Richard Steece – Herpes Serology HSV 1 and HSV 2 Type Specific Diagnosis from the Public Health Pers

hello everyone welcome to today's live broadcast herpes serology hsv-1 and hsv-2 type specific diagnosis from the public health perspective I'm dr. Tiffany Mackenzie and I'm a scientific affairs manager of infectious disease and I'll be your moderator for today's event we are delighted to bring you this educational web seminar presented by lab routes and sponsored by dias Oren design is a global leader in the field of biotechnology for more than 40 years the company has been developing producing and commercializing reagent kits for in vitro diagnostics worldwide it offers the broadest range of specialty tests available in the immuno Diagnostics market and continually invests in research and development using its own distinctive expertise in the field of immuno Diagnostics to deliver a high level of innovation for more information about the asourian please visit www.dent.umich.edu/license oh we'll try to answer as many questions live as we can you can enlarge this slide window by clicking on the screen icon in the lower right hand corner of the slide window and finally if you have any technical problems viewing or hearing this presentation please click on the support button at the top right of your presentation window or submit your problem through the green Q&A button in the lower left this is an educational webinar and thus offers free continuing education credits after the webinar is over please click on the C e button located in the bottom left corner of your webpage and follow the process to obtain your credits and finally now I would like to reduce today's speaker my friend and colleague dr.

Richard STIs dr. Richard sneeze is the public health laboratory director for the state of Tennessee Department of Health he comes to us today with over 30 years of experience in public health and is one of the nation's leading Public Health Laboratory experts he has also worked internationally and provided support for many organizations including the Centers for Disease Control and Prevention the CDC the association of public health laboratories aphl the American Society for Microbiology ASM the clinical laboratory standards institute cos I and the US Department of the Interior DOI for projects sponsored all over the world in Asia the South Pacific and the United States territories and Europe among his multiple roles driving public health initiatives dr.

Smith has recently served as the National chlamydia laboratory coordinator for the CDC national infertility prevention project the IPP and a science advisor to the aphl dr. Steve's is currently the chair of the STD subcommittee for the aphl and serves on several other key aphl committees he is a board certified diplomat of the American Academy of microbiology ASM I will now turn it over to dr. Richards fils for his presentation thank you keep setting I really appreciate that I want to thank everyone for taking time out of their busy schedule today to call in and listen to this presentation and in particular I'd like to thank the asourian for the opportunity to be spending some time with all of you here this morning or this afternoon depending upon what region of the country that you're located in as you can see from the slide the title of the presentation today is herpes serology hsv-1 and hsv-2 type specific diagnosis from the public health perspective and if we look at the next slide we can look at the objectives and for us to really understand the recommendations and and all the issues surrounding type-specific serological testing we need to get on the same page so we need to talk a little bit about some of the other items related to her lisa-marie screening it's like the epidemiology of herpes infections a little bit about the transmission the pathology is from the clinical manifestations we also need to describe enough that's available to diagnose hsv-1 and hsv-2 infections and the difference between isolation and identification versus serological assays and the respective role in herpes diagnosis we're going to talk about the CDC sexually transmitted disease treatment guidelines that were published fairly recently in 2015 and talk about the role and the appropriate use of type-specific serological tests in addition we're going to talk a little bit more about the guidelines recommendation as to why purpose type specific screening should not be used at this time in the general US population well before we go into that I wanted to put this slide up here this was an article that it that appears and has appeared in Cosmo table third magazine and December 2015 and kind of followed it as some fairly good health related articles certainly on STDs I guess some termination in there in the past and this particular article is about her piece and the title of it is are we too afraid of her piece it's mostly a benign skin condition that millions of people have and that was the title of the article in cosmopolitan individuals can certainly check that out I'm sure probably online or may have copies of that but there were several quotes in there they called it that I thought were rather interesting and one of the quotes in they are they call data that herpes it's just a skin rash if you leave and get the skin rash and also another court it's ironic that herpes has a stigma but nobody dies of it well I want you to kind of keep these things in mind as we go through the presentation today and at the very end of the presentation maybe we can visit this a little bit to see it if maybe it's a little bit more complicated than that or if maybe there's just a little bit more to the issues of herpes and herpes infections let's start out with the epidemiology today genital herpes is a chronic or life mono viral infection once you're infected with herpes virus you're infected for life herpes virus just loves to live but nerve cells and it can go and hide there and persist for long periods of time before it the conditions are right and it may or may not reoccur another may be an aggravation of the original infection so once you have it you have it forever there's two HSV Cyril types hsv-1 and hsv-2 hsv-2 is responsible for the majority of cases of recurrent shinola produce in the United States and then uh appears back we used to say that hsv-2 was below the belt if you will or genital infections and HSV one was above the belt oral and order higher bolivianos type infections and in many areas of the country that's still true however in many areas of the country or in certain populations you do see some differences for example in California you may see hsv-2 hsv-1 in equal numbers below the bill and you can see that in other certain populations too MSM populations so you need to look at your specific area your specific population the people that you're testing to determine whether hsv-1 or HSV tias is more prominent about Airport below-the-belt according to CDC is approximately a million new cases of HSV every year this estimated this is least fifteen million individuals in the US that have genital HSV infections and the majority of persons infected with HSV to have not been diagnosed with generally so we're going to talk a little bit about that throughout the presentation of the tak that most herpes infections are asymptomatic in the u.s.

Approximately fifteen and a half percent of adults between the ages of 14 and 49 have specific hsv-2 antibodies hsv-2 so prevalence is higher in women and men in all age group and varies by race and ethnicity and the big thing to remember is the maturity of genital herpes infections are transmitted by persons unaware that they're infected or asymptomatic when transmission occurs so when I used to get phone calls from individuals that you know this SOB gave me herpes and I know he had herpes or she knew I had her she had herpes they probably didn't know that they were actually infected they probably were telling the truth it and we're aware because again the majority of the cases are asymptomatic so we're going to talk about this throughout the presentation this is slide from CDC it kind of reinforces what we just talked about the so prevalence in women is higher than an old white women higher than men when I'm higher than in black men and also the higher rates that we see in the black population again another example of racial inequities racial disparities that we see with with some of the other STDs in in addition to herpes so transmission let's look at the transmission hsv-1 and hsv-2 can both be transmitted sexually and perinatally there's really no difference between the transmissibility between the two viruses efficiency of sexual transmission is greater from men to women and vice versa and having general HSV infections increase an individual's risk of acquiring HIV infection twofold purpose is not a particularly hard Eve iris is not a particularly strong virus it's very susceptible to drying so it's readily inactivated by joining most soaps inactivated herpes viruses hydrogen peroxide alcohol a variety of different agents can inactivate atrophies fairly readily so for my transmission is uncommon but it has been documented so it doesn't trigger but not very commonly because it it just doesn't last long outside the human body pathology we already talked about herpes once you have herpes that remains with you for life it remains latent it goes back into the the nerve cells and it just lives there just happy as a clam until the next possibility or the next type of stress causes it to come out and reactivation as we know can be precipitated by multiple unknown and some known factors we've seen on college campuses that for example as you get closer to finals week or in the middle of finals individuals with total sorts and stress can pop that down so herpes can certainly be reactivated by stressful stressful conditions sunlight or bad sunburns we also see that sometimes triggers reactivation or herpes virus in some individuals hormonal changes monthly changes in women can also trigger that and that's a variety of other things that we know and and things that we don't know that can cause these reactivations of herpes virus reactivation Navy visible you may see the lesions or sub critical viral shedding may occur primary infections are generally more prolonged and severe and that makes sense the body hasn't seen the virus before you have no mo no logical capabilities you have no pre-existing antibodies no specific cellular immunity and so when an individual is infected in at first case that primary infection antibodies take time to develop your cellular immunity takes time to develop and that come into play so that's why your primary infections are generally more prolonged and severe secondary infections are generally shorter another shorter duration and hsv-2 may have more recurrent infections that hsv-1 there to work pragmatically this is important that's one of the reasons when we get into and the discussion about laboratory tests we'll talk a little bit about typing this virus and there's other reasons why we want to type it too but pragmatically is certainly one of those this is a nice slide from CDC and it kind of points out what we just kind of talked about on the first episode of you little gremlin website of the slight infection type first episode primary infection with type 1 or type 2 at that time listen to the joke is not here and not been exposed to hsv-1 are hsv-2 so they have no pre-existing antibodies and no pre-existing specific some of the other immunity a case the lesions and symptoms that are listed here can be severe and and certainly prolong an example of the first episode in a non-primary case the next lie and tie to where you have a pre-existing hsv-1 infection it can actually moderate that because there is some cross protection and you can look at this chart it is a good example of why this occurs why when antibodies are present and can modulate or turn it from a more milder infection then that first primary episode we talk about the clinical manifestations and here we see some primary revisions or case of primary infection with these lesions the penis and I want to point these up for a couple of reasons one this is not when when a lot of it is just think of four pieces and especially individuals that have had their headquarters you know how the sick of it gets these diseases started getting a little bit or they're getting a little bit dried up and little crusty these are not ideal lesions who do I use for virus isolation you would want to have fresh nice specifically gence for that your success of getting an isolate cell culture or a direct test or PCR for that matter certainly decrease the longer the infection goes when the lesions are starting to dry and crust up that's not the time now this is a individual that says well you know I get these every about every two three months you can take the specimen but you also want to tell into does you know come back the next time early on when these things are fascicular so we can get a good specimen because that's the if there's anything about it reoccurs it's nice for the opportunity to try and yet isolates and to confirm that so these again it not that not the best reasons to actually try and get a nice little probe this is a picture of a recurrent ulcer clinical notification they you can see the recurrent ulcer it's an ulcer and it doesn't look like a vesicular lesion could certainly can confuse with something else there's other things that can cause ulcers and we're going to talk a little bit about that confusion in just like a couple minutes cervicitis we talked about asymptomatic shedding it was an individual at the case of cervicitis that individual may be feeling perfectly normal aches no pains no fever no nothing and they have my little shedding and be aware of it so cases cervicitis you can see why individuals have may transmit this virus and not even be aware that they're infected this slide is actually a good slide and it shows two two different things it's light on the products and it smells nice vesicular lesions these are the lesions that you want to look for to get a nice to click on a specimen from if you take and aseptic ly break that lesion open with a forceps or tweezers or whatever you have in the clinic and you take that swamp as long as it's not a cotton tip which chefs beware calcium alginate swab which all can be toxic to herpes just a rayon or Dacron swab and you be taking the soap bed swab up at the fluid that's in these particular lesions and rub the base of those cells if you're not causing the patient some discovered you're most likely not collecting the specimen vigorously enough so that's one thing that you need remember if you you should be causing the page a little bit of discomfort to be collecting that specimen properly if you take that specimen properly at this stage put it in specific little transport medium and out of the lab and there's no huge delays in getting that to the lab you're going to get herpes virus on that specimen almost all other tests that we have will probably get a nice good positive out of a nice fresh lesion like this another thing to note that herpes lesions can occur on any part of the body there's been cases especially with younger individuals of individuals Auto inoculating themselves scratching and picking it away at a cold sore and scratching another area on the body and trance infected and transmitting that virus if there's a broken skin abrasions and the virus gets on that particular area through scratching or whatever it can gain a foothold and it can infect so you may see these potentially on any area of the body we used to see an occasional case generally hsv-1 indents doing dental work and and Nicorette cut you know in the knuckle area particular and develop our piece Whitlow don't see that as much as we used to see that because people were a little bit more cognizant of that and a little bit more careful with drugs and HIV and other types of infections now so we don't see that it's common so we used to but it can occur in any part of the body and the dead giveaway are these specific event Allegiance they're very characteristic you see something like this especially if a patient comes in and says yeah yeah I can piece every month you know I had this three four times now in the last year you know it's pretty much a dead giveaway there's not much else that looks like this that's going to reoccur not much so HSV diagnosed the clinical diagnosis itself can be insensitive individual may be asymptomatic as we saw from one of the previous slides the cases cervicitis individual certainly having a an episode and may not have even known it at the time so the clinician certainly is not going to see that unless they're doing a routine pelvic exam and then it was not going to know when they're shedding so they can be relatively insensitive just looking and trying to find lesions and certainly nonspecific when you see all the lesions or one mole of lesion or an ulcer that we saw earlier there certainly could be confused with something else or even something now related to an infectious agent so clinical diagnosis itself often needs help the key of course you see these recurrence these particular legions pretty diagnostic in this cases so therefore clinical diagnosis should always be confirmed by laboratory testing using specific virology tests culture or non culture or serological tests some sort of test to confirm that and the reason other than oftentimes a clinician may or may not be sure when they look at a lesion the second reason is psychologically I've seen many instances where an individual is clinically diagnosed but they just be infection but it's there's there's something about taking a specimen and sending it to the lab getting that or AB result back and a clinician X economy you have laboratory diagnosed herpes herpes won't have is too whatever and then going into the counseling message you know here's what you need to do here's how I mean adjust your lifestyle etc oftentimes individuals seem to pay more attention to that than just a clinician saying oh yeah looks like a herpes virus and may or may not come with some specific counseling so those two reasons I think it's extremely important that you confirm this with specific laboratory tests let's look at some of those laboratory tests we have a by rollin on culture which is long they consider the gold standard and we also see if you look at the bottom you can see PCR the gold standard so and we just confuse well we're not going to fuse then we're going to talk a little bit more about that as we go through these but barrel clothes are wrong pens that can consider the gold standard and it is a good test and it's some of the preferred tests for patients with fresh genital ulcers or other fresh lesions and it's still necessary to determine antiviral resistance at this point in time we don't know the specific sequences we don't have techniques to molecularly determine the antiviral resistance patterns in herpes virus yeah it's just a matter of time as we move into the more into the molecular and the sequence again that we probably will have but at this point in time we still need a culture to look at antiviral resistance antigen detection or direct detection from regions with the FAA or possible some of the EIS CDC suggests they may be slightly better than culture for detecting HSV in healing lesions of course that assumes that you're taking that scab crust off and you're you know really scraping and causing some discomfort to obtain that specimen I haven't seen any data to really strongly support this but you know CDC suggested that it may be cytology as a mirror press Mir they're insensitive and nonspecific perhaps Pap test was not developed to diagnose surface infections no nothing you can I occasionally see a herpes infection there but it shouldn't be you specifically HSV diagnosis PCR really has been the replacing our culture for quite a long time as the method of choice for HSV it's extremely sensitive and we're going to talk about the relative sensitivities and specificities in a few minutes it's certainly the preferred test pretty taking a chesty and spinal fluid or needle samples CNS type specimens look at cell culture there's still conventional culture there are sites they're still doing conventional cell culture the use of variety different cells because they're looking for a lot of viruses not just for these viruses and there are systems that you should be like shell but I also several different viruses but also it looks specifically for just herpes virus something might be enzyme-linked that if I roam digital normally well system of a Elvis system from diagnostic hybrids but the one thing that you want to remember in the city CDC recommend disable and tight with the DFA when you see ourselves on the left part of the slightly nice fibroblast cells uninfected and slides and cells in the middle you can see the Robbins cells you can see some giant cells and you can look at it and you could almost tell where the type of cells and the cpe that it's herpes virus and in many cases you can almost and it's the type by almost by looking there because wonder have these two but you should confirm obviously with da you can't even hundred percent so a nice DNA to confirm that because they remember prognostically you're going to see more recurrences with two than one and in addition the information for your population that we talked about a few minutes ago 50% of the cases are below the belt with hsv-1 and hsv-2 in your particular region the reason we know that is because we typos so we know that epidemiological information so it's important for a couple of reasons to type these and to differentiate herpes one and her loose – and it's currently the CDC recommendations also that some of the advantages of cell culture it does require my virus so you need to get these at a fairly early stage nice particular lesions take them properly that we talked about a few minutes ago and I think of those infected cells and you need special virus transport media a transport of the right conditions it works very well it can be used related at all locations you know labia or buttocks wherever you might find these lesions it has a high specificity when you see the specific CPE and according it by the blood cells it's pretty difficult to mistake you know herpes CPE from other types of viruses that you might isolate no cells or few exceptions but generally it's pretty difficult not to be able to identify that if by the way the cells grow in cell culture in your specific CPE and also we used to differentiate hsv-1 and hsv-2 only talked about why that's important and the antiviral susceptibility testing we talked about why that is important also some of the disadvantages well it's comparatively expensive certainly more expensive some of the nine culture techniques there's many variables as well the cells themselves the medium the transport condition technically it's a little more difficult than a culture test not useful with asymptomatic patients you don't want to routinely take and just a cervical a urethra or swab type specimens when you see no lesions so individuals are they symptomatically shedding are potentially asymptomatic Lee shedding and probably not that tests of choice for that there's somewhat of a delayed turnaround time also one of three days of ours has to grow however if you take a good fresh specimen transported in the right conditions to the lab with the right transport medium etc you're probably going to see that virus in 24 hours herpes likes to grow in most cells actually frozen all cells it's not too many cells that it doesn't grow in but it does grow very well and it grows very fast certainly by three days you're going to detect probably 95 to 99 percent of the herpes infection since cell culture occasionally I've detected positive South 5 to 6 to 7 days but that's been very rare and probably came from specimens that were or their legions etc but a fresh specimen usually a year the viruses chew through your cells by the next day very quick growing the sensitivity can be low again as the leaders begin to heal and you can get false negative results in those situations okay let's look at someone and culture test well we already talked about the direct smears it stains the zinc smear are saying stain the faa in the products it is and some of the enzyme in molasses if we look at some of the advantages they aren't really relatively inexpensive and they're fairly rapid but they're very insensitive so they shouldn't certainly should be used in critical situations not with newborns regularly a minute term or suspected encephalitis or see a CSF or any critical type specimens and the stains that saying it's a nonspecific stain and they also require lesions so there's several disadvantages of these tests and they're not recommended really at this point of time the nucleic acid amplifying test excellent tests one of the first ones that was developed PCR using the raw slate cycler Mayo Clinic dr.

Tom Smith and colleagues at Mayo kind of developed this early protocol at least one of the major sites that were using this protocol they had many workshops back several years ago the American Society for microbial mediums the clinical neurology symposium and and really tried to transfer this technology out into the virus labs I remember attending a couple of workshops with that dr. Smith and some of the crew from nail relates to my psyche they work very well and you can also type a time that used a melting curve and you could type and isolate from increased sensitivity and specificity it was a great little procedure and there's procedure to still use that light cycler and or other machines and amplification methods Luminex they called r-tx he likes a little self-contained little plastic apparatus contains everything cartridge and a beanie protec every stomach virus k2 the accent excellent amplified tests and techniques for detecting HSV infections the advantage is like I mentioned before they're the most sensitive tests they provide rapid turnaround time meaning same-day results any and in most cases you know have good they can be used to differentiate hsv-1 from the hsv-2 and it's definitely the tested choice for looking for herpes and spinal fluid or infections in the central nervous system etc a place where you're more than likely not going to find either by a virus or not a lot of virus present it's definitely recommended for those types of specimens and it has high specificity 99 percent or greater some of the disadvantage is depending on the version it might not be suitable for large volumes screening if you did lots of herpes virus it does require a high technical skill although with the newer nucleic acid amplify tests are getting to the point where cell culture probably requires a higher degree of technical skill than medic like as an amplified test in most cases special facilities are a clean area while you no longer really special facilities but you do need to keep kind of a clean area getting more more forgiving with again cartridges for everything self-contained and much much more able to run these on the regular lab bench but you still ideally would want to keep those in a nice clean area anytime you're trying to do that look like jessa they're fairly expensive certainly one of the big drawbacks and not all the Nets that are available are FDA cleared okay let's start talking about some of the serological assays there are a variety of different tests that are available hsv-2 rapid tests the Fisher's review hsv-2 it goes the old test from diet not and technology that now fishery the Reuters Fisher is either selling for them or somebody want them out I don't see I only see the Fisher name on it nowadays and the herpes select Express hsv-2 from focus and also the chemo luminescent assay the lesson on the essaouira hsv-1 and hsv-2 type specific test so we're going to talk about the difference between the type specific here in a minute and why that's critical enzyme immunoassays herb you select one a few from focus hsv-1 and two from Trinity and there's other manufacturers that do have out of summer recess Western Blatt I'm not aware of any commercial Western blot kit that maybe I'm not aware of any when most Western blot as needed I know some of the private labs some private labs are doing at the University of Washington probably is a leader in that it's a very difficult test to standardize and to read so people the University of Washington will have experience in doing western blots so if you need to have a list of what for some reason you know you might want to consider that very good at what they do there's also there you select one into a lot focus the only problem with that is right now CDC doesn't recommend that because it uses the same recombinant antigens as they use in their enzyme a little essay tests however one thing to remember is what you do screening assay even if you're using something that has the same recombinant antigen a simple repeat doesn't crease your positive predictive value that's one of the reasons that we do that like HIV we be tested it increases our productivity back that's just something to keep in mind but currently it's not recommended in the treatment guidelines serology advantages of serology if the test is designed like that yes or in some of the other essays to detect glycoprotein 1 G 1 and G 2 you can't differentiate between hsv-1 and hsv-2 infections we served a lot of serologies for herpes virus before glycoprotein one in glycoprotein 2 and we're even identified and we could detect antibodies but we couldn't differentiate we couldn't tell well there's one know whether it was 2 and what are those lesions that he saw genital lesions that you saw and he picked up a positive serology result whether that really came from our who's 1 infection from from the lips whether it really was related to HSV – so without using a specific test that can differentiate those two specific antigens HSV serology is currently not recommended so the tests that are labetalol the sense that he doesn't vary a bit between 80 to 90 percent the specificity is in the high 90s and you get rapid turnaround time again unique same-day result with these tests there were very good assets for doing what they design to do they're moderately expensive they're technically less than concert tests and other antigen tests and they may not distinguished like a protein G 1 and G 2 depending on the version so you need to make sure that if you're requesting a serological assay as a clinician that that test can differentiate between those and that's what you're asking that test to do I'm not sure why you would want to know just whether the HSV antibodies are not it probably would provide very little clinical information to you so make sure that whatever site you're using does utilize something that can differentiate and and type hsv-1 and hsv-2 sarah logically so where do we use the type of specific serological tests according to the CDC and Public Health recommendations cases were recurrent general symptoms or atypical symptoms with negative HSV PCR repulsor occurred to confirm clinical diagnosis without laboratory confirmation to manage sex partners of persons with genital herpes especially in discordant couples and if they just were the wife or perhaps a husband as infected and the wife opposite partner is not man Diesel's especially in cases where they're thinking about having children white becoming pregnant if she's negative zero negative and the husband so positive for examples so to manage those types of partners to provide education and to eliminate some of the risk factors that might be associated with transmission from a positive partner to a negative to a current negative partner CDC also suggests that type-specific serological tests should be considered for persons presenting for an STD evaluation especially in the middle from multiple partners individual is having multiple partners engaging in high-risk activities they haven't been evaluated before for STDs this would be a good example than individually that should be evaluated individuals that are infected with HIV MSM or men who have sex with men at an increased risk for HIV infection they participate – activities those individual shows also a screen or suggested that they be screen with type specific asses however you can see why screening and the general population is currently not indicated because of the amount of people that are shedders asymptomatic setters and the amount of people that have hsv-1 and hsv-2 at different locations so spinning in the general population at this time it's probably not useful and certainly not recommended by CDC at this point in time IgM antibodies well IgM antibodies can be detected and they can be detected in primary HSV infections if you know it's a primary infection unfortunately that'd be very common to be able to know that we're sure co-infection with another HSV type hsv-1 in sir positive individuals that are acquiring HSV – and a dual infections IgM can also be produced by GM computer reproduce be produced in reactivated HSV infections so therefore IgM antibodies are not a reliable indicator primary HSV infections and it's generally not recommended at this time to screen using IgM and IgG an antibody assay most of the information or much of the information that we talked about this afternoon actually comes out of the CDC STD treatment guidelines do you see below the chapter or part of the guidelines to talk about the principles of managed by the general for herpes and we're going to talk about some of those again I mention this because these recommendations are available online you can go online at the CDC govt website you can download base you can actually order these from CDC and they have some nice world charts also you can order so there's some other materials that you can get from CDC and to look at specific recommendations policies but certainly for the recommendations for genital herpes and if you want more details and / and some of the things that we've gone over this afternoon the guidelines are going to provide a lot more detail by we're going over this afternoon so patient management what do we do for the patient well counseling it's critical constantly regarding the natural history is that sexual and perinatal transmission methods to reduce transmission extremely important individual needs did he talk to you about lifestyle changes defining the responsibilities that they have to their sexual partners extremely important that individuals communicate back and forth one another the desert where some of the how they can lower some the risk of transmission after the use of condoms for example and so there's a lot of information and that's available again on the CDC website but that counseling should be an integral part of patient management antiviral therapy well what does antiviral one out there for your chemotherapy yeah well I can control or partially control the signs and symptoms of herpes a couple things to remember it does not eradicate latent virus may cause the virus did have a shortened of course infection and it may keep the virus from recurring quite as many times it does not eliminate the virus once you've had the virus you will continue to have that virus it will not eliminate that virus from the body also it does not affect the risk the frequency or severity of recurrences after the drug is discontinued when the drug is discontinued herpes can reactivate at any point in time and it can certainly even when they're on a suppressive therapy but maybe just for lesser time period but when that drug is taken away you go back patient gives you your space or step one antiviral medications and we have some excellent antiviral chemo therapies available to us the cycle there is generally this the first chemotherapy antiviral chemotherapy of choice that most cycle of here and damn cycle appear and I generally topical therapy with antiviral drug versus is generally not recommended in most cases CDC recommend the regimen for a first clinical episode as the anti viral chemotherapy beauty community choice is that cycle of year either in 400 over 200 milligrams either three or five times a day for seven to ten days followed by a Bella cycle appear in phencyclidine the case of the first clinical episode depending from the severity of that and again for more specific information consult that the the guidelines antiviral therapy can be considered for suppressive therapy for recurrent general herpes can also be considered for episodic therapy for recurrent genital herpes and treatment severe diseases and in the case of really severe disseminated herpes virus and those recommendations are all in the guidelines general herpes during pregnancy most mothers are there but some acquire Neil never heard these lack histories of clinically genital herpes yet most individuals are asymptomatic or infected and don't know they're infected the risk for the transmission to the neonate is high 30 to 50 percent among women who acquire general her Beast near the time of delivery or at the time of delivery risk individuals you know dates that are born from an infected mother they do acquire a herpes infection have a high probability high mortality and morbidity so herpes does it is associated with mortality and it's also associated with mortality it was in case of herpes encephalitis not real common but it does happen in women with histories of recurrent herpes or acquired genital herpes during the first half of pregnancy over 4 the risk is fairly low for transmitting that for the neonate prevention of neonatal herpes and depends on of waiting acquisition during the late pregnancy avoiding exposure of the events of legions during delivery if they are present so all pregnant women to certainly be asked whether they have a history of general her these vary not only asked but as specific questions event that they ever experienced lesions and the lesions here etc so very little history should be taken and again there's more recommendations in the guidelines on how to handle and how to avoid and how to treat neonates that aren't affected with herpes so in conclusion its herpes just a benign skin condition or something that we should take serious what we talked about a lot of serious things here today and so I think you have to answer that question yourself an excellent should individuals infected everything a big H on their forehead well of course not there shouldn't be a stigma because there's so many people that are infected with herpes versus it's not the end of the world and if it was still need to receive the correct counseling and messages is it true that nobody dies from herpes infections well that's not true we do know that individuals do die from herpes infections in particular infants that are infected during the birth process from an infected mother so it is a big deal so it is true that through appropriate testing proper education patient management and counseling individuals should be able to live a healthy normal life without guilt so we answered all the questions that were brought up Cosmo oh I'm not sure I guess we think we can take a look at that ourselves so at this point like the end the presentation if there's any questions that we'd like to try and answer those thank you very much for your attendance today Thank You dr.

Steve for that brilliant presentation before we get started on the question and answer session I would like to remind our audience how to submit questions you can submit questions by typing them in the Q&A box which can be found by clicking on the green Q&A button in the lower left of the presentation window we'll try to answer as many questions live as we can and our first question for dr. Spieth is could you please go over dr. Spieth if a woman has an outbreak of HIV at delivery what are the recommendations yeah good question it remember from the presentation CDC reminds us that you know all pregnant women should be asked whether they have a history of genital herpes and examined carefully especially at the onset of labor and women without symptoms or signs of general herpes warts proteome can can deliver vaginally although c-section does not completely anem ly eliminate the risk for HSV transmission to the neonate women with recurrent genital herpes lesions at the onset of labor should deliver by c-section to reduce the risk of the neonatal HSV infection from occurring and that's right out of the CDC guidelines so there's a little bit more information in there if you want to follow up and read up on that a little bit but I think that probably answers the question for you wonderful thank you for that dr.

Steve next question a really quick definition question you referred to on the transmission slide slide eight to four might can you define what for my transmission is sure oh my sir generally inanimate objects that are capable of transmitting infections to humans things like doorknobs toys or in the case of HSV may be sexual toys you know etc so any in an inanimate object that somebody would COFF on or contaminate somehow that could transmit an illness or a disease to a human okay great next question here the person writing in asked my understanding of difference between hsv-1 and two is that if you get HSC one below the belt it is only a one time infection or outbreak whereas hsv-2 in the oral oral area is only a one time infection or outbreak is this true entirely hsv-2 certainly has more recurrence and prognostically you know that the chances of it recurring more frequently or it or it regularly regular intervals is certainly more common than hsv-1 and an individual that's infected below the belt if you will they just see one they may see a single outbreak but generally they'll see a recurrence but rather than five to six perhaps a year or or five to even a dozen a year it may be you know one or two certainly reduce occurrence if they if they do appear so they do occur not as common but they do and generally less frequency if they do reoccur it's a really interesting informative response thank you and to the next question is it easy to do molecular molecular or polymerase chain reaction testing of hsv-1 or hsv-2 in the blood well as far as the ease of doing PCR course you know PCRs PCR I mean it's pretty easy to do in blood or any other types of specimens I think with the question you're probably asking is that is it a good specimen – it's blood a good specimen to test for hsv-1 or HSV – going to click acid amplification and I you know there's not a lot of data because we don't routinely test that you know it's more like spinals or or infants and secretions and body body tissues and etc generally with most viruses there's a very short by reaming stage if there even is one so I would say you know it would not be a specimen of choice could it ever be detected in blood well certainly in cases of infant disseminated conditions etc but I think it would be very poor choice to consider using under routine circumstances thank you for your input on utility of molecular testing and different sample types this next question is an excellent excellent point what clinical advantage is there to knowing if a patient has HSV one versus HSV to again you know kind of what we said in the presentation prognostically you know HSV one it genitally certainly below-the-belt tends to recur less frequently and certainly less severe in most cases than HSV – so prognostically is probably the the the biggest reason and of course we did mention you know that kind of the epidemiology reasons of being able to differentiate so you could kind of know in your population you know what you were seeing so so probably the prognostic difference would be the major reason to know whether it's HSC one or two excellent so going back to more of a public health question how effective our condoms in preventing the spread of HSV I know you touched on it but do you mind going over that again sure that's actually a really good question basically CDC says and has the data to support the condoms when they're used consistently and correctly they can reduce but not eliminate the risks for genital herpes transmission is we have to remember the most of most cases of herpes are transmitted by persons unaware that they're infected or are asymptomatic so individuals most likely would not be using condoms in those cases anyway in addition since lesions can appear in different areas of the body you know the condoms only only going to be able to protect what it covers so they can be very effective depending upon where the lesions are and how they're used but they will not eliminate the risk completely excellent thank you for making that point next question about serology this is an excellent point about indications as you consider serologic assays you consider them that they should be recommended to test pediatric or immunocompromised patients and I think what I would what I would say is I would refer you to the guidelines and then the guidelines do recommend you know an animal immunocompromised especially individuals of history so there's a lot of combination information that you would look for as to whether you'd want to make that decision and so I suggest you know you can look into the guidelines you know for more specifics on that and of course any of these should be discussed with the individual clinicians the the basis clinicians too so so I would refer you back to the guidelines for more specifics on where they actually do recommend that these be tested okay excellent thank you for referring us back to the guidelines another interesting question about HSV types so are there more types of HSV for example three four and so on we spoke about agency wanted to type specific tests today but can you speak about other serology type sure well you remember when we look back when we first started identifying herpes viruses herpes one herpes to a couple of first viruses that we identified varicella-zoster chickenpox son Omega virus epstein-barr there on the herpes virus groups and as we discovered new ones we started numbering those so if we do now then the norman glacier is actually you know to refer those there just by their serial type and they all cause a variety of different things you know and there are specific tests both isolation and nucleic acid amplification tests and serologies for for the other ones like chickenpox settle make love iris etc so there are there are multiple herpes viruses and now you may see them referred to as as humans human herpes virus 3 or human herpes virus four or five but that just relates back to the in most cases to the ones that we've already known existed in a couple of the new ones that we've you know discovered that were caused by herpes viruses so so it's just kind of a kind of a different nomenclature for for some of the viruses that we've already named well I think we have time for just one more question which want to be mindful of everyone's time so I have one more a really excellent serology question here so dr.

Steve you indicated the serology tests having sensitivity with an eighty to ninety percent currently FDA is asking for at least ninety five percent sensitivity in comparison against Western blots or immuno blots and five ten caves of missions could you please comment on this well I think when you look at the serological assays that have been submitted in the past oftentimes FDA's criteria you know is changed over time and when a test gets FDA cleared and you know I find it's very uncommon for FDA when they do come out with changes or more restrictions to go back and and decertify or not or are unclear a specific test so there there have been tests and there's a lot of tests that are that are FDA cleared and been through the processors tested that are not specific for hsv-1 and hsv-2 that are FDA cleared so I think it's probably good that FDA continues to look at this and trying to raise the standards and to provide reasonable guidance to sites that you know it certainly doesn't prevent older tests you know that have been FDA cleared with less sensitivity and specificity to still be available or on the market if you will so I guess among stories it's a good thing that that FDA is constantly doing this and evaluating it and it just you know makes those tests you know reform even better with the input that they get from the old test and from individuals that are doing these so so I think it's a good deal that they that they do look at these and occasionally change their standards but it still doesn't get rid of a lot of the tests that were already cleared out there that's an excellent answer as dr.

Stephen thank you so much speaking to the increasing standards of the FDA and how we manage those tests that are currently cleared and raising the standards for the next generation so if there are no more questions I know there are a number of questions actually that we didn't get to in there excellent and we will address those doctors speech and I will address those as quickly as possible following this webinar but if they're just in to be mindful of time we're going to wrap this up but I just want to once again thank dr.

Richard Steig for his excellent presentation and I just want to double check with you dr. C's do you have any other final comments you'd like to make before we wrap this up today no other than if anybody has any follow-up questions please you know address them you know to in a proper way back to the website either to Tiffany or myself well we will certainly be glad to answer those for you well excellent thank you so much dr.

Steve and I also like to thank our sponsor dia Sauron for making today's educational webcast possible and just as a reminder today's webcast will be available for on-demand viewing through September 17th 2016 you will receive an email from laberd's alerting you when this webcast will be available for replay and we invite you to forward this on to your colleagues who may have missed today's live event so thank you so much everyone for attending it was really our pleasure and have a great day.

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