This Podcast Will Kill You - Ep 25 Put your hands together for: Gonorrhea!

Episode Date: April 30, 2019

This bug deserves a big round of applause and not just because it’s nicknamed “The Clap”. Check out this week’s episode to gasp in wonder at the tricks that Neisseria gonorrhoeae uses to tiptoe past your immune system. Then prepare to cringe at some old-timey treatments for the disease while we trace the history of this ancient pathogen. Finally, make sure you have a quarantini or placeborita in hand for when we chat about the not-so-cheery outlook for this particular sexually-transmitted infection. Believe us, this is one episode you’re not gonn(orrhe)a want to miss. See omnystudio.com/listener for privacy information.

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Hi, parents and kids. We are discussing a sexually transmitted disease today, which means we're going to be talking about sex and genitals. So if you want to veto that for your five-year-old that's listening, put your earbuds in now. January 18, 1763. I this day began to feel an unaccountable alarm of unexpected evil, a little heat in the members of my body sacred to Cupid, very like a symptom of that distemper with which Venus, when cross, takes it into her head to plague her votary. But then I had run no risks.

I had been with no woman but Louisa, and sure she could not have such a thing. Away then with such idle fears, such groundless, uneasy apprehensions. January 19th. The evening was passed most cheerfully. When I got home, though, then came sorrow. Two, two plain was Signor Gonorrhea. Wait, there's more. Thus ended my intrigue with the Fair Louisa, which I flattered myself so much with, and from which I expected at least a winter's safe copulation, it is indeed very hard.

I cannot say, like young fellows who get themselves clapped in a body house, that I will take better care again, for I really did take care. However, since I am fairly trapped, let me make the best of it. I have not got it from imprudence. It is merely the chance of war. I mean, it goes on and on. Like, there's much more, but that's just, yeah. Oh, my gracious. Isn't it so good? What is that, what is that from?

Okay. So that is from James Boswell. So James Boswell was the, he was the biographer of Samuel Johnson, who's a literary figure. Okay. Yeah. James Boswell throughout his life, throughout his journal entries at least, became infected with gonorrhea at least 19 separate times. 19. So this is merely one of them.

I just, he really, you should take some time and just go and seek out the entirety of these. Read his whole journal entries? Yes, yes. Man. Hello. Hello. I'm Aaron Welsh. And I'm Aaron Alman Updike.

And put your hands together for gonorrhea. The subject of today's episode of... This podcast will kill you. Welcome. Welcome. We're going to have fun today. I can tell. Oh, yeah. I mean, if that journal entry is any indication.

Right. Okay. So what are we drinking to talk about? about gonorrhea? We're drinking, of course, burning love. And it is burning because it does contain. Halapino simple syrup and tequila, lemon juice, and a cucumber slice. Just for freshness. It's pretty delicious, I got to say. It is delicious. I'm really enjoying it. And as always, we'll post the full recipe for this quarantini, as well as our Plici Burita, our non-alcoholic version, on all of our social medias.

You can find us on Twitter at TPWKY, on Instagram and Facebook at this podcast Will Kill You, and on our website at this podcast will kill you.com. And if you ever feel like reaching out to us, you can email us at this podcast will kill you at gmail.com or go to our website for an entry or a contact form. Yep. Cool.

All right. Let's do it. Right after this short break. 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.

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Gonorrhea. Let's get into it. So gonorrhea is caused by a bacterium. It's called Nisiria gonorrhea. Gonorrhea-e. I never know how to pronounce all those vowels. There are so many vows. at the end of that word. I know. It's, it's a lot. Nyseria gonorrhea is closely related to

another bacteria that some listeners and you, Aaron, will definitely have heard of. Do you remember what it is? Menangitis? Yes, Nyseria meningididus, which causes meningitis. So, all the nyseria are gram-negative diplocoxy, which means that they stain pink when we use stains to look at them under microscope. And they're just these two little balls. It's going to be a lot of that, isn't it? Yeah. Yeah. Okay.

So, I'm just going to really, we're going to get right into how all this goes. So we all know how gonorrhea is transmitted, I think, right? Well, maybe you should just do a refresher just in case. I mean, okay. So gonorrhea is transmitted via sexual relations. So you can get it from all the kinds of sex. sexual intercourse, vaginal, oral, anal, and in any direction, giving, receiving, doesn't matter. And for adults, that's pretty much the only way that you're going to get gonorrhea is via

sexual intercourse of some design. Okay. In neonates, so in tiny baby infants, it can be passed from mother to baby during delivery, during birth, during passage through the birth canal. Right. So in general, in this country and in most other countries, we screen pregnant people for gonococcal infection. This is often called gonacoccus or gonacoccal infection or just gonorrhea. So I'll probably use all those words interchangeably.

But yeah, infection in a newborn is actually pretty serious. And so you screen for it during pregnancy and then you treat it and that reduces the risk of neonatal infection. Mm-hmm. Cool. Okay. So, cool. So what happens when you get exposed after a fun night to gonorrhea? Basically, the bacterium, which has been deposited into your body, will adhere to your epithelial cells.

Okay. Either along the vaginal canal or on the endoservics or in the anal canal or. Or I wrote penile canal and then I realized that's just called your urethra. your urethra. And it attaches to these epithelial cells using pilli, which are basically, isn't that fun? I didn't know that until I started researching this. Yeah. So pilli are basically these long, stringy protein bits that bacteria have.

They're kind of like, you remember those sticky hands that you used to get from the 25 cent machines? Oh, yeah. Like throw them out and stick them on your wall and then your mom gets mad at you because you ruined her white, walls. Well, and then they get covered in fuzz and they don't stick anymore? Yes, just like that. But so, you know, like, if you throw that out and stick it and then you let it go, it like flings towards the wall, right? So that's kind of what these pill I do. They reach out, they grab onto the epithelial cells, and then they contract, and that sucks the bacteria up against the epithelial cells. That's so cool. It's very cool. And it's great if you're in something like a urethra or

up against the cervix because you're probably going to have fluid rushing through those tubes. And so you want to be able to stick on and grab on real tight. Yeah. So gonorrhea is good at that. And once it sticks on, it starts to replicate, basically right then and then there. It doesn't, it's not a virus. So it doesn't have to infect yourselves. It just grabs a hold and then starts replicating. Wow. It's pretty fun. Yeah. And then once it colonizes, once it starts growing, it stimulates the release in your body of a whole bunch of pro-inflammatory molecules. So this basically stimulates your immune response. So then a whole bunch of immune cells, especially neutrophils and macrophages,

which are kind of the first line defense against bacteria, they come in, and in normal bacterial or other bacterial infections, they'd be able to phagocytize, which means swallow up, essentially, eat the bacteria, and then help clear the infection. But gonorrhea are sneaky little suckers. And they can actually survive inside of neutrophils. Oh, that's amazing. I know.

So when you look at like a swab from someone who has a gonorrhea infection, if you stain it, you'll actually see neutrophils just full of gonorrhea bacteria. Oh, my gosh. It's very cool. Like a Trojan horse. Yes. Yes. Maybe.

I don't know. Sure. The neutrophils normally kill bacteria by using reactive oxygen species, but the Niceria can actually, what's the word I'm looking for, neutralize those because they have an enzyme called catalase, which helps to neutralize that. So they can just survive inside of the neutrophils, which I think is very cool. That's awesome. And because they're recruiting a bunch of neutrophils and macrophages, that is also what kind of results in the symptoms. that we see. So if you get a genitoh urinary infection, let's talk about what kind of symptoms you'll actually have. First of all, most of the time you won't have any. Most infections are

straight up asymptomatic, which is part of why it can spread so easily because anything that's spread by sexual contact, like in certain populations, it's going to be pretty easy to spread. and if it's asymptomatic, then it never gets detected or treated, so you just keep sharing the burning love. So for a genitoneary infection, if you get infected in the urethra, you're going to see dysuria. So that means painful urination because you've got basically inflammation going on along the lining of your urethra. And then you'll also get a discharge. And that discharge will be either white or yellow or green. Okay. And it's mostly neutrophils. It's mostly neutrophils, dead cells, and bacteria. And then even those neutrophils are often full of gonococcal bacteria as well.

So all of the stuff that you are secreting is full of, it's like packed with gonorrhea bacterial cells? Absolutely. Yeah. Yeah. So that discharge is super infectious. Okay. You also can get infection of the epididymis. So if it can. travels through their urethra and back down into the epididymus, which is the tubes that surround the testis where the sperm actually have to travel through, then you can get what's called epididamitis, which is infection inflammation of the epidemis, and that can be very, very painful. So you can have testicular and scrotal pain on top of painful urination and urethral discharge. If you get an endoservical infection, so an infection of the vaginal canal and the cervix at the top there, it's even more likely to be asymptomatic than a urethral infection.

Okay. If you do get symptoms, they're often mistaken for a bladder infection or a vaginal infection like a yeast infection or a bacterial vaginosis or something. So you might have some dysuria, you might have some vaginal discharge or some bleeding in between periods. But more often, there are no symptoms in people with an endoservical or a vaginal infection. And when you say more often, like, can you give me a number to the percentage of cases? I don't have a number. I was trying to find solid numbers. And it's just like most of the time in endoservical infections, it's asymptomatic.

Okay. And most of the time in urethral in penile infections, it is symptomatic. Or it's more likely to be symptomatic. Yeah. Though in both cases, it can be asymptomatic. The problem with endoservical infections is that they can spread. They're asymptomatic, so they're less likely to be detected, and they can spread from the endosurvics to the uterus or the fallopian tubes, which causes what's called pelvic inflammatory disease, or PID. PID is a very serious disease.

It can cause abdominal and pelvic pain, fever, abscesses. It kind of is considered a more systemic infection, and it can lead to infertility. because it can really severely damage the fallopian tubes and the uterus itself. And it also can cause scarring on the fallopian tubes that can increase the risk for future ectopic pregnancy, which is when an embryo implants outside of the uterus. And that can be very dangerous. Very bad. In rare cases, epididymitis can also lead to infertility,

but it's more common that in people with a uterus or ovaries, you end up with infertility as a complication of a gonococcal infection. You can also get rectal infection. All holes here. It's usually asymptomatic, but you kind of do have the same symptoms. Discharge, anal itching, soreness, bleeding. You can also get a pharyngeal infection, an oral infection. So I have heard stories from people who work at the student health clinics of kids coming in,

they think they've got sore throat, and it turns out it's. It's gonorrhea of your throat. Oh my gosh. Isn't that? Oh, I got a kick out of it. So it causes the same symptoms as like sore throat? Yeah, it's basically just a sore throat. It's a pretty minor infection.

And even in your throat, it's usually asymptomatic. Okay. So that's why gonorrhea is so easily spread. It's because in so many cases, it's just completely asymptomatic. So, yeah. But gonorrhea, while. It can cause these symptoms and this type of infection just kind of right away, right after it attaches and starts to colonize. It can also pass through that epithelial cell border, which is essentially your body's protection against bacteria.

It's like first line defense. So it can make its way past that epithelial cell border and then make it into your bloodstream. Yikes. And if, yeah, if Nyseria makes it into your bloodstream, it's very, very bad. it's called a disseminated gonococcal infection because it's disseminated amongst your whole body through your bloodstream. And it most often will then go to your joints and your synovial fluid around your joints and your skin. And it'll cause dermatitis and arthritis. And in very rare cases, it can infect your meninges just like it's cousin.

I don't know. Do you call bacteria in the same genus cousins? Relative. Just like it's relative, Niceria meningitis, which is a very common cause of meningitis, Niceria gonorrhea can also cause meningitis if it infects your meninges of your spinal cord or your brain. Wow. Yeah. Yikes.

So that's bad. Bad news bears. In neonatal infections, when an infant gets infected, it most commonly results in an ocular infection. It'll get into their eyes as they pass through the birth canal. And this can cause blindness. It's really, really, really bad. Yeah. So that's why we screen pregnant women and most neonates when they come out, they give them erythromycin eyed drops just in case.

Yeah. So that's just to cover all the bases because that would be terrible. It also can infect babies. It can go pass through their eyes and get, because that's a mucous membrane where there's a lot of blood flow, it can get into their bloodstream and cause disseminated infection in babies. as well, which can be life-threatening, especially because babies have basically no immune system to help protect them. Also bad. Yeah.

Also bad. It's not a great disease. No, they never are. They never are. It is preventable, though, which is cool. Condoms work. You're right. So that's great.

What about? Treatment. Treatment? Great question. It is still treatable today. So, yeah, as of now, there is one recommended treatment, and that's recommended by the CDC and the WHO. If you get diagnosed with gonorrhea, you will get an injection of Cephtriaxone, which is an extended spectrum cephalosporin antibiotic. You get an injection of that.

And then you also get a single dose of a whole gram of a xithromycin. and you pop that oral. And then that will take care of the gonorrhea. It also takes care of chlamydia because it's extremely common to have co-infection. I was trying to find one solid number on how common gonorrhea and chlamydia co-infections are. And I couldn't find one solid, but in some studies I found, it was like up to 40% of people who were diagnosed with gonorrhea were also diagnosed with chlamydia. That's really interesting. Do they call it a the same areas? Is there competition or is it facilitation or what? That's a really good question. I don't know specifically. I don't know if it's just because they're transmitted in exactly the same way and have the

exact same risk factors. So if you have one, it's really likely to have the other. Or if there's any kind of interactions that go on between the two bacteria, I'm not sure. Interesting. It's a great question though. Yeah. But it's super common. Azithromycin will clear both a resistant gonorrhoal infection that's resistant to the septriaxone but it will also additionally take care of the chlamydia so that's why we give both okay so if you if you've ever been diagnosed and been like why do I need this giant horse pill and a shot in my butt I assume they put it in your butt I'm not positive though that's why yeah okay so yeah that's that's the biology it's a pretty it's a pretty straightforward bacteria as far as they go

I feel like. Yeah. It seems like it goes there to do the job that it came there for. It does the job and then you treat it, hopefully. Hopefully. Yeah. Okay. So how did we get here, Erin?

Where did this bacteria come from? Okay. And oh my gosh. Tell me how it got its name. I can't wait. Okay. Right after this break. 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'Keefe'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. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. 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'Keefscompan.com slash this podcast and code this podcast at checkout. Texting privacy policy and terms and terms posted at textingterms. Texting enrolls you for occurring automated text marketing messages. Message and data rates may apply or apply stop, opt out. Visit ISSA online for details.

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There's a passage in Leviticus in the Old Testament that declares that men with runny penises are unclean. not in those words, but more or less in those words. And Hippocrates describes genital ulceration and how it is sexually transmitted. We've also got Abu Bakar Muhammad Ibn Zakaria al-Razi, so Razi. Again. Again. Yeah. He's everywhere.

And even Sina, so Avicenna also is the Latinized name. They seem to describe urethrold discharge and urine retention, both of which are characteristics of gonorrhea. Now, any, I mean, any one of these could be referring to many other sexually transmitted infections, but gonorrhea is definitely old as is its name, which was given by the Greek physician Galen in the second century CE. So, like, Ghanos, it was a long time ago. For a long time, it was tied in with syphilis. And so, and it had, it went by many different names in different places. and so on. So it's interesting that this one was the one to make it through the whole way.

But gonorrhea is from gonos for seed and row for flow. So just sort of seed flow. Yeah. That's kind of yucky. I mean, by at least the 10th and 11th centuries, gonorrhea seemed to be pretty prevalent, or at least prevalent enough to lead to the creation of laws that were to prevent any activity that spread the disease of burning pee. It also may have had a hand in secularizing medicine in some places because physicians were ordered to treat everyone with the disease without being able to refuse based on moral objections. Oh, interesting. So, yeah, along with like leprosy and some other sort of more stigmatized diseases.

But even so, no one really paid much attention to gonorrhea alone for another few hundred years. But before I get into that, where did it come from? Yeah. And I couldn't find a ton of good info on its evolutionary origins, but according to one of my sources, there are two possibilities. And neither of which is particularly exciting. But one is that it came from an avarulant strain in the vaginal and rectal mucosa, which mutated into a virulent strain. Okay. Another was that it came from the nasopharynx and mutated into a virulent strain via oral sex.

So, yeah. I don't know when this occurred or where, but it would have very, required a decent population density to be sustained and then spread throughout medieval times, though not as big of a population as something like measles. And that's because the long duration of infectivity and the possibility of sort of these latent infections, yeah, probably help. Asymptomatic. Yeah. Yeah. Okay. Around the 1500s is when it began to be called the clap, which is its colloquial, one of its colloquial names. I had to be, no idea that it was gonorrhea that was called the clap. Oh, yeah. Well, because I think a lot of people

think it's chlamydia because C makes a less sense. Climidia, yay. Yeah. No. Gonorrhea. Okay, so why did, why was it called the clap? There are a couple of hypotheses. One, which is the most likely one, is that it refers to Les Clapiers, C-L-A-P-I-E-R-S. the clapier. There you go. Which is the French word for brothels. Really? A possible source of infection.

That's what they were called. Yeah. I never knew that. Another I read somewhere is that it causes a clapping sensation when you pee. And the most horrifying one I found was that it refers to a common treatment for gonorrhea infections in men, where you were supposed to clap the penis hard to get the pee flowing again. maybe using your hands, maybe using a book and a hard surface. Oh no.

Yikes. Yeah. But for much of its history, gonorrhea was overshadowed by syphilis, which we will definitely be doing an episode on. Big time. Absolutely. Cephalus is major. It's huge.

Yeah. But syphilis had settled down enough around this 15, 16th century for people to start taking note of this other disease and distillery. describing it. And one of the hurdles to tracing this early history, of course, relates to that where gonorrhea and syphilis were assumed to be the same disease with gonorrhea to be more the mild precursor to full-blown pox of syphilis. That makes sense. One guy in the 1700s decided to settle this once and for all. He wanted to prove that they were the same and that gonorrhea was the secreting form and syphilis was the skin form. So, he, he was a good thing. So, he was a lot of the same. He wanted to prove that they were,

He took the postular discharge from an infected person and then smeared it onto himself. Onto his... Yeah, onto his penis. Oh. Unfortunately, he came down with syphilis. So he didn't really prove anything. But I guess, yeah. So he swabbed somebody's, like, ulcer or something.

And then, or what did he? What it seemed like is that he took the discharge. So the direct quote was postular discharge. Okay. So I don't know if it was from the, like from the urethra or if it was from a sore, a pox. Yeah. In any case. I mean, yeah, you get discharged with, ooh, that's so yucky.

Yeah. Well, anyway, the pathophysiology of gonorrhea was still under debate. Maybe the discharge was caused by ulcers in the urethra. Maybe it was from the seminal vesicles. No one really knew. But as was the root of transmission. One popular view, as you might imagine, is that it came from women. Of course.

It originated in women, I should say. It would only originate in women. It's the only logical explanation. Yep. One surgeon said, quote, This thing resteth in their secret places, forming therein pretty little sores full of venomous poison being very dangerous for those who unknowingly meddle with them.

That's our title, Resteth in your secret places. Other theories acknowledge that intercourse was a likely source of infection, along with non-sexual things like gout or rheumatism. Eventually, though, gonorrhea and syphilis got their separate entries and as result separate cures. I think you know that one of my favorite parts of doing this research for the history is coming across the old treatments that were used. I think this is one of everyone's favorite parts.

Okay. Are you ready for gonorrhea? I can't wait. Let's start with the easy ones. Rest, avoid alcohol, avoid sex. Yeah, okay. Seems reasonable. Inject some mercury into the head of your penis.

It worked for syphilis. Why not gonorrhea? It didn't work for gonorrhea. It did not. Atropine. Throw back to Belladonna. Yeah. Widened that urethra. All right, let's take it up a notch. Maybe some bleeding and purging. Maybe some leeches.

Yeah. Seems right. On your wean or what? Uh-huh. Yeah. Okay. Yeah. So let's see. Where's another one? Take the milk of a woman, like breast milk, I assume. A little sugar. oil of violets and barley water and administer it with a syringe.

I mean, that could have been our quarantini, but... Good God. I don't have any source of breast milk around here. Sure. Isn't that why Craigslist exists? And if that doesn't work, you can always resort to urinating with your penis in warm cow's milk. Just plop. it into cow's milk and then pee. That's a very interesting idea, you know. I'm not opposed to that

idea and concept. Yeah. Yeah. Well, eventually the treatments became a bit more tame with lavage or washing out of the urethra as the most common treatment. Often the symptoms of virulent gonorrhea would disappear after a few weeks. I can't really say cured because microbial confirmation was not possible. And something called GLEET, G-L-E-E-T, was left in their place. The new word for me, too. What is gleet? Gleet is basically the post gonorrhea clear or cloudy discharge without any other symptoms such as pain or urination problems. It's also probably what gave gonorrhea its other nickname, the drip.

Ah. Yeah. Gleet. That's a good word for that. I can imagine exactly what it is. Yeah. I'm never going to forget it. Mm-mm.

Gleet was usually treated with astringence, which probably didn't do anything because glee usually disappeared around the same time that the person stopped using the estringence. It's probably just irritating your penis more. Yeah. But wait, there's more. Of course there is. So the word boogie. Have you come across boogies in med school?

I don't know how to answer this question. Okay, so then it doesn't sound like you have. Okay, bougie didn't always mean bourgeois. Okay. No. No, no. Sometimes, after male became infected with gonorrhea and recovered, his ureth would remain obstructed and urination was difficult. Maybe from the gonorrhea itself, maybe from the treatment, physicians didn't really know.

But to treat this, bougies were used. Bougie, meaning a thin, flexible instrument made of silver, lead. or wax. They're still used today, by the way. Like, boosies are still around. Sort of like a sound, but not really a sound. Anyway, after giving the person a painkiller, the boogie would be inserted into the urethra.

Sometimes it would be left there for days, only removing it when you needed to pee. Other times. I'm sorry. So this is like, you said silver. lead or wax? Yeah, it's got to be a little flexible. Okay, and it's like a rod.

Yeah, flexi wire rod. Uh-huh. And you just poke it up there. Yeah. And leave it. Yeah. We will post some pictures of boogeys. Excellent.

Oh, yeah. There are some great old illustrations of like the variety of bougies, especially once they became more popular in like throughout the 1800s and things. And then there was like electro something. Bougie and then there were... Oh, no. And then there were ones that were like linked together with tubing and yeah. Okay.

But one of the most horrific ones is that there were some bougies that would have a corrosive crystal at its tip, which was designed to clear the passage by like eroding whatever the inflammation was. So people actually died from that. Yeah. Yeah. But a surgeon's reputation could be made or... destroyed on how well he could work his way around a urethro with a bougie.

Yeah. Awesome. And so we don't really see throughout history, we don't really see a lot of descriptions of gonorrhea in females. We just get sort of this male specific thing. And as such, we also don't get very many women-specific treatments. Right. Treatments for female patients, though, the ones that are listed weren't much better. Most included a frequent and thorough cleaning of the vulva and vagina and treatment with silver salt or other chemicals.

Irrigation of the urethro was also done sometimes with a treated solution. And finally, sometimes, the cervix was cauterized with silver nitrate. Or a medicated wick was inserted. Yeah. More often than not, though, the prescribed treatment was just weighted out, which often led to infertility. Mm-hmm. Yeah. If these early veneerologists had anything to say about gonorrhea and females, it was that they were surprised at how much milder the infection seemed.

Diagnosing gonorrhea and females was more difficult because physicians had a tough time distinguishing between normal vaginal discharge and gonorrhea discharge. So doctors often relied on the next best thing. Patient history. But not firsthand. No. Oh, no. Doctors took the word of. quote, those whom we look upon as men of veracity, meaning a dude could say, I slept with her and now

I have gonorrhea, so she must have given it to me. And that would be basically the diagnosis. Wow. Yeah. Awesome. Cool. In the case of gonorrhea, it was pretty much always a one-way street from vagina to penis. That was how it was perceived throughout most of history. Some physicians did note other signs of gonorrhea infections in females, including inflammation of the labia and clitoris, but there wasn't a lot of attention paid to any internal indications of the disease. Shocking. Right. The cervix, which is recognized today as a principal site of infection, was rarely mentioned.

And that's because up to the 19th century, physicians who were almost without exception male pretty much never performed vaginal exams. Right. They're never going to be looking up there. No. No, God forbid. they take a speculum and peek inside. And if the woman was unmarried, forget about it.

In the 1800s, people finally started talking about where gonorrhea came from and how to prevent it. Was it a specific infectious particle? Was it just random inflammation? According to someone named Sweetie-Aar, I don't know how you pronounce that, Sweet-Auer, it was the latter. And he set to prove this by injecting an aqueous solution of ammonia, strong enough to give it a, quote, burning taste.

into his urethra twice. What? Yeah. He said that the second injection caused the most pain he had ever experienced. So the next morning, no surprise, he had some seepage, a considerable evacuation of purulent matter of the same yellow-green color as that of a virulent chowd-pice, aka hot p gonorrhea. So he concluded,

His conclusion was that gonorrhea was nothing more than simple irritation of the urethra. Oh, dear. Uh-huh. And he did this by... To himself. What a weirdo, man. I mean, do you not, like, I am amazed at the self-experimentation that went on. Yeah, that's bold.

These are precious parts. Yeah. I mean, and don't worry, there is some human experimentation for prisoners and people who can't... Don't worry. advocate for themselves. Just wait for our syphilis episode for plenty of that. Yeah. Others attribute it to something female-specific, like if you had sex with a woman who had a

certain vaginal discharge or maybe she was on her period. And then there were predisposing factors, too much sex, sex that goes on too long, and unnatural sides of the male organ. I don't know which direction. Which direction? Alcohol or rich diet, et cetera, et cetera. By the late 1800s, we're finally getting to the age when the mysteries of so many infectious diseases are revealed, the age of microbiology, or the beginning.

And gonorrhea is no exception. And the name that you might most associate with gonorrhea is nicer. It's Niceria, gonorrhea. But there was another mostly forgotten physician who made huge contributions to the understanding of the disease. His name was Emil Nogorath, and he was a German physician who was especially interested in pelvic inflammatory disease. He was, I wanted to put this tidbit in.

here. He was a workaholic who spent hours and hours at his desk, keeping himself awake with tons of coffee and putting his feet in a bowl of cold water under his desk. Just to keep him away? Yeah. That's so funny. I feel like we could have used that when we were finishing our dissertations. Anyway, after many clinical examinations of which the majority of subject were female, he announced his findings that, one, One, gonorrhea was likely a latent infection and that glee could still cause infection in women. Two, gonorrhea did affect females and that it was a common cause of infertility in both sexes. And three, gonorrhea was extremely prevalent.

He estimated that 60% of men in large cities in the U.S. had had gonorrhea at some point, and that 60% of those men would infect their wives. And that men could give the disease to women was itself kind of a revolutionary thought. But unfortunately, his conclusions were not well received at the time, primarily because American physicians took those prevalence estimates as a direct attack on the morality of American males. But the suggestion of gonorrhea as a latent infection made it more difficult to treat clinically. How could you tell one an infection was over if you couldn't use Gleet to guide you? Fortunately, in 1879, just a few years after No Garath announced his findings,

Albert Nicer, the namesake of Niceria, Gonorrhea, isolated the bacterium, making it possible to identify exactly when a person was no longer capable of transmitting the infection. Whoa. Which is pretty cool. Yeah. Gonorrhea had been fairly well described in adult males and very poorly described in adult females, but as you mentioned, there is another group that is commonly. affected by the disease. Infants. Gonorrhea can cause this conjunctivitis in newborns,

which can lead to blindness if left untreated, like you said. And despite the fact that gonorrhea and females was so poorly characterized, the link between the infection and this outcome in infants was discovered in the early 19th century, helped along by more horrific experiments in which the eye pus of one of these infants was inserted into a male urethra, producing gonorrhea within a few days. Whoa. Yeah. Still, it wasn't necessarily conclusive because sometimes babies were born to mothers who did not appear

to have gonorrhea. But the discovery of asymptomatic infections would clear that up over time. But even though the link between gonorrhea infection in a mother and eye infection and the newborn was discovered, it was still not able to be treated. And that was a huge problem because cases were growing. So by the mid-1800s, up to 2.000. 12% of neonates and European hospitals developed the eye infection. Whoa.

20% of those developed corneal ulceration, and 30% of those became blind. Oh, my goodness. So that's huge numbers. That is huge numbers. 12% of babies infected. Good gracious. Yeah.

Okay. So let me introduce you now to a German obstetrician named Carl Siegman-Frans C-R-E-E-C-R-E-C-D, I don't know, C-R-E-E-R-E-I-D, who in the 1850s founded one of the first gynecology departments in Europe at our favorite, one of our favorite historical hospitals, Cherat-E-A-S still in existence today, and featured on that amazing show that we have talked about. Anyway, so when he was at this hospital, he noticed the high rate of eye infections born to mothers infected with gonorrhea, and he tried all manner of things to try to lower

the cases. He tried to douche the vagina prior to delivery. Didn't work. He tried to wash the eyes of the infant with a borax solution. Didn't work. He, yeah, finally, he tried wiping the eyes with cotton wool and plain water and then adding a drop of 2% silver nitrate. And that worked like a charm. And the technique was picked up all over the continent. Okay. And then we've got finally the isolation of the bacterium itself, which happened in 1860s. by the 24-year-old Albert Nicer. Unfortunately, there was no suitable animal model for gonorrhea. So, because this is an exclusively human bacterium,

so what remained but to conduct human experiments. Oh, dear. Human volunteers were produced, inoculated, and subsequently found to have gonorrhea. Volunteers. Volunteers. In quotes. In quotes. Yeah.

So finally, it was accepted that this bacterium, caused gonorrhea. Even though a lot of progress had been made towards identifying the causative agent of gonorrhea and describing its clinical symptoms, treatment still had a really long way to go. And this was a problem because gonorrhea can be fatal and frequently was in the 1800s as a result of bacterial endocarditis. But fortunately, gonorrhea reached a turning point when antibiotics were developed. In 1937, clinical trials of sulfonamides were shown to be moderately effective against the disease, but the victory was short-lived. By 1944, only seven years later, only 25% of people with gonorrhea were being cured due to the emergence of resistant strains,

and doctors had to dust off their boogeys. Fortunately, penicillin took over as a primary and very effective treatment for the disease, and by the late 1940s, was widely used. Initially, because gonorrhea was so sensitive to penicillin, doctors were like, well, we don't foresee any resistance occurring. But within, yeah, right? I mean, come on, history repeats itself, people. But within 10 years, resistant strains had emerged and become, obviously, a major problem. Yeah.

Then streptomycin was introduced, and resistant strains emerged once again, blah, blah, blah. It's been this continual struggle to find one drug to effectively treat gonorrhea. So, and I'm sure you'll tell me all about the horror show that's going on today. You might expect that the prevalence of gonorrhea would decline over the 20th century with the availability of antibiotics. But if you look at a figure of rates over time for certain countries, you actually see a huge increase starting in the 60s. And that increase actually represents what is called a gonorrhea pandemic that peaked in the mid-1970s. occurring in places like the U.S., Sweden, Canada, and the U.K. Epidemiologists point toward a few things that could have caused a huge increase,

and it was probably a combination of things, like changing perceptions and sexual practices. People were having a lot more sex with a lot more partners, a huge population boom as the baby boomers became sexually active young adults, and the greater availability of contraceptives such as the birth control pill, which did not protect against STIs. In any case, the disease began to decline again. And I don't really know why. I don't know if there were certain public health campaigns that went on.

But gonorrhea today continues to make headlines as these super bug resistant strains have totally gotten out of control. So, Aaron, tell me more about those guys and about where we stand with gonorrhea today. I can't wait, too. So let's talk quickly just about the status of how, how, how will you? many people are we talking when we talk about gonorrhea? And then we'll talk a little more in depth about the antibiotic resistance because that is sort of the main part of the current story of gonorrhea. Okay. Okay. So in the U.S., according to the CDC, they estimate about 820,000 new infections of gonorrhea every year. 820,000. It is the second most commonly reported

communicable disease in the U.S. after chlamydia. Wow. Which is the number one. Well, goes hand in hand. Seems to make sense. So in 2017, there was over 555,000 cases that were actually reported. And so the number 820,000 is the estimate.

So that means that it's estimated that 270,000 people each year are getting infected with gonorrhea and just don't know it. So that's a bummer. That's a lot of people. It's a lot of people. Worldwide, the World Health Organization estimates 78 million people are newly infected with gonorrhea every year. 78 million. Wow.

That's a lot. This is much more prevalent than I realized. Me too. People don't really talk about it that much. I knew that it was one of the most common STIs, but I had no idea that it was. Yeah. So the U.S. Public Health Task Force currently recommends screening only for certain populations of people. So it recommends screening for any women with vaginas who are sexually active under the age of 25 in any kind of sexual relationship,

women who are over the age of 25 if they have multiple partners every year, and any men who have sex with men. that is the U.S. Public Health Task Force recommendations. And a study that I found that looked at whether this type of screening protocol, so screening every year, regardless of if you're in a monogamous relationship or not, just if you're sexually active, I found a paper that looked at from 2000 to 2015 whether this type of screening actually reduced the incidence of gonorrhea. And it found that it did. But what's interesting is that they also looked at other screening

scenarios. So what if we did universal screening of everyone of a certain age group, regardless of their sexual practices, just whether or not they're sexually active? And you can actually reduce incidents even more is what they found if you did more universal screenings. That makes complete sense. People who are in monogamous relationships, maybe one person doesn't realize they're in a monogamous relationship or one person that seems they are. Right. Yeah. Yeah. So yeah, so overall, it's a very common disease. So screening in general makes a lot of sense, especially because there's such high rates of asymptomatic infections. But the big story with gonorrhea is antibiotic resistance. It's definitely the most important part of the story. Antibiotic resistance has been detected in basically every country that has gonorrhea on its reportable diseases list. So everywhere where there is gonorrhea, there is antibiotic resistance. resistance. There's resistance to all of the drugs that you mentioned that used to be used to

treat gonorrhea, so the penicillins or the beta lactams, streptomycin, and all of the fluoroquinolones as well. In addition, there's also resistance to some cephalosporins, which is why now the only drug that's recommended that is still considered effective are the extended spectrum cephalosporins like Cephtriaxone, which is what we treat with. The scary thing is that in over 50 countries, they have reported resistance to these drugs as well. Ooh. Yeah, that's bad. I mean, it's what you'd expect.

Right. And we're also seeing increasing resistance to azithromycin, which is what we give as a backup in case gonorrhea is resistant to seftriaxone. So now it's our main line of defense and our backup line of defense that is becoming resistant. So the reason, or one of the reasons that we see such high rates of antibiotic resistance is that there's a lot of different mechanisms by which bacteria can evolve antibiotic resistance. They can evolve ways to inactivate drugs. So just sort of attacking the drug itself and inactivating it. They can alter their cell membranes that the antibiotics use as targets so that the antibiotics can no longer bind and actually do their job.

job. They can also evolve new mechanisms to export the drugs out of the bacteria once they make it in, or to prevent the bacteria from getting in, sorry, to prevent the antibiotic from getting into the bacteria to begin with. And all different classes and groups of antibiotics that we've developed so far have different mechanisms of action. And some bacteria are good at developing resistance against maybe one class of antibiotics. So, they can change their cell membrane so that penicillins can't bind as well. But then maybe they can't figure out a way to export it. So they can't be resistant to all antibiotics. Gotcha. It turns out that Nyseria gonorrhea has shown the ability to develop resistance in basically all of the

ways that bacteria can develop resistance. Cool. Yeah. So it's really good. They're really good naturally at uptaking and recombining, so shuffling around DNA from the environment, and because they have those pilli, which they use to grab onto the walls, they can also use pilli for what's called conjugation, which is kind of like bacteria sex, where they transfer DNA from one bacteria to another. And what they often transfer are plasmids, which are those little round pieces that usually or very often have antibiotic resistant genes on them. So Niceria are really good at that.

So that's why we see such high rates of antibiotic resistance. And very quickly, because you can have like a single Niceria bacterium just giving its genes to all of the other bacteria around them. Yeah. It's great. That's amazing. Yeah. So obviously there's a lot of interest in. developing better methods of treatment.

Unfortunately, from what I found on the World Health Organization website, there's only three candidate drugs in the pipeline in development for treatment of resistant gonorrhea. Oh. Yep. There's like three new drugs in the pipeline. One of them is, I think, either in or just finished phase three trials. I don't know if those trials went well. And then the other two are still in phase two clinical trials.

So they've still got a long way to go before they're on the market. Okay. So then the next natural question is if we can't develop better antibiotics. Vaccine. What about vaccines? There's a lot of discussion about this. There's nothing very close on the horizon. Okay.

Progress for a gonorrhoea vaccine in general has been very, very slow. So we have seen development of vaccines for other STIs like HPV, which is excellent. There's also a vaccine in development for HSV, so herpes, sylplex virus. Gonorrhea, not so much. Gonorrhea and syphilis are proving to be very, very difficult to try and develop vaccines for. However, I did find one paper that was very interesting that was just looking at a mouse model that suggests that at least in theory, it should be possible to stimulate the right kind of immune response that you would need to even be able to develop a vaccine. Because we'll talk more about

this in the vaccines episode, but basically for a vaccine to be able to work, whatever bacteria or virus you're trying to fight has to stimulate an immune response that creates a memory response. Right. And so if that... bacteria don't do that to begin with, then your body never develops memory. And so your body can't just fight them off every time you get infected. Right. So it does seem that at least in theory, it's possible to generate that type of response with some gonorrhea antigens, which are the surface proteins of gonorrhea. Why does it not create a memory? Goneria have huge amount of antigenic variation, like massive antigenic variation. So there's tons of different strains. And there's

tons of variation in those cell membrane proteins. And so they're really good at evading our immune system. And then on top of that, they're really good at fighting off our body's first-line defenses, which are those neutrophiles and macrophages because they can just live inside of those cells. Okay. Okay. Yeah. That makes sense. So people are working on it, it seems. It's definitely far in the future. It's nothing that's going to be happening in the next few years or anything like that. But yeah, that's gonorrhea. Wow. Yeah.

That was a good one. Yeah, it was. I had fun. I did too. I learned a lot. Me too. Clap, clap, clap. Let's give ourselves a round of applause.

That's another good title. It is. I really like that. I like that a lot. Well, should we do sources? Yes. Okay. I read sections of a book called The Scars of Venus, a history of veneerology by J.D. Oriole. And I'm sure I'll be going back to that for future episodes. I also use the Cambridge World History of Human Disease, edited by Kenneth Kippel, and some papers that I will put on the website.

Awesome. And I have several really interesting papers, mostly about the current epidemiology of gonorrhea. So as always, we will post our full source list on our website. This podcast will kill you.com. Just go to the episodes tab. And you can find every source that we used in all of our episodes. Yep. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you guys for listening.

We love making this podcast and we love that you listen to it. Oh, and if you haven't heard already, we have merch. We have merch. So go check that out. You can get to it from our website. This podcast Will Kill You.com slash merch. You can also get to it from the Exactly Right Media website. Exactly right, media.com slash merch.

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