Chapters Transcript Video Strange Bedfellows-Discussing What's New in STI Diagnosis and Treatment Options Without further ado, join me in welcoming Doctor Andrew Newman, a distinguished pediatric infectious disease physician and assistant professor here at UCS Benioff Children's Hospital Oakland since 2021. Doctor Newman completed his undergrad education at the University of Wisconsin. Madison followed by his MD at the Medical College of Wisconsin. He completed his pediatric residency at Children's Hospital Philadelphia, followed by his pediatric infectious Disease fellowship at Laurie Children's in Chicago. He currently serves as the medical director of the adolescent HIV clinic and as the associate fellowship director of the pediatric Infectious Disease program here at Cho. His clinical and research focus is on sexually transmitted infections, HIV prevention, care, and health equity. Today he'll be guiding us through emerging diagnostics and treatment strategies for a variety of STIs in his talk, Strange Bedfellows. So join me in welcoming Doctor Andrew Noon. Hi guys. Um, thanks so much for, uh, inviting me guys, uh, inviting me here today. Um, a lot of this focus, this talk is really just gonna be, uh, reiterating and going over the, the recent 2021 updates to, uh, testing and treatment strategies for our most common STIs. Um, I have, as is always the case, far too many slides to get through it, um, and so I'm gonna try not to rush through them, but if, uh, at any point I am talking too fast, if you guys can put it in the Q&A. To, you know, say that Anders fellow needs to slow down, I will not take offense to it whatsoever. Um, my hope is that you come away, uh, learning about the updates and learning about testing and treatment strategies, um, and I believe these, uh, slides will be available to you guys at the end, um, but, uh, without further ado, we'll kind of launch right into it. Oh, and thank you, Jay, for that, uh, wonderful introduction. I don't know if I'm distinguished quite yet, but I'm working on it. Um, so disclosures and disclaimers, um, again, I've got, uh, really nothing to disclose, uh, you know, UCSF pays me, but no one else does, I promise you that. Um, but the other big disclaimer here is that, uh, we are gonna be talking about STIs, um, and there are at least one slide where we're gonna go over visual identifiers and kind of mimics. And so, um, I know it's 8 a.m. but I'll forewarn you there are gonna be some, uh, pictures of infections on genitals this morning. All right. So, uh, our big learning objectives today, so we're gonna talk about a little bit of the epidemiology and epidemic of uh sexually transmitted infections or STIs here in the US with a specific focus on adolescent patients within California. Um, we're gonna talk about the new, uh, updates on treatment and testing for the most common STIs, and that being gonorrhea, chlamydia. We'll do a little bit of PID or pelvic inflammatory disease, and then we'll, I'll try my best to kind of help delineate the testing algorithm for syphilis. Um, it's always a fun time to talk about syphilis, so, um, we'll, we'll do our best there. And then if Time allows, we'll talk a little bit about the testing and treatment of mycoplasma genitalium, uh, a pathogen that seems to be in the background, but seems to becoming more prominence and non-gynococcal urethritis. And if time allows, we'll talk about a great new prevention strategy called doxyep, uh, which was help, uh, which a lot of research actually went down here at the, uh, uh, UCSF, uh, on our adult side. So, um, you know, I'm talking to a group of pediatricians I assume, so I know you guys all know this, but why is it important to discuss STI testing and treatment we're discussing adolescent care. So teenagers are having sex again, this state only goes up to 2017, so it's already a decade old, but as you can see, um, from, you know, the ages of 13 to 18, uh, around 40% of our population is having sex. Um, as teenagers get older, the more likely they are to have sex, uh, reaching to a peak at age 20. Uh, they're having more than just vaginal sex, and again I'm going through these quickly is that the numbers are just for illustration, but, um, you know, we often talk about just the insert of vaginal sex when talking with teenagers, but it's really important to expand your definition of it and expand the definition to teenagers when talking about it, just so that we know we're giving them right testing and treatment strategies. Um, and then on top of that, with all of this, uh, as best as we're trying, our incidence of STIs continues to decrease you over a year here in California. You'll notice a lovely dip in 2020, um, that is, uh, certainly related to COVID, um, not just, uh, you know, decreased or increased isolation, but also decreased access to testing, and so that's probably a false dip, and we're starting to see it rise back up to the pre-COVID levels as testing ramps back up again. Uh, when we talk about, uh, infections, you know, it does seem that a large burden of disease happens to our, uh, teenagers and young adult populations with them being the lion's share of new chlamydial infections, as well as new gonorrhea infections, um, a little less in the HIV AIDS category and early syphilis infections but still present, um, and then that also disproportionately impacts our non-white teens and young adults with again, um, the lion share happening with uh within our black community. Um, and so, uh, the, uh, testing and treatment of STIs really does affect our adolescents and young adults and in particular, in particular our most vulnerable populations, and so this is a matter of both medical importance but also medical equity to ensure all teenagers have access to a healthy future. So, diving right into these 2021 updates, um, the big, uh, couple of big salient points here is that we now use the term infection instead of disease when we're talking about sexually transmitted infections. Uh, the rationale for that is that a lot of these um infections can be asymptomatic. Disease describes the actual symptoms they're experiencing infection describes the pathogen. Um, and so even with an asymptomatic infection, we still wanna treat as uh spread can still continue and eventual disease can happen. Um, we're talking about testing and treatment, uh, for the rest of this, uh, presentation, we'll talk about, um, infection around based on the patient's genitals or biological sex or gender expression. Um, when you're talking with your teens really to highlight here that it's really important to speak plainly about sex and to discuss the type of sex that teenagers are having. At all if at all possible, avoid the term sexually active. It's a little ambiguous. um, teens will sometimes say, well, not active, um, and that they're not having sex right there in the room with, uh, with you taking the history, or they just didn't have sex right before they saw you, but they're, they've had sex before and they're continuing to have sex. So avoid that term if possible, just say, are you having sex or describe the sex act to make sure uh that you're uh providing adequate care. And then the uh big important 5 Ps when discussing sexual care, so uh partners uh they have they have one partner or more than one partner uh practices in terms of how they're having sex, what protection they're using from STIs, any past history of STIs, and what's their pregnancy intention. Uh, always remember that California allow California law permits uh confidentiality with regards to sex and STI treatment, um, age 12 and up, so you don't necessarily need. Uh, sorry, 13 and up. You don't necessarily need a um adult present, nor do you need to inform adult about uh testing or providing care, uh, for teens and young adults. Um, I'll kind of breeze through this, but um, we'll talk about mostly uh the overlap of a bunch of uh disease phenotypes for a lot of these, uh, STIs. This is just kind of a general information slide as to what that disease phenotype looks like. Um, but jumping right in, we're gonna go to our pathogens. And our first on the block is gonorrhea. So, um, this is our first kind of test question. I'll just kind of introduce it, uh, we'll go over the answer right at the end of the block on gonorrhea. Uh, but this is a 17 year old 60 kg girl who's coming in with 3 days of dysuria and white discharge, um, that she noticed in her underwear following unprotected vaginal sex one week ago. You did a urine test, it shows that she's got niceeria gonorrhea, and so the question now is what's the best course of treatment? Our options are a single pill of oral ciprofloxacin once, an IM dose of ceftriaxone at 250 mg plus an oral dose of azithromycin at 1 g at once. Um, I am ceftriaxone at 500 mg once alone, or oral cefixim at 200 mg twice a day for one day. So, um, kind of breaking down our numbers again, so, uh, we're kind of following the trend within the US that US is the gray line, California is that, um, kind of more teal appearing line in terms of incidence of new gonorrhea infections within the United States. We're following national trends and that um while we had a great dip in the 90s, we're rising again, um up to the 2020s. Um, when, oh, all right, sorry, I mixed up my slides here. When we talk about gonorrhea, um, it is more likely to be asymptomatic in, uh, young women, but the lion's share of new incident infection actually does occur in young men. Um, and, uh, kind of background on gonorrhea here. So it's caused by our, uh, uh, gram-negative diplooxi, uh, nasterio gonorrhea. Um, it can cause asymptomatic disease, which as I mentioned, is more common in women, but also has the potential to disseminate and cause sepsis, which is a little bit different from the other STIs, uh, and infection in general results when we've got direct contact with uh uh mucous membranes of another infected individual, um, regardless of symptoms, so you can still spread or still spread infection. Uh, even if you're asymptomatic. Oh. In terms of symptoms and disease, so, um, we kinda got the gamut of uh what it affects and where. So we've got our asymptomatic infections which occur typically at the cervix, urethra, uh oropharynx, or rectum. Um, most typically we think about genital urogenital disease, so cervixitis, Bartholonitis, uh, vulval vaginitis, or PID, um, for those with the vagina or those with the penis, we've got, um, abscess urethritis, uh, or epididinitis, sorry, urethritis can occur with both, uh, genital phenotypes too. Uh, non-genital disease, uh, we've got peri hepatitis with the Fitz Hugh-Curtis syndrome, uh, pharyngitis or proctitis. And then, again, this can disseminate uh in certain individuals or if it's left to linger long enough, so that can lead to septic arthritis, which can even be a polyarthritis, um, tenosynovitis, or even uh uh skin infections with pustuar or skin lesions. In general, for testing, we are moving far, far away from uh culture now, uh, with our more advancedAT testing or nucleic acid amplification test. It is our most sensitive test. Um, unfortunately for, uh, culture, it's, it's quite difficult to grow and so, um, sensitivity drops down to about 50% even when you catch the mucopurulent discharge. Gramsan itself is also, um, pretty specific, but again, not sensitive. Um, sites of testing, again, you can send urine testing, um, or a swab of discharge from uh the vagina or the cervix. Um, we also recommend rectum or pharyngeal swabs as well, uh, if, uh, depending on the type of sex, uh, your patient is having. And then here's the big update for the 2021 uh MMWR treatment CDC guidelines. Um, so we have uh moved away from uh recommending azithromycin any longer for empiric treatment or or definitive treatment for uh gonorrhea infection. It is now just recommended to give a single dose of ceftriaxone at an increased dose of 500 mg once. Um, if they are more than 150 kg, that dose doubles to 1 g. Um, if, uh, for some reason they can't make it into your clinic or there's, um, issues around that, you can trial oral cefixime, which is an 800 mg dose once. We recommend avoiding that in cases of pharyngeal gonorrhea because there are increased treatment failures associated with pharyngeal gonorrhea. Um, and if there's an allergy to cephalosporin, specifically ceftriaxone or the third generation cephalosporins, um, the recommendation is I am gentamicin plus oral azithromycin, uh, 2 g, and ignore that or there, that's, uh, something I forgot to delete. All right. Um, so the rationale for this change, uh, broken down in the, in the guidelines. So, um, I'll show you some data in just a second, but we're seeing increasing rates of azithromycin resistance among our gonococcal isolates. Um, and because of that, it was found that, uh, azithromycin, um, isn't recommended any longer, just to kind of, uh, uh, decrease that selective pressure, um, on gonorrhea and hopefully reclaim azithro as an alternative agent in a few years. Um, this will also go hand in hand for our change in treatment for chlamydia, which I'll get to next. Um, with that in mind, we're gonna, we've seen a decreasing rates of ceftriaxone resistance, which has been really nice. And so, um, the thought is that we can rely on ceftriaxone alone, um, now for, for gonococcal treatment. Um, but there's still that fear that, uh, as we kind of change our selective pressures on gonorrhea, we'll see a compensatory rise in ceftriaxone resistance, and so they've increased the dose to try to already overcome that. And so if you can intermediate isolate, it's still, it's not that you're gonna be influencing further resistance. Um, so all in all, uh, 3 rationales for change, all leading to the single recommendation of a one time dose of ceftriaxone. Um, here's just to, uh, show you what our rates of, uh, um, azithromycin resistance are. So, uh, if you guys have never looked at the data, this is the just, uh, GIS project, the gonococcal isolate, uh, surveillance project. Um, gonorrhea is actually one of our most resistant, um, bacterial agents, uh, far more than any other species, um, but, uh, the CDC continues to monitor it and as you can see, we've had a huge jump up, um, starting around 2014. Um, with the amount of, uh, islets, uh, that were found to kind of have a warning value around isithromycin resistance all the way up to 10%. I don't know why the color didn't come in here, but this is for our third generation cephalosporins that kind of lighter blue is cefixim, which again hit a peak in 2010, uh, dropped down to 2014, that darker blue is our ceftriaxone resistance. Um, and so you can see that, um, in general, third resistance of third generation cephalosporins has dropped. Uh, the ceftriaxone is a little bit variable, but thankfully we're um well under 1%, um, for, for both forms uh of our third gen uh cephalosporins. All right. So, um, after treatment, um, follow-up testing is recommended in certain circumstances. So for all cases of pharyngeal infection, regardless of symptoms, uh, we recommend a test of cure for pharyngeal gonorrhea with a NATS-based swab 7 to 14 days after treatment. Uh, for those with rectal, um, or I should say urogenital, not just urethral but rectal or, uh, urogenital disease, um, 3 months after treatment, we do recommend repeat testing just as there's an increased rate of reinfection in patients. Um, it is not a test of cure, it's just to kind of continue to screen them, um, regardless of symptoms, just be based on risk. Um, you, uh, California law does permit for partner therapy, and so, um, their most recent partners should be evaluated for treatment and then all partners who had sex with the, uh, person who was recently diagnosed with gonorrhea within 60 days should be evaluated, so it's not just the most recent, but, um. Anyone for the last two months. Uh, you are allowed to provide, um, uh, express partner therapy, which could be suffixing 800 mg once if they have their own provider, it's still recommended to do the IM dose of ceftriaxone that we know um that that can be a bit difficult to obtain. And then in general for all of your patients, it's recommended that they abstain from all sex, um, uh, for 7 days. After treatment. All right, so, uh, this is again the question at the top. So our 1717 year old 60 kg girl, uh, coming with dysuria and white discharge after unprotected vaginal sex one week ago, uh, she's got, uh, gonorrhea, um, and so our best course of treatment with the updated. Guidelines, there we go, is now the intramuscular ceftriaxone dose at 500 mg. Um, for those of you that are recognized B, that used to be our old regimen, so that's kind of the shift here. Um, so we're moving from B to C now as our recommended treatment. All right, uh, moving on to chlamydia. So, uh, can start with our pre-test case here. So we've got a 16 year old male, he's coming in for as well child check, uh, during a confidential portion of his visit, he lets you know that he is having sex with his boyfriend and that they rarely use condoms. He's a receptive partner during anal sex, which is he describes as the bottom which colloquial term, uh, used. He is not experienced any dysuria or rectal pain, uh, no rectal or penile discharge or sore throat, but, uh, being the great attending that you are, um, you do do a screening test of all sites for STIs and rectal testing does come back positive for chlamydia trachomati. So what is the best? Course of treatment, um, we either have oral levo, uh, once a day for 7 days, oral doxy 100 mg twice a day for 7 days, 1 g dose of oral azithromycin once, or oral oral erythromycin 500 mg twice a day for 7 days. All right, so, uh, kind of pulling back that graph a bit again. So again, we, California is not bucking any national trends. We're following them quite closely, even with chlamydia. Um, again, we've had a steady rise since the 90s, um with a drop in 2020, that's more related to COVID than anything else. Um I wish it was related to just the actual drop in cases, but um we're starting to see that data rise up again. Um, it's kind of a reverse graft almost a gonorrhea, but, um, women, uh, take the lion's share of, um, infections with our instant infections with chlamydia, and it can be uh asymptomatic as well in both, uh, both persons, um, but again, women are more than men in this area. Um, and then for chlamydia, so again, it is an intra obligate intracellular uh bacteria, uh, with the, um, uh, uh, kind of life cycle off to the, the right side there. Um, it's the most frequently diagnosed STI across the US and certainly in California. Um, when we talk about causes of urethritis, we've got gonococcal urethritis and non-ggonococcal urethritis, which is a pretty big, um, catch-all term, but chlamydia takes the lion's share of the non-ggonococcal cases. Um, it does often more, it does, um, more often result in asymptomatic carriage than it's, uh, causing gonorrhea. Actually they're not related at all, but, uh. Um, but you understand. And then, um, again, similar, uh, mode of transmission where it is contact with, um, uh, mucous membranes of another person who's got an infection regardless of symptoms. On the right there, um, we're really focusing on errovars D through K for this lecture, so that's those are the main cause of the urogeneral disease and the most common here in the United States. In other countries, we do have uh erroars A through C which cause trachoma or kind of uh diffuse eye disease, often in neonates, um, and then in uh even further uh uh other countries in the world, they have the L1 through L3 seroars, which causes lymphogranuloma verrinium veneum. Um, which is not endemic to the United States, um, so, uh, you know, depending on, uh, travel history, it can present a little bit differently, but, uh, we're gonna focus on erroar's DK and neurogen Cs for this lecture. Um, similar to gonorrhea, again, we have asymptomatic infections of all these sites. Uh, similar general disease presentation, so urethritis, um, uh, for both, uh, for those with a vagina, you got cervisitis, Bartholonitis, uh, salpingitis, endometritis, and then PID, and then, um, for those penis, uh, they can have epididymitis in addition to arthritis. Similarly, again, we can see peri hepatitis, pharyngitis, proctitis. You can get a reactive arthritis. It's a little bit different than what we see for gonorrhea, where gonorrhea causes direct infection of the joints. This is more a reactive process, so, uh, inflammation of the joints caused by a local Chlamydial infection within the genital tract, uh, or anal tract, um, but not direct infection of those joints. So it's reactive. Um, and then again, LGV or lympho granuloma venereum, um, which is, um, uh, kind of around the UG area but not technically in the urogenital tract. Um, testing wise, again, very similar. So uh our blanket recommendation is still to use nucleic acid amplification testing. We do not recommend culture at all. It is an obligate intracellular pathogen, so exceedingly hard to culture if we ever can do it. Um, so avoid culture and still gram stain won't work at all for the same reasons. Um, instead of testing again very similar, you can send urine, um, for that, or you can do swabs of discharge from the vagina or cervix, um, or swabs directly of the rectum or pharynx, depending on the type of sex they're having. And then big 2021 treatment update. So, uh, we have shifted our recommendation from uh azithromycin to now oral doxycycline recommended for all cases. Um, it's a bit longer, so it is a 100 mg twice a day for 7 days. Um, and we'll get into the rationale for why. If you think that there's going to be difficulties with a patient tolerating, uh, doxycycline or with compliance to a one-week course, um, you can, uh, use oral azithromycin, but that's a conditional recommendation. Um, if there is allergy to doxy or is it or any contraindication to either of those medications or levofloxacin can be used, um, again, uh, for a seven-day course. And then for pregnant patients, we do avoid doxycycline, so they'd still get the uh recommendation of oral azithromycin 1 g, um, or you can trial oral amoxicillin, but, uh, azithromycin is a stronger use case and, and a better history for clearance. So the rationale for the change actually has to do more with our rates of rectal chlamydia. Um, for uro general infections, we actually still have really great evidence that azithromycin is effective in clearing disease. Our cure rate for doxycycline is 100% for urogenital disease for azithromycin is 96%. So quite similar. Uh, on the right side of the slide, you'll see a graph here that is um testing and cure rates for specifically rectal infection. And uh that top blue line, um, now the couple of blue lines, but um ultimately that blue line is what's representing doxycycline therapy for rectal chlamydia, as you can see, um, by 4 weeks it approaches 100% in the complete case population, um, uh, with the protocol kind of driving that up versus the intention to treat. Um, the, uh, reason for the change, uh, that orange line is azithromycin. So as you can see, the cure rates at 2 weeks have dropped down to around the mid to low 80s, and then at follow up at 4 weeks, um, it drops even further, uh, to about 70%, and uh you might be asking yourself why if at 2 weeks. It was cured. How did it pop back up and we get less cure at 4 weeks. Um, there's a thought here that there's a biologically crudescent phase that does occur because of these, um, intracellular elementary bodies kind of coming back up, um, that's more often seen with azithromycin and doxycycline. So that's why the curerate actually drops over time instead of increases. All right, so follow-up testing, so we do recommend repeat testing similar to gonorrhea for 3 months, uh, 3 months after treatment to again a higher rate of reinfections. Those who that we recommend a test of cure for include those with persistent symptoms. Um, again, since we're recommending a week of therapy now, there's any concern about adherence, uh, to that full week of therapy, um, if, you know, depending on the partner and their treatment course, if there's concern for rapid reinfection, or if they are pregnant, they do need repeat testing within 4 weeks. Um, and then we don't recommend any repeat testing at uh less than 4 weeks because then that will likely still be positive and that may be reflective of old disease. Um, and, uh, for partner therapy, again, very similar to gonorrhea, again, anyone who, uh, recently had sex with the individual who has the infection should be evaluated for treatment and all partners for the last two months should be evaluated. You are by California law allowed to prescribe express partner therapy, and again, here we recommend doxycycline 100 mg twice a day for 7 days for EPT. All right. Kind of an offshoot. Again, both gonorrhea and chlamydia are associated with pelvic inflammatory disease, but um chlamydia kind of takes kind of the, well, I should say lion's share, but it's seen a little bit more frequently than gonorrhea. So I grouped it here. Um, for those that have seen it, the diagnosis can be difficult to make for uh pelvic inflammatory disease as it's kind of a wide spectrum of, of phenotypic presentation. Um, they can be asymptomatic, um, but it can also just be a subtle disease like dyspaunia or abnormal vaginal bleeding. Um, and certainly you should consider, uh, uh, pelvic inflammatory disease and all those, um, uh, with, uh, cervical motion tenderness, uterine tenderness, or a neckal tenderness. Um, you have the option to trial oral therapy, um, if it's mild to moderate disease, and the big caveats here for when you absolutely need to do IV therapy is if there's concern for a surgical emergency, um, that not only includes, um, any abscess around pelvic inflammatory disease, but say they've got right lower quadrant tenderness and you wanna make sure they don't have appendicitis. That's an absolutely great rationale to send them into the emergency room for evaluation and consideration of IV therapy. Again, if there's an abscess on ultrasound, um, they should absolutely be referred into the emergency room for drainage and IV therapy if they're pregnant, if they've got a fever greater than 38.5. Um, or an inability to tolerate or comply with any of the oral medications due to nausea or MSS, um, or if you've started therapy on them and they're still having the same continued symptoms despite the oral therapy. With that in mind, our big update to our pelvic inflammatory treatment guidelines, um, was kind of this shift, uh, for chlamydial treatment as well as the more um strong recommendation to include metronidazole in therapy. It used to be a, a conditional recommendation that they kind of moved it uh now towards absolute. Uh, use. So our outpatient recommended regimen, uh, for those that, uh, can, uh, use an outpatient therapy is that oral doxycycline, um, this time for 14 days instead of 7 days cause it's a little bit more advanced than just a simple chlamydial infection. Uh, with the addition of oral metronidazole, uh, twice a day for 14 days, and then the consideration of either a one-time dose of ceftriaxone at 500 mg to again cover for gonococcal infection, or, um, you can use IM cefoxetin in this situation as well. Most come compounded with uh oral probenecid to allow for uh uh more delayed distribution and longer dosing with the IM dose. All right. So jumping back into our question that we started at the top of the uh block here. So again, this is our 16 year old male. Um, they're coming in, they're having unprotected anal sex and they are the receptive partner. Um, no symptoms, but testing, uh, from a rectal gnat does show that chlamydia trachomatous. And so our best option now based on the 202,212,020. Guidelines specifically to for rectal chlamydia is oral doxycycline twice a day for 7 days. Again, the old regimen would have been that C answer oral azithromycin, but we were moving away from it for due to increased treatment failures with azithromycin, particularly in rectal uh chlamydia, but again, the recommendation is for all chlamydial infections to use doxycycline. All right. uh, and then finally, uh, this tricky guy, uh, syphilis, um, we do get a lot of calls, uh, in our department about syphilis because, uh, testing treatment is, is never straightforward, and we welcome those calls because they are, well, they're interesting to work through always. So, um, we've got a 17 year old man, uh, he comes in again for routine well child check. Um, he has a history of primary syphilis. It was adequately treated two years ago, and his last RPR that was sent, uh, 1 year ago after treatment was non-reactive, so, uh, completely negative testing. He started having condomless vaginal sex, uh, 6 months ago with partners he met quote unquote on the apps. Uh, so he's had more than one partner in the last 6 months, uh, and has not used a condom at any single time. He doesn't report any symptoms, but you would like to re-screen for all STIs. And so in this case, what is our best test set to send to assess for a new syphilis infection. So, uh, bit complicated, but um, certainly a scenario that we do run into, um, not too infrequently. So, uh, we've got TDPA and FTA antibody test, our Talladum um EIA or an RPR and we'll, uh, we'll hopefully be able to answer that question at the end of this block. All right, so, um, we, uh, had a big uh surge in syphilis back in the 1940s, and thankfully they've never risen back up to that level. I should also mention to the scales on our syphilis graph here are much lower uh than those on chlamydia and gonorrhea. So, um, much lower incidence in general of primary syphilis, both in California and across the United States, but as always, California is not bucking any national trends, we're actually above the national trend for incidence of primary syphilis. Again, small dip in 2020, but that's related to COVID. Um, again, our lion's share of primary and secondary syphilis does occur more in our male population, um, and again it's kind of our, uh, you know, firmly mid adult, I guess you'd call a 25 to 29 year old, um, uh, uh, also our young adults at 20 to 24, less less seen in our 15 to 19 year old population. So syphilis is caused by that wonderful spirocheat uh reponema pallidum. Um, it occurs through direct inoculation, uh, when, uh, you have sex with someone who also has syphilis. Um, oftentimes described it with an ulcerative lesion. However, you can have asymptomatic shate through mucous membranes. So again, there does not need to be a lesion present in order to pass on the infection. Uh, there are 3 different stages of infection. Uh, each has different characteristic signs of infections, and there is a latent period where you can be infected, um, and have zero symptoms whatsoever. As best as I can, I made this little chart, uh, hopefully to, to kind of decrease some confusion. It's taken off from the red book. It's actually the 32nd edition I took it from. We're now on the 33rd, but not much has changed in terms of the phenotype of uh syphilis. Um, so primary syphilis, in general, we think of the incubation period from anywhere from about 1 week to 3 months. Um, that's your, um, shanker. It's a painless, often painless ulceration at the point of infection. So, uh, kind of around the urogenital area. Um, you can also have non-tender lymphadenopathy associated with an inguinal lympha uh, uh, sorry, non-tender inguinal lymphadenopathy associated with it. Secondary syphilis um can often occur 1 to 2 months after the primary infection has occurred. So, um, you know, you add that maybe to the 10 to 90 days against it's a very wide window. Um. Uh, but it can be characterized by a flu-like illness. Um, you also, uh, can sometimes see a generalized maculopapular rash, often copper colored is the big distinct coloration that we see more, uh, or a light red color. It does include the palms and soles, um, and we also do see something called condylomalata, which is also a urogenital rash that looks a little bit different than the paintless shanker, and we'll go over the rashes in a bit. Um, really latent, that is when a patient has no signs of disease, um, but is positive in terms of our screening tests, so is infected. Um, the big differentiation between early and late latent period is when the infection occurred and how you can time it. So if you know it's been within one year. Um, then we would call it early latent if it's been more than one year since they've, uh, had the infection or you don't know how long it's been going on, we would just call that late latent infection. And then finally, we've got our tertiary disease, which we don't often see in children or young adults, um, outside of neurosyphilis. Um, but that often occurs decades after the initial infection. Uh, that includes cardiovascular syphilis or aoritis, um, those, uh, the gummas or the breakdowns around the face. Um, neurosyphilis is often included in tertiary syphilis more because of treatment. Guidelines, but, um, just for you all to know, neurosyphilis can occur at any point, uh, during the primary, secondary, or latent phases. So if you've got a patient that is positive on RPR or other syphilis testing, and they've got a headache that won't go away, or other neurologic symptoms, um, that I would still suspect neurosyphilis, uh, even though it's been a short time. All right, so, uh, this is the warning here, um, so we will have some pictures of genitals ahead. All right, so, uh, just to uh look at some mimics of um syphilis here, we're not gonna talk about it, but, um, uh, shankroid is also a genital ulcer disease that looks very similar, uh, to, uh, the hanker of uh syphilis, and they're also named very similarly, just to make it even more confusing. Um, the big highlights I wanna pull out here is that the shanker of syphilis has a nice rolled rounded edge here. Um, it's often a little light red, it's painless, it's kind of a deeper ulceration. Um, as opposed to the shankroid where you don't have that kind of nice, um, not perfectly round, but you've kind of got more of these sort of pigeonous edges here. It's not as deep. Um, there's not that rolled edge here, and it's also quite painful, so it's a painful genital ulcer disease. Um, chain court is often not endemic to the United States, so, um, I would suspect it, um, if in those returning travelers, uh, who have genital ulcer disease. And then um we've got on the left here condylomaatta, which is again uh associated with secondary syphilis. Um, versus, uh, candoloma acuminata, uh, which is HPV or genital warts. Um, here again, they look very similar, but there's kind of more discrete, um, uh, varicated, uh, lesions here on the condoloma cuminata or genital warts versus this kind of more a raised macular, still a little bit um rough and rugated, um, edges here, but uh a little bit more macular appearance for condylomalata. So, um. If at all suspicious, I think it is OK to send an RPR or other syphilis-based testing, uh, as I will certainly say that all of these do look very similar to each other, but um, these are kind of the big differences. All right, and here is where it gets real fun when we talk about our testing options and what they mean. So we often break these down into non-treponeal testing and treponemal testing. Both of those are to detect syphilis, uh, but they differ in the range of sensitivity and specificity. Um, so our non-tre tremal testing, so that's our VDRL or RPR. Um, we often express that as a tighter, so positive, and then either 1 to 11 to 21 to 41 to 8, and uh, onward. Um, it is directly impacted or should be directly impacted by disease, so you will see a rise in tighter as infection occurs without infection or without treatment. You should see a drop in tighter towards negativity after uh you've completed uh adequate therapy. Um, we do recommend, uh, if you're going to, you know, trend these labs, which you, you, we do recommend you do trend these labs, but, um, you cannot compare a VDRL test to an RPR. Those are separate tests. So if you use an RPR stick with an RPR. If you use a VDRL, stick with the VDRL. Try to get them at the same lab as there's some in lab variability, unfortunately. Um, and there are false positives. We are aware of that. There are multiple medical conditions and even pregnancy, uh, can lead to a false positive test, um, and if there's questions about, about that. Uh, you can always give our office a call. Uh, the next thing we move over to, so that's often, uh, it used to be the, the main screening test was our non-treponemal testing, and we'll get to how that changed, um, but for treponemal testing, uh, that is our EIA, FTA antibody test, or TPPA, um, that's often used as our confirmatory test after the initial screen is positive. Um, it is usually, I will say stays positive after initial infection and adequate therapy. So it sticks around. So once you get a positive TPPA or EIA or FTA antibody tests, um, if you're concerned for reinfection, you should not resend this test. It will stay positive for the rest of the patient's life. I will say some do go negative, uh, within 5 years if you caught the infection early and treated it adequately, but the, the general uh uh uh teaching is that it will stay positive. All right. Oh, that's blurrier than I wanted it to be. I'm so sorry about that. So, um, this is our traditional pathway for uh screening, uh, for syphilis. Um, so right up at the top again, we start with our screening test, that's the RPR that's negative, uh, we would say that syphilis is unlikely unless you've got overt disease, at which point we can talk a little bit more about retesting or um still standing the confirmatory test. Um, if it is positive, um, then we do send a confirmatory test again, false positives do occur, um, so that treponemal test is often the TPPA or the FTA antibody test, and again, if that's positive, so you've got two positive tests and syphilis is likely whether it's past or present. Um, or if, uh, if you've got a positive RPR but a negative TPPA, then we would typically say syphilis is unlikely. Um, the big change, uh, which is, I will even admit it's confusing for everyone, including myself sometimes, um, but with this reverse algorithm for new first time infection, you can start with the treponemal test, um, and so, uh, it's often a rapid uh treponemal test, either the EIA or CIA. Um, if it is negative, uh, we would immediately jump to saying syphilis is unlikely and you can stop there. If it's positive, then we kind of go back to our non-treponemal test to gonna get a second test to confirm this. So that's either the RPR or VDRL where it gets confusing as if the RPR or VDRL or both, um, are negative in this scenario, we still recommend a second trepoemal test to kind of clinch it. Um, in that case, it's gonna be, we want it to be different than the EA or CIA it could be the TPPA or the FTA antibody test. And if you've got a second trepomal test that's negative, syphilis is unlikely. If it's positive, syphilis is likely and you should go ahead and treat. Um, the big caveat here again is that this is for new infection or first time infection. If a patient has had syphilis before, I told you they've been treated for syphilis before, uh, TPPA, EIA, CIA, all these tremal tests will likely stay positive for the rest of their life and are not reliable, and you should just stick with RPR or VDRL. Um, well, didn't talk talk about this. The rationale for this was actually conducted among uh pregnant patients, um, and it was found that about I think closer to 10% or 5 to 10%, um, may still have a negative RPR or VDRL, but the TPPA positive suggesting infection in pregnant folks. Um, uh, and that this would be a missed infection. Uh, we've seen a rise, unfortunately, in congenital syphilis, um, and so the, uh, rationale for change here for new infections was to try to catch more, uh, pregnant persons while they are pregnant to allow for treatment and decrease, uh, the rate of congenital syphilis. Um, our treatment, uh, our options really, uh, haven't changed except we've got a stronger uh use case for doxycycline, which is nice, um, but the recommendation for, uh, primary, secondary, or early latent syphilis is just a one-time dose of IM penicillin. Um, if they've got an allergy to uh allergy to penicillin, you can use doxycycline for 14 days. Um, for late latent syphilis, that's where we recommend, uh, a once weekly dose for 3 weeks, uh, with iron penicillin, or, uh, you can use uh doxycycline for 28 days or 1 month. And then for either tertiary syphilis, uh, which hopefully we won't be seeing too much of, or neurosyphilis, which we do see from time to time. Uh, they do need to be admitted for IV penicillin for about 10 to 14 days. Uh, big thing to forewarn your patients about is that as the Gerhartheimer reactions, so that is the breaking up of the trepanine, uh, releasing kind of an inflammatory milieu, um, leading to an acute febrile reaction in the 1st 24 hours after treatment. It can be myologist, it could be headache, um, and we often see it in early infection over late, latent infection. Um, it is not an allergic reaction, um, and so they can still receive penicillin. It is just related to, again, uh, you effectively treating syphilis and the body responding. Um, antibiotics are fine to give for this. NSAIDs or Tylenol, um, won't affect therapy or the effectiveness of therapy and will lead to some symptomatic relief. Um, and the symptoms should resolve within 48 hours. If they do not, um, then that's not the Jaro Herzheimer reaction. All right, and then follow up testing, um, and so after you've tested positive ones, again, your options are now only RPR or BDRL again, continue that at the same lab. Uh, we recommend follow-up testing for serologies at 6 and 12 months for primary and secondary syphilis, and then 6, 12 and 24 for late late latent or for early latent or late latent syphilis, as well as our tertiary syphilitic diseases. Uh, we want the, uh, reemal testing titers to decline fourfold within one year. Um, and if they don't, uh, then that likely indicates uh treatment failure. So for example, if they start out with a, uh, tighter of 1 to 8, um, and it has only dropped to 1 to 4 at repeat testing at a year, that's not a, um, big enough decline. Uh, and so we would, um, assess for, again, do they have neurosyphilis, do they have HIV or if not, uh, send to us and we'll, uh, we'll work to see what's going on. And then other considerations following infection. So I mentioned, you know, if it doesn't decline, consider HIV, but honestly if you would, and you heard it at the top of the hour I'm one of the adolescent HIV providers, please always send an HIV test if you're testing for syphilis. Heck, please send a HIV test when you're testing for any STI ever. Uh, they kind of go hand in hand in terms of how you can get them. So, um, we really, really, uh, would love, uh, more testing done on our population for HIV. Um, for pregnant patients, um, I don't know how many of you take care of any pregnant patients, but, uh, we, uh, do not recommend doxycycline during pregnancy. Uh, and so, uh, penicillin is the only option here, and if they're allergic to penicillin, they do have to be referred to an allergist for desensitization. Um, for sexual contexts, it's a little bit different, um, and again, it's, we, we, we, uh, EPT is a little bit different too, but, um, for those, uh, who, um, Uh, were diagnosed with primary, secondary, or early latent, um, and if they had sex, uh, with the person, if they've had sex with someone in the last 90 days and recently diagnosed with primary, secondary, or early latent syphilis, we just recommend treatment for the partner in that scenario, um, as it can be a delayed time to positivity on RPR or any of our other tremal tests. So just go ahead and treat, uh, with a one-time dose of iron penicillin or the um 14 day course of doxycycline. If it's been greater than 90 days. Um, then, uh, the partner who had sex with the individual who's got the syphilis infection, um, they can be tested and then you can base your treatment based on the results of those tests. So if it's negative, you don't necessarily need therapy if it's positive, um, then it's either primary, uh, syphilis or, um, early latent syphilis. All right, so, circling back to our test question around testing, um, so again, I, we've got our 17 year old um man here who's coming in, uh, for a check. Uh, he's previously had syphilis, was adequately treated as evidenced by the fact that he had non-reactive RPR after treatment. Um, he then started having sex again without condoms and has had more than one partner. Um, so you want to reevaluate him for syphilis. So, uh, as we kind of talked about, the only testing available for a patient who's had syphilis before is a non-treponemal test, which is either an RPR or a VDRL. So in this case RPR is our answer. All right, and how am I doing on timing? Um, Jay, do we have time for me to go over this last block? Uh, I think we can we go, we, yeah. Oh yeah, OK, all right, I'll move through it generally quickly, um, but, uh, for, uh, uh, for just knowledge sake here, um, these 2020 guidelines help to highlight a little bit more about uh mycoplasma genitalium, which is um an uncommon STI but when we're seeing a little bit more with, with a little bit increased frequency for non-gynococcal urethritis. But if we do not have data as it's not a tract, uh, infection at this point, um, for public health departments. Um, but it's an intracellular fastidious bacteria, does not have a cell wall, it makes it a mycoplasma, um, and it's very difficult to culture. Um, it's a varying prevalence rate and data is not currently collected by our Department of Public Health, um, but it's the second most common cause after chlamydia for non-gyococcal urethritis, so it's about 10 to 30% of cases, um, and we're seeing an increased rate of drug resistance specifically around the macrolides. Um, for, uh, we don't necessarily know if it causes asymptomatic infection. It's a big question up in the air. People can test positive without symptoms and right now, um, we'll get to it, but even if they test positive, they're asymptomatic, there's no treatment recommended at that time. Um, but for now, uh, we do, uh, consider potentially asymptomatic colonization. Um, around the cervix, urethra, or the rectum. Uh, it can cause cervixitis, can be a component of PID, uh, it does cause urethritis, um, uh, particularly, uh, recurrent or refractory disease after they've gone through typical treatments, uh, for gonococcal or non-gonococcal urethritis. And then can cause, and we think can cause epididymitis. And then for non general disease, it's a question questionable relation to infertility. Um, and again, that's still being worked out by research. Uh, questionable cause of prostatitis and then questionable cause of proctitis as well. Um, really, the recommendations of nucleic acid amplification test, uh, you can culture it, it just can take exceedingly long, um, uh, and it is again exceedingly hard to culture. And the instead of testing here again is either urine or, uh, cervical or vaginal swabs for na testing. Um, it's not recommended at this time to do, uh, rectal swabs. Um, the 2020 update was a little bit more definitive in terms of what the treatment regimen is, uh, so it's oral doxycycline for 7 days, um, uh, twice a day for 7 days, similar to our, uh, uh, chlamydial treatment, um, and then that's followed by oral moxifloxacin at 400 mg once daily for 7 days. Uh, the rationale for this dual approach to therapy is that, um, the mycoplasma species generally has intermediate resistance to, to doxycycline. It is thought though that, um, this, uh, seven-day lead-in helps to decrease the bacterial burden, um, allowing for more penetration of moxifloxacin, um, and clearance of the infection. So it's not necessary that we expect any, uh, improvement in symptoms or, or definitive treatment with doxy. We're just trying to decrease the bacterial burden to make our oxy a little bit more effective. Um, we do not have resistance testing available in the US, um, that's mostly in the UK, uh, and well outside the US, but in the off chance you can somehow secure it. Um, if you do, uh, get that your isolate is macrobite sensitive, uh, you can actually do the doxycycline and then, um, oral azithromycin. So it's a 1 g loading dose day one and then 500 mg daily 3 days after. Um, again, we don't routinely, we can't, uh, send it here in the US, uh, at this time. There's no commercial lab platform, but, uh, in the off chance you can, uh, this is highlighted in the recommendations, and then again macroli resistance is just our assumption for most of the US isolates, so that's the recommended regimen above. And then again, follow-up testing, we don't recommend a test of cure in this uh scenario right now, as if the patient is completely asymptomatic. Um, if the symptoms per uh persist for longer than one month after treatment, uh, we would consider repeat testing and then you can give us a call and send them our way. Um, we do not recommend treatment or uh repeat testing, um, uh, less than a month, even in the case of persistent symptoms as that nat positivity can stick around and be reflective of all disease. Um, At this time, we don't recommend empiric treatment for partners, um, unless testing cannot be done on a partner of the individual with the infection. So they should just get tested if they're negative, um, uh, nothing there, uh, or nothing to do there. If they're positive and asymptomatic, um, it's not a hard and fast recommendation to treat, but you can consider treatment. There's not defined guidelines on that at this point, as again, Uh, we don't know the colonization rate, um, and, uh, uh, transformation to infection, uh, quite yet for mycoplasma. All right, and with that, I think I've got 10 minutes left, so I'm gonna stop, um, and we'll skip over the Doxy Peppa, uh, two slides there, but those slides will be available to you. Um, so big updates again, please screen your adolescents for STIs, uh, especially if they're having sex, uh, make sure to describe the type of sex to them to make sure that they're, uh, not just, you know, very, uh, rigid in what their definition of sex. Oral sex is still sex, you know sex is still sex. Um, so make sure to highlight that for them. Um, you know, uh, we've got our treatment update, uh, uh, treatment. Updates for our uh uh gonorrhea, chlamydia, and then our uh screening guideline update for syphilis as presented in 2021 guidelines. um, and then we didn't highlight doxype, um, but just now if you guys want more information about that, there are CDC guidelines on that right now, um, but it's a great tool for those 1616 and up, um. I think 1616 to 18. Sorry, now I'm confusing myself. Either way, uh, uh, check the CDC guidelines. It, it can be available for some of your patients to help prevent, uh, infection, uh, with gonorrhea, well, mostly chlamydia, uh, some syphilis and maybe gonorrhea. All right, and here's some useful links, and there we go. Thank you so much, Doctor Anders. Uh, I feel like we have, we could have talked about this, uh, topic for the entire day if we really wanted to, um, and the, the questions are just rolling in right now, so let's get to it, um. In the past, uh, we were always taught to treat a patient for gonorrhea, and if they have gonorrhea positive, then to treat with azithro, thinking that we're treating chlamydia, uh, simultaneously, it seems like we're getting away from that and we're just doing monotherapy. We just assume whatever turned out positive is positive, correct. Um, so, yeah, it's, it, it, uh, I would say, I would say it depends on your follow-up, um, uh, regimen. So, uh, the, these, uh, guidelines are based on known, um, infections. So I would say if you've got a patient in your clinic and you're screening them for it, um, and you're highly concerned for gonorrhea or chlamydia, you can still consider, um, giving them both treatments right now. I, I should have highlighted and thank you for, for, um, noting this, that these, uh, the treatment guidelines here are. For um defined infection for empiricism you can still cover both organisms. The empiricism though now for, uh, chlamydia now is the doxycycline for 7 days, uh, and not just the 1 g of Eithro. Um, again, the, that's a soft recommendation if you're not concerned for rectal chlamydia, um, and if you're concerned for compliance, but, um, uh, good highlight there empiricism, uh, recommendations have not changed, uh, uh, and you can for both. So if you can still treat simultaneously if the chlamydia comes back negative, you can stop the doxy. Yeah. Oh, I actually, uh, see this next question. So the, the question that chat here for EPT or express partner therapy, uh, around the law, um, does it, uh, does, um, insurance pay for it? Um, so what I meant by, uh, that it's allowed by law was was that you do not need to see the partner of uh the indexed patient. Um, in order to still legally be able to prescribe them antibiotics. Um, in terms of insurance coverage, that's uh, that I actually don't know, and that would actually probably depend on the uh partner's insurance, but legally you are able to prescribe medications for, uh, partner, uh, patient's partner without having seen or examined them, um, uh, within California law. OK. Great. So the question, if just a review for everyone who can't see all the questions, is that the express partner therapy, we can send in prescriptions to a patient who was positive to their partner, but we're not sure about where the money comes from, but the insurance should be able to maybe cover for, but we can at least prescribe it is what I'm understanding. Mhm mhm. The next question. Yeah, can you comment a little bit on, oh yeah, yeah. No, no, go ahead, Jay, sorry, I like to talk, you know that. No worries, no worries. Uh, can you comment a little bit on penis papal pearls and on male patients, we tend to see a lot of them, and there's a lot of concern around them. Do I just offer reassurances or is this something that I should be a little bit more cautious around and offer additional testing for maybe some of the atypical organisms if they have risk factors. Yeah, so I guess it would depend really if you're, if you're defining that this is a penis uh you know, papal pearl, so it can kind of more benign, um, skin uh lesion. Um, I would, I would still, you know, work them up for our standard STIs, um, you know, if it looks more vesicular, if you can unroof and test for HSV, uh, if it's, um, uh, uh, altered in any way, you can certainly send uh an RPR. Um, if, if you've kind of ruled out kind of our more typical infections, they don't have risk factors like travel to another country where they've had sex, where we wouldn't typically think of our standard STIs that we do here in the US reassurance is what I would offer, um, and so it's gonna kind of depend on their, uh, risk. Uh, for, for STIs as to whether or not they're true pearls versus just an abnormal, uh, phenotypic presentation of an STI. So I would still kind of dig in a little bit, um, and, and see if there's, there's, uh, any concern there that this could be an STI. But, um, if all things are ruled out, they're not having sex, um, I would say this, I, I often do this. Uh, I, I ask about sex, um, if they say no, I still offer STI testing, um, you'll find that some folks still take you up on that and then. You know, uh, they might be positive and that's OK. Um, uh, disclosure doesn't always have to happen, but as long as we're doing the correct testing, that's all that matters. And then sort of along that line is if a female uh were to disclose to their male patients that we're seeing that they're positive for HPV, is there anything that we have to do for this, uh, or is the Recommendation still to do the HPV vaccinations and there's not much else that we do. Yeah, yeah, so that is Jay hit it right on the head. So our only recommendation at this time is just to make sure they're fully vaccinated and if not, uh, make, uh, start, uh, kind of catch them up to the vaccines. There's no empiric testing that we would do. Um, uh, unless there are new lesions, and, and if lesions occur, certainly the, the gamut of treatment for, for genital warts, the topical treatments, um, is available to them, but there's outside of recommending vaccination or making sure they're up to date on vaccination, um, there's not much beyond that. Sounds good. Um, this is a really good question from Doctor Noamisannazi. Um, why, why are OB still sending RPRs only if this is the newest recommendations for first line, uh, or first time, uh, syphilis, uh, infections screening? Um, can we, should the practice be changing and, uh, is this something that we should be discussing with our OB colleagues, uh, in the community? Yeah, I, I think based on the 2021 guidelines there is for at least first time syphilis infection, um, there is a, uh, I wouldn't say push, that's not the right word. You can still use either algorithm, but this new algorithm was adopted because of kind of missed syphilitic infections in pregnant individuals. And so, um, You know, I can't say, you know, why, why we haven't shifted over quite yet. Um, I know our adult colleagues, uh, are, have got a great eye on, on syphilis, particularly here in California, um, but, uh, you know, it's Sometimes change is hard, um, and familiarity with kind of our typical algorithms tends to lead into what we do, um, even, even with kind of these newer changes. I will say there are, I know a few hospitals have adopted the uh change to doing the trimal testing first. We actually have a patient admitter right now who uh was caught that way. Um, but, uh, the, I, I agree, I think, you know, if, if it's, if it's gonna catch more infections, it would probably be worthwhile, uh, to send these treponeal tests, um, first for those without a history of syphilis infection. Perfect. Uh, I'm gonna go a little bit out of order. Uh, how about testing, uh, sorry, uh, how about treatment for newborns to mothers who are uh positive with syphilis, uh, commenting a little bit about that that this is gonna be a whole topic so. Man, uh, old topic, uh, that we could do actually, uh, Doctor Charlotte Shea, it's kind of one of her areas of interest and expertise with, with regards to congenital syphilis. Um, I, I. I should start at the top. I was not gonna be able to get to congenital syphilis because it is its whole wonderful lecture that we could kind of go into in the testing and treatment algorithms for a child born to a mom with inadequate therapy. In general, um, we have kind of these tiers of classification for congenital syphilis related to proven or highly probable, um, possible congenital syphilis, unlikely, and then no congenital syphilis. So there's a tiered system. You got a red book, uh, it's on page 880 of the. The newest thirty-third edition, I know, cause I was using that a lot this weekend. Um, but, uh, there is, it is recommended, uh, for a mom with inadequate therapy for syphilis, uh, during the pregnancy to screen, uh, and work up the child for congenital syphilis and then to follow our treatment algorithms. And again, we're more than happy to help out with that. It's a question we do get, um, pretty frequently. Yeah, and I, my personal experience with it is that the public health department is also very hands on with these patients as well. Yes. Um, oh, great. Other question is many of my patients are on doxy for acne prevention. Does this change any of the testing or treatment guidelines? It does not, uh, at, at, at this time, I should say, you know, there's not carbides, but what I would say from are known for our doxy pet population who are taking, and I know I didn't need to go into it, but who are taking doxycycline, um, after unprotected sex to prevent infections. A lot of the data is on Uh, those who had a pretty routine frequency of, of unprotected sex, so I'm using it not daily, but, um, weekly if not a little bit more, um, and the recommendation still there is for breakthrough uh for breakthrough chlamydial infections to still use doxycycline. So, um, it should still be effective, um, as opposed to gonorrhea, chlamydia is, uh, decently still susceptible to our, to our, um, standard therapies. Um, the again, the recommendation change about rectal chlamydia, I think had to do with just penetration of the drug in that space. Got you, got you. I think that brings us to 9 o'clock unfortunately, so, uh, we got through a lot of the questions. We got through a majority of them, but, um, happy to like turn around and, uh, I can take some, uh, I think just for the sake of everyone else's schedules too, uh, but, um. Is it OK if uh if you share your email or your contacts so that people can reach out with their questions if possible? Yeah, absolutely. Um, so my email, actually I don't know if it's shared or not. Um, it's my first name, full name Alexander.newman@ UCSF.edu. Um, I will try to get back to you as soon as possible. I will fully admit I am terrible with emailing. Um, so if you don't see a response in a week, just send me another one again. I, I promise you it's my fault, so. Perfect. Thank you so much, Doctor Newman. Uh, it's been a great talk, uh. Can't wait for the additional talks on this sort of topic. So yeah, we have a great week. I think I talked earlier too, but we'll we'll try to, we're gonna plan some HIV based um talks to Anne's gonna come in uh uh towards the later half of this year and then um I'm gonna work on eventually, uh, figuring out when I can do a, a talk on pre-exposure prophylaxis for HIV among our adolescents. So I'll look forward that uh forward to that in the coming year-ish. Can't wait. All right, thank you. Thanks. Bye. Created by