether this area is recognized as being something that is a valid health concern that can cause these symptoms and signs in patients. So, it does take a patient trusting their own intuition and keeping at it and doing some research on their own. And then asking that physicians are willing to learn. They want to help their patients. We need to have education. And so, I was always happy when a patient educated me about something new and there’s a lot that needs to be taught in all these different illnesses. They’re much more complex than what physicians are taught. And then when you put them all in combination, then you’re dealing with a whole other level of complexity.

Dana Parish: I can totally appreciate that. It is a complicated stew and it’s a miracle when we do find doctors like you and when we do get to the right care because it’s so confusing, it’s such a confusing maze for the patient. I saw 12 doctors and most of them really wanted to help me. And they were trying, especially, I’m thinking about my internist, you know, she knew me for a long time before I got Lyme, and she knew that I wasn’t crazy and she was concerned about my symptoms, but she just truly did not know why I had them. And then, you know, when I went into heart failure, she was so concerned, but again, nobody, not even the cardiologist, at the time, considered that it could have been an infection. I kept saying, could it be from the tick bite? And I did have a lot of neuropsychiatric stuff, anxiety, and depression, and could it be from a tick bite? And they all said no, you know, so I feel like it’s great to hear you say (to patients), be educated, come in with some information, some data, maybe even some stories like the ones we’re going to talk about today and present them. Because I think doctors would be super open to it. It’s just, there’s a big black hole in medicine around these issues. I’d love to hear about some of your multi cases. I know you’ve had some really fascinating, at least if you don’t mind talking about one or two where you discovered what might have been a root cause.

Charlotte Mao: Well, I would say in a number of the pediatric cases I saw with prominent neuropsychiatric and psychiatric manifestations of PANS/PANDAS-like presentation, it turned out that mold was a big triggering factor. And in at least a couple of cases, the home was found to be very contaminated with mold in the basement. Strangely, it was when the Christmas decorations got brought up from the basement into the home. This was two different kids who already had complex Lyme disease/Bartonella and a PANS/PANDAS picture. Their symptoms markedly worsened or re worsened. And then when the mold got remediated in the house, there was a remarkable turnaround in the patient.

Dana Parish: Can you talk more about the clinical symptoms and the resolution of those symptoms?

Charlotte Mao: Yes. It’s the kind of presentation that you see with PANS/PANDAS—intense OCD behavior, with anxiety through the roof. You see oppositional behavior or anger, aggression, rage kind of symptoms. You can have physical kinds of symptoms as well. That’s part of the PANS/PANDAS complex. So, for instance urinary voiding problems are something that gets described—for instance, kids who have no problem all of a sudden are wetting their beds at night. And restrictive eating, that’s another anorexia-type picture, but a form of obsession. That’s their version of OCD. You can see suicidal ideation that is obsessive, that is their version of OCD. And you can see the tics, of course, as I mentioned before, the motor tics. You can see learning problems, basically cognitive problems. With PANS/PANDAS sometimes kids can have a sudden drop off in their penmanship ability i.e., their handwriting. It’s a whole constellation of symptoms like this and you can see any combination of those symptoms. Another physical sign is a certain kind of rash, it’s called a ‘streaked rash’ or a like rash that has been associated with Bartonella infection where you can see it often on the back. It’s sometimes very prominent, these streaked lesions, but also in unusual areas. Sometimes it could be in the groin or under the arm. And they can sometimes be fiery red, but then fade to look more like striae or stretch marks that, for instance, women see on their belly when they’re pregnant. So, a child with neuropsychiatric symptoms and a rash like that, you need to think about Bartonella.

Dana Parish: Again, we should say how common Bartonella is. Were you the one I was talking to about how Bartonella really wasn’t recognized so much until HIV?

Charlotte Mao: Yes

Dana Parish: But it was just not recognized! I didn’t have HIV and I had a very, very severe case of Bartonella that caused heart failure and a multitude of other things. And I am convinced I also had Lyme. So, there’s overlap. I don’t want to say I know a hundred percent, but I’m very suspicious, just given all I know about these organisms, that it was Bartonella really driving my illness and how difficult it is to eradicate. We need to just reemphasize that it’s so under-recognized in medicine, but it’s still so, so common in the population. And it’s all over the world. It’s common in Asia. People think these are just northeast problems that only affect you if you live in Connecticut or if you live in Vermont and unless you live there, you don’t have to worry about it. That’s completely not true! It’s all over the place.

Charlotte Mao: Exactly. There was a study that recently came out, published by a Chinese research group, and they estimated that 14% of the world population is infected with borrelia. 

Dana Parish: That’s enormous. It’s still probably an under count. It’s still probably more. The CDC keeps doubling, tripling its numbers about what it estimates. I think it’s huge. And it’s  been the elephant in the room for so long. I think Covid may have opened the door to talking about and understanding better what a horrible, multi-systemic infection can do. Now we can say, ‘So, doesn’t it make more sense when your patient comes in?’ I’ve talked to doctors about what the Lyme patients have been going through. We’re saying we have weird sensations, we have brain fog, we have joint pain, we feel weird. We can’t concentrate. We’re tired. You know, all these kinds of things where you weren’t believed. Now everybody’s going, ‘Oh my God!’ And starting to understand. 

Charlotte Mao: I think there’s a lot for the Long Covid treating community to learn and research community to learn from clinicians and researchers who have studied long Lyme.

Dana Parish: Absolutely. Now, congenital Lyme is a really important topic that I know you know so much about. Congenital Lyme means that a mom who’s pregnant can pass it on in utero to their baby. So, can we talk a little bit about that? Is it, is it real? Is that really happening? 

Charlotte Mao: Yes. So, controversial. But it is real. It’s been shown that Lyme can be transmitted from a pregnant mom to her baby. What isn’t known is how commonly it occurs. What is the range of adverse outcomes for transmission? What are the best treatments for the mom? A systematic review that was done a couple of years ago by Canadian researchers, as well as researchers from the CDC, showed that there clearly seems to be improved outcomes when mothers are treated compared to when they’re not. First of all, I should say, it’s an area that absolutely needs more research. Some research was done earlier, maybe in say, the eighties and nineties. But then there’s really been a quiet period where—some of the epidemiologic studies that were done, say in the nineties—there seemed to be the feeling that maybe this isn’t as serious or as frequent a risk as we were initially concerned it might be. Then the attention seemed to fall away from the issue. And yet the early case reports were of babies being severely affected. We’re talking about infants that died: it could be stillborn or spontaneous abortion or early neonatal death. So, shortly after birth the babies who had died and were autopsied, the spirochete was shown in different organs. There you have a definitive case that the spirochetes were transmitted from mom to infant. But then the studies that were done subsequently showed a range of heterogeneous outcomes. And the feeling was, ‘Well, there’s no congenital syndrome that’s shown up.’ And so, those were all just coincidence. However, as we’ve been discussing throughout this whole interview Lyme presents in children and adults with such heterogeneous symptoms, could it not be the same in children? So, I would say that the early case reports raised some real concerns. There are studies in animals that have raised real concerns too and that a lot more attention and research needs to go into this topic.

Dana Parish: I agree. I’m just going to go on the limb again and say, I think it’s very prevalent, and I have always found it curious that so many kids get diagnosed with Lyme and yet parents never see a tick bite. And the kid never sees a tick bite. They have symptoms, two, three years old, the kid’s knees hurt, all of a sudden, they stop walking, they don’t want to walk anymore. And I hear all kinds of stuff like this so commonly from parents. And you would imagine that if you have a baby or a toddler, you’re going to notice a tick bite on them. You’re giving them a bath; you’re constantly paying attention. You know, it just doesn’t make sense to me that it’s all vector born.

Charlotte Mao: I would say that in seeing my patients, when you get a really complete history of not only the child, but also their siblings and a family history, I wondered about a number of them ‘Could this be a case where actually they acquired the Lyme vertically from mother to child?’ Sometimes when the mom wasn’t diagnosed herself with Lyme disease but described to me a constellation of symptoms and signs over time, that made me think maybe she is in fact infected with Lyme disease. We talked about syphilis before and the spirochetes, how—there are many overlaps and parallels between syphilis and Lyme. And, again, congenital syphilis is something that’s well recognized. And the manifestations in children who acquire syphilis congenitally, it’s a very heterogeneous range of manifestations as well. They can present both early or decades later. And so, what you brought up before about a child who all of a sudden presents with joint symptoms and arthritis, and there’s no recollection at all of a tick bite. We, of course, need to study this more to prove it. But could that potentially be a late manifestation of an infection transmitted at birth? 

Dana Parish: It’s not a crazy thing to think, you know, you hear it so much. At some point the light bulb goes on. I think Lyme is so ubiquitous in the population, and it’s often asymptomatic or minimally symptomatic. I also know that it can cause fertility problems. And I see these patterns and I really hope this research gets done. And I was thinking about this case that you told me about a few years ago, about OCD. This is not on the topic of congenital Lyme, but a child with OCD who had her tonsils and adenoids removed. Can you talk about that?

Charlotte Mao: I know what you’re talking about. It’s a different case. This is a really fascinating case series of PANS/PANDAS patients. Reported by researchers at Stanford. And one of the cases was a young teenager with very severe OCD who also happened to have chronic recurrent sinusitis problems. She had been identified on imaging studies to have a cyst in her sinus. This is interesting because there is also this thought by a number of physicians who see these patients with complex Lyme disease and Bartonella, that either of those infections can potentially be associated with cysts forming in different areas of the body. I’m going to take a little aside here. Lyme, for instance, can cause a Baker’s cyst, which is a cyst behind the knee. Sometimes those can even rupture and cause severe pain and symptoms. Many cases, described in the literature of Baker’s lung disease presenting with a Baker’s cyst. But going back to the teenager with PANS/PANDAS, she had sinus surgery done to remove the cyst. And there’s actually a quote from the patient right in the journal article, and she says, ‘When they took that cyst out of me, they took the OCD right away with it.’ And that was just eye-opening to read. That makes you wonder. Could it be possible that a cyst could form just like it does behind the knee? Could it form in the sinuses? A lot of times we see those, and we just think of those as being incidental sites that just happen to show up on imaging and don’t really have any kind of clinical relevance. But something like that has to at least make you wonder, is it possible that it could be a manifestation of one of these infections that’s contributing to these psychiatric symptoms?

Dana Parish: I think about it a lot. And I remember Dr. Neil Specter told me that some people are just very cystic, and he talked about a parasitic infection that frequently causes cysts.

Charlotte Mao: In the case of parasites, it’s as if the body is trying to wall off this infection, this organism. So, it gets encased in this cyst. And those are described with parasite infections, for instance, it could be in the brain, something called neurocysticercosis, or in a muscle, or in a liver, a parasitic infection called the echinococcosis. So, is it possible that the same thing is happening with Lyme or Borrelia, where the body is walling it off? It’s a really interesting thought.

Dana Parish: It is. And it’s also interesting that there’s this other dimension to this whole illness, which is parasites. We don’t have to get into that. Well, we could do that another time, but, you know, I wasn’t even thinking along those lines. But that’s another hit. And I think that it’s absolutely a misconception that it’s not common or it’s not possible to get parasitic infections in the US. A lot of  people say it’s so rare. But again, we’ve found out over time that many things considered rare are actually quite common.

Charlotte Mao: I do think that parasitic infections are more common, even here in the US, and that they can be similar to what we’ve talked about before— the mycotoxins. But they’re yet another hit that can complicate the response to treatment. And again, more research needs to be done in this area. Absolutely. But the thought is that these parasites or mycotoxin hits can complicate response to treatment or can worsen these infections. Like Lyme and Bartonella, they pull the immune system in a certain direction that’s sort of different from the direction it would go to respond to an infection like Lyme borrelia.

Dana Parish: As we’re talking, I realize that the list just keeps growing about the things that we need to rule in or out when we have kids that are presenting with non-obvious, complex problems. I think infections, parasites, mold, these environmental issues, etc. There are chemicals in our food, there’s glyphosate. All these things are playing a role in chronic illness, and it’s so frequently being missed and just not really being addressed, and not being talked about in the medical community. I know parents are going to want to know about testing their kids because we know the testing is not great. It’s pretty bad. It’s not a secret. So, what are the best tests that parents can ask for and advocate for? What kind of a doctor should they be seeing? How do they even approach this? Where is the best starting point if you’re worried about your child?

Charlotte Mao: That’s a very good, excellent question. And complex. We talked before about the controversy in the field and testing is one of the big controversies. The standard approach to testing is to do a two-tiered Lyme antibody test. The general thought is that patients with early Lyme disease can test negative because it takes time to develop the antibody response. However, the standard teaching is that patients with late Lyme disease should have an antibody response on this test. And yet, when you go back and look at the primary literature on which the criteria are based, it’s very interesting. There are so many things I was surprised by when I started really researching the field. The diagnostic criteria are actually based on a single study. And the study is not a particularly large study. In fact, when you look at the study itself, there were two parts to it: There was a retrospective review of patients who had already been diagnosed with Lyme, and then a prospective study – that’s looking forward to newly diagnosed patients. They reported how sensitive it was, and the testing criteria that they had developed or that they were proposing in a variety of different patients—including patients with arthritis, patients with neurologic presentations—and the arthritis patients do tend to test positive and very positive on the Lyme antibody test. It’s the neurologic Lyme patients where you don’t see as consistently positive testing or a strongly positive test. In the retrospective portion of the study, I think for the neurologic patients, 72% were detected as positive. And in the prospective portion of the study, it was 84%. So, that means that you’re missing up to 28% of cases. If it’s 84%, you’re missing up to 16% of cases. And that is not something that I think has been thoroughly addressed. So, the important thing for physicians and patients to know is that although this two-tier testing is standardly used, it will miss a lot of patients who are in fact infected. And there are ways to get more sensitive testing. You can use specialty labs that do more complete analysis. So, I would say if your child has a confusing constellation of symptoms and signs where no one seems to know exactly what’s going on, and they test negative on standard testing by Lyme disease, and you research about the symptoms, the potential symptoms and signs of Lyme disease, and if you think that it should be something that should be considered more in your kid, then I would ask your physician about doing testing at one of the specialty labs that does more complete testing. Now, it might be that your physician is unaware of that type of testing or how to get it. And then there is a group of clinicians that are very well-versed in using these specialty labs and who frankly take a broader view of Lyme disease and what is standardly taught. So, it might be that you will want to consider having a second opinion with one of those clinicians and ask about evaluation for Lyme disease and diagnostic testing.

Dana Parish: How do we find them? How do patients get information? Where do we send them to ILADS?

Charlotte Mao: Well, ILADS is one organization that has a roster of physicians who do take this broader viewpoint. And Lyme disease.org I believe has a roster of physicians that they can refer to. So, there are a number of different websites. And having talked frankly to friends, I believe this is actually more common than a lot of people realize. So, you might have friends and colleagues who have gone through the same thing for themselves or for their children or for a family member. And getting personal referrals also is always helpful.

Dana Parish: I agree. Also, I should say that when I was diagnosed with Lyme and I was diagnosed besides a rash and one of the things I learned was that there was a lab—part of a Stony Brook hospital on Long Island called Stony Brook Labs—that does a pretty good Lyme test and it is often covered by insurance. I don’t know if you use that in children?

Charlotte Mao: I do. I’ve used Stony Brook and I think they’re an excellent lab. Another lab I should mention that I also really like to use is called Medical Diagnostic Labs. MDL based in New Jersey. I think those two labs both do excellent Lyme antibody testing. What you want to make sure gets done is something called the Western blot or a blot. That’s considered the second-tier test. Usually, it’s not done unless the first-tier test is positive or equivocal. But I personally would advise requesting the western blot or immunoblot regardless of the first stage result, because the first stage result is too restrictive. It looks at the amount of antibody and there are some Lyme patients who are trying to make antibodies, but they aren’t meeting that high enough level to pass first stage tests. And yet, if you go on to do the second stage test, you will see what are called Borrelia-specific bands. So, they are bands that are specific to the Borrelia organism. The bands represent antibodies being formed to proteins of the organism. And you see these on this thing called a western blot where the proteins get divided by or get distinguished by their size. And the different sizes are represented by these different bands. Now it’s tricky. You need to have a clinician who’s well informed in terms of interpreting the information as well. So, I guess my bottom line message is that the testing is more complex than what physicians are generally taught. And so, you need someone who takes a special interest in this to really understand the ins and outs of the different bands and which ones are specific. And ultimately Lyme really needs to be a clinical diagnosis. This is always important because you can see someone who has positive bands on that test but has no symptoms,

Dana Parish: Huh.

Charlotte Mao: Yes! I talked about that before. You know, you can be asymptomatic. Or they could be leftover bands from an old infection that has been adequately treated, and so you really need to go by clinical symptoms and then ask, Are my lab tests supportive or not of the clinical diagnosis? But to make the clinical diagnosis, you need to know all the different ways that Lyme can present. So, layer of complexity upon complexity.

Dana Parish: So, a lot of physicians who have a lot of experience in this area will institute antibiotics even if they’re not a hundred percent sure, but the clinical picture is screaming live borrelia, they will institute a small trial of antibiotics to see what happens. And a lot of times it’s extremely informative. Do you think that that’s something clinicians should do or should consider in these cases if you have all negative or incomplete tests?

Charlotte Mao: Yes. What I personally believe is that Lyme disease and the associated infections and hits that go along with it needs to be a specialty area of medicine similar to the way HIV is within infectious diseases. There are doctors who do just HIV medicine and are thoroughly versed in it. And Lyme is as equally complex, if not more complex. That is my hope that eventually that  will be the case. So, you may have a physician who doesn’t have a thorough understanding of Lyme disease and the complexity of it, and the kinds of responses you can see to treatment. You can actually see worsening before you see improvement. So, I wouldn’t say that I would advise just an empiric course of treatment. It really requires such careful evaluation, not only for Lyme disease, but to rule out all other potential causes.

Dana Parish: Absolutely.

Charlotte Mao: Then if you have ruled everything out even if you don’t have definitive diagnosis of Lyme by the lab testing, because say it is equivocal, I think to be someone who’s experienced with this, I wouldn’t say just go ahead and give it a try because what’s the harm kind of thing? You need to know what you’re dealing with.

Dana Parish: Let’s talk about tick bites. So, I have an adult doctor— obviously you know Stephen Phillips very well—he treats tick bites, and he advises treating tick bites. I don’t know what the thinking is for kids?

Charlotte Mao: Personally, I always do. What would I do if it were me? I would treat a tick bite because the best response you’re going to get is early. Usually with any infection, treating early on, preventing it from ever occurring is the right decision. And so there are standard recommendations for when to consider giving prophylactic antibiotics for a tick bite. And, again, I think what I found is when I researched this it’s actually more complex and confusing than what the standard recommendations are. So, for instance, one recommendation is that the tick has to be attached for 36 hours in order to transmit the Lyme spirochete. And that’s because the spirochete resides in the tick’s gut. And it takes that long for it to travel from the gut to its salivary glands and saliva to then get transmitted to the post. Now while, you know, that’s generally the case, in fact, transmission has been documented with tick bites that are less than that 36-hour threshold. In fact, Willy Burgdorfer, who was the discoverer of Borrelia Burgdorferi  in an interview said himself that he didn’t go by that cutoff threshold because there can be ticks who are partially fed, who detach from a host. So, you know, they aren’t fully engorged. They detach. And the spirochete has already traveled from the gut to the saliva. It’s disseminated and then they reattach to a different host. And so, in that case, and according to Burgdorfer he says you can transmit right then if the saliva is already infected with the spirochete. And that occurs, I think he said in that interview, in about 5-10% of infected ticks at the time of attachment. So, that’s something significant to consider. So, I wouldn’t go by that 36-hour threshold or feel comfortable that if the tick is attached for a shorter period than that, you’re home free. A lot of times you don’t know how long the ticket is attached.

Dana Parish: There is a review or a study by Michael Cook, I’m sure you know about this, where he says, basically there is no safe time for a tick to be attached. There is no known documented amount of time you’re safe. It’s just simply something that needs to be debunked over and over and over. And we talk about it a lot in the book. Because so many people fall through the cracks with this. They’ll think, ‘Well, it was only on for 12 hours. And I know because when I went to bed, I had to walk the dog. And I woke up and I saw it.’ Well, I hear from a lot of these patients a couple weeks later and they’re pretty sick. Their doctor wouldn’t treat them because it wasn’t attached for long enough. That’s a mistake.

Charlotte Mao: And also, there’s other pathogens that absolutely have been well documented to transmit (faster). For instance, Powassan virus is another tick-borne infection that can be sometimes deadly. Even as little as 15 minutes. That’s one thing I do advise considering is if you have the tick sending the tick for tests, I’m the kind of person who likes to get data. And so, I would advise starting prophylactic antibiotics before you get those test results back because the earlier the better. And you want to do it within, usually 48 to 72 hours is described as the cutoff, but as soon as possible. Then you can test not just for Lyme disease, but a host of different infections.

Dana Parish: Okay. So, one more thing that I feel that we need to debunk while you’re here is the recommendation that you should only take one dose of an antibiotic, one dose of doxycycline if you get a tick bite and it’ll prevent illness. It actually just prevents the rash.

Charlotte Mao: The study that was done on which that recommendation is based did just look at the erythema (EM) rash and not at long term outcomes. And as we’ve been saying this entire talk, you can have this period of latency or dormancy and then present with symptoms later. So, the standard recommendation is to give a single dose doxycycline? I think the group of clinicians that take this broader view of Lyme disease and recognize the really complex, sometimes chronic illness that can develop, will often use longer courses. And I think justifiably, so if you’re going to be able to prevent infection that could potentially cause debilitating illness later on by giving us a longer course of antibiotics. Everything is a risk benefit analysis. In that case, I think again, it’s another huge area of research that needs to be done. But it’s true that that study didn’t optimally look for outcomes. And in fact, one thing that you can see sometimes with prompt treatment is that you can actually delay or even completely stop the development of an antibody response to the infection so that down the road you might not be able to detect it on antibody testing.

Dana Parish: That’s a huge, huge thing people need to know. It’s a big deal.

Charlotte Mao: Yes. My personal opinion is— and I can’t back it up with randomized control trials or understand it in terms of a risk benefit analysis— just knowing this organism and how it causes the disease, and the mechanisms by which it can cause disease, it is logical to think that it could be beneficial to do a longer course.

Dana Parish: So, parting words for physicians, your colleagues, your well-meaning open-minded colleagues that would really like to learn more.

Charlotte Mao: Frankly, sometimes if you hear that an area is controversial, don’t assume that the alternative view is crazy and fringe. And if you really study whatever the topic could be, in this case Lyme disease, you’ll often find that there are very valid reasons for that controversy and for the alternative viewpoint. I was very humbled by that experience, frankly, because I started off with a standard view, and when I think back on some of the things I said to patients that I discounted… I didn’t think that they had Lyme disease based on what I had been taught in the standard paradigm. It was supposed to be very unlikely that that was the case. And when I look back at those cases, knowing what I know now, I know that I missed some cases. So, I think you’ll be really rewarded if you explore this. It’s a fascinating disease. And I keep on going back to syphilis because of all these interesting parallels and overlaps. It was said that if you know syphilis, you know all of medicine. And in some ways, I think that you can say that with Lyme disease too, the deeper you go into learning about it. There’s so much education that I need about Lyme disease and there’s so much research that still needs to be done in the field, but you’ll find that the story is much more complex and different than maybe what you had been trained to believe. And I would encourage reading widely in addition to reading the primary literature and going back to the historical literature. Because as I said before, there are just beautiful clinical descriptions and a lot of the early studies that were done that really reflect more of the complexity of the manifestations of Lyme disease. But there are also some excellent books. Of course, you are in Dr. Phillips’s book. But another book that was so educational for me was written by the mother of some of the first children who were diagnosed with Lyme disease in old Lyme, Connecticut. Holly Murray. Brilliant woman. Now passed away. But she authored a book called The Widening Circle, very smart. She had no formal training in medicine or science, but she knew from her own symptoms as well as symptoms in her children that there was something more complicated going on. She would spend hours and days and nights in the medical library at Yale researching and keeping copious notes with dates on her own and her children’s symptoms. And she does a beautiful job of conveying the complexity of this illness and the confusing array of symptoms. She has enormous insight of someone who lived with the disease herself and seeing it in her children over so many years. 

Dana Parish: There really is something to the intuition that both clinicians and patients develop living with this contested disease. That’s an incredible note to end on and such an important message. The light that you’re bringing to this, and I know that your favorite thing in the world is not necessarily doing a public interview. You are a brilliant clinician and researcher and medical detective. I admire you so much. The community has been so grateful to have you and to have the credibility that you bring to this cause being a Harvard trained doctor and having this huge career as an HIV researcher and doctor, it’s, it’s so impressive. I learn more and more about you. As you know, I’ve known you for years now, and I keep learning more because you’re so humble. I just keep learning about all the things that you do. I can’t thank you enough. And on behalf of the Bay Area Lyme Foundation, we’re so happy that you joined the science committee and thank you so much for being with me today on my first podcast. This is such an honor and a pleasure.

Charlotte Mao: Thank you so much. It was a real honor for me too. And I’ll just say, you know, as I mentioned before, it was a humbling experience for me, and I did learn so much from my patients and the parents of those patients. And so, that’s the other thing I guess I would say, just going back to what you recommended I tell physicians is really listen to your patients. And, again, Sir William Osler, the famous physician, said, listen to your patients. They are telling you their diagnosis. And I think that’s a very apt phrase for Lyme disease.

Dana Parish: Thank you so much. That was a great, great quote to end on. Thank you, Charlotte. I really appreciate it. And, please come back. We can talk about more. We’ve got so much more to talk about. This is just the beginning. Thank you for your time. That was wonderful.

Thank you for joining us for this episode of Ticktective, a program of the Bay Area Foundation. For more information and to get involved, visit bayarealyme.org.