Clinical Education Initiative INTRODUCTION TO THE CLINICAL MANAGEMENT OF STDS. Marguerite A. Urban, MD

Transcription

1 Clinical Education Initiative INTRODUCTION TO THE CLINICAL MANAGEMENT OF STDS Marguerite A. Urban, MD 7/19/2017

2 Introduction to the Clinical Management of STDs [video transcript] 00:00:08 - [Jessica] So at this point, I'd like to introduce our speaker, Dr. Margie Urban. Dr. Urban, like I said, is an associate professor at the University of Rochester. She's also the medical director of Monroe County Sexually Transmitted Diseases Clinic. Dr. Urban graduated from the Medical College of Pennsylvania and is certified by the American Board of Internal Medicine. Her research interest is related to sexual behavior, sexual risk reduction, and sexual health. Dr. Urban is the author and co-author of numerous journal articles. So, Dr. Urban, at this point I'll turn it over to you. 00:00:43 - [Margie] Okay, thanks very much. Well thank you for inviting me to speak today. And as Jessica said, I'm gonna try to do a little bit of an introduction to STDs. No, my slide's not advancing. Hold on. 00:01:06 Okay. So I have no disclosures. I do want to clarify though that I will mention some testing methodologies and some treatments for STDs that are not FDA approved but are researched and CDC recommended. 00:01:24 Here's some learning objectives to avoid some common misconceptions about- some common assumptions that people make when making a sexual history; talk a little bit about exam and specimen collection and also do sort of a general update of the big three: syphilis, gonorrhea and chlamydia. 00:01:46 So to get started what are sexually transmitted diseases? And I like this quote which is from back when I was just really young in the field of sexually transmitted infections. And it came out of a major report issued by the Institute of Medicine in And they defined STD as not a specific term but a term that denotes more than 25 infectious organisms that are transmitted through sexual activity and also the dozens of clinical syndromes that they cause. And here's the list they proposed back in 1997 of STDsboth the organism and the syndrome. So you'll see on here some we know very well- gonorrhea, chlamydia. Mycoplasma hominis is sometimes listed. Mycoplasma genitalium is a newer one that wasn't specifically listed in here. And even more recently, we have Ebola virus and Zika virus. So this is a field that, it's not stagnant. It really continues to evolve. And of course we can't possibly address all of these things today. 00:02:51 So as I said I would like to focus a little bit on the big three: syphilis, gonorrhea, and chlamydia. And really when you talk about syphilis you really just have to go to the news. You see headlines about syphilis almost every week. 1

3 00:03:09 And here you can see that the CDC in April issued a specific syphilis awareness program as part of STD awareness month in April. And they developed several new tools that I would recommend you to look at on the CDC website. 00:03:30 So when we talk about syphilis, I'd like to look at this slide to give some historical perspective. And you can see on the far left side back in the time of World War II, there was lots and lots of syphilis which was typical in war time, and the green line is total syphilis. The two redish lines are recent syphilis defined as primary and secondary and early latent on this slide. And you can see there are some peaks back in the '40s. In the mid to late '40s, we had the end of the war and also the development of antibiotics for the first time and syphilis became treatable with initially some other antibiotics but ultimately penicillin, which continues to be the treatment of choice. And rates declined and then remained stable until the mid to late '80s into the early '90s. And you can see that green line peaks a little bit there in That was actually right when I was ending my training and I thought that I wouldn't ever see a case of syphilis and I ended up at the Philadelphia STD Clinic at that time seeing about 25 cases per day. And then in the mid '90s with a lot of effort and a lot of attention about HIV which also happened at the same time, syphilis rates really declined to record lows only to start to rise again. 00:04:50 And we can see now when you zoom in to more recent times, we have some fairly rapid rises particularly among the men who have sex with men population. In the last couple of years on the far right hand side, MSW stands with men who have sex with women and the dotted green line is women, and those rates also are starting to rise in 2014, :05:17 When you have rising rates of syphilis among women, you also run the risk of having congenital syphilis, and there have been recently published MMWR articles detailing rises and cases of congenital syphilis as well. And unfortunately we've had some cases here in New York of congenital syphilis. 00:05:39 Times have changed a little bit in where cases are being diagnosed. So I wanted to point this out in this slide that for a long time the rates of diagnosis were split among, particularly in men, among largely STD clinics and other facilities outside of publicly funded STD clinics. And you can see with this new rising cases and the number of cases diagnosed outside of publicly funded STD clinics has really taken off. So that's been a little bit of an issue because we really had record lows of syphilis before And a number of clinical providers who were trained in this period of record lows syphilis cases really hadn't ever been exposed to the clinical manifestations of syphilis. So there are a number of sort of anecdotes of people seeing syphilis and not recognizing it in their clinical practice outside of dedicated STD clinic. 2

4 00:06:50 And this slide looks at primary and secondary syphilis with the divisions of men who have sex with men, women, and men who have sex with women. And the darker brownish color are those who are HIV negative known at the time, and the lighter tan color are those who are HIV positive. And you can see pretty strikingly in the men who have sex with men category, it's fairly equally divided of new syphilis cases already having HIV. These are the figures from These days, I really first started to be looked at in the mid 2000s, it was 50% as well. And even a little bit before that also 50%. So we've not really made a lot of progress there. And so with every syphilis case, you really have to be concerned about a possible exposure to HIV if that patient does already have HIV. 00:07:50 This is looking at syphilis distribution across the states, and the darker colors are higher case rates. And you'll see that New York is in the darkest color. If you count it out, we actually end up being seventh in rates of syphilis across the states. But if you look a little more closely and break down by county, you can see that it really varies. And I've been following these types of graphics for some time and for a long time, the hot spots for syphilis in the state of New York were really only in the metropolitan areas. And you can see from this slide that a number of counties throughout the state including some very rural counties are starting to see cases. So this recent uptick in syphilis cases really has been state wide. 00:08:50 So just a little bit about the clinical symptoms of syphilis. Syphilis as you know is divided into stages and the stages that have the numeric terms- primary, secondary, and tertiary- are the stages that are associated with clinical findings. The remaining stages are known as latency and by definition, the infection is latent at that point so there are no symptoms or physical findings. So the first stage of syphilis is primary syphilis. It typically occurs within the first three months after exposure, usually about three weeks after exposure but it can be out to 90 days. And the classic manifestation is a ulcer at the site of exposure. That ulcer is referred to as a chancre. And the classic description is that that ulcer would be painless. Generally, it's associated with some non-tender adenopathy adjacent to the ulcer, so if the ulcer is genital the adenopathy is generally inguinal. So if the ulcer and the adenopathy resolve spontaneously and since these are often located in spots that are not easily noticed by the patient, since they don't hurt, they don't necessarily notice that they have a chancre. Shortly thereafter the organism disseminates and can cause the manifestations of secondary syphilis. This is a little hard to characterize exactly what are the manifestations of secondary syphilis because the organism is widespread in the body and it has the capacity to really affect partially every part of an individual. So it's quite an inflammatory condition. And pretty much anything that you can put itis after you can find in secondary syphilis. So may have dermatitis or a rash, you could have hepatitis or nephritis or iritis, or really inflammation pretty much anywhere. We classically think of secondary syphilis as being most notable for the rash because that's generally what, what we as providers see that tips us off to the diagnosis. And that rash has some characteristics that can be helpful. The rash typically starts as a macule and progresses and can become papular and then what's called papulosquamous, where it starts to scale a little bit. And then ultimately, it gradually fades and heals. It's not generally an ulcerative rash. Other manifestations of secondary syphilis are condylomata lata. These are sort of warty like lesions that are 3

5 generally in the genital area that could also be in the throat. You can get patchy alopecia. There are some oral lesions knows as mucous patches, and as I said pretty much any itis. And then finally tertiary syphilis I'm not really gonna talk about today but it does have some physical findings and they could be aneurysm, gummas, and you may have a variety of CNS effects. 00:12:09 Here are some pictures of syphilitic chancres. These are from our practice. And the classic description is a very well demarcated lesion such as in the upper left hand corner here. That's a fairly punched out lesion, fairly clean. It doesn't usually look very purulent like you might see with chancroid. And the most helpful physical finding to tip you off if something is likely to be a syphilitic chancre is an indurated edge. The other common cause of genital ulcers which would be herpes, which is overwhelmingly more common than syphilis; that doesn't have an indurated edge. So if you have a genital lesion that where if you try to press the edges together, the lesions sort of resist you. That's a little bit more suggestive of syphilis than it would be of herpes. You can see here though not all lesions are classic. So some of these look more irregular and sort of ratty edges, some of them the base does not look quite as clean. The one in the bottom right hand corner looks to me more like it could have even been a herpetic outbreak but was actually syphilis. And you can see on the upper right hand corner, there is a healing lesion that if you were to see it even it were maybe even a little bit more healed than this, you might miss that this was once a genital ulcer. 00:13:37 Here are some pictures of rashes. These come from CDC. And it gives you a sense of how the size of the lesions may vary. So you can see in this left hand side, there's one very large patch and sometimes depending on the distribution, this might be mistaken as pityriasis rosea. On the right hand side, you can see that that looks a little bit more raised and almost urticarial. I can say I've been seeing syphilis for, as I said I started back in I've seen a lot of cases of syphilis and I am ever surprised that it can manifest in so many different ways that pretty much any rash I'm willing to consider that it could be syphilis. 00:14:22 The classic teaching is to consider syphilis when you see a rash on the palms and soles, and that is not because it's always on the palms and soles but rather because so few other conditions cause palmar or plantar rashes. These tongue lesions are what is known as mucus patches. Sometimes these lesions in particular are known- the ones shown in all of these pictures- known as nickel and dime lesions 'cause that's often the size of the lesions that one might see with syphilis. 00:14:58 This was a clinical case and you can see here not at all like the classic scattered maculo rash; these are much larger lesions. And this patient actually had a fairly extensive work up looking for psoriasis, all turned out to be syphilis. And you can see in this upper picture there was some patchy hair loss as well. You can have findings in secondary syphilis that are not rash but just the inflammatory response. So just adenopathy. And this patient had really adenopathy visible across the room. We haven't talked about 4

6 testing yet but he did have a positive syphilis test known as an RPR and quite a high number at 1:256 and this was not associated with HIV. 00:15:48 So what about clinical diagnosis? I've tried to sort of emphasize that clinical diagnosis is tough because the manifestations of the condition are so varied. If you see an absolute classic chancre in somebody who says that I've had a new sexual partner, particularly an MSM who, given the outbreak we're having right now maybe your clinical diagnosis is pretty strong. Palmar and plantar rash may be pretty strong, but the wide distribution of possible manifestations made clinical diagnosis really not so great. There's not good microbiologic techniques you find the organisms so we're really left with blood tests and that's really the main stay of the diagnosis. But like most things with syphilis, even this is a little bit complicated. The classic testing known as the RPR, rapid plasma reagent, is a non-treponemal test. So it's a non-specific test. It actually detects human anticardiolipin antibody which goes up in inflammatory conditions. And as I've said syphilis is quite inflammatory, and it's the most inflammatory in secondary syphilis. So that's when you see the highest levels of RPR. But because it goes up with inflammation it goes up in other conditions, including something like HIV which can give you a false positive RPR or lupus or endocarditis or a number of other inflammatory conditions. So if using an RPR to diagnose syphilis, you also have to confirm that non-specific test by doing a specific treponemal antibody test. I've listed a couple of examples here that are the most common. Fluorescent treponemal antibody. There are now a variety of different ELISAs or EIAs that are specific antibody tests. There's another one called a TPPA. And you really need those tests to accurately diagnose. 00:17:55 I get a lot of calls about syphilis testing because it is a bit confusing. Aside from being inherently confusing it's become a little bit more difficult to interpret because not every laboratory does the same flow of testing. What had been done for many years, probably 50 years, was a traditional algorithm when one ordered a syphilis test, you got an RPR. That's the non-specific one I was just referring to. And if that was not reactive as it's shown on the left here, you would say that patient doesn't have syphilis. With one little caveat that if they were very recently exposed it's possible to test it wasn't positive yet. It takes the body a little bit of time to develop antibody. If the tests were positive because by definition it's not specific, you would confirm it with a second specific test. And if that were positive, you know you have syphilis, and if that were negative you would say that was a false positive. 00:19:01 Nowadays I'd say maybe a third to half of laboratories are doing a different kind of algorithm, and that's because the newest syphilis tests that are out are tests that allow the lab to automate the testing and do very large volumes quickly with less personnel. These are largely ELISA type test. They are specific antibodies. And because they can be done quickly and automated, they're done first. So it's kind of flipped the algorithm on its head and when one orders a syphilis test from this kind of lab, the first test that's done is the specific antibody. If that's not reactive, you're sort of in the same situation as before if say the person doesn't have syphilis or maybe it's very, very early and two weeks from now the test will be positive. If it is reactive, now you're not actually confirming it but you are running a second test, non- 5

7 specific test, in an effort to assess how active the disease may be. That second test, the RPR, if it's reactive, you're in the same situation as before. You have two positive tests that are consistent with each other and that patient has syphilis either past or present and may well need treatment. If that second test is negative, we end up in a situation that we never had before because our algorithm was different. Initially and actually as the FDA has approved these tests, you would be able to stop and the initial plan was to just assume all those patients with an initial treponemal positive RPR negative had syphilis past or present. But there were so many positives and in situations that seem quite unlikely, that has led to a number of evaluations of both the past and the populations where the tests were done. And the current standard protocols recommended by CDC is to repeat a second specific treponemal test, now an FTA or a TPPA, and to essentially use that as the tie breaker. So if that's reactive you say yes the patient has syphilis, if it's not reactive you say this initial test was a false positive. This does result in some confusing situations, particularly when you're in pregnancy and you really want to be quite certain of your results. So it has added a layer of complexity to the laboratory diagnosis of syphilis. 00:21:50 Just a quick word about treatment. As I mentioned, penicillin was developed in the '40s. It is still absolutely the treatment of choice. The treatment of syphilis is really the simplest thing about it. It's a single dose of IM benzathine penicillin for syphilis of less than one year's duration. And that's by definition primary syphilis, secondary syphilis, and latent syphilis when you can prove that it's been present less than one year. If the patient is penicillin allergic, doxycycline is the current alternate recommended agent for 14 days. For late latent syphilis, so that's syphilis with no symptoms that has been present more than one year, you wanna give treatment for a bit longer because you want this organism to be dividing. That's how the penicillin works. You wanna have penicillin on board for a longer time. And that recommendation is IM benzathine penicillin once a week for three weeks. And the alternate is doxycycline 100 milligrams twice a day, I'm sorry that's a typo, for 28 days. As I mentioned earlier about half of the new cases of syphilis in men have HIV already, so a diagnosis of syphilis should prompt consideration of testing for HIV. 00:23:12 Another clinical manifestation of syphilis that we need to be aware of is recent reports of more than expected cases of ocular syphilis. As I mentioned before, syphilis can pretty much cause any itis. So it does cause iritis and sometimes retinitis. 00:23:30 And in 2015 there was a little blip noted on the west coast of cases of ocular syphilis, particularly in men who have sex with men who are coinfected with HIV. And a few of those cases actually had such severe disease that they had ended up with blindness as a sequelae of the infection. At that point the CDC issued a sort of case alert and asked for reports to be sent to CDC of ocular syphilis. And in the most recent where you look at this in late 2016, they had updated to almost 400 cases in 20 days. Most of these have been in those who had co-infection with HIV among men who have sex with men but not all. I can say that as soon as this report came out within about two weeks, we solved two cases here in Rochester. So this has prompted me to change my practice to make sure that I really pay special 6

8 attention to visual symptoms. Most of these patients present with some sort of visual complaint; it's generally floaters, sometimes blurred vision, sometimes a cloudiness to their vision. And if they have that complaint they really should be seen by an ophthalmologist to look for ocular syphilis. 00:24:52 Because the eye is a protected space even though much ocular syphilis actually occurs during the phase of secondary syphilis, the treatment is the same as if you had neurologic syphilis. So you get IV penicillin instead of just IM penicillin. And then one last update on syphilis. In addition to the newer automated syphilis ELISA test, there is a new CLIA waived syphilis point of care rapid test. This is also a specific antibody test. It's CLIA waive so it can be done at the point of care by someone who's not a nonhealthcare provider. And it provides a positive or negative result. In the studies, it looked pretty good but in practice thus far it has had a fairly high false positive result up to almost 50%. So it is very helpful particularly in the point of per setting when it's negative; it suggests that the patient does not have syphilis. But if it's positive, it doesn't distinguish past or present disease and with an almost 50% false positive rate it's hard to know how to counsel that patient. So its really usefulness is as a negative predictive value. 00:26:16 So I'm gonna switch topics a little bit and go to gonorrhea. There's not so much new under the sun in gonorrhea. It's a disease for many, many, many years but the things that really draw our attention now are worries about resistance. I'll just tell you sort of the latest updates about that. And the other thing that I really wanted to emphasize particularly in this month in HIV is the use of nucleic acid amplification test for extragenital testing. I'll show you a little bit of data about that. 00:26:54 Here are CDC epi slides about gonorrhea. You can see we have that same blip back in World War II with high case rates of gonorrhea then. Gonorrhea was also treated by penicillin in the '40s. And you can see a rapid decline in cases of gonorrhea, then a big upsurge in gonorrhea in the late '60s when there was sort of a sexual revolution if you will in the United States. And then in the same timeframe when syphilis was being controlled, we had really dramatic drops in cases of gonorrhea. And that has continued until very, very recently when, again, we started to have a rise in cases. 00:27:39 Men and women had been fairly equally affected by gonorrhea until very recently when with this recent rise there have been a more rapid rate of rise amongst men. 00:27:54 Here's the same distribution across the United States. Again, darker is the highest case rates. And you can see that the south absolutely with southeast has very, very high case rates of gonorrhea and here in New York kind of in the middle. 7

9 00:28:12 But again like politics everything is local. Where I am in Rochester is the upper portion of New York with the very dark brown and we have particularly high case rates of gonorrhea here. So you can see gonorrhea pretty widely distributed throughout the state. 00:28:31 These are age graphs and gonorrhea is largely a disease of younger people as opposed to syphilis which is more evenly distributed across ages into older ages as well. And the peak age for women is 20 to 24 and 15 to 19. And the peak ages for men are 20 to 24 and 25 to 29. And it's about 500 per hundred thousand if you keep that in your mind when we talk about chlamydia 'cause it's quite different. 00:29:05 And gonorrhea also is very disproportionately high among minorities, particularly Blacks in the United States. It tends to be densely concentrated in cities and can even be densely concentrated at fairly small locations in cities which are often termed poor populations when you epidemiologically map them. 00:29:29 These are New York State data that follow gonorrhea case rates suggested by age over time. And I thought it was interesting that way back in '92 men and women were fairly equal and then female cases were higher than men until just about 2013 when male cases overtook. 00:29:53 Here's the classic manifestation in men. This is gonococcal urethritis. It's a thick purulent discharge. Men typically notice this. Nobody ignores it and they're quite aware of it. It's quite symptomatic. It's usually a short incubation period. The book says three to seven days. In my clinical experience, it's much closer to three days. But like everything in medicine, nothing is absolute so you can have asymptomatic infection occasionally maybe 10, 15% of the time. Men with symptoms use strong words about the symptoms. They say it's dripping. I am burning. I definitely have something wrong. And as I say they have this visible purulent discharge. If you're able to do a gram stain you would see the organisms on gram stain. 00:30:46 Here's the corresponding condition in women. Less well studied than in men, a little harder to evaluate because the point of infection is typically cervical, so it's internal. This upper photograph shows a cervix with frank purulent discharge very similar to the man I showed you on a slide previous. Obviously that's very, very abnormal. And you can see that with gonorrhea. The slide below is a normal cervix which you can also see with a positive test for gonorrhea from the cervix. The cells that are infected are the columnar cells, so they are the more internal cells of the cervix. So you may not see any purulence. Sometimes you will insert your swab and what looks like a normal exam on the outside when you remove the swab from the os you'll see a little bit of purulence there. Women have symptoms about 50% of the time as opposed to men about 90% of the time. And because it's internal, the woman perceives these symptoms as vaginal discharge, occasionally dysuria, occasional cervical bleeding which will be reported as spotting. And as I said the exam can be very, very variable. 8

10 00:32:08 With gonorrhea, the thing we're really concerned about is drug resistance. It's been named on all of the sort of top 10 list of bugs to worry about by all the various bodies that do that like WHO and CDC, et cetera. There's real cause for concern here. 00:32:28 The organism is quite adapt at altering itself to avoid antibiotics. So we have already gone through penicillin, tetracycline, and quinolone, and the organism has developed resistance to those. Currently about a third of isolates in the US are resistant to quinolones. And it turns out the changes that the organism has to make to become quinolone resistant aren't harmful to the organism. So that resistance persists even when you stop using the quinolone. Penicillin and tetracycline also fairly widespread, about a quarter of gonorrhea are resistant. Azithromycin is a concern because the threshold for resistance is fairly low but so far when testing all comers resistance is fairly low. There are now a smattering of reports of resistance to azithromycin in the United States though. And cephalosporins, which have been our main stay of therapy for the last several years, there are very disturbing reports of both decreased susceptibility within the laboratory and actual decreased susceptibility and clinical failure reported in some places in the world. This has occurred in not widespread reports but in sort of scattered reports in Japan, western Europe, the Pacific and South Pacific. And the concern is like all the previous times that resistance has first been reported, it is really just a matter of time before that spread throughout the world. These reports have been more common with the use of oral cephalosporins like cefixime than with ceftriaxone, but they have occurred with ceftriaxone as well. Most patients have been MSM but not all. 00:34:37 This is a graph that looks at rising MICs of cefixime. So the MIC is how much antibiotic it takes to inhibit the growth of the organism. You want that number to be very, very low. And as it creeps up eventually it correlates with clinical failure. And as the MICs have crept up it's not been random; it has been more commonly seen among isolates obtained from men who have sex with men and also among isolates obtained from the western United States. This is exactly the same pattern that was seen when quinolone resistance was first reported. And if you're old enough to remember, there was a time when we treated gonorrhea differently in the West Coast than we did in the East Coast because of the development of quinolone resistance which started in Hawaii and sort of trapped across to the east. 00:35:36 There are a couple recent reports of rising MICs to azithro which actually has an FDA approval to treat gonorrhea is no longer recommended by CDC for treatment. So there were reports in Seattle, in China. 00:35:52 And most recently there was a report that actually was just published as well as presented of a group of eight gonorrhea isolates in Hawaii who were being tested as part of a surveillance project. So it was not associated with their clinical care. So they were tested later. And these eight isolates were found to have very high MICs to azithro through resistance. They were all also resistant to penicillin, tetracycline, and 9

11 ciprofloxacin. And five out of the eight also has slightly high MICs to ceftriaxone, so this was a real concern. They did further analysis and it seems that the eight isolates all arose from a single clayed or clone if you will. They couldn't find any relationship amongst the patients. There were eight isolates from seven patients. They were all heterosexual. They all had typical symptoms and findings. They were all successfully treated with the standard regimen. But it was a concern that there is an isolate out there that does have a multi-drug resistance and a slightly high cephalosporin MIC. So this could be the one that evolves to really develop through cephalosporin resistance. 00:37:17 All of this concern has led to some changes in recommendations for the treatment of gonorrhea including a recommendation to give two drug therapy specifically with the goal of treating gonorrhea. So we give ceftriaxone plus azithro not because we're treating chlamydia with the azithro but because we're trying to use two drugs to attack gonorrhea from two different foci. The ideal is to dispense these at the same time certainly within 24 hours. And if you cannot give azithro for some reason, some allergy for instance, doxycycline as the second drug is considered an acceptable alternative. If for some reason you can't give ceftriaxone, you don't have access, cefixime is an acceptable alternative but, again, always with the two drugs. Test of cure using these regimens is not recommended anymore except when you're treating pharyngeal infection which is a bit more difficult to cure. That is a change from the prior iteration of CDC treatment guidelines. 00:38:29 What to do when you can't use these regimens is a little bit of a conundrum. There has been a small study that looked at gentamycin plus high dose azithro two grams versus gemifloxacin plus two grams of azithro both had virtually 100% cure. These were with usual gonorrhea. This was not especially resistant gonorrhea. But it does give you a potential alternative if you can't use a cephalosporin to treat. Unfortunately, gemifloxacin is not available right now. I'm told that it may still come out but so far we can't get it. So you're really left with gentamycin IM plus azithromycin two grams as an alternate for those who are seriously penicillin allergic. 00:39:21 And I'm gonna flip to chlamydia. The most important thing you can say about chlamydia is that there's a lot of it. Rates remain very, very high. Nucleic acid amplification test, PCR types of test are the gold standard for testing. And I'm gonna go into extragenital testing about both gonorrhea and chlamydia a little bit in this section. 00:39:46 These are CDC slides about chlamydia and you can see they just steadily increase. This is a little bit artificial because chlamydia is more often asymptomatic than gonorrhea is. And so how much chlamydia you find really depends on how much you look for it. So if you do testing, you find it, if you don't do testing you'll think you don't have a lot of disease. So it's very hard to follow trends if testing is inconsistent. 10

12 00:40:18 This is the age breakdown. And I wanna remind you that gonorrhea, the case rates in the highest age range was about 500 per hundred thousand. And here you can see in young women, 20 to 24, it's almost 4,000 per hundred thousand. So really the thing to think about with chlamydia is it's very, very common, very prevalent. It's in the same younger distribution age group with the highest being 15 to 24 for girls and 20 to 29 for boys. We'll get to that, it's largely asymptomatic so you really need to be doing testing. 00:40:59 Like gonorrhea it's also over-represented in a minority populations, particularly Blacks in the US. 00:41:08 Here's the breakdown of, again, darker colors are higher rates. So again, in the southeast we have the highest rates in the United States. New York is in the sort of second tier. 00:41:21 And compared to gonorrhea if you'll recall this is a little bit more widely distributed not quite as densely concentrated in metropolitan areas. And you can see, again, it's sort of, it all depends on where you are, how much disease there are. You see high rates in New York sort of in the Albany area, up in the north country, and here where I am in Rochester and again in Buffalo. 00:41:49 And this is New York State data excluding New York City. And just like the national data, it's sort of just a continual slight tracking upward. 00:42:04 The clinical manifestations of chlamydia are different than that of gonorrhea even though the sites of infection are largely the same and the cells that they infect, columnar cells, are the same. Chlamydia has a slightly longer incubation. In men probably five to 10 days rather than sort of the three to seven days. And more than 50% of men have no symptoms. The medical terms for the symptoms of chlamydia are the same- discharge and dysuria- but the terms that the patient uses are not. A man with chlamydia does not typically say that it burns when he pees, they'll say words like tingling or there's an itch inside, but these more vague kind of terms. So it's a much less inflammatory type of presentation. When discharge is visible, it's typically clear or mucoid or occasionally mucopurulent. 00:43:00 Chlamydial cervicitis. Now we're at more than 80% asymptomatic. So you're far more likely to not have symptoms than to have symptoms. And again, just like with gonorrhea if you do have symptoms as a woman, you perceive those symptoms as vaginal symptoms, a vaginal discharge, occasionally vaginal spotting. Occasionally people will report pain with sex. Like gonorrhea, the exam can be quite variable from a normal exam. To a more the second picture is sort of a friable columnar epithelium area that is very edematous. The second picture is very edematous, the third picture's very friable. Both of these 11

13 findings are statistically more associated with chlamydia than with gonorrhea. So those findings may be a little bit helpful to point toward a diagnosis of chlamydia. 00:43:55 Treatment for chlamydia has not changed recently. It's still azithromycin one gram as a single dose or doxycycline 100 BID for seven days. There's some alternates listed here. The important point here is that your one gram of azithro is a single dose only because of the pharmacokinetics of azithromycin. So it remains with you for five to seven days. You as the patient are not cured that next day even though you're no longer taking medication. So that's an important reminder to patients that they need to not resume sexual activity for that whole week. 00:44:34 The CDC has issued some new guidance about urethritis, about the diagnosis of urethritis. In the past the guidance was that if you had a visible discharge on exam whether that be mucoid, mucopurulent or purulent, you could diagnose urethritis. If you had a gram stain that was greater than, equal to four white cells in the past, that was diagnosis of urethritis. Now that's been lowered to only two white cells or if you have a positive first void urine with a positive leuk esterase. It's interesting that this change in diagnostic criteria comes out of a study from Denver where they were able to link the number of cells on a gram stain particularly to the diagnosis of chlamydia. And there was a clear breakpoint between one and two cells. The really only two cells did correlate with the diagnosis of chlamydia in that report from Denver. What CDC says, if you are seeing a patient but you don't have access to a gram stain so that you can't distinguish if there are cells or if there's gonorrhea in cells, that if you have at least one of these diagnostic criteria to go ahead and test for both gonorrhea and chlamydia. And if there are symptoms but no physical findings to only empirically treat if the patient is very high risk. If they have symptoms and physical findings, to go ahead and empirically treat for both. So if you had a visible discharge to go ahead and empirically treat first GC and chlamydia. 00:46:19 And then just a word about the testing methodology. I think probably most who are dealing with care for HIV have access to some sort of amplification test for the diagnosis of gonorrhea and chlamydia. The MMWR came out with updated recommendations back in 2014 listing the preferred specimen for men to be urine which is equivalent to a urethral specimen, and for women to be vaginal which was equivalent to a cervical specimen but superior to urine. In that same document, they also reviewed the use of these tests that are not FDA approved but are often validated by laboratory to be used to test extragenital sites- both the pharynx and the rectum. 00:47:12 And I just wanna show you one study that is pretty impressive because it's so large. This comes from 2014 from a network of STD clinics that do surveillance among men who have sex with men. They had a variety of different protocols but they were testing for GC and chlamydia. And this was conducted between 2011 and

14 00:47:37 So the patient or depending on their individual protocols, they had a patient collect or clinician collected urine, urethral, pharyngeal, and rectal specimens. They were tested based on their own individual protocols by NAATs or a culture. And as I said this was quite large- almost 22,000 individuals. 00:48:00 Here's a complicated slide looking at the breakout of all of those various cities and what they found at urethral, pharyngeal, and rectal. And really the punchline that I want to tell you is that it turned out that 52% of their gonorrhea cases were diagnosed at extragenital sites. And that was much more efficient when that was done with NAAT testing. 00:48:26 The results were almost identical for chlamydia. 52% of their cases were diagnosed at extragenital sites and again, much, much higher rate of diagnosis when using NAATS. 00:48:42 And the real critical finding of this report is that when they looked at in the first column here, those who had positive GC test of the throat, 73.8% of them had a negative urethral test or a negative urine test. Those who had positive GC of the rectum, almost identical 72% had a negative urine. And pharyngeal was not very commonly done for chlamydia, but when you looked at rectal chlamydia, it was almost 90% were positive at the rectum but negative at urine or urethral. So if one is testing men who have sex with men and only testing urine or urethral, you are missing the majority of cases of gonorrhea and chlamydia. 00:49:32 This has been replicated in a number of much smaller studies in the MSM population and now there have been a few looks at women as well. The results are not as dramatic, but this comes from the STD clinic in Baltimore. When they did a similar evaluation, they found that 30% of their GC cases were missed if extragenital tests weren't done, and 14% of their chlamydia cases were missed. This is still I think evolving of how to handle extragenital testing in women, and there are number of groups that are starting to report on their experience with that. But I think in men who have sex with men, the evidence is fairly clear that if not doing extragenital testing, definitely there's already a big risk. 00:50:24 CDC now recommends pharyngeal gonorrhea and rectal chlamydia and gonorrhea screening for men who have sex with men and for all those with HIV at least annually and every three to six months if there's ongoing risk. There is some risk; there have been a number of mathematical models that have looked at this and the conclusions are that you really can't curb these epidemics without including these extragenital sites. 13

15 00:50:59 And just to, I did mention that cases of gonorrhea in men have been rising recently, and there is some thought that this could be due to an uptick in testing of extragenital sites in men that could be accounting for some of that rise. So when you start talking about doing extragenital testing, that raises the question of how do you know who to test? How good are you at knowing who needs that test? And that really leads you to the importance of taking a sexual history, and there's lots of good reasons to do a comprehensive sexual history. It really is important to have healthy sexuality be part of general medical care. It's used to establish risk for STDs and HIV, risk for pregnancy, contraception and certain into this is what sites to screen and how often should you screen? It helps to know that partner management issues and to do accurate and pertinent counseling with your patients. 00:52:08 I think maybe this population would not, this population of our audience on a call of this month in HIV maybe doesn't have these common assumptions, but in general medical practice, we do still frequently find that there are a lot of assumptions that providers make that sex may only be penile-vaginal intercourse, sort of awkwardness around referring to people's sexual partners, contacts, or spouses, or partners, but you have to come up with terminology that your patient in whatever their situation is, understands and is able to communicate with you. Condom use, heterosexuality, gender exclusivity. So a number of common misconceptions. 00:52:58 And sexual health assessment includes both a traditional sexual history. And again, I think probably a common error is to only think about your individual patient and not the sexual history of their sexual partners, which pertains to your patient's sexual health. So you really need to consider monogamy and exposure in both the patient and their partner. And I think maybe a thing that has changed over the last 10 years is an emphasis on how much kind of ancillary behaviors, particularly substance use behavior, affects sexual behavior. There has been a great deal of research looking at both alcohol use and a variety of different drugs, stimulant drugs in particular. 00:53:48 So all of these are important considerations in sexual history and I've put here some verbiage which is often helpful to providers that are not familiar with or at ease in discussing sexual histories with their patients, and I'll send this with these handouts to Jessica so that they can be forwarded to everyone who signed in to today's webinar, but it's some phrases to use to review relationship status, sexual behaviors, substance use behavior, other healthcare-seeking behavior and some, we often bring up intimate partner violence as well. 00:54:34 And then finally, I just wanna end with what's important when you're thinking about a physical exam? We've talked about the many manifestations of syphilis which requires you to really look fairly extensively, and when doing a full physical exam on both men and women, you do need to examine sort of all the exposed parts where you've just obtained your sexual history about. 14

16 00:55:00 So with that, I know I'm a little bit late. We have a few minutes for questions. These are some very helpful references. The CDC's website about STDs is really outstanding and they have a Treatment Guidelines App for both ios and Android phones that's also very helpful and the CEI has a line where you can call and ask questions about HIV, Hep C and STD. If you ask about STD, most of the time, you'll end up with me personally. So with that I'll turn it back and see if we have any last minute questions. 00:55:37 - [Jessica] Thank you so much, Dr. Urban. That was fantastic. So at this point, if you would like to unmute yourself individually to ask a question, you can do so and again, that's clicking the red microphone to the right of your name and making it, so it's no longer red, then you're unmute and can talk. Otherwise you can chat in your question to CEI host and we can read them out. So Dr. Urban, we do have one question asking if you have data for vaginal versus urethral screening in women? Should our standard of care be to do pelvic exam vaginal screen, or is the urine collection acceptable? 00:56:15 - [Margie] Well, the data are that vaginal is superior to urine, but it doesn't have to be pelvic exam. It can be a self-obtained vaginal swab. I think all but one NAT platform is approved for self-obtained vaginal swab, so there is a little caveat that that has to obtained in a clinician, in a healthcare facility. It's not obtained at home and sent in, but the patient can come in and go into the bathroom and use a selfobtained swab rather than giving a urine sample and that is superior to urine. It's about a 5 to 7% increase in sensitivity. 00:56:59 - [Jessica] Okay, great. Thank you very much. Are there any other questions for Dr. Urban? We're just about at 1 o'clock. I just have one question, I would like to ask. You talked about how providers who maybe don't typically see syphilis, might miss it, might miss some of the symptoms, so I was wondering what would, you know, if you could have one suggestion for providers for something to look out for that they should immediately think syphilis, what are just a few things that they should definitely be cognizant of? 00:57:33 - [Margie] I could say three, I guess. - [Jessica] Okay. - [Margie] I'd say any rash. I've had dermatologists who've actually sentenced themselves to come and rotate at the STD clinic because they felt so guilty for dismissing a rash and not doing a, ended up diagnosing syphilis on a biopsy instead of doing a blood test. Any rash, unexplained adenopathy, I think should prompt a consideration of syphilis and we have seen people that sort of gone down a lymphoma work up rather than get a syphilis test. And genital ulcer I think, if you're thinking about STD and you see a genital, ulcer I think most people would think syphilis. It would only be if you're not aware that syphilis 15

17 is back, you're likely to fall down there, but so any genital ulcer I think most providers would consider syphilis. 00:58:28 - [Jessica] Great. Thank you so much. So thank you again to Dr. Urban for leading this presentation. Thank you to our funder, the New York State Department of Health AIDS Institute Clinical Education Initiative. I also apologize because I forgot to say this at the beginning, but everyone should know that Dr. Urban is also the director of the Clinical Education Initiative STD Center for Excellence at the University of Rochester, so just everyone note that. As a reminder, you will receive an with instructions on how to evaluate today's presentation and claim your CME or CNE credits. And next month, this month in HIV webinar will be on August 16th with Dr. Carlos Del Rio presenting the basics of resistance testing. So thank you everyone for joining us. Thank you, Dr. Urban, for leading this great presentation and we hope you'll all join us next month. [Video End] 16