National Clinical Training Center for Family Planning



Podcast TranscriptTitle: Testing and Treatment for SyphilisSpeaker: Dr. Ina ParkDuration: 00:19:57NCTCFP (00:04):Hello, and welcome to the Family Planning Files, a podcast from the National Clinical Training Center for Family Planning. The National Clinical Training Center for Family Planning, is one of the training centers funded through the Office of Population Affairs to provide programming to enhance the knowledge of family planning stuff. I'm your host Katherine Atcheson. In today's episode, the finale of our three episode series on syphilis, we'll discuss the proper testing, treatment and follow up care for syphilis infections.NCTCFP (00:33):For those who turned into our first two episodes, we are once again, joined by Dr. Ina Park. For new listeners, Dr. Park is an associate professor of Family Community Medicine at the University of California, San Francisco School of Medicine, is medical director of the California Prevention Training Center and is a medical consultant with the Centers for Disease Control and Prevention where she was one of the coauthors of the forthcoming 2020 CDC STD Treatment Guidelines. Welcome back to the podcast Dr. Park.Dr. Ina Park (01:02):Thanks for having me, Katherine. I'm looking forward to talking about this. It's a topic that can cause a lot of confusion for clinicians.NCTCFP (01:07):In our last episode, we discussed the potential symptoms that patients might present with if they have primary or secondary syphilis and how important it is to test when someone has a genital ulcer, rash or new neurologic issues. But syphilis does have a latent stage when patients are asymptomatic, is screening still appropriate then? If so, which patients should be screened for syphilis and how often should it occur?Dr. Ina Park (01:32):So, both the CDC and the U.S. Preventative Services Taskforce, or USPSTF, both recommend routine screening for patients who come from high prevalence populations. So both organizations have recommendations to screen cisgender men who have sex with men, persons living with HIV. Those folks should definitely be screened for syphilis. But the USPSTF doesn't really give clear guidance on how often to do it. On the CDC's part though, they recommend that men who have sex with men and persons living with HIV be screened at least annually. And then as frequently as every three months based on their sexual risk. And then for patients who are taking HIV preexposure prophylaxis or PrEP, there's a recommendation to screen every three months for syphilis and other STIs.NCTCFP (02:14):So there are some indicators that can help a provider determine a need for syphilis screening, even if the patient is asymptomatic. What other types of behaviors or other socio-demographic factors are associated with increased risks of syphilis and should be noted by providers?Dr. Ina Park (02:29):For persons of all genders, behaviors, such as condomless sex with multiple partners, sex in conjunction with substance use and any sort of exchange sex, so exchanging sex for drugs or money, those are all associated with the risk of syphilis. And then of course, even if you, yourself are not engaged in these activities, if your partner is engaged in any of these activities, that would also put you at risk.NCTCFP (02:50):What about screening during pregnancy or as part of preconception or interconception care?Dr. Ina Park (02:56):The USPSTF, CDC and then professional societies such as ACOG and the American Academy of Pediatrics, they all recommend screening for syphilis at the first panel visit. The USPSTF doesn't really weigh in on repeat screening later in pregnancy, but the other organizations recommend screening for syphilis for at risk women. And so, that's at 28 weeks and at, then again at delivery. Women who are at an increased risk or at higher risk include those living in communities with a high prevalence of syphilis, women living with HIV and those with a history of incarceration or commercial sex work. But listeners should note that guidelines really differ from state to state. So you really should check in with your local public health guidelines and authorities when it comes to syphilis in pregnancy.NCTCFP (03:39):So now that we've outlined some of the factors that can indicate screening for syphilis in asymptomatic patients, let's talk a little bit about what types of tests are available. During our last episode, you mentioned that most clinicians don't have access to tests like dark-field microscopy that directly detect Treponema pallidum, the bacteria that causes syphilis. This means clinicians are reliant mostly on antibody testing. Can you tell our listeners about the different types of antibody tests and how they're used in practice?Dr. Ina Park (04:07):Sure, there's currently two types of antibody tests out there in use and both types of tests need to be performed to make a diagnosis of syphilis and both tests have limitations. So, the first type of test measures something called nontreponemal antibodies and the most common of these is the RPR or rapid plasma reagin test and I'm sure many of your listeners are familiar with this test. It's not actually measuring antibodies against Treponema pallidum, believe it or not. What it's actually measuring is antibodies against antigens such as lecithin or cholesterol or cardiolipin. These are things that are in our cell membranes, but they get released if there's inflammation or cellular damage. So this can also happen in other infections or inflammatory conditions and not just with syphilis.Dr. Ina Park (04:49):So, I'm sure all of your clinicians have seen, you know, these false positive RPRs that can occur in different situations. And then the other thing about the RPR is that it can actually miss one in four cases of primary syphilis, which is that early first stage of syphilis. So it's just not very sensitive at that early stage. So, more about the RPR that your clinicians are familiar with is that it provides a numerical titer, and that's stated as a ratio. So it's either one to four, one to 16, one to 256. Those are examples of the titers that you get. This number really reflects how many dilutions of the specimen the lab has to perform before the specimen is no longer positive. So, the higher the titer, the greater the level of antibody that you have.Dr. Ina Park (05:30):And, the RPR test is a nice one to follow over time because you can monitor the patient's response to treatment. And one issue with the RPR that we talked about that there are conditions other than syphilis that causes positive titers, and those can include auto immune diseases, cancer, hepatitis and other infections. So we always do a second test. It's always necessary to do a second test to make sure the patient really has syphilis.NCTCFP (05:53):So, what is the second type of test? What is it measuring and how is it different from the RPR?Dr. Ina Park (05:57):So, the second type of test is measuring antibodies directly against the bacterium Treponema pallidum. So it's referred to as a treponema specific test. And that's what used to confirm a positive RPR result. And, there's more than a dozen of these tests actually approved by the FDA. So listeners might be familiar with the TPPA or the FTA-ABS as two examples of Treponema specific tests. But there are also many enzyme and chemiluminescence immunoassay out there. Those are called EIAs or CIAs. And, the thing about Treponema tests is that they can actually become positive sooner than in RPR in someone with that early primary syphilis and aren't associated with false positive results with other infections or inflammatory conditions. So, here's a clinical pearl for folks out there.Dr. Ina Park (06:40):If you suspect primary syphilis, it's good to order actually a treponemal test and an RPR at the same time because if the RPR misses the diagnosis, the treponemal test is likely to pick it up. And that’s something that you often have to special order because many people, if they just order an RPR, the treponemal test isn't done automatically. But if you suspect that it's primary syphilis, you can actually ask your lab to perform both tests at the same time. So there's a couple important caveats to both of these tests.Dr. Ina Park (07:06):So, once someone is infected with syphilis, that treponemal test is going to remain positive for life, even after you get successfully treated. And so, it's not really that useful in someone who's already had syphilis and they give these qualitative results. So it's like a yes or no answer, it's positive or negative. And so it can't really tell you whether or not you're having a response to therapy.NCTCFP (07:25):So traditionally, my understanding is the non-specific RPR is performed first. And then if that's positive, then the treponemal specific test is performed. But I understand that now some laboratories actually perform the testing algorithm the other way around and do the treponemal test first. Can you tell our listeners a little bit more about that?Dr. Ina Park (07:46):Sure, you know, in the past decade, there's been increasing use of the treponemal EIAs or enzyme immunoassays for syphilis testing. And the reason why is that these tests can be fully automated. So there's an advantage to the lab who they can use them to process more than 100 specimens at the same time, whereas with the RPR, each test has to be done manually. So the laboratories who use these immunoassays have reversed the algorithm. So they start with the treponemal specific test of the EIA first. And then if it's negative, then your testing stops right there. But if it's positive, then the RPR is done. So here's the twist.Dr. Ina Park (08:19):If the RPR is negative, you now have somebody who is treponemal EIA positive and RPR negative. And these are people we never knew about when we were doing the traditional RPR based algorithm. So there's discordance specimens and another treponemal test has to be done usually something like a TPPA to resolve the discrepancy between the first treponema; test and the RPR.NCTCFP (08:41):After these three tests, what if the treponemal EIA is the only test that's positive?Dr. Ina Park (08:46):Well, so then most of these are false positive EIAs. And if the patient's risk and the clinical probability for syphilis are low, then typically just reassure the patient, you tell them nothing more is needed. But if someone is concerned because of their risk factors or sexual behavior, that the patient could have early syphilis, you can repeat the whole algorithm again, or just repeat the RPR in two to four weeks because if something is brewing, it should appear by then. And that would you know, sort of cover your basis to make sure you're not missing anything.NCTCFP (09:15):And what if the EIA and the TPPA are positive but, the RPR is negative?Dr. Ina Park (09:21):Okay, so this is when you need to talk to the patient and find out if they have a history of syphilis because if they've already been treated for syphilis in the past, remember those tests are going to remain positive for life. And so, if they don't have anything going on in their sex life right now, there's no chance that they've been re-exposed then there's really nothing more that you need to do, they've already been treated. But if this is someone who recently had a new partner, then this could be an early infection and their RPR might actually become positive later because the RPR is often negative early on an infection. So you can repeat the RPR in two to four weeks and If there is a new infection brewing, it will allow time for the development of the non-treponemal antibodies and then your RPR should show up positive at that time.Dr. Ina Park (10:00):People who've never been treated for syphilis before who have these two positive treponemal tests, should be staged and treated. And if they don't have any symptoms or physical findings, then most of the time these patients are going to be staged and treated as cases of late latent syphilis. And you can listen to the prior episode of this podcast which covers how we actually stage folks.NCTCFP (10:19):So, your mention of staging effecting treatment plans is a good segue into discussing how syphilis is managed once it's diagnosed. You refer to a patient that is having late latent syphilis. Can you talk about how the treatment for syphilis differs for patients with early syphilis versus late syphilis?Dr. Ina Park (10:35):Sure, so for everybody, the mainstay of syphilis treatment is still penicillin. Even after more than 60 years of using this therapy, it's amazing that Treponema pallidum hasn't developed any antibiotic resistance to penicillin. But, you know, as you mentioned for patients who have primary, secondary or early latent syphilis, and so this early latent syphilis is asymptomatic syphilis that was acquired in the last year, then the treatment is a single shot of benzathine penicillin. That's 2.4 million units, and that's an intramuscular injection.Dr. Ina Park (11:01):But for patients with late latent syphilis, so that would be asymptomatic syphilis of more than a year's duration, then you have to give them three shots of benzathine penicillin. You give them 2.4 million units once a week for three weeks as an intramuscular injection. And then, you know, in earlier podcasts, we've talked about neurosyphilis, ocular syphilis or otic syphilis, then you have to actually bump it up to IV penicillin. And that's 18 to 24 million units a day and that's for 10 to 14 days. I recommend that listeners consult the CDC treatment guidelines or download the free app from CDC on their phone, which contains more detail about the recommended and alternative therapies for syphilis.NCTCFP (11:38):So while it's great that penicillin is still so effective against syphilis, I know that unfortunately it is an allergen. What can be done for patients who are allergic to penicillin and test positive for syphilis?Dr. Ina Park (11:50):There are a lot of patients who think they have a penicillin allergy because they might've had a rash to penicillin as a child, but those are not true allergies, such as anaphylaxis. For a non-pregnant patient who has a true allergy to syphilis, which includes anaphylaxis, wheezing, hives, facial swelling, the CDC would actually recommend using doxycycline instead. So that would be 100 milligrams of doxycycline twice a day for 14 days, if you have a patient with primary, secondary or early latent syphilis.Dr. Ina Park (12:16):But then for those with late latent syphilis who are truly penicillin allergic, you need to take doxycycline for 28 days and that is a huge commitment. Compliance is an issue with doxycycline. So we really try to use benzathine penicillin whenever possible. So, in our clinic for example, when patients say that they had a rash to penicillin as a child, but they never had any symptoms of what we would think is a true IgE-mediated allergy, we actually just go ahead and treat them with penicillin and we just observe them for 15 minutes to ensure that there aren't any issues.NCTCFP (12:46):If the patient is pregnant, what do you do?Dr. Ina Park (12:48):Well, if the patient is pregnant, you really don't have that many options. If there is a true penicillin allergy, you don't have any alternative therapies at this point. Those patients unfortunately have to usually be admitted and desensitized often in an intensive care unit setting and then treated with penicillin. The other thing to remember for pregnant women with late latent syphilis is there's very little wiggle room around the spacing of the dose of penicillin. So for a non-pregnant adult, if the patient's a few days late for a dose, it's okay. In the CDC treatment guidelines, it mentions even 10 to 14 days spacing could be okay if the patient is late for their second or third shot. But for pregnancy, there's very strict dosing requirements. So if a patient pregnant misses a dose, the guidelines actually recommend starting the series of three shots over again completely.NCTCFP (13:32):Just to clarify for our clinicians, why is doxycycline not appropriate treatment for a pregnant patient?Dr. Ina Park (13:38):So, the concerns around doxy are really around effects on the developing fetus, so that’s suppression of bone growth and staining of developing teeth, unfortunately.NCTCFP (13:46):At this point, the patient's been successfully treated with either penicillin or doxycycline, but they still require some follow-up. After treatment, how soon should you recheck RPR titers? When would you expect a patient to become RPR negative?Dr. Ina Park (13:59):This is a great question because the tendency is for clinicians to check maybe too often and too early. So for patients with primary and secondary syphilis, the clinical evaluation and repeat testing should happen at six and 12 months after treatment. So remember though that if they happen to be a man who has sex with men or someone who has multiple partners, or if there's someone who's using HIV PrEP, then they would be due for repeat screening anyway at three months after treatment. So, if they're in one of those sort of, categories, then you would be testing again at three months.Dr. Ina Park (14:30):But this is a good time to mention as well that in anyone is diagnosed with syphilis regardless of stage, you should get testing for other STIs and HIV as well. But in terms of what you asked about becoming RPR negative, what you're really hoping for is a fourfold decline in the titer. So in the patient who started with a titer of one to 64, what you'd ideally like to see is have them going down to one to 16 or less in a 12 month time period. So as you mentioned, they could become completely RPR negative during this time as well, but it can definitely take longer than 12 months for that to happen. And that doesn't mean that they failed therapy.Dr. Ina Park (15:05):In some people, actually have an appropriate decline in their titer, but then they just don't go back to being RPR negative. They just have this low positive titer that persists for years and even decades. And for those patients, if they have a low level titer to begin with, if you see their titer rise by fourfold, for patients who have a low positive titer to begin with, if you see a fourfold rise in their titer, then that could be a sign of reinfection.NCTCFP (15:30):What would be the follow-up protocol for early latent or late latent syphilis?Dr. Ina Park (15:35):For early latent or late latent syphilis, you'd go ahead and check titers at six, 12 and 24 months. Again, you want to test all these patients for HIV and other STIs. And if they have other indications for more frequent screening, then they might actually be getting syphilis testing more often than what I've outlined here. So again, if that's a patient with early or late latent syphilis who is on PrEP or something else, they might actually get a test at three months anyway. But for those folks who are just having syphilis and no other reason to get tested, then you check titers at six, 12 and 24 months.NCTCFP (16:07):And what happens if the patient's symptoms don't resolve or their titers don't decline as you'd expect, or maybe they even increase without signs of reinfection?Dr. Ina Park (16:16):So, it's uncommon for patient's symptoms to persist after treatment, but certainly if they do, then repeating treatment would be the way to go. And if the patient develops neurologic symptoms or they have a sustained fourfold increase in their titer that lasts more than two weeks, then I would get a CSF exam to rule out neurosyphilis. But if people's titers don't decline after 12 months for primary or secondary syphilis or don't decline after 24 months for latent syphilis, then it would also be time to consider getting a CSF examination. So there's a ton of nuances involved in managing patients for follow-up, interpreting titers and weighing when to repeat treatment versus when to do a CSF examination. So I would suggest that listeners go to the CDC treatment guidelines for more detailed information on these sort of, less common scenarios, as well as just more guidance on interpreting titers and determining treatment. It's a hard thing to talk about in a short podcast.NCTCFP (17:10):Of course, as you mentioned, a rising titer can also indicate re-exposure and reinfection. What advice do you have for clinicians who are addressing reinfection in patients?Dr. Ina Park (17:20):So, the most important thing for clinicians to do is take a careful sexual history. So if the patient has been sexually active since they were last treated for syphilis, especially with multiple partners, then that would really favor, to me, reinfection rather than a failure of the original treatment.NCTCFP (17:34):That is excellent advice. But unfortunately our time is almost up today. But before you go, Dr. Park, what resources would you recommend for clinicians who would like help managing a difficult case?Dr. Ina Park (17:45):So the CDC funds the national network of STD Prevention Training Centers to provide an online consultation service and it's called the STD Clinical Consultation Network. So the majority of consults we receive are about complex syphilis management cases, like I talked about earlier. And the service is available to any of your listeners online. It's at . So that's . And clinicians can enter in their contact information and the details of their case.Dr. Ina Park (18:11):So experts in our network answer consults during the week, Monday through Friday. And consults are answered anywhere from one to five business days, you get to select as the provider what you want. And we get lots of questions about managing follow-up titers. So we can certainly help anyone who feels stuck out there.NCTCFP (18:27):Thank you so much for joining us today, Dr. Park and for sharing your time and expertise. It has been a pleasure talking with you across these three episodes. For more content, including our first two episodes about syphilis, search for the Family Planning Files Podcast or subscribe to our show on Apple Podcasts, Google Play, Spotify, Stitcher or wherever you listen to podcasts.NCTCFP (18:49):For a transcript of this podcast, as well as other online learning activities and continuing education opportunities, please visit our website at . This podcast is supported by award number 5FPTPA006029-02-00 from the U.S. Department of Health and Human Services or HHS, Office of the Assistant Secretary of Health or OASH, Office of Population Affairs or OPA. Its contents are solely the responsibility of the presenters and do not necessarily represent the official views of HHS, OASH or OPA.NCTCFP (19:29):Theme music written by Dan Jones and performed by Dan Jones and the Squids. Other production support provided by the Collaborative to Advance Health Services at the University of Missouri, Kansas City, School of Nursing and Health Studies. And thank you to our listeners for tuning in today. We hope that you'll join us next time for another episode of the Family Planning Files. ................
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