This Podcast Will Kill You - Ep 94 Chlamydia: Double Trouble

Episode Date: April 19, 2022

With this episode, you’re getting much more than you probably bargained for, thanks to the quirks of Chlamydia trachomatis. This small but mighty bacterium can cause a number of different conditions throughout your body, most notably in your eyes and your genital tract, and the resulting infections, if left untreated, can lead to substantial and permanent damage. In this episode, we focus on the two most common forms of chlamydia infection, trachoma (eyes) and chlamydia (genital tract), and discuss the similar pathway through which this bacterium leads to these distinct diseases. While the biology of trachoma and chlamydia may be similar, the history of these two infections could not be more distinct. Tune in to hear what ancient medical texts have to say about trachoma, how surprisingly recently chlamydia was recognized as an STI, and where we stand with these two incredibly common infections today! See omnystudio.com/listener for privacy information.

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This is a job for Indeed Sponsored Jobs. In high school, I heard the rumors and saw the writings on bathroom walls of the quote, dirty people who slept around and got STIs like the clap. I never wanted to be like them, and I thought I was better than them for being, quote, cleaner and selective about whom I was seeing. I thought I was doing everything right. So you can imagine my surprise when my senior year of high school, my then partner and I tested positive for chlamydia. I was shocked and confused, wondering how it had happened. I felt ashamed and dirty, angry both at myself and my partner. Thoughts like, I'll never have sex again, and my life is over, flashed through my head.

I even blamed the person my ex contracted it from. I felt betrayed by my partner, thinking, how could you do this to me? But after a conversation with my doctor, who was very familiar with these cases, my assumptions about the disease were thrown out the window and replaced with a new understanding. A simple round of antibiotics, and we'd both be fine. I felt the stigma had dropped, and I wasn't shy to tell my story, to let others in the same boat know that it isn't the end of the world, and that you are not defined by a diagnosis. I was proud to handle it the way I did. Then college came, and it followed me. I hooked up with a person who turned cold towards me days later. I knew something was off, and I asked them about it. They told me they heard

about my past. They said that they had heard, quote, something about chlamydia, and it scared them. They were ashamed for being intimate with me as someone who was once diagnosed with this infection. They thought I was dirty and that it made them dirty too. The feeling of rejection cut deep, and I begged him to keep his voice down. Doing what I was. I could, I told him some of the facts I knew. How men are usually asymptomatic, how antibiotics are used to treat it, condoms are one method of prevention, and how it can increase the risk of pelvic inflammatory disease in women. Still, I was so angry and shocked that this had happened. Of course they didn't know better, but maybe they should have. I was upset, both for the judgments

they made about me, but also anyone who had been diagnosed with an STI. I thought to myself, why am I to Why not my male partners? Why not the disease itself? What blame is there to be had anyway? I have learned my lesson that what matters in sexual intimacy is not rumors and history, but who someone is at their core and whether or not their values and understanding of the world aligns with yours. What's important is mutual respect and open and healthy communication. STIs can happen to virtually anyone. and your value as a person has nothing to do with your sexual health. You are not a diagnosis. I feel like that is just such an important message, right? Like, you are not a diagnosis.

You are not your diagnosis. It's my favorite. I had a whole paragraph at the beginning of my notes that's all about why it's so important that we talk about chlamydia because it is so common and we need to reduce the stigma. So I love that firsthand account. Thank you. Yeah. So that story was sent in by one of our listeners. And I, yeah, I just want to say a huge thank you to both this listener and also to everyone who has ever submitted a first-hand account because it is a really vulnerable position to be in, right? Like you're kind of bearing your soul, talking about your experiences, something very personal to you. And that's difficult to do. And I just want to acknowledge that and say thank you. And also that it's so wonderful and impactful because I feel like it really drives home that like these diseases do happen. These things happen to people who are living their everyday lives.

And yeah, I think it just sort of reinforces once again you are not a diagnosis. Yeah, yeah. Hi, I'm Erin Welsh. And I'm Aaron Olman Updike. And this is, this podcast will kill you. Welcome to Chlamydia. Welcome. Yeah, this is an interesting one because it's sort of like a two,

for the price of one episode. I would call it even 2.5, as you'll hear in the biology. Mm-hmm. Yeah. Hmm. I'm very intrigued by that. So is it a certain time of evening? What time is it?

It's quarantini time, according to, I'm actually wearing a watch today. You are. What are we drinking this week, Erin? We're drinking happy as a clam. get it dinner shows up every night whether you're prepared for it or not and with blue apron you won't need to panic order takeout again blue apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip there assemble and bake meals take about five minutes of hands-on prep just spread the pre-chopped ingredients on a sheet pan put it in the oven and that's it and if there's truly no time to cook dish by blue apron meals are fully prepared just here

Eat them in the oven or microwave, and dinner is ready. And here's the exciting news. Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another recurring charge. Order now at blueapron.com. Get 50% off your first two orders plus free shipping with code this podcast 50. Terms and conditions apply.

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It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. just visit o'Keefscompany.com slash this podcast and code this podcast at checkout. A timeless wardrobe starts with pieces that are built well from the beginning. From the fabrics to the fit, everything needs to last beyond one season. And that's how Quince approaches design.

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How could we resist? at tequila. And basically, it's your standard Bloody Mary, but with tequila instead of vodka. And yes, we do know that we made a Bloody Mary for typhoid. But it's with Clamato, so it's different. And it's with tequila instead of vodka. So hopefully that's different enough. And in any case, we'll post the full recipe for the quarantini and the non-alcoholic

clamado-based placebo-rita on our website, this podcast, kill you.com and all of our social media channels. On our website, you can find all sorts of things like transcripts, sources for all of our episodes. You can find links to music by Bloodmobile. You can find links to our bookshop.org affiliate account. You can find links to merch and Patreon, probably a few more things that I'm forgetting, but, you know, that's enough. Check it out. Go there. And just real quick, I wanted to mention again that if you have a firsthand account that you might be willing to share on the podcast, please shoot us a message on the contact us form on our website or send us an email at this podcast, We'll Kill You.com. I'm also putting it on my to-do list to create like an FAQ or like a first-hand account link so that maybe things will be set up more easily on the website and you can get more information. Oh, well, then, shall we?

dive into this episode. Let's do it right after this short break. Climidier. Is that how you would say that? Climidia, chlamydia, with an E at the end? Yeah, sure. Climidier are gram-negative, obligately intracellular bacteria, of which there are several different species. And they infect a pretty wide range of hosts, and within those hosts, a wide range of body sites. So, we'll talk in this episode about different tissue tropisms, which we've talked about before, but that essentially just means which cell types these intracellular bacteria like to infect.

There are two major species of chlamydia that infect humans, primarily. That is chlamydia pneumonia, which causes pneumonia. So it infects our respiratory tract, and chlamydia trachomitis, which is really the subject of today's episode. But other species can cause respiratory or eurogenital or cloacal or conjunctival

infections in mice, birds, cats, pigs, marsupial, snakes, turtles, guinea pigs, koalas, and probably other animals that I didn't mention. And some of these other species, just as like a fun side note, for example,

Chlamydia satasi, if I'm saying that right, is often a zonzoic. monotic pathogen that can cause disease in humans. It causes a disease called cytocosis, but it's primarily a bacteria of, I believe, birds. Anyways, all of that to say, that today we're focusing on one species of chlamydia, and that is chlamydia trachomidus. This is a human-specific bacterium, but there are at least 13, maybe 19 different syruvars. And these serovars cause different diseases, kind of a number of them. Let's get into it.

Syrovars, A, B, and C, cause an infection of the eyes that's called trachoma, which can lead to scarring and blindness and is a really important major cause of blindness in many parts of the world. serivars d through k cause what most of our listeners are probably familiar with as chlamydia, the sexually transmitted infection. And then the L-serivars, of which there are several, cause another sexually transmitted infection called lymphogranuloma venerum. Oh.

So it's like three different serovar groups that cause three different types of diseases, more or less, There's some nuance there. So what I'm going to do here is take a pretty big picture view and talk about what all chlamydia trachomitis has in common. And then we'll go over the kind of different presentations of those diseases. Because it turns out, even though each syruvar infects different tissues and maybe causes slightly different diseases, there's a lot of similarities in terms of the basic biology of how this pathogen works.

That's so interesting that there are like distinct syrivar's. Yeah. The differences among these serovars are they genetic? Is it just how they act? Is it expression? Like what is the origin of those differences? Yeah. Oh, it's a good question, Aaron.

I wish I had a good answer for you. I don't. And that's not to say that it might be that a good answer exists out there. better than what I can explain it. But what it really comes down to at a very basic level is differences in tropism. So the different syrovars have a tendency to infect different tissue types. And that probably is based on some specifics of their genetics. Okay. But as we'll see, especially the classically sexually transmitted serovars, D through K, actually have a fairly wide tropism. So it's also differences in just the kind of epidemiology of where you find them and who

tends to be infected and things like that. Fascinating. I want to know so much more about tissue tropism. So wouldn't that be fun? Wouldn't that be fun? So chlamydia, like I said, it's an obligate intracellular bacterium. So it can't replicate without entering a host cell. Chlamydia bacteria are kind of fun. They have two different parts to their life stage. One is a kind of spore-like infectious form called an elementary body. And that's what actually infects ourselves. And once these bacteria actually enter ourselves, they actually differentiate into an active form that replicates prolifically. And then we'll transition back into the infectious elementary body to leave ourselves, and go on and infect more cells. Interesting. And so you mentioned that this was a spore-like condition. What does that mean exactly?

It means that they are hardy and they are not extremely metabolically active. They're not completely inactive, but they don't replicate and they're not very active. And they're a little bit hardier than most bacteria. How hardy are we talking? What's the environmental durability of it? I didn't see how long they're. environmental durability is. It's not like a true spore. It's not like drying out and surviving on surfaces. It's not anthrax. No, no. Good question. So chlamydia, all of the different serovars of

chlamydia trachomitis is transmitted generally by direct contact with secretions. And what secretions depend on what tissue we're talking about. But in general, clemedia trachomitis has the ability to infect any of mucous membranes. So anywhere that you have wet, vulnerable epithelial cells, you could get infected. That means eyes, nose, throat, penis, vagina, anus, primarily, and associated structures. And like I kind of touched on a lot, the different serovars have different tissue tropisms. So serovars, A, B, and C, tend to like the epithelial cells of our eyes and our nose. That's their preferred tissue tropism. That's where they do the best.

D through K, most often infect our genital tract, but can also absolutely cause infection in eyes or throat. And then the L-serivars, the ones that I think we think of the least often. They also tend to be sexually transmitted, so primarily infect the anogenital region. But what's really different about the L-serivars is they have a tendency to invade past just that epithelial cell layer and cause a much deeper infection, which I think is fascinating and really does set them apart from the other serivars. Interesting. And so the deeper tissues that it invades, what are those deeper tissues made of?

Oh, great question. It tends to invade into the lymph nodes. And we'll talk a little bit more about that when I talk specifically about lympho granuloma veneerum. I know. I can see your face. Yeah, okay. But despite those differences, at pretty much all of the sites of infection, one thing that Chlamydia does across all seravars is it induces a pretty intense inflammatory reaction from us. And so what we'll see when we talk about the different symptoms is that while those symptoms are going to vary, of course, depending on what tissue is infected, depending on which mucus membrane is exposed, The inflammatory reaction itself is universal. And as we talked about in our endometriosis episode, that inflammatory reaction that our body generates can often result in scarring. And this scarring can have chronic or long-term consequences. And that's across the board regardless of tissue type. So when we talk about chlamydia, there's always the acute initial infection, but then there's also the potential for this inflammation to cause scarring that can.

and cause more permanent or progressive damage? I find that really intriguing because as I'll like briefly touch on, these microbes have been evolving with humans forever, forever. So it seems like that it would be selected for to have not so much of an inflammatory response or not cause so much inflammation, either from the human side or the bacterial side. Well, what's interesting is that, yes, this is a pathogen that's been with us for a very long time. This is a pathogen that actually has a really intimate relationship with our cells and with our immune response. So what it actually tends to do is block a lot of pro apoptotic.

So it blocks a lot of processes that just straight up kill infected cells because that's what our body usually does when it recognizes an infected cell is just kill it. And instead, what chlamydia tends to do is modulate progression through the cell cycle in a way to try and promote chlamydia's own growth and survival for as long as possible. So I suspect that the inflammatory response is more of a last ditch. Like, let's do what we can. So it's this constant battle between this bacteria that's inside of our cells and our body trying as best it can to fight it off, but then causing damage in the process. Gotcha. Yeah. Do our bodies clear chlamydia infection on their own? Excellent question. They absolutely can. Yes. Okay. And so does the inflammatory response then vary substantially from person to person and like the tendency to scar and stuff like that?

Probably. Yeah. Okay. What factors might contribute to that? Oh, Aaron, whenever we ask about host factors, my answer is great question. We've got to have Angie Rasmussen back on to ask her. No, that's a really good question, though. But yes, it presumably definitely would vary person to person. What those factors may be is probably the subject of an intense amount of research. All right. So that was Chlimidia in general.

So now let's kind of go through the different syrovars and sites of infection to understand what these diseases actually look like. So serovars A, B, and C cause trachoma. A lot of listeners may have never heard of trachoma, even though it is one of the most common causes of infectious blindness worldwide. But these serovars are generally transmitted from person to person by direct contact from eye and nose secretions. So think, rub your eye on your hand and then touch somebody else or, you know, you're nuzzling with your baby, snuggling with. snuggling with your kid and you get their goopy eyes and nose all over you, or you're sharing a towel. It can also be transmitted by eye-seeking flies, although the relative importance of

eye-seeking flies and all of these various modes of transmission, it's a little bit like, we don't know which is the most important. But anyways, as an acute infection, an initial infection, these serivars of chlamydia trachomitis cause a muco-perulant conjunctivitis, so an infection of the eye and the conjunctiva. And it generally is self-limited, like you asked, Erin, it usually resolves. However, reinfection, especially in children, is incredibly common in endemic areas. And so trachoma, the disease that results, is the result. of either longitudinal continued active infection, which can also occur if you don't completely clear it, or chronic inflammation that results because of repeated infection, and this inflammation can

actually persist even after infection is resolved. And in either case, whether it's a, you know, continual infection or continual reinfection with inflammation, it results in significant scarring to the eye and to the cornea. Right. So it tends to be young children who are infected frequently and recurrently, but the scarring takes place over the course of decades. And what really happens is that the scarring, it causes the upper eyelid to kind of turn inward, which then eventually progresses to something called trichiasis, which is when the eyelashes

in turn and begin rubbing against the eye. like, sorry, I know eyes are difficult. Eyes are difficult. It is that, yeah, I saw a lot of pictures and descriptions in the books that I read. And it sounds so, like, painful and horrifically uncomfortable that it's, yeah. Yeah, exactly. Like, I think we've all had the sensation of having an eyelash stuck in your eye. Right.

Imagine all of them. All of them and always. It's not like you can just take it out. It's the way that your eyelid has turned. And so this, in addition to being incredibly painful, incredibly uncomfortable, this constant rubbing actually leads to additional scarring of the cornea. And this is what leads to blindness. Gotcha.

And so the prevalence of scarring and blindness in adults relates to their exposure as children, which is kind of an important, like, public health concept, because it's an acute infection that then causes this chronic disease and chronic scarring. Right. It helps with who to target to disrupt this cycle of transmission or this chain of transmission. Exactly. And it really has to be a kind of multi-tiered approach because you have to both, you know, prevent the disease in children and treat the disease in children. But then you also have to be able to deal with the after effects of the chronic infection in adults. Mm-hmm. So that's trachoma.

Next to go into the chlamydia that everyone is probably more familiar with, and that is serivars D through K, sexually transmitted clemedia. So these are the syrivars that tend to cause anogenital infections. So in people with a penis, chlamydia loves to infect the cells that line the urethra. Inflammation in this area is going to cause a urethritis, inflammation of the urethra. Often it's called non-gonococcal urethritis, which I think is just so silly because it just means like, well, it's not gonorrhea. I have a little section about that. I can't wait. You'll understand where it came from and why people started using it in the first place.

I can't wait. In people with a penis, this urethritis can also be complicated by epididymitis, which is inflammation of the epididymis, which is where sperm are stored in. transported in the testicles. And one thing that's really important to know is that even in this population, when it's a penile infection, 30 to 50% of the time, it's completely asymptomatic. So someone is not going to know that they're infected and potentially infectious. If someone is going to become symptomatic, then the symptoms usually are like a pain or burning when you pee because of that inflammation or maybe a little bit of clear or white. discharge. In people with a cervix, 70 to 90% of the time infection is entirely asymptomatic.

That's so interesting that it's a different rate of asymptomatic. Like, why is that? Well, I think it's largely because the symptoms that you're having from a urethritis are the pain and burning with urination because you have urine passing over these inflamed cells. but with a cervacitis, which is inflammation of the cervix, which is the most common place that you're going to have infection in someone with a cervix, in a sexually transmitted chlamydia infection. The cervix is pretty high up in the vagina. And so even if you do have that bucropurulent discharge, which is what you may have, you might not notice it. It might not be painful. You might not have any other symptoms.

And so you can have things like a little bit of bleeding after intercourse or if you did like a speculum exam, you might see the cervix look a little bit swollen or have a little bit of bleeding if you, you know, did a swab. But you might not feel that necessarily or notice it in terms of symptoms. That makes sense. That makes sense. Yeah. Interesting.

Now, if a person with the cervix can also have a urethritis, right? because the urethra is really, really close to the vaginal opening, and that might be more likely to be symptomatic, but you might think it's a UTI or a bladder infection. Right, because the symptoms are going to be similar. What about the anus? The anus absolutely can be infected, and it may or may not be symptomatic. We'll talk more about the anus in a little bit. Don't worry. I won't leave out the anus.

Perfect. Good. I'm relieved. Now, I want to focus on the cervix for a little bit longer because one of the things that makes chlamydia infection especially dangerous, considering how often it's asymptomatic, is that with a cervical infection, if it's untreated, about 20 to 40% of the time, that infection can progress upwards through the endometriot canal because this is a bacteria that's spreading from cell to cell, it can spread through the uterus and up into the cells that line the

phalopian tubes. So it can cause an endometritis, which is inflammation of the endometrium, the cells that line the uterus, or a salpingitis, which is inflammation of those fallopian tubes. And if an infection ascends into the uterus and the fallopian tubes, that can become a persistent infection known as pelvic inflammatory disease. And that inflammation, just like it can happen in the eyes with the trachoma serovars. can cause a lot of scarring over time. And this scarring is a big risk factor for both infertility as well as ectopic pregnancy, which can be a life-threatening emergency. So I have a few questions. Number one, can you talk a little bit more about pelvic

inflammatory disease, what that is? Yeah. Pelvic inflammatory disease is when a bacterial infection spreads up into the uterus and the fallopian tubes. So it's very often caused by chlamydia, but it can also be caused by gonorrhea, which I think we talked about in our gonorrhea episode, or it can be caused by a number of other bacteria. Just bacteria? Generally bacteria, yeah. Okay, okay. And then another question is about ectopic pregnancy.

Why is that associated with chlamydia infection that has ascended? Great question. Because that inflammation can cause scarring in the fallopian tubes, such that even though, So sperm might be able to make it through the fallopian tube to fertilize the egg. The egg can't make it back through the fallopian tube to be able to implant or all the way through the fallopian tube to be able to implant safely in the uterus. So it implants ectopically, which just means outside of the uterus. Okay. Yeah.

So in terms of infertility, what is the process by which this inflammation from chlamydia causes infertility? Is it sort of certain steps or is it multiple steps or is it just like the general inflammation? Yeah, it's the general inflammation and the scarring that occurs because of that inflammation. Gotcha. It's not like something that happens overnight or over the course of even, you know, a few days. This is the result of a longstanding untreated infection or repeated infection that's untreated in general, similar to trachoma in that way. Right, right. Chlamydia can also lead to infection in a newborn during delivery.

Most commonly affects the eyes and causes a conjunctivitis. Or can descend the respiratory tract and cause a pneumonia. So this is really a very versatile bacteria. So the one that can cause a pneumonia and newborns is not chlamydia and pneumonia, but... Right. Chlamydia trachomitous. I mean, clemidia pneumonia could also cause pneumonia and newborns, but... normally, yeah, chlamydia trachomadus, if someone is infected during delivery and delivers

vaginally, then the baby could become colonized and therefore chlamydia trachomidus pneumonia. Wow, okay. Yeah. Very versatile. Mm-hmm. Really is. Now, the L. Syrovars, we haven't even touched on, so I'll breeze through it really quickly. But these are the ones that cause lymphogranuloma veneerum. This is a disease that tends to be more deeply invasive than the other serivars. So they establish an infection not just in the epithelial cells of say the cervix or the urethra or the anus, but they infect cells deeper in our submucosa and then are able to disseminate through our lymphatics to our lymph nodes and cause a more systemic infection. Now what's interesting about this, especially, is that it used to be considered a relatively rare disease in high-income countries,

and classically was described as like a painless ulcer, followed by lymph node swelling, etc. But over the last few decades, has become a much more common pathogen that more predominantly affects the anogenital region and can cause significant inflammation in the rectum in people that are having receptive anal sex. Interesting. Yeah. And of course, the other serivars of chlamydia trachomitis can also infect the anal region. But this specific serotype seems to really like the anal region and can cause a more disseminated infection. So it can cause things like rectal bleeding, pain, a mucoid discharge.

It can cause something called tinnismus, which is this horrible sensation that you have to have a bowel movement even when your rectum is empty. so it can cause a lot of muscle spasm and be really painful. So the symptoms can actually be confused with inflammatory bowel disease because these symptoms really overlap. Huh. Mm-hmm. And is this just because it has a tendency to invade more deeply? And so, like, the infection itself is just more intense and almost systemic kind of? It is.

And it is harder to treat. It needs a longer course of antibiotics. Okay. Exactly. Yeah. I swear I'm almost done. but there's like one more thing I can't not talk about. And that is that clemody infection can also cause what's known as a reactive arthritis.

Oh. Which happens weeks later after an infection. And it can cause arthritis. So pain in the joints and inflammation in the fluid in your joints. And also a conjunctiveitis, which is fascinating. Like how did the inflammation make it all the way up to your eye after just a urethral infection. I don't know the answer to that. We don't know the answer to that. It's really unclear if this reactive arthritis is caused by a persistent chlamydia

infection or if it's caused by just our immune response causing this inflammation that that becomes more widespread. Chlamydia is not the only cause of reactive arthritis, salmonella, campbellobacter, ursinia, a lot of other bacteria, are also associated with reactive arthritis. But one of the papers that I read said that up to 4% of people with an acute chlamydia trachomitis infection go on to develop reactive arthritis, which is way higher than I thought. Yeah.

Okay. Questions. Okay. This is for all seravars of chlamydia trachomitis? I think it's mostly D through K, but I don't think that it's impossible that any of the serivars could potentially cause this. Okay. And would this happen even if you go on a course of antibiotics and clear the infection that way?

Great question. I think yes, potentially. Okay, so this is like the chlamydia trachomidus is no longer there, but your body is still reacting to something. Well, yes, but the bacteria are off. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keeffe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture.

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is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keefscom. This Podcast and code this podcast at checkout. Adobe Acrobat Studio, your team's home base, collaborate within a shared BDS space. You've got your docks, your plans, your specs, and then invite the crew to build what's next. They talk off the team works.

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Visit renofi.com or R-E-N-O-F-I-com to get started today. Day. NMLS number 180-2847. Terms apply. Not all borrowers or properties qualify. Equal Opportunity Broker. Not able to be recovered from synovial fluid in people with reactive arthritis, but it's unclear whether they are active, infectious bacteria or not. Remember, there are multiple stages of the life cycle of chlamydia. And whether or not antibiotics are effective in treatment is really up for debate right now. So it's unclear. It's one of these areas that much like so many, you know, chronic and autoimmune inflammatory conditions, it, again, is right for

research because we just don't really understand this reaction. How long does it last? I think it tends to resolve even without treatment within at least a few months. Okay. Yeah. Wow. Fascinating. It is really interesting. And I mean, that's Chlimydia trachomidus in not quite a nutshell, but like maybe several. Like, like that is. A bag of peanuts. Yeah, a bag of peanuts. Or like hot boiled peanuts where you have like five sometimes in a shell. Yeah.

You know, I don't eat hot boiled peanuts. That's true. That's true. I mean, I've eaten peanuts. Hot boiled peanuts are the best, though. Yeah, well, anyways. It is still a treatable infection. All of the different syruvars are treatable, which is great.

And it's all with the same antibiotics, either doxycycline or a Zythromycin. Of course, longer for the more deeper infection, like I mentioned. Antibiotic resistance. It's a thing. It's a thing. And that is part of why it used to be that in the U.S., sexually transmitted chlamydia was treated with a one-time dose of azithromycin, but now there's more data that shows that actually curates are better with doxycycline, even though it's a longer course. It's seven days. So, yeah, antibiotic resistance is definitely a thing. I think it's not yet as severe as, say, with gonorrhea. Mm-hmm. But let's hope we don't get there. Yeah, I was going to say, just wait, just wait. So, yeah, any other questions? I don't know if I answered any of your questions adequately.

You did. No, I feel like I'm all set for now, but I'm going to keep thinking in the back of my head as I tell you the history. Can you please? I want to know all about it. Yeah, I'll take a quick break and then I'll get into it. Just like with the biology section, I feel like we can split the history of chlamydia trachomitis into multiple parts as well. But in this case, I'm going to do it in two parts based on its name. So there's what we can think of as the chlamydia part of the story. So that's what I'm calling the disease as an STI, like the pathogen. as an STI. Yeah. And then there's the trachomitis or trachoma part of the story. So the bacteria as the cause of this eye infection, the severe chronic eye infection. Yeah. And that's kind of how I decided to approach this history, except for the fact that I am going to be giving trachoma more airtime than chlamydia as an STI, partly because, and I was a bit surprised to find this, that trachoma has a much deeper and a much more extensive history than chlamydia as an STI, because that was really only recognized as an STI fairly recently.

Really? Yeah. Which, of course, it doesn't mean that it only emerged as an STI recently. But in terms of, like, clinical recognition, yes. Huh. Yeah. So, kind of like you did, I'm going to start with the evolutionary history overall, and then I'm going to go into trachoma and then talk a bit at the end.

end about chlamydia. So I'm going to call this the trachomidus chlamydia approach. I love it. Thank you. For quite a while, people thought that chlamydia were mainly mammalian pathogens, infecting mammals and a few other animals intracellularly. But then in the late 1990s, some researchers observed chlamydia acting as endosymbiance inside free-living amoebe. They're not in the same genus, like, for instance, one is called paraclymydia, but they are related to these intracellular pathogens. Okay, okay. Yeah, and this showed that not only are chlamydia way more diverse than people previously thought, but also much older, like 700 million years old. Oh, that's, yeah, but we're not going to go through all 700 million years of history. Let's

kind of get to where the human chlamydia-specific strains or species that were interested in, right? So chlamydia trachomidus, essentially. The strains of chlamydia that cause eye infections, apparently diverged from the strains that caused genital infections around 2 million to 5 million years ago, which is around the time that Homo Habilis and Homo erectus evolved. So these guys have been with us for, you know, like we said, as long as we've been human. Yeah. Forever. And ancient writings further confirm that. So now is where I switch to focus on trachoma. Okay. So even though trachoma has probably always impacted humans, the transition to larger settlements and decreased mobility would have provided more opportunities for the infection to spread to more people, both within communities and also along trade routes. And its widespread prevalence is it's evident in the fact that trachoma, is described in so many ancient texts, like so many.

Really? Yeah. Let's go through a few of these early mentions, starting with the more vague mentions and then getting more specific. Okay. There's a description from sometime during 2,600 to 2,700 BCE about an emperor in China undergoing surgery for trichiasis. Hmm.

And there are inscriptions of eye disorders found on animal. bones and tortoise shells from around 1,100 to 1,600 BCE, and there are also Bronze Age epilation forcepts used for removing eyelashes found in Sumeria from around 2,600 BCE. Wow. Yeah. The first specific references to trachoma come from around 420 to 581 BCE in China, and in these references, Trachoma is described with terms including, quote, pepper seed like lesions and, quote, milt like granules. And copper, octopus, and garlic rubbed on the eyelids was a commonly recommended treatment.

Then we have writings from Sush Ruda from the 700s BCE, who is an ancient Indian physician and surgeon that I've mentioned on the podcast at least a few times, like I think many times. specifically, I actually look this up in our diabetes, rabies, and organ transplantation episodes, for example. I love that you looked at up. I did, I did. So Sushrudo wrote about how the inner eyelid gets rough and thick and how the eyelashes can grow inward and how your eyelid can also turn inwards and cause the lashes to rub against your eye. It's like pretty like spot on trachoma, right? The early history of trachoma, honestly, it reads like a who's who of the early

medical texts because up next is our old friend the Ebers Papyrus. I was hoping you'd say that. Of course I was going to say that. So in this classic text, which is from around the 1550s BCE or so, we've got lots and lots of different treatments for eye disorders, including onions. Gazelle excrement applied to the eye with a vulture feather. Oh, wow, specific. Epilation followed by the application of lizard or bat blood. Okay. Uh-huh. Interestingly, both Plato and Aristotle suggested that trachoma was contagious,

with Aristotle going so far as to suggest that you could get it just by looking at someone who had it. Oh. Yes. But it would take quite a long time, of course, before they were vindicated in this belief. And we have another friend yet who is joining us, which is Hippocrates and the Hippocratic texts. Yep.

And in these texts, there are descriptions of the fig-like appearance of the upper lid and intern lashes. And also some suggestions that the condition could be prevented by avoiding the cold winds from the north and the warm winds from the south. Like what winds are you left with? Just avoid all winds. Avoid all winds. You can have an easterly breeze. That would be fine. Okay.

Yeah. Yeah. But also, I really love these treatments. Drinking wine, bathing. Yep. I'm down for that. Purging, nope. Blood letting, nope.

Or applying a cleansing medication to the affected area. Okay. Yeah, we've got some decent ones in there. Yeah. And of course, there were also surgical procedures that were recommended to treat trachoma in these texts. In the first century CE, the ancient Greek physician diascorities was the first to use the word trachoma, meaning roughness to describe the condition. and a little over 100 years later, Galen described the four stages of trachoma. I mean, I could honestly, I could go on and on this entire episode just like listing these other ancient texts that have references to trachoma, like those by Avicenna and Alcahal, the ophthalmologist, among others.

And also, like, you know that I would love to get into some of these, you know, these incredibly varied treatments used egg white mouse ear. frog's blood, the bile of a goat, et cetera. But even without doing that, even without going further down this rabbit hole of like ancient texts and trachoma, I feel like it has given us a pretty good sense of how widespread and devastating a problem this was. Yeah, I honestly had no idea. I mean, it makes sense even now, like looking at the distribution and how many people are still at risk and affected. Like, it makes sense, but I never realized that. Yeah, me either at all. I really thought before researching this episode, this is going to be an STI history where I'm going to talk about like when people realized chlamydia was different than gonorrhea, et cetera, et cetera. And then I realized like this is really fascinating and important and it just gets more so. Because if you thought it was widespread in the ancient world, of course it's only going to get more widespread as global population increase, as mobility increase, and so on. Yeah.

So I'm going to mention one more thing in kind of like olden times before jumping all the way ahead to the 1800s. Okay. So during the Crusades in like 1,100 to 1,200 C.E. You had a ton of crusaders and pilgrims that were venturing to the Holy Lands and many of them came back with trachoma. One of them possibly being St. Francis of Assisi, who was actually blind at his death in 1226. I'm loving this. All right. So now let's get to the 1800s.

And why the 1800s, you might ask? So from the ancient times to then, of course, trachoma was around. It was written about, it was described, it made an impact. But also it was kind of used sometimes as a catch-all term, as this umbrella term to describe, you know, both the acute phase and the chronic phase. more eye infections caused by other pathogens. It was not really featured as sporadically or studied very intensively, but all of that would change around the early 1800s. And the reason for that change is, of course, war.

Specifically, the Napoleonic Wars. Poor Napoleon has been featured on this podcast for way, like so many. times for all of the disastrous campaigns where he was just basically his army was wiped out by various diseases, right? All the way back in season one, we talked about him in yellow

fever. In our typhus episode, we talked about how an unbelievably huge number of his soldiers died from typhus while trying to march up to Russia. But with trachoma and Napoleon, we find ourselves not

in Russia or Hispaniola, but rather in Egypt. From 1798 to 1815, Napoleon decided to wage a series of campaigns, basically all over the place, to try to gain more control over the European continent largely by disrupting British colonial and economic rule. That was his aim. In July 1798, Napoleon landed near Alexandria, Egypt, and then he and around 40,000 French troops marched to Cairo. And the purpose of the Egypt invasion, from what I can tell, was essentially to establish a foothold in the region so that they could try to disrupt one of the main sources of British economic power, India, by driving the British out of that subcontinent. So they were like, all right, we're going to set up shop in Egypt, and then from here we're going to just get, like we're going to defeat the British. Okay.

It also came with the plus of establishing French trade in the region. Not long after they arrived in Egypt, however, Napoleon's troops began to experience many of the illnesses you'd expect a traveling army to, dysentery, excessive dehydration, and also eye infections. By late September, the prevalence of eye infections or inflammation had grown enormously. For example, in one battalion of 300 soldiers, 125 had eye inflammation. severe enough that they were effectively blind. Wow. And had to rely on their unaffected comrades to point their guns in the right direction from the trenches. Oh, dear.

Mm-hmm. And the high prevalence in this battalion doesn't really seem like a one-off because in an expedition in October 1798, 1,400 French soldiers developed ophthalmia out of 3,000, so nearly half. Wow. And the condition was not restricted to just the French soldiers fighting, but also the people they were fighting against, namely Turkish and British troops, although Turkish troops later switched sides and fought against the British. So everyone was affected, essentially is what I'm trying to say. And the British Army seemed especially affected by eye inflammation after around March of 1801. One report from the time described how out of an 8,000 person division,

1600 soldiers developed ophthalmia in September and October, and 158 became blind. Just like a lot. That's a lot of people. Napoleon's invasion of Egypt marked a turning point in the history of trachoma because it led to huge amount of interest in the disease, especially from military physicians. And it also led to the infection spreading much more widely. When these British and French troops returned to Europe from Egypt, many of them brought

Tricoma back with them, and basically everywhere they traveled on their journey home, trachoma followed. For instance, French troops landing in Sicily in 1801 on their way back from Egypt, kicked off an epidemic of Tricoma that didn't peak until 20, 12 years later, just rows and rows and rows, yeah. Oh, my gosh. This time of the Napoleonic Wars and really in the years after was a period of great upheaval and mobility across huge parts of Europe.

And trachoma was, you know, was not alone in this. It was just one of the diseases that took advantage of this disruption and widespread travel. Trachoma moved from Sicily to Hungary, France, the Netherlands, Germany, Russia, and on and on and on, essentially everywhere, and it especially became a fixture in armies. Ophthalmia first showed up in the Russian army in 1818, and within 20 years, nearly 80,000 Russian soldiers had been affected. Thousands of soldiers in the Dutch and Belgian armies became blind or partially blind, and during the Crimean War, so like, 1861 to 1867 or so, quote, 4% of all disability in the army was due to ophthalmia and 5% of the total discharges were because of blindness, although these rates were approximately half what they had been in the 1830s. Wow. Yeah, so 10% of the discharges being due to blindness in the army.

Wow. Yeah. And so, you know, doctors, military doctors and also, civilian doctors had plenty on their hands in terms of trachoma. And as you might expect, one of the things in the front of everyone's mind was how to control or prevent this disease, which in the years before germ theory was tangled up with a debate on whether trachoma was contagious or not. Was it warm rains or cool nights? Was it a dusty atmosphere or cold wind that led to outbreaks? Or was it the sharing of hand basins, not. not washing regularly, sharing towels, not cleaning bedding, or not using pillowcases, etc. And in reality, it was kind of a little bit of both.

Because, you know, having access to clean your face or not sharing towels, one big part of it, and some environmental factors playing another part through seasonal changes in fly prevalence, for instance. While some doctors continued to work on the control aspects of trachoma, others began to concentrate and specialize on how to treat the condition. The author of the book that I read for this compared trachoma to Helen of Troy. But rather than ships, trachoma was the disease that launched a thousand hospitals. I loved that. By the mid to late 1800s, trachoma was a pervasive problem. everywhere. And it wasn't limited to just the military. Entire hospitals and medical divisions were

created to treat it. And trachoma also played a big role in making ophthalmology a specialization and profession in itself, rather than, you know, it being just a part of generalist care, like generalists who have an interest in ophthalmology. Wow. I had no idea. I know. The history of trachoma is so much deeper than I realized. And it's also just, I really find it interesting to think about the origins of different specialties and specializations in medicine. Oh, my gosh, I know. Yeah. Governments established trachoma schools attended by children who had trachoma or other eye conditions, because like you said, it was so prevalent among children. And it also became a notifiable disease in many places. By the second half of the 1800s, researchers had

fully established that trachoma was indeed contagious, even if they wouldn't discover the causative agent until 1907. But knowing that trachoma was caused by an intracellular bacterium didn't stop people from characterizing the epidemiology of the disease. Familial transmission was common, children under seven had the highest prevalence, seemed to be strongly correlated with access to sanitation and clean water, and it seemed to be most prevalent. among low-income households. And of course, these last two characteristics, so low-income households plus lack of access to sanitation or hygiene practices,

these marked the disease as a social status indicator. Similar to many other diseases that we've talked about on the podcast before, tuberculosis, hookworm, trachoma, these were the diseases that the poor brought upon themselves just by being poor. That was like the narrative, right? These diagnoses became wrapped up in a person's identity, labeling them unclean. I feel like that's still the problem with trachoma and why we don't know anything about it. Absolutely. Absolutely. Although some control strategies for trachoma involved providing care to people who had the disease, many of them focused more on limiting the spread of the disease to wealthier populations, right? It wasn't so much let's manage and stop the cycle of transmission.

It was like, let's keep the cycle of transmission over there and not let it spill into here. Yeah. Which is not only cruel, it's also ineffective. It truly, truly is. So it seems unclear whether or not trachoma had been present in the U.S. prior to the arrival of Europeans in the 1400s and 1500s. But in any case, the late 1800s saw a similar increase. in Tricoma in the U.S. that the rest of the world was experiencing. And this rise in cases was blamed

on immigration. Throughout this time period and into the early 1900s, millions of people were leaving their homeland, which was often somewhere in Europe, to travel to the U.S. and try to find more opportunities or be with their family or escape some of the horrible situations that were happening, like famine, you know, many, many, many different reasons. And I'm not going to go in depth about the immigration politics of this time because I don't know enough about it. And there's probably better podcasts and resources out there. But I will say that as immigration increased in the late decades of the 1800s, so did resentment and anti-immigration sentiments, which eventually led to policies aimed at reducing immigration by especially targeting people that they didn't want to admit into the country. For instance, the Chinese Exclusion Act of 1882 or other laws or acts that prevented people from being admitted if they had certain diseases, including, but not limited to epilepsy, quote, insanity, tuberculosis, cholera, typhus, ringworm, and trachoma.

Hmm. In 1897, the U.S. Surgeon General called trachoma, quote, a dangerous, contagious disease, and instructed medical officers to examine all immigrants. The examination process itself was painful and not at all sanitary, which probably led to further spread of trachoma. You're like, let me check your eyes. Okay, next, let me check your eyes. Oh, you have trachoma. Oh, let me check the next person's eyes. Right.

Right. If you were suspected to have trachoma, the officer would mark a big chalk tea on your shirt, and you were sent to the contagious disease hospital to wait it out to see whether you had acute conjunctivitis or if it was trachoma. And if it was trachoma, that was bad news. Over 95% of those with trachoma were deported. Whoa. Mm-hmm. And if you were fortunate enough to be in the 5% not deported, you could remain in the U.S. in hospital for treatment, but that usually took about six months. Whoa. Uh-huh. Because remember, this is all pre-any sort of effective antibiotics. Right. Antibiotics.

Yeah. No antibiotics. Yeah. In 1902, the U.S. ramped up their restrictions against Tricoma by placing a $100 fine on every shipping company per Tricoma case brought to the U.S. So then these companies started to do like Port of Origin screening sites. and these additional restrictions led to Tricoma becoming one of the main reasons that prospective immigrants were rejected. What?

Let me read you some numbers to give you a sense of just how much Tricoma played a role in immigration. Quote, between 1897 and 1924, some 21,75,8,875 immigrants were examined, and 33,8475 immigrants were examined, and 33,847 were debarred because of trachoma. So it would be like 0.16%. Wow. Another quote. It was common to have 2 to 5% of prospective immigrations rejected. 85% of those rejections were due to trachoma.

I, wow. I know. You would think that based on how seriously the U.S. was taking, trachoma in the context of like immigration stuff, that there would be almost no trachoma in the country, right? Oh, you'd think, right? You'd think, right? That's logical. Of course that's not true, though.

No, no. The first detailed look at trachoma in the U.S. came out around 1911. That year, a physician from Lexington, Kentucky, released a report that showed just how prevalent trachoma was, especially in eastern Kentucky and across rural Appalachia through to Kansas and Oklahoma. Rates of trachoma in these regions were comparable to, or greater, much greater than many of the countries from which people were emigrating. For instance, Native Americans were among those most impacted, with an average prevalence rate of 23%. But it gets worse. In some Native American boarding schools in Oklahoma, that number would shoot up to a horrific 92%. 92%. Yeah. Oh my. This report did kind of awaken public health officials to the tremendous issue that

trachoma already posed in parts of the U.S. And so they created trachoma hospitals and state-specific control programs. And over the early 1900s, especially the 1930s and the 1940s, trachoma did sharply decline in the U.S. and in many countries in Europe where it had been prevalent, essentially countries that were like higher income countries. And I think it's not the easiest thing to tease out exactly why this decline occurred and how much these treatment centers contributed versus infrastructural improvements in things like sanitation and clean water that made it possible for people to regularly practice, like these hygiene practices that would help them keep their face clean, et cetera.

based on the timing of the declines, it's possible that antibiotics like sulfonamides played a role. But if they did, I have to feel like it was a fairly minor one. Since the decrease seemed to happen in many places long before the widespread introduction of these antibiotics. Which is really interesting in the context of current events. It certainly is. Yeah. Yeah, I feel like this is such a good illustration of how. disease prevalence can be reduced through changes in infrastructure rather than just treatment alone. And I think it also shows that like treatment alone is never going to be sufficient.

Nail head. But as usual, this decline in trachoma was not universal, nor did it happen evenly across the landscape. In the U.S., for example, trachoma persisted in many Native American communities through the 1980s. And in Australia, it continues to be a problem in indigenous communities. And there are many regions around the world that still have high rates of trachoma, which I know you'll talk more about Aaron. It wasn't really until the mid-1900s that international organizations, like the WHO, started trachoma control programs for some low and middle-income countries.

And they set an elimination goal only in the mid-1990s, which honestly, it really surprised me after reading about this history where I was like, wait, it's preventable, it's treatable, and it also has an absolutely enormous impact on quality of life. Yep. So I've almost gotten all the way to the end of the trachoma history part without even talking about the causative agent, really, and like how it was identified and who discovered it and so on. And one of the reasons for that is, like I said earlier, knowing exactly what caused this condition didn't seem to be necessary to stop the cycle of transmission and reduce prevalence in some places. But what the identification of chlamydia trachomitis did was allow people to distinguish trachoma from other acute types of eye inflammation, enable them to see which treatments might work best, and also let them look for, other ways that this bacterium could infect humans, such as genitally. Genitals.

So let's go back in time to when chlamydia trachomidus was first identified. The late decades of the 1800s could be considered the heyday of germ theory. People were identifying bacterial or parasitic causes of diseases left and right. I mean, really, like, can you imagine the dissertation would be like, I looked in this person's boogers and I found this. Boom. Give me a science or nature paper. I don't think they existed back then, but. In theory. In theory, yeah. And so when a disease existed that a bacterium or parasite wasn't easily, like, or readily identified,

it wasn't like, oh, this must not be infectious. It was often assumed that it was a transmissible filterable agent, aka a virus. And trachoma fell into this category. At first, of course, until 1907, when Halberstetter and von Prauzec used a special stain to visualize the bacteria in trachoma. But they didn't realize at that time that it was bacteria they were seeing. They thought it was intracellular protozoa that appeared to cloak the nucleus of the cells they infected, which gave rise to the name Climidizoa after the Greek word for cloak. Oh, that's fun. Yeah.

And, of course, it was later changed to chlamydia once people realized that they were not protozoa, but bacteria. So now that people had found what caused trachoma, did that mean that they would also be able to link it to the genital infection? Not exactly. If you think back to our gonorrhea episode, I think I mentioned how. I didn't check my notes, prior to the identification of the gonorrhea bacterium, it's hard to tease apart which historical descriptions of genital infections are actually gonorrhea versus

something else based on symptoms alone. Right. And the identification of Niceria gonorrhea allowed people to finally say, this is definitely gonorrhea, which also meant that they could say, well, I don't know what this is, but it's certainly not gonorrhea. and we can't treat it with the same things as we do gonorrhea. Right. And so this is how non-gonococcal urethritis or nonspecific urethritis became a diagnosis.

It was this diagnosis of exclusion. That makes sense. People did look for the cause of non-gonacoccal urethritis, which I'm just going to call NGU moving forward. But one problem was that it wasn't just one thing causing it. Right. Later research has shown that it can be caused by chlamydia trachomitis, mycoplasma, genitalium, trichomonas, among others. But people didn't know it was like all of these things could cause it at that time. Yeah.

So if you're a researcher, let's say you're like digging in some secretions and trying to find out what the cause of this infection was. And you're like, I think I found it. I got it. And then you go over to a friend, take your little horse and buggy, go over to a friend and you say, I think I found it. you see it in your secretions? And he goes, no, I don't. This is something totally different. So you didn't get the right one. Right. You just feel really bad about yourself. You're like, every my experiment failed. Right. And you're like, I'm leaving academia and I'm not, I can't do this anymore. I quit. I'm going to make a podcast.

Sorry, that was funny. That was really good. Thanks. But researchers did try to minimize this. confusion about what caused NGU by seeing if they could distinguish among different types of NGU. Okay. How long was the incubation period? What were the symptoms? How long did they last? Things like that.

And one of these people who was trying to characterize NGUs was named Ludwig. And I don't know how you pronounce this name, but I'm very excited about it because it is spelled W-A-E-L-S-C-H, which is very close to Welsh. and so I'm just going to call him Ludwig Welsh. And he described a, quote, rare form of NGU that had an incubation period of 10 to 14 days. The course of the disease was mild but long, and it was difficult to treat using the antibiotics of the day. Okay. Additional work also showed that the mucous membrane in cases of Welsh urethritis, as it would be called, was reddened with soft multiple infiltrates.

quote, like the nodules in trachoma. Interesting. People had made a possible connection with the trachoma agent and genital infections before this. One gruesome experiment even involved taking material from people's genitals who had NGU and then applying that to the eyes of monkeys. And sure enough, they developed an eye infection. There's definitely no eye cook approval on that one for sure. No. But it seems like the trachoma agent was just a tricky bug to work with. And it was hard to know what it was or what it wasn't responsible for, including trachoma, because there were still some debate about that. And also there was no ability at the time to culture it. And even with welshy arthritis, sometimes people saw chlamydia in the scrapings of infected tissue under the scope and other times they didn't. But the link seemed strong enough.

for at least one researcher to suggest that this well shirithritis was, quote, a genital trachoma. The debate continued for decades, but in the 1930s, American ophthalmologist Philip Thigason drew a link between neonatal ocular infection and being exposed to genital infection during birth. And later that decade, he also showed that trachoma could be treated with sulfonamides, which was actually a pretty huge deal at the time. After the introduction of penicillin in the 1940s, which could be used to treat gonorrhea but not NGUs, interest in NGU and the possible link between trachoma and genital infection increased even more. But the real turning point for both trachoma and chlamydia would come about in 1957.

Earlier, when I said that scientists thought that trachoma could be caused by a virus, they weren't actually that far off, right? Right. Chlamydia trachomitis acts like a virus in many ways, right? Right. And this similarity to viruses where they have to basically hijack a host cell's machinery to replicate, it kept researchers from being able to culture them for 50 years after their initial identification.

Wow. 50 years. Yeah. It's a long time. And that made it really difficult to like fully characterize the bacterium, see its life cycles, and see like where it was involved. Right. In 1957, Tang Fei Fan, along with a research team,

was able to culture the bacteria in a chick embryo. This was a huge breakthrough because it allowed people to culture large amounts of these bacteria, which led to careful characterization of its infection cycle, diagnostic tests, exploration into vaccines, antibiotic sensitivity testing, and so on. and two years after chlamydia could finally be cultured, it was isolated after delivery from both the cervix as well as the eyes of the infant who had inclusion conjunctivitis. People were finding more and more chlamydia in genital infections, and by 1965, the number of cases of NGU, many of which were chlamydia, possibly most of which, finally surpassed that

of gonorrhea in the U.S. really illustrating how important it was to be able to distinguish among these NGU infections, right? It was no longer enough to just say they're NGU. That's the NGU. Finally, chlamydia as an STI became a clinical entity in the 1970s. What? I know. And even then, it would be another 10 or more years before it became a notifiable disease in some places.

in the 1980s is when people started to discuss the possible ties between chlamydia and pelvic inflammatory disease and infertility. And it seems like around the time of that research is when chlamydia began to be labeled as a disease of promiscuity, especially promiscuous women. Which is really no different from how women were viewed historically as the sources of STIs, but not. people who needed to be treated themselves, right? Which is, I can't even tell you how frustrating, especially in the context of chlamydia today. But anyways, that's my personal high horse, and I'll step off. No, it's, it is, it is really frustrating, especially when you read these descriptions of treatment that were not that old, right, from the 70s, the 80s.

And the way that they describe treatment is that in order to reduce chlamydia in men, we should prescribe antibiotics in women. Oh, and I guess it'll treat them too. That's fascinating. Because I literally just read a paper that was like, what if we actually screen men, can we reduce the rates in women? Because we still aren't screening. We still aren't screening. Are you serious? Yeah. And people with a penis, it is still not recommended for general screening. It's, wow. Yeah. And the link between infertility and chlamydia seemed to be used to push this like judgmental moralistic narrative where infertility was the punishment for being promiscuous. The world was witnessing a silent but deadly epidemic of infertility.

Oh, God. Things like that. And all during this, cases of chlamydia did seem to be on the rise, although it was only routinely included. in STI statistics in the U.S. in Europe, starting in 1990. So I realized this was kind of just like a brief foray into these two different diseases with very distinct histories and social impacts, and I could have probably spent an episode on each of them. Had we known?

Had we known. But I think that what they both show us, going back to kind of like the theme, I feel like for this episode, is how easy it can be for a diagnosis to become wrapped up in someone's identity. And how important it is that we don't let that happen. Yeah. So, Erin, I would love for you to tell me more about where we stand with chlamydia and trachoma today. I can't wait to right after this break. When it comes to trachoma, this remains the most common infectious cause of blindness worldwide. Yeah, it's really common.

It's really common. It's responsible for blindness or visual impairment in almost 2 million people, which is about 1.4% of all blindness worldwide. And globally, an estimated 136 million people in 44 countries across the globe live in trachoma endemic areas and are therefore at risk of infection, which is a lot of human beings. It's, yeah. Yeah. And like you kind of mentioned, Erin, the World Health Organization, the World Health Assembly

has targets for like global elimination, which sounds so great. But the initial target date was 2020. Whomp, womp, womp. So the new target is 2030. How are we doing with that target, by the way? Well, I actually have some great news on that front. Thanks for asking. As of March 7th, 2022, 14 countries have newly reported achieving elimination goals. So I feel like that's something worth celebrating. That's huge. Yeah, that's very big. Unfortunately, the COVID pandemic put a very big damper on public health efforts in 2020. Half as many people received corrective surgery to treat trichiasis.

and reduce the progression of visual impairment, and way less than half as many people as in 2019 received antibiotic prophylaxis or treatment. So that's a big bummer, but we're still at least seeing progress in a lot of places. So that's really good. That's great. Yeah.

And like we kind of talked about before, the strategies to kind of treat this, I'll post the World Health Organization's like information for people who want to read more, but it is a very multi-tiered approach, which I think is important. Not only do they target infrastructure to be able to increase access to clean water and sanitation, which is going to be able to reduce the spread of infection. It also includes antibiotic treatment in mass antibiotic campaigns, especially in hyperendemic areas, because this does tend to be a disease that in certain areas will be at really,

really, really high prevalence, and then in other areas will be at much lower prevalence. So mass antibiotic campaigns, and then also surgical correction to be able to reduce the progression of disease in people who already had it as children. Where are some of these hyperendemic regions? Like, how is this distributed across the globe? Great question. So across the globe, it's the most economically disadvantaged and rural areas of Africa, Central and South America, Asia, Australia, and the Middle East. So the kind of most economically disadvantaged, poorest, most rural regions that tend to be the most hyperendemic. Gotcha. In terms of the STI chlamydia, we are talking about the most common bacterial sexually transmitted infection. Yeah. The most common one.

The most recent studies that I read estimated a global incidence of 131 million new cases every year. That's a lot of cases. A lot of humans with an estimated global prevalence of around 4% or so, 3.8 to 4.2 of people with a cervix, so a cervical infections. And anywhere from just under 3% to about 7% were the estimates that I saw of people with a penis. Surprisingly, to no one, we don't have as good of data on penile urethral infections because most countries do not universally screen people with a penis for infection the way that they do screen young adult people with a cervix universally. which is, again, something that I hope will change in the next coming years. And importantly, it does tend to be young adults.

Age 18 to 26 tend to have the highest prevalence. So overall, it's probably close to 3 to 4% of the population, adult population, infected at any given time. Gotcha. That's a lot of humans. And in the U.S., as of 29,000. there were over 1.8 million cases reported annually. And if you look just at the highest risk group that we screen, that we have good data on, that is people age 15 to 24 with the cervix, the annual incidence is over 3,700 cases per 100,000 people. Okay.

That is incredibly common. It's very common. So I feel like one of the things that I hope that these numbers really highlight and kind of going back to what you were talking about, Erin, about how chlamydia infection has been used in the past to have a lot of shame and stigma specifically associated with it. This is an incredibly common infection. It is not something that only a certain type of people can have or only. a certain type of people are going to be at risk for. When we're talking about sexually transmitted bacterial infection as common as this, anyone having sexual contact of any kind is going to be at some risk of infection. People having multiple different kinds of sex or sex with multiple people,

of course, are going to have a higher risk. But whether you're having any type of sex with one person or multiple people, things like using condoms can decrease our risk. Getting tested, getting treated, talking about this infection and making it less shameful so that we have an awareness about it is the way that we reduce this infection. Because it's not that it's inherently bad or shameful to get a sexually transmitted infection, but they can be really serious. And we have ways to reduce the risk and to be able to treat these infections. So I think that's really important.

Yeah, that was really well said. I agree with that. Thanks. And speaking of prevention, what about vaccines, Aaron? What about vaccines, Aaron? Yeah, we don't have one yet. Yet. I read a really interesting paper that was looking at all clematias.

And over the last 70 years, there have been at least 220 different vaccine trials. And in the last 10 years alone, there's been an average of 12 vaccine studies per year on Chlimydia, which is like one a month. So that's thrilling. Not all of these studies have been on our friend Climedia trachomitis. A lot have also been on species affecting koalas, which that's a spoiler. So far, still not. No vaccine. But, of course, lots of people doing fantastic research to get us closer. Speaking of fantastic people doing research to get us closer to a chlamydia vaccine,

I am very excited for next week's bonus episode when I get to chat with not one but two researchers working on chlamydia in domestic animals and wildlife, including koalas. Dr. Martina Yelochnik and Dr. Sam Phillips, both from the University of the Sunshine Coast in Queensland, Australia, will be joining me to talk about other chlamydia species of wildlife or veterinary health importance. We'll be talking about how these infections have led to declines in certain animal populations, as well as the latest news regarding a chlamydia vaccine for koalas. So make sure you don't miss it, because it's going to be great. I can't. I really can't wait. Well, that's chlamydia and trachoma. Yeah, this was a very packed full episode. Yeah, yeah, it's a good way to say it. Should we round it out with some sources?

We sure ought to. I had a few, but what I really want to highlight are two. One is a book called Tricoma by Hugh Taylor, and that is a fantastic overview of everything, trachoma. And then for chlamydia, there is a chapter by War Boys from 2019 called Climedia, a disease without a history. I read a lot of papers for this since there was so many different aspects of it. So I'm not going to specifically shout out any in particular,

but suffice to say, if you want more details on the specific immunization, immunology and cell biology, pathophysiology of clemody at trachomitis, I've got papers for you. If you want more details on reactive arthritis, got a couple papers for you. You want more on those 70 years of vaccine research? Oh, I got it. More on trachoma. It's there. Check out our website, this podcast will kill you.com, and you'll find a list of every single

source from this episode and all of our episodes. There's like 90-something. Yeah, there's 90-something. Thank you again so very much to the listener who sent in their first-hand account for this episode. Again, we really appreciate your willingness to put yourself out there and be vulnerable. Yeah, thank you. And thank you also to Bloodmobile for providing the music for this episode and all of our episodes. And thank you too, exactly right?

Listen, follow, and leave us a review on Amazon Music, Apple Podcasts, or wherever you get your podcasts. And don't forget, you can listen to new episodes one week early on Amazon Music or early and ad-free by subscribing to Wondry Plus in the Wondry app. And thank you to you, listeners. We really appreciate you listening, and we hope that you liked this episode. We do. And a special thank you also to our wonderful, generous patrons. We love you. Well, until next time, wash your hands.

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