so i'm delighted all of youare in the room today ready with clickers inhand to participate in this very interactiveworkshop on new directions in sti clinical management, highlights from the 2010 cdcstd treatment guidelines. so if you're willingto go with me on this ride today though ishould probably introduce myself because although i knowsome of you in the audience, i'm not sure all of you knowexactly who i am or what i do.
so my roots are i'mactually a pediatrician and a pediatric infectiousdisease specialist and i do still practice atboston university medical center on thursday afternoonsdoing same day sicks with adolescents actually. that's my primary focus atthis point in my career. the other thing is ido still, i don't think about stds all the time andi still am a pedi id doc over at bu medical centerso some of you will see me,
my name on charts thererelated to that as well. but the one majorportion of my life now is that i have a position atthe massachusetts department of public health wherei'm the medical director for the divisionof std prevention and that actually comeswith it the ownership of one of eight wonderful,clinical training grants that focus particularly on postgraduate medical education. and years ago when susangray and i were but residents
and fellows together we dreamedof doing things like this but we would haveto do it on pennies. and now here we are, fastforward 5, 10 years later and we can actually do thesethings as joint operations, partly off of cdc funding formaking sure that clinicians stay up to date in the area ofstd diagnosis, management, and treatment, andsexual health as well. so we cover the newengland region, and if any of you are eagerto learn more, today is
but a teaser of whatyou could learn. you could spend a lotmore time, valuable time in a vaginitis workshoprelearning how to do wet mounts. oh yeah. [laughter] so beforewe begin, today's goals are to gain some insightinto hot topics in the std clinical managementworld, highlight areas of the 2010 std treatmentguidelines that should be read for, carefully for finalrecommendations and we're going
to do this interactively. so here's a fun thing for thoseof you who are not so much in the know about how theseguidelines come about. well of course they comeabout from a committee right? and a committee, oncesomebody told me-- it must be like a benfranklin quote or something-- all stomachs, no heads, thatultimately it's very hard to decide things on committee. and that sometimesundoubtedly explains some
of the more schizophrenicmessages and pieces of the document if you're everwondering why one place seems to say something and the otherplace says something else, well, experts don't always agree. however, the treatmentguidelines development process does wind up being evidencebased on some principle outcomes of std therapy that are notalways the outcomes you and i as clinicians practicingin clinic focus on. they do focus onmicrobiological eradication.
they do focus on making surethe patient feels better from the signs andsymptoms point of view. they do focus on prevention ofsequelae, but they also focus on prevention of transmission. there is a very clearpublic health message that comes across. these are the cdc std treatmentguidelines and i'm going to highlight some of the reasons that that might be reallyinteresting for us as clinicians
to understand why it'sso different and why in some settings, you know,kind of be aware of the fact that we are overprescribing antibiotics in some ways contrary towhat we do with our messages with our kids who haveviruses and we don't want to overprescribe antibiotics. these are sometimessomewhat different messages. okay, one of theinteresting things about the recommendedtreatment regimens are
that they're distinctlypreferred over alternative regimens. this may not have beenso clear before 2010 but at this point the cdc'ssort of saying, listen, you better have a reallygood reason to pick something on that alternative list likea terrible allergy directly to the drug on therecommended list because the recommendeddrugs are actually on the recommended list becausepercentage points maybe not
always statisticallysignificant may be better at microbiologic eradication or something else madeit slightly better based on evidence, based on research, and therefore it hitthe recommended list, not the alternative list. here's a fun little detail. they're alphabetized unlessthere is priority of choice. so the fact that ceftriaxone ishigher on the list than cefixime
for gonococcal treatment is asubtle thing telling clinicians, if you read the finerprint in the first 10 pages of the 120 page document whichi'm sure you do all the time, it says actually they'realphabetized unless there is a priority of choice and ceftriaxone isactually really recommended over and above cefixime. huh. a not so funthing to admit, you know how long ittakes to get these things
out the door of the cdc? they were reviewedin april of 2009. they didn't get publisheduntil 2010, december 17th. and it is because tom frieden,literally the guy at the head of cdc, has to sign off on it. a bunch of agencies have tosign off on this thing, okay? and the mmwrq isprobably as long as a loop around the equatorat this point. so it is a very inefficientprocess
which tells you almostimmediately as soon as the darn thing is publishedit's already probably slightly out of date, but youdo with what you can. cdc is getting savvier aboutgetting the word out not only through this network of stdhiv prevention training centers of which there are eightclinical ones across the land, but they have all sorts ofmagical things on their website like pocket guides andteaching slides and charts and there's an app for that.
there is now an ebook on thecdc std treatment guidelines. i downloaded it to my ipad whichi only got a few weeks ago. you know what the thingis just like a recycling of like the paper version. i don't know that it'sany better but it's kind of fun you can getit on your ipad. prevention and screening issues. there are some newmessages in 2010. the 2010 new messagesare, first of all,
there's a whole new section,it's at the bottom of the slide, screening and correctionalfacilities. never before datafrom epidemiology in correctional facilities about how many percentagepoints higher is the prevalence of trichomonas, is theprevalence of chlamydia, is the prevalence of gonorrhea. how jails wind up being, andcorrectional facilities wind up being nexuses ofcommunication of sti's
and potential transmissionback to the community. and cutting down on jailtransmission arguably with a captive populationmight cut down on community translation. so for those of you who mightwork with dys or children in custody or even adolescentsand young adults post captivity, etcetera, these aresome of the things that you might think about. there's a whole new section.
in terms of the older sections, in pregnant women asymptomaticbv or trich screening or hsv-2 serologic screeningstill not recommended. adolescents, they expanded theexplanation of benefits arguably for an adolescent,savvy audience, the stuff that they talk about in the cdc std treatmentguidelines is probably too basic to be honest. it's much better to go to a talk
such as martha perry'stalk that's coming up. for men who have sex withmen, it has become very clear that the nucleic acidamplification tests, and i'll tell you how toget these, for the rectum and the pharynx arerecommended for screening. and for women who have sexwith women, this offering of the hpv vaccine, thisidea that bv is common but screening is stillnot recommended are some of the newer messages within the2010 std treatment guidelines
which tells you right now that the cdc std treatmentguidelines are not all about treatment. there's a whole section onprevention and screening, there's a whole section under each disease once you'vediagnosed the patient with it, some counseling messagesspecific to that disease, counseling messages specific to partner managementrelated to that disease.
how many days out youneed to go to think back about the patient'sprevious partnerships to know who should be treated withexpedited partner therapy. all sorts of details like thatare actually in this document because they are very concernedabout the public health aspects and prevention of disease. okay without furtheradieu, let's dive into one of the biggest changes within the 2010 stdtreatment guidelines.
we have a 20 year old guy,presents with complaints of burning with urination andurethral discharge for one day. three female sex partnersduring the last year, didn't use condoms withany of these partners. previously hiv and std negative, but last checkupwas over a year ago. upon exam, this is not anot straightforward case, this is pretty straightforward,pus at the urethral meatus. no epididymitis, no inguinaladenopathy, no systemic systems.
how are you going to treat him? vote now. [ pause ] low dose ceftriaxone im,higher dose ceftriaxone im, ceftriaxone combinedwith azithromycin or straightforwardazithromycin at 1 gram po. how would you want to treat him? would you want togive him more drug as a shot or as an oral drug?
all right, most of youare shooting from the hip and you're doing to givehim dual therapy probably with the idea in mind that thisis urethritis and you don't know yet what the cause of hisurethritis is so you're going to cover broadly,broadly right at the point where he has, he needs care. he's already symptomatic. you want to interrupt thechain of transmission, ceftriaxone im 250 andazithromycin 1 gram
and you would be correct. i'm going to changethe story a little bit. what if he weren'tso symptomatic and you did thisas a screen, okay? and it came backjust as gonorrhea. unusual. it's unusual. only 10% of male urethral casesthat we know of with the type of circulating strains of neisseria gonorrhea thesedays are they asymptomatic
enough at the urethra that theguy is walking around with it, could transmit it still, only10% of them are asymptomatic. 90% of them do reallycause that pus, okay? but if you knew thathe only had gonorrhea and you had eliminated chlamydia from the equation could yoube a little bit more narrow with your drug use here? or could you choose a wholeanother drug that's an oral option like ciprofloxacinor cefixime or cefpodoxime?
and this is not a question ofwhat the recommendation is, this is a question ofwhat you do in practice. what do you actuallydo in practice? so what's your answer? all right, let's seewhat the audience votes. okay so most people are stillgiving 250 of ceftriaxone and it, a few people are alsogiving ceftriaxone 125 still, but virtually no one is actuallyusually using a quinolone or using cefixime 400 milligram,
that tablet formulation isactually back out on the market as of april of 2008, orcefpodoxime 400 milligrams po. okay, there wasn't reallya right answer to that one, but let me tell you what therecommendations are okay? because that one was justwhat's your practice? the recommendation is nowofficially go with ceftriaxone if you have ceftriaxone or if ceftriaxone's reallyunavailable then you can go with cefixime, butyou need to co treat
with azithromycin 1 gram po or doxycycline 100 milligramspo bid for seven days regardless of whether or not you'veeliminated chlamydia or not. and the reason is because ofthe concerns that i'm going to delineate on thenext few slides related to evolving gonococcalresistance. this is going to happen andthis is likely going to happen in the next decade of our life. let's go back to the fact though
that the gonorrhea treatmentguidelines also actually highlight one veryparticular fact. if you're pretty sure thatthe infection is solely at the urogenitalsite, yeah you can go with ceftriaxone or cefixime. but you know what, if youhave a sneaking suspicion or very high suspicion thatthe pharynx might be involved, and there it's theflipside, gonorrhea hanging out in the tonsillarcrypts, hmm,
probably asymptomatic90% of the time. only 10% of the time do you get that glaring exudativepharyngitis that you might even seejust like group a strep. okay? definitely asymptomaticcarriers running around. you really need to treat thosepatients with the possibility of oropharyngal infectionwith ceftriaxone 250. cefixime not enough drugto get really deeply into the tonsillarcrypts to be running
around in the serum long enough. the efficacy points reallydo drop for that site. okay, and here are someof the data that have yet to be published still. chris hall is stillworking on the manuscript but they presented itat a series of meetings and what i've done here on thisslide is summarized a bunch of things and theseslides will be available after the talk justnot beforehand
because then it ruins thefun of the quiz questions. so efficacy data for agentswith activity against gc, let me walk you through it. ceftriaxone 125, cefixime400, cefpodoxime 200 versus 400 were actuallytested in trials and cefuroxime 1 gram po. now granted thesetrials are not very big. i mean you just don't, insome places in the nation, particularly new englandwe don't have a lot
of gonococcal disease, andthank goodness for that, but they looked at the site, isjust the urogenital or rectal. ph includes pharyngeal okay? and what you see is forevery drug at every dose, pharyngeal infection is probablyconsistently the cure rate is lower for every drug, okay? except for maybe arguably,well it's still efficacious 94% of the time for ceftriaxoneat 125 and they haven't even completedall the studies for 250
but we hope it wouldbe better for that. okay and that, the sameholds true for cefpodoxime and other drugs, but other timeyou talk about the pharynx, it's just harder toget rid of the bug from that particular areawith the same dose of drug. so the concept here is that thecdc has promulgated a series of recommendations thatdual therapy may hinder the development any microbialresistance. the thing we weredoing all along
for our presumptive urethritiscases actually might have been driving the fact that we have yet to see extremegonococcal resistance against third generationparenteral cephalosporins like ceftriaxone whichif you think about, at the 250 milligramdose is a lot smaller than what you couldeven give for a rule out sepsis case, right? so 250 milligrams, arguably wecould still go up from there
and we may see that inthe coming years actually. dual oral therapy maybe more efficacious for pharyngeal gc treatment butthe data are yet to come in, so the cdc was unwilling inthis very evidence based series of guidelines to sayanything about the combination of cefixime and azithromycinorally. and what we do knowto be the case is that we have verylimited options in cephalosporinallergic patients.
but this really has to be yourcephalosporin allergic patient, not your peni-allergic patient, but your cephalosporin allergicpatient because the rates of cross reactivity betweenthird generation cephalosporins and penicillin areless than 1 in 20. less than 1 in 20 andprobably even less than that. and there are details withinthe std treatment guidelines to tell you thatyou as clinicians, when you use a parenteral thirdgeneration cephalosporin are
practicing in recommendedguidelines. now that having been said, if you're in a private practicesetting and you have some risk of anaphylaxis, nobody reallywants to own that burden. but you have options. but let it definitely besaid that the cdc has laid it out very clearly that thisat least is a recommendation to back you up that theparenteral was really the way to go.
the other parenteral medications that maybe would work wouldbe a drug like spectinomycin and it's a little scarybut that drug isn't even on the market anymorein the united states. and forget aboutdesensitization, cdc was crazy when they recommended that. it just isn't very efficient torecommend it for a lot of people who are more and moregonorrhea's actually being diagnosed in theprivate setting.
azithromycin remains inyour back pocket but it's in the tiny details ofthe gonococcal section, it requires two grams to actually effectivelytreat gonorrhea and we do have two mmwr's ofcourse from the western part of the nation california andhawaii usually being the first to see the signals ingonococcal resistance, okay? and they definitely havealready seen signals of high grade azithromycinresistance.
and treatment failureshave already been seen even to two grams, which, as you allknow, have you given two grams to your patients before inan effort to treat them? they tend to throwit up more too. it's not very well tolerated. so let me give you a littlebit of history as a reminder and the key point here is wejust don't want to relive this. so this is what we have donein the past with gonorrhea. well in the 30's it was actuallyeven sensitive to things
that weren't even arguablythings that were antibiotics but were more likepotassium, permanganate, silver salts, mercurochrome. in the 40's we finallygot to penicillin. in the 44 35% treatment failurewith sulfonamides which started in the 30's, so onlya decade later. and 72, the penicillinregimen increased to 4.8 million units per,plus probenecid but that was because it was inresponse to the fact
that a few decades before, although penicillin therapyhad started it was started at a lower dose and the lowerdose was no longer working. by the 70's, 80's--80's we're talking about tetracyclineresistance being reported. by the late 80'spenicillin's taken off the books and 2000's concern regardingrising quinolone problems which we don't tend to useas much in pediatric medicine because still almost noquinolones are available for use
in under 18 at leaston the fda books. so if you want to beofficial about it, we're not really supposed to beusing it with those patients. and where are we now? in the last two decades alreadythere have been many reports from japan and hong kong--so it always starts in asia-- and there have been manyreports of resistance to second generationcephalosporins then third generation oral cephalosporinsand now an isolate from japan
that was reportedearlier this summer that was resistantto ceftriaxone. so we know that it's probablywithin the next decade that we're going to seesomething that's resistant to everything that's currentlylicensed on the market. so what's happening now is cdc'ssponsoring a series of trials on dual therapy going backto older drugs in combination with the newer ones likegentamicin as an im shot. i can't even imagine howpainful that must be,
combined with thingslike ceftriaxone and we will see thedata soon enough. so if you're everfaced with a case that you think might be failingtreatment in front of you, you might be the first one, hopefully you won't be thefirst one in new england to find this-- it would be rare. it was probably going to be,first signal's going to be in california orhawaii, but if you do,
call your local departmentof public health. try to get a culture. hmm, not that easyto do necessarily. try to get susceptibilitytesting done and report to cdc for additional help reallymore than anything else. immediate, real-time help. you can use gonococcal naat bythe way, probably within one to two weeks for diagnosis from a nucleic acidamplification test.
the kind of dna test that mostof us are using to diagnose or screen for gonorrhea atthis point in our careers, like the aptima tma or thebecton dickinson gen-probe. all of those are nucleicacid amplification tests. so ala csi, you could use theseas rapidly as one to two weeks, by the way we think,one to two weeks after. clearance of gonorrheais faster than clearance of chlamydia dna okay? so you heard it here, thestudy has yet to be published
but the cdc's alreadyespousing this notion, okay? so you could use thosefor test of cure. they're not recommending it yet,only if you have a suspicion. and i don't know if we'regoing to be going back to this, but i sure do wonderif the resources and the thought behinddo i have a lab that i could send a gonococcalculture to if i wanted to should i actually ask thelab could they receive something sent in a culturette tube, wouldthat work to grow gonorrhea?
those are reasonablequestions to ask your lab if you're ever faced with thisquestion of is it resistant to something that you just gave. okay, so before we goonto the next case, questions about gonococcaltreatment because that wasreally quite a change in the 2010 treatment guidelines that you really should be doingdual therapy for everybody for a lot of good reasons.
i'll tell you there'ssome controversy about it. there's some experts inthe field who did not feel that that had enoughevidence to support. so not everyone's doing itand certainly departments of public health i don't believeare calling clinicians just to remind them not to do thatif they only use 250 milligrams of ceftriaxone for justa straight gc case. no questions? okay we're going tomove on to screening.
all right 16 year old runawayfemale brought in by dss for medical clearanceprior to foster care. she is asymptomatic butshe reports oral, vaginal, and anal sex with multiple malesin exchange for a place to stay. so you're going to offerthe following gonorrhea and chlamydia screening. a urine naat, a urine naat plusa rectal pharyngeal culture for gc and chlamydia. or a urine naat plusrectal pharyngeal naat,
that dna test or that rna test. genital swab naat, anypart, just a genital swab. a general genital swab plusrectal pharyngeal naat, or you're going to look up the 2010 treatmentguidelines for guidance. i gave you an out. okay, let's see what people say. you're going to use nucleicacid amplification testing and it looks like themajority of the room wants
to do just a generalgenital swab. wow the word is getting out. excellent. but there's still some people who are doing a smatteringof other things. you know what, doing anyscreening whatsoever trumps not doing any screening,so that is all good. all good. okay, despite the factthat all of you who know this and use this know thatthat's the cleaning swab,
not the actual sample swab. this is a bad picture, sorry. haven't had a chanceto revise that. chlamydia and gonorrhea naattesting is still not fda cleared for rectal and pharyngealspecimens, but now it is the preferredtesting method over culture because it is several percentagepoints better in terms of sensitivity and specificitywhile it used to be measured against culture, it's nota very good gold standard
if it doesn't detectas many infections. so specificity'sactually very good now with the newest generationassays that amplify chlamydia and gonorrhea dna and rna. so cdc was unable to arguelabs, the fda into approving it or getting any of the commercialmanufacturers to do the studies for extragenital sitesso they went another way. they twisted the arms of somemajor national laboratories as well as the fact thatthey twisted the arms
of all the publichealth laboratories that they alreadyhad connections with and they ran validation panels, and many public healthlaboratories across the nation willdo samples for you, or nationally every clinician in their back pocketcan force their lab to send their sampleto quest or labcorp. i own no stock.
i have no commercialdisclosures. those are the two majornational ones that we know about and the list is growinglonger every day that have run a validationpanel to sub, clear this testing for use for clinicalresults okay? so other tests are beingverified by other laboratories and the concept we'removing toward and the mmwr that i hope is stuck inqueue will be published in the next few monthswill be that the idea is
that the self collected vaginalswab may in fact be more, slightly more sensitive than anyother female sample, even urine, even the cliniciancollected endocervical swab. the self collected vaginalswab might be better. any speculation onto why? any guesses? they've run studies and they'realways consistently a few, a couple percentagepoints better. yeah?
>> it's just a couple of percentage pointsbetter though right? >> yeah just a few. so any screening beatsno screening, absolutely. and urine as a veryconvenient specimen, relatively less invasivespecimen, still a very goodspecimen to get. always in the 90's percent. those of us in the field havebeen speculating that women
in the bathrooms collectingtheir own samples are spending great quality time with theirvaginas twirling the swab like it always wassupposed to be twirled. if you read the packageinserts on all of these, you as the clinician aresupposed to have contact time with that area fora good 10 seconds, 15 seconds when you go to do it. but all of us asclinicians have been trained from clinician babyhood tomake the patient comfortable,
to minimize the time instirrups, to do all of this. and i think we carrywith that the idea that just touchingit is good enough. probably not. look at the package inserts. definitely look atthe number of seconds that the manufacturer saysthat it should be in contact with the tissues todo this correctly. okay so that's coming.
self collected vaginal swab. you heard it herefirst, maybe not. but, and also the ideathat you can get rectal and pharyngeal screening foryour high risk patients, okay? and i mentioned someof these here. i want to point out one otherthing related to repeat testing and repeat screening forhigh risk individuals who have already demonstratedtheir high riskiness by the fact that they've carriedthe infection before,
they are by definition ina sexual network that had that particular disease. so they are very highrisk for reacquisition within the next three monthtime horizon particularly for gonorrhea and chlamydia so there is a standingrecommendation from the cdc to repeat screeningthree months later. it's not test of cure,it's repeat screening. and by then, the deaddna should be gone, okay?
so that repeat nucleicacid amplification test for chlamydia is certainlygoing to work at three months, definitely for gonorrhea. is that clear? getting a lot of nods. yes? susan gray. >> so i'm just thinkingabout some of my at-risk, high-risk patientshaving oral sex. >> um hum.
>> do you think that i shoulddo an oral swab once a year for them? >> i kind of picked thedss case as most high risk because she was doingcommercial sex work. what it amounted to iscommercial sex work. the guidelines areactually not clearly saying that all adolescentsneed to be screened in the oropharyngeal region. why? probably the most commonorganism floating around there
out of chlamydia and gonorrhea,which is it going to be? it's going to be chlamydia. everybody who has ever donestudies on the oropharynx, even with the newergeneration of chlamydia testing, the newest generation ofchlamydia testing can't find it, doesn't, don't find it more than one percentagepoint of the time, okay? and moreover, itdoesn't hang out there as long as gonorrhea does.
gonorrhea kind offinds its happy home in the tonsillar crypts. chlamydia doesn't seemto do that, doesn't seem to be as transmissible. so current guidelines even from the cdc say veryclearly don't screen anybody for chlamydia but you canscreen the high risk individuals for gonorrhea and gonorrheaof course prevalence points, way fewer prevalence pointscompared to chlamydia.
so in many populationsit's not worthwhile, it's not consideredworthwhile to routinely screen for gonorrhea in the oropharynx. okay. let's talk aboutwomen and the rectum related to gonorrhea and chlamydia. do they have to reporta history of anal sex or will it be sufficientto do a genital swab, like a vaginal swab? will you capture the majorityof transmissible infections
for gonorrhea and chlamydia? for women it's arguedyes, you will. for men who have sex with men, it's clear the answeris no you don't. very clear. you'll miss over half ofthe transmissible infections if you don't swab theanus on the report of recipient anal sex, okay? but for women i thinkit's definitely clear
that one genital swab, probablythe vaginal swab will be reasonable and the best screen, although cdc's notsaying don't use urine. they're just sayingthe best screen. doesn't take optionsoff the table, it just gives you moreconfusing, confusing options. yes, atsuko [assumed spelling]was next and then i'll go to-- >> katie. >> katie. yes, whosename i just blanked on.
okay. >> if someone, so working inthe er there have been patients who come in and said ijust had unprotected- you know the bu student who drank too much last nightjust had unprotected sex yesterday wants to be screenedfor everything today, is, if they were exposed to gcor chlamydia will that show on the screening testjust 24 hours later? >> not necessarily.
we think it'll show relativelyquickly, and sometimes if you have enoughcontact time and whatever-- well it'll show in twodifferent ways atsuko. it's possible that they'recarrying their partner's material still and it'snot actually true infection in that case. regardless, that individual hasjust essentially described a higher risk situation foracquisition and transmission of stis and arguably what youshould do in that situation is
that person deservesscreening anyway. that person deservesscreening even if it was only aprevalent infection from previous to that day. so you can't be sure. you get them when you can. we are a very convenienceoriented service, those of us who are inadolescent medicine. so i would argue, goright ahead and do it,
but explain to the patientthat that may not be reflective of the day before, thatif they really want to capture the day before,even if this test is negative, coming in approximatelya week to two weeks after the event is areally good time to come in. and of course all sti's arenot created equal right? so maybe chlamydia and gonorrheayou can detect within one or two weeks with thesesuper sensitive naat tests, but what about hiv?
what's the windowperiod swallowed down to? what about syphiliswhich is much lower risk, much lower prevalence except inyoung men who have sex with men. and what about trichomonas? it would take a littlelonger to develop symptoms, certainly within the week or so. maybe hard to detect ifyou're not symptomatic. we don't usuallyscreen for it still. >> [i'm] doing a [inaudible]team rotation during residency
and being told that for cases ofpossible abuse that you wanted to get a cultureas a gold standard. is that still true eventhough these tests seem to be better than culture? um hum. great question. there are actuallysections of the guidelines that address sexual assault andthe usage of all different types of laboratory tests, std tests in particular forsexual assault.
that is based, herewhat's governing what we do as clinicians is at leastin part what is acceptable within a court oflaw to be, huh, something that a case cannotbe challenged on, okay? so in many courts of lawthey're finally moving forward and what they're doing in childprotection is they're wanting to confirm that one positive with another positivethat's a different test. so it's simply a differentamplified portion of the genome
to make doubly certain that whatever chlamydiatrachomatis they found was actually chlamydia trachomatisof the sexual variance that are screened for in thenucleic acid amplification tests and there wasn'tcross reactivity to, god forbid, somethingelse, okay? for gonorrhea, the crossreactivity dependent on the test can happen. so if you amplify it intwo different platforms,
some courts of lawwill now accept that. but it matters very muchwhat your local practice is and consulting with[inaudible] over and children's and my colleagues like bobsege and his team over at bmc, probably worthwhile tosee whether or not courts of law are starting to acceptit in massachusetts, okay? culture still remainsa gold standard because of the specificityrelated to it. if you grow it out on a plate
and you know darn sureit's neisseria gonorrhea, not neisseria meningitidis,not neisseria sicca, lactimica or anything other, yeah. so that's what you're runninginto here and i would talk to the colleaguespecific in that area. but it's definitely shifting. that's the good news. it's definitely shifting. there are, carolynblack published a paper
about the specificity in thosechild sexual abuse settings. it's a good recent paper,only about two years old. okay-- we're going to move on towhat amounts to ept right? so, not really aquestion about ept yet. i'm curious to knowyou in the audience, before today what was the mostcommon method you would use to treat partners ofchlamydia infected patients? would you encourage thepatient to bring their partners
in with them when theyreturn for treatment? would you, and youcan only pick one, sorry there's noway to pick both. give the patientextra medication to give to their partners? give the patient a prescriptionfor their partners regardless of what you knew aboutthe legal landscape? counsel the patient about theneed to self refer partners? call the health departmentbecause it's their job.
none of the above becauseit's definitely a health department job? so let's see whatthe audience thinks. what had you been doing? >> there's also the postcards. >> the postcards. or going onto a website,the website that's like-- >> [inaudible] >> yes.
>> inspot.org. inspot.org i think. it's out by san francisco. i should've put that up there. ah well, okay. well it looks like about halfof the population in here, about half of 20people are saying that they usually counsel thepatient to, about the need to self refer theirpartners for treatment.
great. at least you'redoing that right? because sometimeswe're only human. i mean unless you're anautomated robot you probably don't do the exact same thingevery time you have a chlamydia patient in front of you. hopefully the majorityof us the majority of the time are remembering that the index patient will getreinfected unless we get their partners in for treatmentsomehow.
so regardless of how youdo it, this is great. thinking about it is the key. it is the most common reportedsti in the united states and i think thoseof us in the field of public health are perpetuallyshocked by the volume of cases we've nowbeen discovering that are completely asymptomatic and we don't actuallyknow the meaning of that. we don't know how many of thoseasymptomatic women are truly
progressing on to pid ifwe don't capture okay? that is one of the greatunknowns surprisingly. but we're still going to do it. in the absence of newerevidence, we need to screen, and when we find it, weneed to treat as clinicians, not as public health people. that's a different concept. the number of cases inmassachusetts alone mushroomed, doubled in 10 years, and thisis definitely a testimony
to more clinicians getting savvyto testing and screening as well as better generation assaysthat detect it better. and patients with chlamydiainfection are at increased risk for reinfection if their sexpartners are not also treated. so what is this idea of ept,expedited partner therapy? well it makes sensethat for that patient, if you give them moredrug for their partners, or you give them a scriptfor drug for their partners or you tell them that theygo to a specific pharmacy
for their partners ashappened in washington state-- they do it pharmacydispensed stuff-- it's going to be at leastas good for reinfection, decreasing your risk ofreinfection as usual care which could've beentelling the patient to tell their partnersabout stuff. but cdc actuallysponsored a study on this and they proved it. it's sort of like, you know,hopping out of a plane,
do you really need the parachuteto make sure that you survive? well, yes. nobody's going to do astudy thankfully of that. cdc's not sponsoringa study on that, don't go away withthinking that. but they did sponsorstudies on ept and the ept trialswere really interesting because basically theproportion reinfected-- so the higher the bar is on thisgraph, the worse you're off,
okay-- was dropped, better, for expedited partnertherapy however you did it, best for gonorrhea. it wasn't statisticallysignificant although it was point estimate-wisedifferent for chlamydia and for the combination it wasdriven by gonococcal disease. so what have we donein massachusetts? we've done chlamydia disease. i'll explain, don't worry.
but here's this website thati was talking about, okay? this is the cdc.gov/std/ept. don't worry about copying it. a you can get it, byou can google it. cdc ept. it's muchfaster to get to it, okay? and this is a screen captureof, it couldn't be more than a week ago they justupdated this, and the date that they updated it isat the bottom of the page. most of the nation has gonegreen and this is entirely
because cdc pushed ept out asa legislative initiative state by state by state, okay? new england's all green. ah, but saying newengland's green doesn't mean that you can do the samething in rhode island that you should bedoing in massachusetts or you should be doingin new hampshire. you have to readthe dizzying details and under each state theysummarize what happens
with the details. and in massachusetts weelect to do chlamydia alone. okay, ept's supported bythe cdc and permissible in at least 30 states. that was 37 at last count. standard treatment for chlamydiainfection is one oral dose of one gram, ept shown to besafe and effective and at least as good as usual care. most states with long-standingept programs also have had no
reports of adverse events. california, been doingthis on the west coast for over five years, close toa decade, no adverse events. they had a hotline,hotline never got used. so here's our clinicaladvisory in massachusetts that connecticut justborrowed by the way also, and we borrowed new york state's because we were not thefirst off the block here. and in august of 2011 weput it on our dph website,
my own systems website. it's not always that easy togoogle my own state department of health website, so if any of you have any troublefinding this thing, here it is. it's the clinicalprovider notification. it went through a number ofclinical provider emails, listservs, but we're not verygreat about getting in touch with docs and nurses whoare actually prescribers. and connected to that very samedocument is the partner patient
information brochurethat should be going out. and this is what we'd liketo happen in massachusetts and most states that haveimplemented ept have requested that the provider who doesit give a patient a very specific brochure. we didn't say you had togive the one that we have on dph website by the way. you have to give itor its equivalent. it's in a q & a format.
it's been vettedsix ways to sunday for like a sixthgrade reading level and there's definitelyencouragement to follow up with clinicians, not to bypass clinical carecompletely, those partners. because really that'sstill the gold standard. and no state in the nationsays oh you providers you have to do ept. no no, it's always couched
as if your patient's partnersare not likely to come in for care or your patient'sgetting repeatedly infected, ept would be a considerationand a recommendation from a departmentof public health. voluntary, not required. that's that point there. and in massachusetts wedelineated three options we recommend, but we didn't takeother things off the table. it could be up to theclinician's imagination.
you can write a writtenprescription or we have a pharmacy board ofregulation carve-out that says that if you write ept in thetop line of a paper script, you don't have to writea name and you don't have to write a date of birth. every other script, every otherprescribed medication needs to have the two identifiers andeven sometimes address i think in the board of registrationin pharmacy saying that the prescriptionhas to have it.
ept for chlamydia, carved out. if your electronic medicalrecord system doesn't permit this, what very clever communityhealth centers have just started doing is creatingept the dummy patient which is really interesting. we'll see if this works. we're going to try to replicateit in a couple of places and see if this actually works becausethen the patient still has to give it to the partnerand the partner has
to carry it to the pharmacy. and then at the pharmacythey still need a name and somebody to pay for it. so somebody still has to admit to be non-anonymizedat that point. and there's one other wayyou could do the written prescription or directdispensation of the medication a few extradoses for all the partners as long as it always trotsalong with those brochures.
i think there's a safety factor when you make somebodytake a script saying ept in the top line althoughthere are more barriers for the partner to get the drug, at least then the pharmacistcan also offer counseling. and the way pharmacies arerolling out in massachusetts is in theory that'syet another point where they can give this partnerdelivered patient information or they can give thisinformation, this clinical,
same frequently askedquestions thing. okay any questions about that? ah, maybe i shouldanswer the question about why just chlamydia. do you want to know how thisthing passed in massachusetts? it passed as a budget rider ona budget that had to be passed. for six years it never gotout of conference committee and then finally al demariathe state epidemiologist works with kevin cranston who's nowthe director of the bureau
of infectious diseases andwe work with the legislators and they basically tacked iton to the august 2010 budget. it wasn't totallyunder the radar screen. planned parenthoodwas fully pulling in grassroots support for this. a lot of legislators gotcalled on ept for chlamydia. but somewhere betweenthe senate and the house, it lost the language that al andi had written in there related to the fact that we wanted
to make expedited partnertherapy really for more than just sexuallytransmissible diseases, but for diseasesdangerous to public health, like neisseria meningitidisor pertussis. i mean how many of you as pediatricians have everprescribed sight unseen tons of extra doses of azithromycinfor a family of an index case that actually has pertussis? that in theory isnot explicitly legal
within the statethat you did it in. it's unlikely to beexplicitly legal. but we do it anyway. we do it in our patient'sbest interests. we do it in our family'sbest interests. so we have to be careful. you should be awareof what you're doing. but i'm just saying, we tried. if we can prove that it worksfor chlamydia, that it's safe
for a few years, ithink we'll be able to broaden the legislationand then bring it down to the regulatory level because regulations areeasier to change than laws. regulations can beeasier to change and we'll change itlater on down the line. >> so [inaudible]-- >> yeah? >> that patient informationpacket probably says something
about if you have knownallergies to this medication or have any questions aboutyour allergies, call us or something like that? >> absolutely. do not take in verybig, bold faced letters. absolutely. it's definitely one of thethings that was framed, and again we can'ttake the credit for it. 37, 36 states went ahead ofus on this endeavor, okay?
so we borrowed a lot froma lot of other states. we learned a lot from otherstates and how they implemented. okay any other questionsabout ept? okay i think we still have somemore time to talk a little bit about herpes, what do you think? all right, so let'sswitch gears. case history, 18 year oldcollege student comes to you with the results of herherpes select focus elisa. hsv-1 specific antibodynot detected.
hsv-2 specific antibody, detected with anindex value of 2. the lab report states thatanything above 1.1 is positive. she has never hadany genital symptoms. she wants to know what totell her husband who as far as she knows doesnot have herpes. he has been her onlylifetime sex partner. she has had no otherhistory of std. what is the next questionyou would want from her?
what would you, what additionalinformation would be helpful? would it be helpful toknow her race ethnicity? which lab she hadthe test done in? whether she is tellingthe truth about her number of previous partners,or all of the above? >> wait i'm confused about whydid she have that test done? >> ah, it's an inherited thing. she may have gone inas a worried patient, asked for std screening and inwhatever facility she was in,
she was also offereda herpes screening. or she maybe heard about thescarlet letter disease herpes and she got screened for herpes. but you're absolutely right,it's not recommended to screen for herpes in anasymptomatic individual because what then do youdo with that information? great question. and that is exactly the point, but you have inheritedthis case.
so what would be the nextthing that you're stuck with? what would you wantto know about her? give me a sense. all right, let'ssee what a little under 20 people would've done. yes, that would be nice. the truth of the situation. it's always niceto have the truth. if to be the windowor the fly on the wall
in that patient's bedroom. well, maybe not. okay, her race ethnicity'sactually really important. we do not live, wheresti's are concerned, it's not a color blind world, atleast not to sti's so i'll get into that in a second. and here are the data to supportsome of the concepts here. and several of you in the roomhave seen me display this slide before but i'll walkyou through it again
because i think thedata are so valuable. it's from fuji xu's articlein jama that was published in 2006 based on enhain's[assumed spelling] data arguably a good population prevalencesampling in the united states of america, national health andnutrition examination survey. and what we're doing is we'relooking at lifetime number of sexual partners increasingacross the x axis here and on the y axis isthe proportion of people with herpes 2 positivityin the bloodstream.
seropositivity, okay? so for every set ofstrata of lifetime number of sexual partners, what yousee is that men versus women, the men have lessseropositivity than the women, but for every stratawithin the age groups, you see that non-whitepatients have higher rates of seropositivity even at thesame number of reported levels of sexual partnershipsprevious to that, speaking a lot to sexual networks, to sexualpartnerships, to dyads,
to relationships, towho you hang out with and who you have sex with ithink, and your risk therefore for acquisition and transmissionhaving nothing to do with actual individual behavior. something to think about. all right, herpes prevalence interms of age group over time. just a reminder, no matter whichyears you look at with enhain's, in general, patient populationby the time in the united states of america you reach the ripeold age of your fifties, you,
the majority of the time80% of you are going to be herpes seropositivefor herpes serotest 1. the one that we used to call theabove the belt herpes, herpes 1. okay? not always above the beltbut usually above the belt, 60% of the time still. herpes 2, it's a quarterof the american population by the time they reach theirthird decade has become herpes 2 positive and only atenth of those people, even less than a tenth of thosepeople ever show symptomotology
from it. but they're sheddingit and transmitting it and there are diseaseoutbreaks related to transmission from this. so there are argumentsback in the field. so what's your advice? you've inherited this patient. you would never havedone sero testing anyway because you knew the guidelineswere not to do serotesting
in an asymptomatic 18 year old, but you've just gottenthis result anyway. and so are you going tointerpret it for her? you're stuck holding the bag. false positive? she has herpes 2 and just neverhad a symptomatic outbreak? she's probably seroconverting having acquired it from her current partner? or actually you're not sure.
you can vote you're not sure. how are you goingto counsel her? it's a tough case. all right, great. let's take a look. all right, many ofyou are convinced at this point she has herpes 2 and just never had asymptomatic outbreak and some of you are thinking not sure.
about a quarter of you arethinking she's seroconverting. great thought given howlow the actual number was. i don't remember if itwas 2 and the cutoff for positivity was 1 or 1.1. okay, so let me goback to this graph. let's say that we agree for thesake of argument she's white and she's only hadone partnership. her odds of carryingherpes 2 at the age of 18 are probably nogreater, as a woman,
at the age of 18 probablyno greater than 10% and arguably considerablylower given that she's had only one sexualpartnership in her life. okay? so when you calculatethe positive predictive value of this particular test, over half the time thistest is going to fail. it's wrong. you have to actually dothe numbers and go back to the way we calculatestatistics for sensitivity,
specificity given the prevalence of the populationserotest positivity. but over half the timein this particular case with a white woman who has hadonly one sexual partnership in theory it's actually, oddsare it's a false positive. very interesting numbers. you have to run thenumbers to believe it. yes? >> what if your strong suspicionwas that she'd had more
than one sexual partner, shewasn't telling you the truth? >> even then, until you reachserotest prevalence on the order of greater than 5%, many timestests don't perform nearly as well as we as clinicianswant them to perform. you really have to run thenumbers given that test, and given a guess which we have. we have good guesseswith enhain's data. you could take thepopulation's sero prevalence and give it a good guessand calculate the true,
positive predicted valueof that positive test. but is it arguably, you knowthat classic two by two diagram? test positive, test positive, disease positive,disease negative? which box is she falling in? that's what you're thinkingof here and we as clinicians, we want to believein these lab tests. we order them. we wouldn't do them
on our patients unless wethought we had some belief, but it turns out that unlessyou reach higher percentage prevalence, it'svery likely that some of these tests are not very good for true positivepredicted value. and we're talking about teststhat are actually very good. the herpeselect in particular, 90's percent sensitivityand specificity. over 95%. and that's what i'mcalculating positive predicted
value off of. this type of sensitivityand specificity. over 95%. still, run it on your100,000 patients and you'll see that over half the time for thisparticular patient it's actually the wrong answer. okay, if your patient isreally wanting to know, there is one more thing. the western blot-- similar to the western blot theway the hiv tests are run,
there is a westernblot assay now out that's commerciallyavailable-- i shouldn't say commercially. it's rhoda ashley's lab out inthe university of washington and you can actually havepatients who can pay, pay for this western blotfor confirmation or denial of whether or not this singletest is actually the true test or the true answer. but i'm going to giveyou one more hint, okay?
although the package insertstates that an index value of 1.1 should beinterpreted as positive, several experts usea cutoff of 3.5. and the positive predictedvalue is as low as 38% in college students with verylow hsv-2 seroprevalence. if the seroprevalencewas only about 3%, the positive predictedvalue was 38% meaning, 62% of the time thetest was wrong. that's seriouslyfood for thought.
i think about it all the timein relation to other tests that we do as well and howmuch test ordering we do. so the issue here is reallyherpes serologies have a lot of limitation. they don't tell you how long thepatient is infected, if they had or will have symptomsever in their lifetime, how likely a person isto shed asymptomatically, and more recent studiesshow that those people who are serotestpositive, serotest positive,
never had an outbreak, neverhad a genital outbreak. clearly shedding. that's the latest studyfrom over the summer that got published outof those herpes experts. anna wald is one of them,larry corey's another. they are clearly shedding evenif they've never had it before. that's why there's so muchtransmission and that's why 25% of the population islikely positive indicating that they've mounted somesort of immune defense.
it's merely a marker of exposurenot a marker of disease. false positives we'vetalked about, and false negatives canalso occur with these tests because it takes so longfor antibodies to develop. remember again, antibodiestake six weeks, sometimes maybe as short as four weeks to develop following aprimary infection with herpes and this we always knew. so the testing issues arelegion, but what's coming
down the pike is somethingeven more confusing, the fact that there willbe a genital ulcer pcr. there is one, it's justthat most of us don't know where to find it right now. becton dickinson doeshave a genital ulcer pcr-- did i get that right? yeah. becton dickinson'sassay is amplifying for herpes dna specifically as anucleic acid amplification test, but the test is now licensed--the news came out this summer--
for genital ulcer disease. active genital ulcer disease,not licensed for shedders, okay? or asymptomatic individuals. just a reminder, othertests that might be useful and these are other testspeople think about igm, igm doesn't really workvery well for herpes. it turns out that people willremount an igm defense even if it's upon reactivationdisease. so igm doesn't tell youabout recency of disease,
the way we learned in medicalschool or nursing school that igm was usually the firstmarker, only got mounted once in a disease lifetime. no no no, it's much morecomplicated than that. igm can actually be mountedupon reactivation of infection. so the igm specific assaysare not specific first of all, nor should they beused for this purpose. okay, so when could youuse serology though? patients presenting for anstd evaluation especially
if multiple partners, hivinfected, and msm at risk for hiv because hsv and hivtied associated transmission acquisition issues,different issue, okay? but it's not recommendedfor routine, prenatal, or universal screening. and the arguments for hsv-2serology screening though are that the experts in the field who are really pushing this ideaare that you could self identify and potentially cutdown on transmission.
you could self identify,cut down on transmission, and they may be motivatedto protect partners from what amounts to a lotof asymptomatic disease much of the time but can be verystigmatizing and harmful in those individuals who do actually have genitalulcer disease from herpes. okay and those are the argumentsagainst-- unproven benefit, effect on sexual riskbehaviors not perfectly known, potential significantcosts, increased demand
on the healthcare system,unnecessary c-sections. if a woman is labeledherpes positive, what does that mean thenext time that she goes to, the first time that sheever goes to deliver? i want to highlightone new treatment issue from the 2010 treatmentguidelines and that is the addition of famciclovir 500milligrams po times one, then 250 milligramsbid for two days
as a new regimenfor recurrent hsv. nothing else changed inthe treatment for hsv. does this arguablyaffect any of us who do adolescentand young adult care? yes. if young adult,famciclovir is licensed for use in those 18 or older. 18 or older, okay? so it's another short course onthe long list of short courses that you could use totreat recurrent infection.
and the short courses are soshort at this point that some of them are even only oneday's worth of therapy. so i'm not sure whyyou would choose to do this one particularlygiven that recurrent therapyfamciclovir, that's that new one, or 1gram po bid for one day. you could use that. acyclovir remains thepedi one of choice. valacyclovir is actuallylicensed for use
for genital herpes in thosewho are of pubertal age and up. interesting fda approval. and the first clinical episodetreatment, okay this is all in the std treatment guidelineswhich you can download easily, hasn't changed at all. tends to be a littlebit longer treatment or until clinical resolution. seven to 10 days or untilclinical resolution. don't forget, this isnot new news in 2010
but in 2006 theyamplified the news about daily suppressiveherpes therapy for people who have recurrentgenital ulcers. those, the few peoplein the population who do have recurrent, consistently recurrentinfections, there are a number of safe regimens known upto at least a year for use. and should discussthe need annually to continue therapywith patients.
now i'm just going to do onelast moment on herpes here and pause to laugh at thecdc std treatment guidelines which i did mention to you earlier also giveclinicians a whole host of counseling messages that theymight do with their patients in the 15 minutes that theyhave with them in the office. um hum. okay so you are supposedto discuss the natural history, the first episode, encouragepartner notification, abstain from sex when lesionsor prodrome are present,
condoms reduce therisk of transmission, transmission can occur whenasymptomatic and the risk of neonatal infectionwhich is new in the 2010 guidelines shouldbe discussed with men and women. and you should counsel pregnantwomen not known to be infected with either hsv-1 or 2 toavoid genital exposure. asymptomatic persons, what doyou do with their diagnosis? this is what you can do. hsv-2, it goes on and on.
and i got to tell you that ihad a long conversation with one of the great nurse practitionersthat i happen to work with, alison marshall, she works over at the south bostoncommunity health center and set up their adolescentpractice i think over there with a whole bunchof other people, and she pulled thisreally great study. a study from 2004 showedthat patients were satisfied with their care if they hadat least 15 minutes face time
with their practitionerso you don't need to spend hours counselingthem on every point that the cdc suggeststhat you counsel on, but the key is probably bringingthem back for that follow up visit to clarify afew key points and say to the patient, sowhat did you hear? the day that i gave youyour herpes diagnosis, what did you really hear out ofthe things i tried to tell you? what is your impression?
what are your questionsnow in follow-up? because much of the initialinformation we try to give them, we dose them up with, we inoculate them,they're not hearing. 48 hours after the visit, gone. and her suggestion, she came upwith this really nice pneumonic. the four 2's just for theinitial visit-- four t's. transmission. treatment.
maybe mentioning it toyour partner, maybe not. and you as the clinicianreally being a therapist with your patient to reallyunderstand what does this disease mean forthis patient, okay? that could be differentfor every patient. okay. yes? go. >> well what aboutwith adolescents where they might be kind
of changing their sexualpartners maybe more often than other age groups? do you offer the dailysuppressive therapy in hopes of kind of decreasing atleast transmission even if they're not havingfrequent genital outbreaks? >> no. the shortanswer is probably no. i do do it based on the people who are having frequentoutbreaks. i maybe don't personally waitfor six, i wait until i see them
on a track because patients whopresent one way tend to present that way over and over andi will have a conversation with my patients about whento start suppressive therapy if it's the rightchoice for them. it's not mandated. but definitely it's thatback and forth relationship with the patient that willclue you in to whether to not it's worthwhile. i basically at this point sitatop the knowledge that a lot
of herpes transmission happens, but that's why we haveimmune systems also. it's not entirely theclinician's burden to stop every herpestransmission event. okay, i think in theinterest of time, is it 2:40? are we going to have to stop? it is this 2:40. okay, let me see whatpossible messages, i think we can skipthe trich one.
i think most of you knowwhat to do with that. the only comment i would'vehad was just the fact that if you think youhave treatment failure, 3 to 5% of the time trich canbe resistant to metronidazole and there's a phone number inthe std treatment guidelines that you can calldown in georgia. they will send you media. they want your protozoanparasites, okay? they want to study thoseprotozoan parasites.
so if you think you have aresistant trich, goodness, call the dph or call thenumber in the atlanta number and you'll get theparasite lab at the cdc. it's not the std lab-- eventually you'llget a hold of them. you'll get some mediaand you'll be able to send it down for testing. in the meantime, the treatmentguidelines do tell you about how to handle your patient with,that may have been resistant
to that 2 grams of trichomonas or may have justhad reacquisition or reinfection, okay? either way, what'syour next step? do you treat with twicea day metronidazole? that's what i justdid with a patient. that's one of the options. do you move to tindamax, tinidazole whichis quite expensive?
hard to get, priorapproval required. could justify it. you have options. they're all listed in thestd treatment guidelines. so let me leave youon that note. some resources thatyou can have here. there are std resources at thedepartment of public health. all departments ofpublic health. there are treatment guidelines.
that having been said, istill want to drive all of you in this room moreand more to the web because the web isthe living document. so as gonorrhea resistanceraises higher on our screen, as changes come, the cdcis staying quite accurate on updating the website evenif they're not very good at publishing mmwr'svery rapidly. they are very good at updatingtreatment recommendations right on that website, and thewebsite is actually very easy
to navigate for treatmentguidelines related to stds. and the last resourceis my own organization. we are one of those eightclinically funded organizations to do the national network ofprevention training centers to keep clinicians up to date. so if you have colleaguesin other parts of the nation that haven't heard about usyet, come to one of our courses. you'll be sold, i swear to you. you'll be sold.
and they're all around thenation and they're also in web form, so go to ourwebsite too for much more than you would ever want to knowabout hpv, syphilis, chlamydia, herpes, hiv, gonorrhea. i'll stick around for questions. [applause] thanks somuch for your attention.
