ORAL SEX: WHAT ARE the RISKS? Angela Branch, MD

Clinical Education Initiative [email protected]

ORAL SEX: WHAT ARE THE RISKS? Angela Branch, MD

3/15/2017

Oral Sex: What are the Risks? [video transcript]

[00:00:00]

[Intro music] - [Margie] Welcome to the New York State CEI STD Center of Excellence Lunch and Learn Series. This is a special edition if you will for the month of April for the National STD Awareness Month and this is Margie Urban speaking. I'm the Medical Director of the STD Center and I'm very pleased to present Dr. Angela Branch, who will be our speaker today. Dr. Branch is an assistant professor here at the University of Rochester in the School of Medicine in Dentistry in the Infectious Diseases Division. She currently has a practice here of both general ID and an HIV practice and I've known her for several years because she did her infectious disease training here for fellowship ending in 2014 when she joined us as an assistant professor. She does have a significant area of research and she's involved in the University of Rochester's participation of the NYAD Respiratory Pathogen Research Center. Her current research activities include surveillance studies for bacterial pathogens, and the nasopharyngeal colonization of streptococcus pneumoniae and also in the development of diagnostic assays for respiratory viruses, including influenza, RSV, coronavirus, human metapneumovirus, et cetera. She's published several peer reviewed articles, reviews and book chapters related to respiratory viral pathogens in adults. And today, she is extending that interest and going to speak on the topic of Oral Sex: What are the Risks? with a little subtitle of much more than herpes simplex. So with that, I'm delighted to present Angela Branch for our Lunch and Learn today.

[00:03:03] - [Angela] Good afternoon, I'm Angela Branch with the University of Rochester, Division of Infectious Diseases. Thank you, Margie, for that great introduction and I'm very pleased to be able to talk to you about something that I didn't have a great deal of knowledge in until I prepared this presentation, but it's really important to my practice with HIV patients, which is the risk factors for transmission of sexually transmitted infections with oral sexual activity.

[00:03:08] I have nothing to disclose. And we have four main learning objectives for this presentation. The first is to determine which pathogens that cause sexually transmitted infections can be transmitted through oral sexual activity, determine the magnitude of the risk of transmission, describe the mode of transmission and lastly to define the clinical syndromes associated with sexually transmitted infections obtained through oral sexual activity.

[00:03:31] So to start, I just want to start with a case presentation because that's always of interest to me and helps me to apply what we learn to clinical practice. This is a case of a 28-year-old male who presents to Monroe County Department of Health STD Clinic complaining of three days of painful mucopurulent penile discharge. In terms of his past medical history, he's HIV negative, last tested one month ago. He does report a history of secondary syphilis infection two years prior and in terms of his social history, he is an MSM patient. He reports two sexual partners in the last three months, reports only oral sexual activity, but he does admit that he doesn't use condoms with oral sex and he reports smoking a pack of cigarettes a day with only social alcohol intake and denies any illicit drug use. He lives here in Rochester, New York and he works as a cashier at Wegman's. So after an exam, where it was noted that he had mucopurulent discharge, both the discharge and a urethral swab was obtained and gram stain culture as is shown here on the left. As you can see, he had these gram negative diplococci

on gram stain and then grew out these cocci on selective media. Interestingly enough, when his urine sample was sent for nucleic acid amplification testing, the amplification test was negative for Neisseria gonorrhoeae, which was a surprising finding considering that his gram stain and culture seemed consistent with a gonorrheal infection.

[00:05:14] So this led to several questions, which we were asking ourselves and which any practitioner would ask himself in this particular situation. Did this patient have Neisseria gonorrhea? If not, what did he have? How did he get his infection? Fourthly, what is the appropriate treatment in this setting? And lastly, given that he only reported oral sexual activity, what preventative measures should we recommend for this patient in the future?

[00:05:42] So, this is the CDC definition of sexually transmitted infections and as practitioners in this field, most of us are familiar with these pathogens, BV, chlamydia, gonorrhea, herpes, HIV, human papillomavirus, trichomonas and other things that they consider sexually transmitted infections.

[00:06:04] I put this up there to contrast with this slide, which are all the sexually transmitted infections which can be associated with oral transmission. This may be novel information for you, it certainly was for me, but pretty nearly everything that you would consider a sexually transmitted infection can be transmitted with oral sexual activity, including chlamydia, gonorrhea, genital herpes, hepatitis, HPV, syphilis, and trichomonas. That was novel information to me and then there are other pathogens which we'll go into later.

[00:06:35] So, oral sex has therefore become an important potential route of transmission for oral, respiratory, and genital pathogens, which will in turn cause disease in the oropharynx and in the genital and anal area. Oro-genital sex is implicated as the route of transmission for gonorrhea, syphilis, chlamydia, trichomonas, HPV, herpes simplex and HIV, as well as other respiratory organisms such as streptococci pneumonemia, Haaemophilus influenzae, Neisseria meningitidis and Mycoplasma pneumoniae, which also can be transmitted by this route and cause urogenital disease. Oro-anal sex is also implicated in the transmission of various enteric infections and I'll tell you a little bit more about that later.

[00:07:24] So what is oral sex? Oral sex is the use of the mouth, the lip or tongue to stimulate the penis, vagina or anus of a sex partner. In the general population, the incidence of adult patients who report that they participate in oral sex is 86.2% for women and 87.4% for men, ages 18 to 44 who report sexual activity with a partner of the opposite sex. In patients who have same sex partners, studies on MSM report an incidence of oral sexual activity of about 67 to 75%, but this may be actually higher due to difficulties in getting people to report accurately. In teenage and adolescents, 33% of teens report having oral sex with a partner of the opposite sex. This is an important group, an important demographic, because even when they may not have engaged in penile-vaginal or penile-anal intercourse, a lot of teens and adolescents are reporting oral sexual activity at early ages.

[00:08:30] So oral sex actually constitutes a significant bidirectional risk for the potential transmission of sexually transmitted infections. And when I say bidirectional, I mean that it can be transmitted from the genitalia/anus to the mouth or throat and similarly pathogens in the mouth and throat can be transmitted to the genitalia and anus and go on to cause disease. And in general, this risk for infection

and infection in general is independent of sex or sexual orientation. It is dependent on the type of sexually transmitted diseases where some have a more efficient rate of transmission from the oral area to the genital/anal area and it also depends on the prevalence of the STI in the population. And more importantly, it's also associated with the type of sexual act that's practiced.

[00:09:23] So how significant is the risk for transmission of sexually transmitted infections with oral sex? I'm gonna focus for this part of the talk on five main pathogens, the ones that you would have most likely the highest risk of transmission of STI with oral sexual activity and the ones that are most frequently reported in the literature and those are chlamydia, gonorrhea, HIV/AIDS, human papillomavirus and syphilis.

[00:09:52] So to start with, let's take a look at syphilis. And one of the sort of the best studies that really looks at this issue of how significant the risk of transmission is with oral sexual activity comes from an MMWR report from 2004 where they looked at a number of patients who presented with primary and secondary syphilis and screened them to see how they may have contracted syphilis. And in this study, MSM patients with primary, secondary syphilis, one out of five of them reported having only oral sexual activity for an incidence of transmission via oral sex of 20%. In the same study, 6.4% of heterosexual men and 6.9% of heterosexual women reported that oral sex was the likely route of transmission for a total incidence of transmission of 14%. So that's not an insignificant risk of transmission with oral sexual activity. And interestingly enough, HIV seropositivity was not a risk factor associated with transmission.

[00:11:02] All right, moving on to gonorrhea and chlamydia. The total incidence in the risk of transmission of gonorrhea or chlamydia with oral sexual activity is about 5%. And there is a lot more in the literature about gonorrhea and chlamydia than any of the other diseases because we do know that you can have pharyngeal infections, as well as established that you can have pharyngeal gonorrhea and chlamydia infections. But just to briefly review what we find in literature. Some of the earlier reports are from the 70s and in this particular study, 5% of about 1,000 participants in Boston who were randomly screened were found to have asymptomatic gonococcal pharyngeal infections. And a history of fellatio was associated with these infections. In another study in 2009, among MSM patients in San Francisco who reported receiving only oral sexual activity, urethral chlamydial and gonorrheal positivity asymptomatic again was 4.8 and 4.1%. In 1977, in this study, excuse me, in this study of 1,253 MSM patients, 15.6% of them had NGU and 8.4% of them had gonorrhea and 2.5% of them had chlamydia and oral intercourse was independently associated with urethral gonorrhea with an increase odds of 4 versus NGU, which had an increase odds of 2 or a two-fold increase of developing NGU with oral intercourse. In these last two studies here, this one from 2006 by Bradshaw and his group identified 329 men with non-gonococcal urethritis and 70% of them where they couldn't identify the causative pathogen, those infections were associated with oral sexual activity. And lastly, in this study that was published in 1999, and International Journal of STD and AIDS, of a study that was performed in Singapore, about 600 sex workers who were followed for six months, 5.2% of them contracted pharyngeal gonorrhea compared to 2.5% of them who contracted cervical gonorrhea, so that's twice the rate of pharyngeal infection compared to genital infection in this particular high-risk group and interestingly enough, inconsistent condom use for oral sex was associated with a 17 times increased risk to develop pharyngeal gonorrhea. So, again, really significant risk with unprotected oral sex in high-risk populations.

[00:13:40] So, the take-home points, because I know that was a lot of literature to sort of review really quickly is that probably there's a prevalence of 5% of gonococcal or chlamydial pharyngeal infections, most of which are asymptomatic. Four to 5% of gonococcal or chlamydial urethritis will result from oral transmission. Oral sex quadruples the risk of urethral gonorrhea and doubles the risk of NGU urethritis, that's unprotected oral sex, and inconsistent condom use in high-risk populations can confer a 17 fold increased odds for pharyngeal gonorrhea. So, again, just highlighting that oral sexual activity, particularly in high risk groups does confer a significant risk of transmission of gonorrhea and chlamydia.

[00:14:31] Okay, moving on to human papillomavirus. So, human papillomavirus is an interesting virus in that it can colonize and infect the oropharynx of people in general population regardless of sexual activity. In fact, in young children, many of them do have oropharyngeal HPV infections which don't really cause symptoms and many of which sort of disappear as people get older. So the overall prevalence of oral HPV infection ranges from about 2.5 to 7% in the literature, depending on what you read, and the incidence was reported at 4%. Men have higher prevalence than women, 10 versus 4%, and smoking, heavy alcohol use, HIV positive status and more than 20 sexual partners have been associated with increased risk of oral HPV infections. If you look over here on the right at two reports from the literature, this one in JAMA from 2012, you can see that there are these two peaks in the prevalence of oral HPV infection where you have this high incidence of contracting oral HPV infections when you're in your 20s and early 30s. And then you have this other peak in prevalence in later years and that's because as you age, more and more of the population become infected, so that you have this peak again in the 50s and 60s. If you look over here at the prevalence of oral HPV infections by HIV status where the light gray is HIV positive and the black is HIV negative, you'll notice that the HIV positive patients here in the light gray, the prevalence sort of stays the same in the community, but it does increase as you get older in HIV negative patients, sort of coinciding with this peak here. So, by the time you get to looking at patients in their 50s and 60s, 15 to 20% of them will be positive for oral HPV infections, meaning that you might be able to detect DNA in their oropharynx with a PCR test.

[00:16:35] So, take home points for HPV, lifetime oral sex and oral sex before the age of 18 is associated with a four-fold increase odds of having an oral HPV infection. Interestingly, HPV 16 is the most prevalent oral serotype that's usually detected, as high as 28% in some studies. This is really important because HPV 6 is actually one of the most oncogenic serotypes of HPV, the one that's most commonly associated with anal and cervical cancer and it does confer a 15-fold increase odds of having oropharyngeal cancer if you have a detectable oropharyngeal infection.

[00:17:14] Okay, so I'm going to move on to herpes simplex virus. I won't spend a lot of time talking about this because if you remember, my subtitle was more than just herpes simplex and I think that's more because I think we know that you can get herpes simplex virus transmission with oral sex, particularly if you have open lesions on the penis or the vagina area or open lesions on the mouth. It seems really intuitive that you can easily transmit oral infections with oral sexual activity. So what do we know, what do we expect as general cues. Herpes simplex virus is a common cause of both genital and oral disease. HSV 2 is a sexually transmitted pathogen with an estimated incidence of 23 million new genital infections every year, so a significant burden of disease in the population. And HSV 1 is typically thought and traditionally thought to cause oral labial disease and is frequently acquired during early

childhood, at least it has been in the past with an estimated seroprevalence of 90% in adults and older adults.

[00:18:20] What's new about herpes simplex virus? It seems like the risk of transmission, if you look at all of the literature and sort of compile it together, it's probably as high as 4% with oral sexual activity. Some specific reviews from the literature that I thought were really interesting is this one from 2003 published in Sexually Transmitted Diseases where 499 or 500 genital HSV isolates collected at a university student health clinic from 1993 to 2001 were reviewed and they found that the incidence of genital HSV 1 infection had increased from 31% in 1993 to 78% in 2001, suggesting that in this younger population, they had a significantly increased incidence of HSV 1 genital infections, which we typically traditionally consider to be the cause or oral labial disease, rather than HSV 2. In another study published more recently in 2013 in Clinical Infectious Diseases, this further highlights this new trend where 3400 HSV seronegative women ages 18 to 30 were evaluated and followed for 20 months and 3.7% of them became infected with HSV 1, 1.6% of them became infected with HSV2 and 84% or the majority of these cases were actually genital infections. So, this large population of women who were followed for 20 months, twice the number of genital infections were caused by HSV1 versus HSV2, so we're seeing this new trend where HSV1 is becoming sort of the predominant strain of HSV causing genital infections at least in young adults. So take home points, the majority of new HSV infections occur in young adults, that's not surprising. HSV1 remains the most common cause of oral mucosal infections, but in young adults, HSV1 is also becoming the most common cause of genital herpes. Reasons for this trend include changing sexual practices, notably oral-genital exposure, particularly in young adolescents and teens, but also what appears to be the lack of pre-existing HSV1 antibodies in newly sexually active young adults and we're not sure exactly what's causing that except to say that they're not being affected as children as frequently as we've seen in the past. As previously recognized, transmission to uninfected partners is likely to occur during asymptomatic shedding as you might tend to avoid sexual activity if you actually had herpetic lesions.

[00:21:04] All right, so I think the last one I'm going to talk about in this particular part of the presentation, assessing the significance of the risk of transmission is HIV. And unlike the other pathogens I talked about, the literature seems to suggest that the risk of transmission of HIV with oral sexual activity is really low. And I'll say, and to just sort of get a sense of how low it is compared to other types of sexual activity is this study published in AIDS in 2014, which assesses the risk for 10,000 exposures based on the exposure route. And as you can see, receptive anal intercourse confers the greatest risk with a risk of 138%, 10,000 exposures to the infected sources followed by insertive anal intercourse. Next would be receptive penile-vaginal intercourse, inserted penile-vaginal intercourse and the last one down here is penile-oral intercourse. And this would be form of oral sexual activity, penile oral intercourse and the risk for 10,000 exposures is roughly four, so significantly lower than any of the other forms of intercourse. Interestingly enough, there doesn't appear to be any risk with vaginal oral intercourse when they look for female to female transmission of HIV. This has been rarely reported and I actually haven't been able to find any studies that reported it. It was just sort of dogma that if you read about transmission of HIV, this is what is stated. It's a statement without necessarily a lot of evidence to support it, so it could be that we don't know what the actual transmission is or there really is no transmission in terms of female to female oral intercourse. All right, so just to look at one systematic review that talks a little bit more in detail about the risk of transmission. This is a systematic review

published in 2008, assessing oral genital transmission and they looked at the different studies that they could really reliably say were done well and there was really only five of them and the per partner estimates were 20% with oral transmission and 1%. There's two studies, 20 and 1%, so really, really different. And the per study participant estimate was 0.37% and in one study there was a per act estimate of 0.04%. So you could say that the risk of transmission with oral sexual activity is about .37% per person engaging in oral sexual activity. However, there are some sort of more high risk conditions. An MSM choosing insertive fellatio or oral sex rather than insertive anal sex, that seems to decrease the risk of transmission by 13 fold, which is why there's a recommendation that oral sex may be potentially used as a way of harm reduction in discordant partners where one patient is HIV positive and one patient is HIV negative. However, oral intercourse with ejaculation is a potential risk factor for transmission and patients who have oral sex and are co-infected with HIV and other STIs which break down the mucosal barrier likely also increases the risk for transmission. So, those particularly two situations, ejaculation and co-infecting STIs potentially increases this risk and increases this incidence of transmission with oral sexual activity.

[00:24:48] All right, so the next thing I'm going to talk about is some of the clinical syndromes that are associated with sexually transmitted infections acquired from oral sexual activity. And we'll just go through all of the entire list of things that I could find and see which ones have the potential to cause oropharyngeal disease and which ones have the potential after transmission to cause urogenital disease.

[00:25:17] So, first looking at chlamydia trachomatis. So the methods of transmission are intuitive. Giving oral sex to a man or a woman who have a genital or rectal infection can result in getting a chlamydial infection in the throat or getting oral sex from a partner with a chlamydial infection in the throat can result in a genital chlamydial infection. Of all of these potential ways of transmission, penile oral transmission appears to be the most efficient. So if you were to transmit a chlamydial infection through oral sexual activity, if the person is colonized with chlamydia in their throat, you can transmit a urogenital infection to your partner, which results is urogenital disease, which is urethritis, epididymitis, prostatitis, proctitis, and in women cervicitis, PID, and of course other infections like LGV and conjunctivitis. In contrast, if a patient has a symptomatic or asymptomatic urogenital chlamydial infection, and a patient performs, another subject performs or a partner performs oral sexual sex on the penis or the vagina on someone who's infected, or the anus for that matter, they could develop a pharyngeal infection and develop pharyngitis. Now the incidence of symptomatic pharyngitis or a symptomatic chlamydial infection is about 1%, so it's actually extremely rare that a chlamydial infection in the pharynx will actually cause symptoms. It's mostly thought to just be a reservoir for transmission meaning that once you become infected in the pharynx, the bacteria will stay there and you can then go on to transmit infection to someone else after performing oral sexual activity on another partner. They may have in some rare cases a mild sore throat and even rarer is that it can be associated with recurrent tonsillitis.

[00:27:18] Neisseria gonorrhea is really similar in the methods of transmission to gonorrhea. It requires a person who's infected in either the pharynx or the genitalia and anal area to perform oral sex with another partner and the penile to oral transmission is, again, the most efficient. Again, if a patient who has a Neisseria gonorrhea infection in the throat performs oral sex on the genital or anal area of a partner who's uninfected, they can transmit gonorrhea and cause a urogenital infection which will result

in urethritis, epididymitis, cervicitis and PID or an anal infection causing prostatitis or conjunctivitis in some cases, and more seriously a disseminated infection. Now if a patient has a gonorrheal urogenital infection and someone performs oral sexual activity on their genital area, the partner performing the oral sexual activity could develop pharyngitis. The prevalence of asymptomatic gonorrheal infection ranges from about 2 to 8% and the incidence of symptomatic infection is slightly higher than chlamydia and ranges from about 1 to 2%, so again, the majority of pharyngeal infections are asymptomatic. When you do have symptoms, it's very non-specific and can be something simple like a sore throat, but you can go on to have more severe disease and it can result in dissemination and there have been reports of acute tenosynovitis as well as other things caused by pharyngeal gonococcal infections. More importantly, patients who develop pharyngeal infections could then go on to have horizontal transfer of gonococcal antimicrobial resistance genes and then go on to infect new partners with these more resistant gonorrhea isolates.

[00:29:23] When a patient does have gonococcal pharyngitis, this is what it can look like. You might see this bright hyperemia of the oropharynx or you can just have a mild to moderate pharyngeal erythema. It can progressively become non-exudative tonsillitis, exudative pharyngitis with or without cervical lymphadenitis, and in severe cases, severe ulceration with a pseudomembranous coating.

[00:29:51] Okay, moving on to syphilis. Syphilis transmission is again similar to what we saw in gonorrhea and chlamydia. Giving oral sex to a partner with a syphilis lesion on the genitals or anus can result in transmission to the oropharynx. Getting oral sex from a partner with a syphilis lesion on the lips, mouth or throat can result in a new syphilis infection either with a lesion on the genital area or potentially a secondary presentation. The lesions that are particularly infectious are the primary chancre, mucous patches, which are also considered condylomata and condylomata in the anal area. The efficiency of transmission is actually estimated at 30%. So this is the highest, probably one of the infections with the highest risks of transmission with oral sexual activity. When you do get an infection from oral transmission, you'll see similar things to what you see in any kind of transmission, which is you might get a primary infection with a chancre, which occurs at the site of inocculation and rarely, it can actually include the posterior pharynx, which might be an area that you might think to look for when you're treating people for STDs. A secondary infection can also be the way that an infection transmitted with oral sex presents and that will present with what you would expect, flu-like illness, adenopathy, synovitis, hepatitis, uveitis, meningitis, the typical rash, the diffuse maculopapular rupture on the trunk and extremities, including the palms and the soles and also you might see these condylomata, which are large raised gray to white lesions on the mouth and the perineum. We typically think of them as being on the perineum, but you can find them on them mouth as pictured here on the right. And these are actually highly infectious, so if you wouldn't think to warn your patients of this or look for this, either in the mouth or on the lips or in the throat, this would be a particularly high-risk situation for transmission with oral sexual activity.

[00:32:11] Okay, human papillomavirus, again not to repeat myself, but the method of transmission is very similar. Giving oral sex to a patient with a genital or rectal lesions like these warts, getting oral sex from a partner with an HPV infection in the throat, and the penis oral method of transmission is again the most infectious. Of note, these condylomata acuminata that you can develop are highly infectious as with any other lesions with herpes or syphilis. Any sort of skin lesions tend to be high infectious because

they just carry a huge burden of organism. Clinical symptoms, it may be asymptomatic and often is, particularly if you have an oropharyngeal infection, those tend to be asymptomatic. If you have these genital anal warts, again, they're highly infectious and they can be very obvious like this picture here, but they can also be really subtle and this is where the potential risk of transmission really lies is that if a subject or a patient has these lesions and their partner isn't aware of them, performing oral sexual activity could result easily in transmission of a genital serotype of HPV resulting in an oropharyngeal infection potentially with something that's oncogenic like HPV16. And, of course, once you do develop these genital or anal warts, you can develop epithelial dysplasia and this could result in vaginal cervical anal penile or head and neck cancers. Of note, there is a 15 fold increased risk for oropharyngeal cancer when you develop an oropharyngeal infection with oncogenic serotypes, particularly HPV16.

[00:34:05] Okay, and then the last condition I want to tell you about with HPV is something that I have never seen, but certainly believe that it happens. Part of the reason I haven't seen it is that it's seem more frequently in children, teens and young adults, so it really was predominantly a syndrome, a condition that's associated with young children, but increasingly now we're seeing it in adult populations. And this condition is called laryngeal and respiratory papillomatosis, which essentially is the development of papillomas or sort of these kinds of warty things in the larynx, the pharynx, and it can even extend down into the lungs. Like I said, it's more common in children. The incidence in young adults in increasing. In children, the incidence is about 1 to 2% and 3.3% in teens and young adults. 100% of patients who are adults who develop this respiratory papillomatosis have concurrent oral cavity HPV infections. So this doesn't alert you that there's no definite association made with oral sex, but if 100% of adult patients who develop this condition have an oral HPV infection, it makes sense that the oral HPV infection is what resulted in these papillomas and that one potential way that you might develop an oral HPV infection is through oral sexual activity. 90% of these cases are associated with HPV6 and 11, but they can also be associated with other serotypes that are more oncogenic. If may and often does result in significant airway obstruction, such as when you develop a lesion here that's obstructing the trachea. And it has a high frequency of relapse. The only real treatment for this is surgical and the surgery is palliative because you know that even if you decrease the burden of these papillomas in the airways with the high frequency of relapse, they very often do come back and sort of the most serious sequelae of this is that these can result in malignant transformations and significant head and neck cancers.

[00:36:13] All right, and then briefly I just want to talk about herpes. We know that giving oral sex to a partner with herpes in the genital area, anus or buttocks can result in an oral herpes infection and getting oral sex from a partner with herpes on the lips, mouth or in the throat can result in a herpes infection in the genital area. In general, oral to genital transmission is with HSV1. Genital to oral transmission can be with either HSV1 or HSV2. Transmission is greater with male patients than in female partners. 70% of transmission occurs during periods of asymptomatic viral shedding. And HSV2 tends to have more prolonged shedding than HSV1. When you do develop a herpes simplex infection, you'll develop painful vesicular rashes, as we know, at the site of infection. It can also present with just a severe pharyngitis and you may not be able to just visualize ulcerative lesions, although patients may say that they have really severe pharyngeal pain and it can result in autoinocculation at distal sites. This is really important because if you have an oral lesion and you touch it, it's possible to inoculate distal sites like the hands, maybe even potentially the genital area. And lastly, I think an important point to

remember is that having these ulcerative lesions either on the mouth, the throat or in the genital anal area increases the risk of HIV transmission because you have these ulcerative mucosal surfaces which if they come into contact with HIV virus could potentially be that they could invade.

[00:39:53] And then the last one, sort of, of the major pathogens is HIV and as I told you the risk of transmission is really, really low with oral sexual activity, but in that setting the highest risk would be from giving oral sex on the penis of an HIV positive main partner. Now why would this act constitute the highest risk? One of the reasons is probably that even if you put a patient on antiretroviral therapy and you're able to suppress their virus in the blood, you can still detect HIV virus in both the semen and vaginal secretions despite having undetectable viral loads in their blood tests. So this means that the risk of transmission with semen and vaginal secretion remains significant even with antiretroviral therapy. The risk of transmission is also increased four fold by the presence of ulcerative STIs and even if you don't have an ulcerative STI, even if it's urethritis from gonorrhea or chlamydia, there's still a risk of increased transmission that's three fold higher than if you did not have a sexually transmitted infection. So, again, that's probably another reason that contributes this highest risk of oral sex being given on the penis of an HIV positive male partner. I won't go into the clinical syndromes. I think we're pretty familiar with the clinical syndromes that you have with HIV, both in acute infection and later on.

[00:39:21] Okay, now I'm going to talk about a few pathogens that are very, very rare to see acquired from oral sexual activity and for whom there are not necessarily any specific oropharyngeal clinical syndromes. The syndromes are pretty much what we know them to be. The first is trichomonas vaginalis. So, trichomonas vaginalis, which is hugely surprising to me can be transmitted by giving oral sex. Usually giving oral sex to a woman with an infected vagina or a man with an infected penis might result in getting trichomoniasis of the throat. I only saw two publications, two reports of this in a Pub Med search and one of them was in 2001, published in Clinical Infectious Diseases where 107 HIV positive patients in Peru were screened for sexually transmitted infections. 38% of women in that study and 50% of the men in that study had at least one sexually transmitted infection and interestingly enough trichomonas vaginalis was detected in the pharynx of three men. So this is one of two reports and the second report really was one patient and actually refers to this report. So, I'm not sure how prevalent this is in the population. It's not something that we think of or we look for, but it may be higher than we know and certainly it seems to be possible. When you do have a patient who develops trichomonas vaginalis infection in the pharynx, you can then imagine that the risk of transmitting it to someone else if they perform oral sex becomes significant. So, a person with a trichomonas pharyngeal infection may not develop any symptoms. In fact, no known oropharyngeal symptoms have ever been described, but they then could go on and infect someone else and the person could develop a genital infection causing vaginitis or asymptomatic or mild urethritis in men.

[00:41:30] Okay, so the next thing I want to talk about is something that is not as rare as trichomonas, but something that we don't usually think about, which is that you can have transmission of what we typically consider fecal-oral pathogens with oral anal sexual activity. So some of the fecal orally transmitted pathogens that have been reported in the literature as being transmitted by oral anal sexual activity are hepatitis A, Shigella, and intestinal parasites and I'll tell you a little bit more about some of what's been reported for those three pathogens. So, hepatitis A is probably the one that's best described and hepatitis A outbreaks among MSM have been reported frequently for many years. There

have been reports of cyclic outbreaks which have occurred in urban areas in the United States, Canada, Europe and Australia and I just put this study here from Columbus, Ohio, where between November 1998 and May 1999, they had an outbreak of 136 cases. Of those 136 cases, 87% of them were men and 71% of them admitted to MSM sexual activity and of those 71, 66% of them reported oral anal sexual activity.

[00:43:10] All right, the second pathogen we're sort of interested in is Shigella and there's a report from 2001 of 230 cases and that was reported to the San Francisco Department of Health. Of those 230 patients, 92% of them were male and 61% of them were MSM and 78% of the MSM reported sexual activity, 50% of which was oral anal activity one week prior to illness. So, again Shigella has been reported in outbreak situations, particularly in MSM patients and seems to be associated with oral anal sexual activity. And lastly, Entamoebae histolytica is a parasite. Rates of entamoebae carriage in Australia and sort of the Pacific area there are pretty high. In MSM populations in Australia, carriage rates are reported to be as high as 37% compared to 4% in the general population and outbreaks of invasive amebiasis have been reported in MSM population as well. Fecal-oral transmission is presumed to be associated with oral anal sexual activity. But I put these two pathogens up, hepatitis A, Shigella and Entamoebae histolytica just to illustrate the point that in patients who perform oral-anal sexual activity, it is possible to transmit enteric pathogens, pathogens that are typically considered to be transmitted by fecal oral methods, and cause sort of systemic infections or even outbreak situations with these typically enteric pathogens.

[00:44:51] Okay, and similar to that, the last thing that I'd like to look at is respiratory and oral pharyngeal pathogens. So respiratory pathogens are things that typically cause respiratory infections, sinusitis, ear infections, pharyngitis, laryngitis, bronchitis, pneumonia, those sorts of things. And you typically don't think of them as being associated with sexually transmitted infections, but they can be in the setting of oral-genital sexual contact. The ones that have been reported in the literature are respiratory pathogens which colonize the mouth and the throat, which is streptococcus pneumoniae, Hemophilus influenzae, and Neisseria meningitidis, all of which can be transmitted by oral genital sexual contact and result in non-gonococcal, non-chlamydial urethritis. I put this article up here because in this article they were describing portions of symptomatic gonococcal chlamydial and non-gonococcal, non- chlamydial urethritis, attributable to oral sex. 27% of their cases were non-gonococcal, non-chlamydial urethritis and many of these included respiratory and oral pharyngeal pathogens which were causing these infections. So, about a third.

[00:46:12] Okay, so which pathogens are ones that you might suspect to cause urethritis and be associated with oral sexual activity. The first is streptococcus pneumonia and there have been a few case reports, one of which I put up here from 1985 of a 25-year-old male who developed mild urethritis and urethral colonization with streptococcus pneumoniae five days after oral genital sexual contact. This is another study from 2016 of patients who developed acute urethritis, 430 subjects, and Haemophilus feces was isolated in 52 of those 400 subjects for an incidence of 12.6% of patients with acute urethritis being caused by Haemophilis feces. In this case here, patients with Haemophilus infections have mucopurulent urethral discharge, about 71% of them, and 8% were HIV infected, 60% MSM. All patients reported recent unprotected insertive oral sexual activity. So, with these respiratory pathogens, it may be asymptomatic, but it's certainly possible that you can have patients who develop urethritis,

particularly in MSM populations, respiratory pathogen infections which are transmitted with oral sexual activity.

[00:47:40] All right, so remember our case from earlier, the 28-year-old male who presented to Monroe County Department of Health STD Clinic complaining of three days of painful mucopurelent penile discharge and then when we swabbed his urethra we got these gram negative diplococci and gram stain and then these things that grew out here on the selective media, which seemed consistent with Neisseria gonorrhea, but when we got the urine nucleic acid amplification test for Neisseria gonorrhea, that was actually negative.

[00:48:13] So, going back to the questions we had at that point, did this patient have Neisseria gonorrhea? Well, the actual answer is no. And if not, what did he have? What he actually had was Neisseria meningitidis, which is a respiratory pathogen that typically colonizes the oropharynx of adults and children. So how did he get this infection? Well, we presumed he probably got it from oral genital sexual activity because that's really where it lives, that's where it can be transmitted from. Then what is the appropriate treatment? Well, as you'll find out later and I can tell you now, it's the same as if you were going to treat him for Neisseria gonorrhea and not surprisingly, he was treated with ceftriaxone and azithromycin before we even knew that he had Neisseria meningitidis and did very well. So, Neisseria meningitidis, otherwise known as the other urogenital Neisseria is a commensal of the oropharynx and a cause of fatal meningitis. There are eight serogroups, that most commonly cause infection: A, B, C, X, Y, Z, W and L, and there are capsular and non-capsular strains. Capsular strains are typically the ones that are responsible for invasive diseases like meningitis, but they can also cause local disease. And non-capsular strains usually do not invade, but they can cause local disease like urethritis. Oropharyngeal carriage is typically of non-capsular strain and is about 10% in the general population and 37% in young adults. So invasive meningococcal disease in the United States is usually caused by serogroups V, C and Y. The incidence has been declining significantly over the last 20 years and a lot of this has to do with vaccination and the case fatality rate when the disease does occur is about 10 TO 15%. There have been outbreaks of group C, invasive meningococcal disease among MSM patients which have been reported. Local disease, in contrast, as defined as meningococcal urethritis, sporadic cases have been reported since the 30s and it was recognized in the 1970s to be transmitted by oral sexual activity, as least early on more common in MSM patients. The current prevalence of meningococcal urethritis is unknown, but it's presumed to be low, probably around 0 to 2%.

[00:50:42] This is a study in 2017 of some of the more recent incidents, outbreaks of pneumococcal meningiditis, actually sort of looking at the prevalence of Neisseria meningitidis urethritis at a clinic in Indianapolis and it reported it as 2.8% of all urethritis cases of 2013, 1.4% in 2014, 7% in 2015 and 10% in 2016, so the prevalence of Neisseria meningitidis urethritis has been increasing in this clinic here in Indianapolis. The majority of cases, at least in 2015 were symptomatic. Interestingly, heterosexual patients and most of them reported oral sexual activity. This is another study of two recent outbreaks in June 2016. It's data from two clinics and CDC's Gonococcal Isolate Surveillance Project in 2015, where there were 52 cases of meningococcal urethritis detected in Columbus, Ohio and 15 cases in Oakland, California. Again, the majority of patients were heterosexual. The majority of them did report symptomatic urethritis with discharge and/or dysuria and nearly 100% of them reported oral sexual activity, highlighting this increased risk with oral sexual activity. The fact that a lot of these cases will be

symptomatic and will look like gonococcal urethritis and interestingly, at least in these three studies or these three locations, the population that this is affecting is heterosexual patients, even though we know from past reports that MSM patients are at higher risk.

[00:52:30] How do you make a diagnosis? Well, you need a positive gram stain and like we saw in our patient where it looks sort of like a Neisseria, it may be gonococcus, you need to be able to grow it out on culture in selective media and when you do nucleic acid amplification test, that will be negative and that would make you think that this is probably not gonorrhea. So you do the amplification test for gonorrhea and having a positive gram stain and culture and negative NAAT test is highly suggestive that this is Neisseria meningitidis species. Again, the clinical syndromes, like with gonorrhea, you can have asymptomatic colonization, but when you do develop urogenital disease, you can have urethritis and epidymitis, cervicitis and PID in women, proctitis and again, if you had a patient with an asymptomatic infection in their genital or anal area, they can then transmit this to a partner who is not infected and the partner could become infected with oral activity in their oropharynx and then go on to have respiratory disease such as pneumonia, conjunctivitis, otitis media, sinusitis and in serious situations invasive meningococcal disease. So the management, currently we treat infected patients and a lot of times we may mis-diagnose this as gonorrhea, so they'll receive ceftriaxone and azithromycin, which would still be appropriate in this setting. And because we don't actually know a lot about transmission from partner to partner, the current CDC recommendations are that partners be treated as well, same as you would if the patient had gonococcal infection. And then just lastly a brief word about vaccines. As you may know, there is a vaccine for Neisseria meningitidis. There are two types of vaccines, a conjugated and a polysaccharide vaccine, which contains four serotypes A, C, W and Y. We do also have a serogroup B vaccine, but that's not routinely given to teens and adolescents and young adults as these conjugated and polysaccharide vaccines are and that's because we reserve it primarily for outbreak situations. We know that the polysaccharide vaccine does not protect against unencapsulated strains, but we don't know what the conjugate vaccine does against unencapsulated strains. So right now, we know that the polysaccharide vaccine would not protect you against local urogenital infections, and it's strongly likely that the conjugate vaccine may not protect you as well. So, in general, it's unknown if vaccination provides any protection against urogenital infection or disease.

[00:55:16] All right, so the last thing I want to conclude with is just briefly looking at strategies to prevent transmission with oral sexual activity and protect patients.

[00:55:29] This is what the recommendations for screening is based on the CDC and I put this up there just to show you that it's really not entirely helpful. I won't go through the whole thing in the interest of time, except to say there's only one situation where we actually screen for pharyngeal infection and that's in MSM patients who will have pharyngeal screening for gonorrhea, at least annually, if not more frequently depending on their sexual behavior and certainly at the time an acute infection is suspected. Under no other circumstances do we ever screen for any sort of pharyngeal infection, not by pathogen and not in women or other male heterosexual patients.

[00:56:10] So, right now there's this recommendation that oral sex equals harm reduction and this what we sometimes say to patients, especially patients who have discordant HIV serostatus or patients who engage in high-risk sexual activity. But it's actually not entirely a true recommendation. Oral sex does

not necessarily equal harm reduction. We also know that we cannot prevent transmission of infections that could affect the oropharynx, because there's really no guidelines for screening, so we don't know what the actual incidence and prevalence is in our patient populations and we don't know how to screen for that because there are no guidelines for that. Therefore, we're sort of stuck with two things. One is to tell patients to have good oral hygiene because good oral hygiene prevents bacteria from overgrowing in the oropharynx and then our last sort of line of defense, and our best line of defense is to really encourage our patients to use condoms during oral sexual activity, as unpleasant as that may be, particularly if they are engaging with oral sexual activity with partners whose histories they don't know, or who they don't know very well.

[00:57:28] To conclude, I just want to leave you with this quote that I'm paraphrasing, I found it online in ProMed Mail, a discussion about meningitis, meningococcal and venereal transmission and it was also quoted in another sort of huge publication, so I thought it was really interesting and very apropos for our discussion today and it says, "Correct identification of the organisms in acute male urethritis might occasionally save a marriage, when the organism is from the wife's throat rather than from extracurricular activities," and I think that that's particularly meaningful after our discussion today because we don't always know what's causing either urogenital or anal or oral infections. It may be a pathogen that you might not expect, so we really need to take a good sexual history and have a high suspicion for things that are not as common or our suspicion is not as high of. Okay, thank you.

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