natural treatment for cough illness disease

>> so this first slide is from dr. quinn's benefited. so this is the logo of the course, are the brooklyn bridge. it's connecting medicine and the folks here have heard me talk about this too many times beside the fact this was taken by my grandfather.

so this is the organism which as a medical student, i saw that in a stained section and decided i wanted to be a micro biologist. i didn't, i became a liver doctor but that sort of become microbiology these days too. so today's topic is self-evident.

there was a time when the great parasitic diseases of man were looked upon as the great neglected diseases was the phrase. things like malaria, a whole range of parasitic diseases, which affect millions and millions of people.

i don't think that sexually transmitted diseases was on that official list although some of them may have been, i don't think so. but this is a group of diseases that have been with us for lord knows how long and it's a panorama that keeps changing.

amazingly enough, the pathology changes. i'd like to say a word about that and with it the severity treatment has dramatically changed and so has epidemiology. although we think that society has advanced in many ways, through communication,

electronics and everything else, there are areas that sometimes defay our cultural sensitivities if that's the politically correct way to put it and they get neglected. i wonder if we'll find out whether our speakers today consider that the sexually

transmitted diseases are moving out for a moment, hiv, hbv and hcv, whether those diseases are great neglected and if so why. let me give you a brief example of what i think of along this changing panorama. let's talk for a minute about syphilis.

it's been blamed on every country in europe, it was thought to be imported from the new world, maybe it has been, i don't know. the french called it the italian disease, the italians called it the spanish disease and the spanish called it the french

disease but it seems perhaps to have come from the new world although where it sprung from there is not quite so clear. but the point is with its introduction into europe and as population density increase, syphilis became wide spread, was highly infectious and was severe

and killed people. it led through different stages which perhaps we'll hear a bit about today, and at least in the early stages was very infectious. but then in late stages, it wasn't so much infectious, probably not at all, but it was

a disease involving the big blood vessels, particularly the aorta which ballooned out something called an aneurism where people lost their mind. i remember being shown in medical school there was a man who was convinced he was napolitano bonapart having other

abnormalities. those disappeared or we will hear. it is known if you know tuberculosis you know medicine. the great pretender because it literally could affect anyone and present in a wide variety of spectrum in those days prescans

and presla16's and other diagnostic stuff. you had to use your head more than the lab sheet and it could be very difficult to know what one was dealing with. there was no real treatment for it although it was shown heavy metals, i don't know where it

came for example you spend one night with venus and a lifetime with mercury. mercury was quite toxic. that isn't a funny thing, sometimes bad things are done for good reasons but where it comes out of it has nothing to do with anything else.

for example, the observation that mercury was a diuretic, now we know how that works, came about through the treatment of syphilissic. then the amazing story onef the great dramas of medicine, those of you who like to read medical history whether it's in

the form of a novel or the real thing, you should read about paul urlich, famous physician, chemist. i think he was a chemist only. i don't think he was a physician but it didn't matter those days. he won the nobel prize for his concept of the magic bullet.

and this is apparently the first time anyone had the idea that you could take something and modify it so it would kim the offending organism but not affect the host. and the organism he was interested in was this trip knee ma so he could see it, he could

give it to rabbits, he had models he could work with. and they knew that heavy metals like mercury could kill the organism but the trouble is it also killed the host or the cells. they found the arsenic also did the same thing so he said maybe

i can modify arsenic chemically so that we targeted a magic bullet to the organism and not to the host. 606 compounds later, he and his japanese colleague -- i believe was his name, came up with the compound -- for organic -- which would give to syphilissic

patients. it was an effective treatment until penicillin came along in the 1940's. and that was an amazing phenomena but the concept of magic bullet is with us today in all forms of specifically cancer chemotherapy.

another nobel prize was given to a german scientist with people with syphilis and the treatment didn't do much good but he gave them malaria and the idea was hyperthermia was good for it. well it took a long time to undo that. but that's probably, probably

one of the great moments of the nobel committee. so what's the point of this? what am i trying to get at? these diseases change. n't in one lifetime they change in terms of the way they appear in patients. the organism's changing, the

hosts are changing, the environment is changing. and the level of education and sophistication in dealing with them on a public health level goes up and goes down and with overcrowding and greater populations and poverty and everything else thrown in, we

now have epidemics. so one of the themes we'll hear discussed today is why sexually transmitted diseases i would argue are amongst the great neglected diseases and are epidemic in our population but we are blinded by on the one hand the tremendous need to do

things in other diseases that more classally are epidemic and lethal and other by some of our social political and other concepts which tie our hands. and the treatments, treatments that are directed at an entirely different directions which you will hear about.

freaments called vaccines. so we are really absolutely delighted that our two speakers, tom quinn and jeff cohen who are leaders in this broad field have been willing to come and speak with us. thompson quinn is head of the national hiva research of the

laboratory of immunoregulation on the niaid. he's also the associate director for international research for the division of intramural research at niaid. and for three decades, he's been a professor of medicine in pathology at hopkins and in the

departments of international health epidemiology, immunology and molecular biology. he's been involved in classical studies, these classical studies of hiv, clinical and epidemiological investigations, 29 countries all around the world.

he's involved extensive collaborations and developments which are influenced our entire thinking about the natural history of these diseases and the problems that are involved in trying to deal with them. so we're very grateful to you for being willing to come.

and our second speaker, jeff cohen who is known to our group because he kindly spoke earlier in this series. jeff got his medical degree at johns hopkins, interned at duke, spent time in boston, receiving more training and clinical training in infectious diseases.

was a research fellow in medicine and microbiology, came to the nih in 1990. and is the chief of the laboratory of infectious diseases at the nih. of his many contributions, the classical, now classical studie on herpes viruses and means to

protect against them are one of the really hallmarks in modern infectious disease. so we're very grateful to both of you for being kind enough to come and speak to us. >> thank you very much for that kind introduction, and it is a pleasure to be here.

in thinking about the topic, sexually transmitted diseases, i have to totally agree this is one of the great neglected diseases of mankind and has been neglected primarily because of the stigmatizing effect. in fact for years most of you know it was called venereal

diseases and it was a certain stigma that was attached to and it's really only been in the last three decades that that has shifted over to more modern terminology of sexually transmitted diseases or stds for short. but the iom took this up about a

decade ago and there's a report on it from the institute of medicine. and they entitled it the hidden epidemic. because so many people as you will see become infected with these deapsz and are unaware that they're infected.

they're not screened for it. and they unknowingly and unwittingly transmitted to their sexual partners over a period of time. and the amount of morbidity if one were to put economic labels on this are truly astronomical. and it sort of defines public

health today, that we really still in 2013 are not really confronting these diseases. and i'd like to take my time to actually impress upon you about these continuing epidemics. that they are not going away, they are persisting, they are aiding in the spread of hiv,

which does get a lot of attention, gets a lot of funding. and they cause a considerable amount of morbidity associated with these diseases. so i thought i'd start with a case. this is a case that i saw about

25 years ago, but it really drives a certain point immediately home. so this site i went to johns hopkins and i was working with the ftd clinics in baltimore city we were screening for chlamydia and we were confronted with this case.

it's an 18 year old young girl presented with lower abdominal pain, fever, chills and she denied any other symptoms. she was in a monogamous relationship with a male partner who she had been with for six months. she was febrile, 39.3 blood

pressure was normal, heart rate was tachycardic and had a respiratory rate of 20. now, on examination is where most of the signs were prominent. as you palpated her abdomen on depalpation, she had excruciating main and on pelvic

examination she had extensive cervical motion tenderness, was really quite painful. and speculum examine revealed an inflammed cervix with the mucous discharge from cervical os. we suspected she had an intraabdominal infection going on and ordered an ultra sound at

the time. that abdominal ultrasound showed multiple air fluid levels and consistent with a tubal ovarian abscess. the abscess continued and the obstetrician gynecologist was concerned they could are you --

rupture and cause sepsis. she ended up having a full hysterectomy bi-lateral and was permanently in in infertile forthe rest of her life. she's at 18 years of age. it raises the question how can this happen. well it turns out we were able

to determine this through the pathologic examination, but this is a specialized photograph looking in the fallopian tube of another while had been infected with chlamydia -- chlamydia is a silent infection in most men and women. but like micro bacteria it's an

intracellular organism that the body tries to wall off and induces fibrous adhesions within areas in which its infecting. so in this woman, what you're looking at are these fibrous adhesions within the fallopian tube itself. if it starts to occlude, then an

awe reasonable start to grow was of the lower oxygen tension and you start to get abscesses that are filled with -- other anaerobes if they comure will cause sepsis. all of this is a hundred percent preventible and treatable if caught early.

if not screened and not treated, women in particular but men as well, will suffer the consequences of these adhesions and suffer chronic pelvic pain, infertility and other consequences. so we nick named the pelvic inflammatory disease or pid.

by definition, it's inflammation of the upper gentle track it includes -- tubal ovarian abscesses like the patient i presented, and a pelvic peritonitis. the stds that can cause this are not limited to just one organism.

so we could be chlamydia -- the most common bacterial std in the united states. or it could be caused by gonorrhea, could be caused by vaginalitis -- it is the one time that one antibiotic is not going to work for a woman who presents with this.

this is a surprising statistic in most people. it is by far the moan common cause to a gynecological visit to the emergency room throughout the entire united states. so a woman who present with lower abdominal pain gets classified in this and if she is

sexually active and could have been exposed to one of these stds that it's almost mandatory that she be screened for it. and unfortunately, it is the young adolescents and young adults that are at greatest risk.

more than 50% of all these cases occur in women under 50 years of age. so let's take a step back. this was somewhat of an extreme case but i wanted to drive home the importance of these diseases, and the consequences in which they occur.

now the world health organization has a branch that tries to estimate how common are these diseases. so they picked four. and tried to do a worldwide estimate of these. now in this actual nawlg of stis, sexually transmitted

infections, we'll use these interchangeably with std. but there's four we could diagnose quite easily and treat and prevent the adverse reactions that individuals have. but first this chlamydia -- 105 million new cases a year. that's incidence, 105.

gonorrhea, about the same number. they estimate 106 cases. syphilis which we just heard about, which has been around for eons forever, were at a level about 10 million new cases every year. and a very common cause of

vaginitis in women, to trick no, sir vaginallist we have 276 this is truly neglected in the sense starting off from the earlier comments and easily diagnoseable and treatable if we put enough attention to that. well let's turn our attention to our own domestic situation.

why did the institute of medicine call this the hidden it's pretty much reflected here. so where is all the attention being focused today. it's hiv. and it's deservedly so because it's a fatal infection without treatment.

but now we can keep this from being a fatal disease and causing a life long infection. but we estimate about 56,000 new cases occurring every year in the u.s. syphilis, we're still seeing about 32,000 new cases, and i'll show you some of that

epidemiology. but if you start to go down for the base of the pyramid, it's trick mieses which women suffer the most consequence, about 7 human pat loam awe virus to which we have vaccine that's totally preventive but yet we estimate 6.2 million new cases a

herpes which you're going to hear from dr. cohen 1.5 estimated new cases a year. and then of course chlamydia which is a reportable disease in it is the number one reportable disease in the u.s. in terms of absolute numbers. we're focused on flu, we're

focused on hiv, we focus on hepatitis and other infections. if you look at note fiber diseases in the u.s., the number one reportable disease is actually sexually transmitted disease, that's chlamydia. gonorrhea estimated at about 700,000.

hepatitis b to which we have a very effective vaccine, we still see 73,000 new cases a year, again acquired sexually. so if you add those together, we see about 19 million to 20 million new stds occurring in our country each year. more than half of those, in

people under 25 years of age. it affects the poor or the lower social economic status so it's now ranked as probably the number one or two health disparity issue which often ten times higher in african americans than whites. stds increase the risk of

acquiring hiv. the institute of medicine tried to put an economic number on it so as to give it some need to congress. and the number they come up with, not me, but they are coming up with these estimates is about $17 billion a year in

treatment or adverse complications. this is not including screening. a few more facts about these stds as they affect the u.s. first of all they occur in both men and women. one of the leading causes of tubal factor infertility.

and that's about 14% of all couples in the u.s. have tubal factor infertility probably related to an std they acquired some time in their life. five and-a-half million people infected with hpv each year. it could be as high as 20 million people carrying hpv and

i'll show you statistics on hpv is of series concern because there are several types that actually cause 80% of all cervical cancers, the number one or number two malignancy facing women worldwide. and in the u.s. about 14,000 cases occur each year, and yet

we have an fda licensed approved vaccine which was developed here at the nih. so let's take a step back and schematically look at the world of stds so you have an individual, they get an infection from another partner. if it's a woman, the worry is

that that will migrate to the upper gentile tract. we call that can lead to tubal infection and fertility, fibrous adhesions for ectopic pregnancy, chronic pelvic pain and other severe consequences for those if the woman becomes pregnant or if it spreads to the fetus or at

the time of delivery, it can result in spontaneous abortion or low birth rate. it has been shown a number of these infections, particularly syphilis actually and the gentile ulcers and herpes in particular can serve as a s indemic seemed to emphasize

spread of boast of those infections together. if the woman is carrying chlamydia infection or herpes at the time she delivers those infections will be delivered directly to their infant at time of delivery. and of course i mentioned the

hpv causing cervical cancers. so these are not just infections that cause a discomfortable burning on urination or a little drip as we used to call it. these are very serious infections, if not dealt with appropriately. let me start with a few of them.

i started with that pid case, the leading cause of pid is usually chlamydia. as i showed on that earlier slide, there's about 105 million new cases of chlamydia a year. 3.5 million of those are in the u.s., it is the most frequentl reported notifiable disease in

we've done studies with partners of these individuals who have chlamydia. we've treated them and then we brought in their partner in more than 50-60% of the partners will be positive. and very high perinatal transmission rates.

in fact, every single baby in the united states when it's born, gets eye drops to prevent the congenital ocular infection of chlamydia and gonorrhea that could be acquired. it's better to screen the woman when she's pregnant before she delivers because this is very

easily treatable disease. so we really mandate that that occur. of course, untreated infection that aren't screened for and aren't treated go on to cause these more serious diseases. we do not have a vaccine currently to prevent chlamydia.

it is one that the niaid is working very hard at, it's within the rocky mountain laboratories has a prototype. and there is hope for the horizon that we will eventually develop one. so what's it look like in the u.s.?

are we beating this infection? and if you look at this from 1991 to 2011, it doesn't look too good. in fact it's on the rise. hence, the hidden epidemic. it just is not getting the attention that it deserves to get.

you might see it higher in women than it is in men and you can see that on this particular graphic if we look at a case rate per age group and the age group being shown right here, 15-19 year old girls, 20-this year old young men. this is astounding, this is per

hundred thousand population. then it drops off which we think is reflection of acquired immune but some people say it's a change in sexual behavior. regardless of what is causing this, it is probably equally high in men, it's just that men don't tend to seek healthcare

and don't get screened. whereas women, we now have strong recommendations that every woman within this age group gets screened twice a year for chlamydia. and if they are positive because it's a note fiber disease, it gets reported.

now there's a big difference again when i mention the disparities issue. look at the rates in african americans versus the other ethnicities. and part of that, i could show this by social economic status or urban living and you'd see

sort of the same dramatic rate. but that's the epidemiology. the life cycle of chlamydia is absolutely fascinating. for years, everyone thought this was a virus. it isn't, it's a bacterium. and it starts out with these elementary bodies which attach

to columnar epithelium which line the cervix or the urethra. they go inside the -- and over 48 hours period repeat the cycle over and over. it is this anti-genic relieve of the elementary bodies that stimulate the inflammatory response.

but it's a very indolent type of infection so many people remain asymptomatic with these infections. it is somewhat different than gonorrhea in that sense. that 80% of men infected with chlamydia will be asymptomatic. the other 20% will develop --

and some develop -- and that will cause a problem for sterility. men who have sex with men get involved with chlamydia involving the rectum and they develop proctitis. it can cause conjunctivitis. if they paul engage in oral sex

they can get -- and there's an immune reaction that can occur in small percent of individuals that are hlrb27 that gets infected and get this reactive arthritis. women follow the same pattern, except for the complications. so about 80% symptomatic carries

but 20% will acquire mucoid -- will be negative for bacteria because you need tissue culture to grow it. we now have nucleic amplified to pick it up. the other ones we talk about -- rectal intercourse -- and again the reactive arthritis that we

see. so the us task force on preventive services for the u.s. came out with recommendations in 2007. they have not changed. and so i thought i would show you what we're supposed to be doing for screening for

every woman who present with serviceitis or pid needs to be tested for chlamydia. all sexually active women, all sexually active women under 25 years of age should be screened at least once a year. annual testing for chlamydia of all women regardless of age who

are at risk, and they define at risk as either having prior chlamydia or any other sti inconsisting condom use, multiple partners or exchanging sex for money or drugs. somewhat liberal definition of what we call at risk. so it's easy to treat.

that's why it's so important that we screen for it. we can screen urine or a vaginal swab or on pelvic exam a cervical swab. and have an answer within a couple hours. if they're positive, single dose of erythromycin is highly

efficacious rate. docky cycline is 100% effective. but compliance is necessary here. the reason for that is always a half life issue of the drug because remember the life cycle of chlamydia's 48 hours. so it would have to go through a

couple life cycles to actually be killed by the antibiotic. the reason is erythromycin on single dose is because it has such a long long half life. if they have what are called the l1 to l3 sero types, we treat them for a longer period of time up to three weeks.

even the erythromycin is given for three weeks. we don't really recommend to test a cure but if they come back within three to four weeks, we could do repeat testing. but rather we strongly encourage our clinical providers to retest all women when they next seek

medical care within the three to 12 months. reinfection rates are extremely high with chlamydia. mainly because their sex partner's not getting treated. so the people in seattle in the state of washington has adopted this.

it is not legal in maryland but it is in baltimore. go figure. we can actually give treatment to the infected person we seein the office and give her or him an extra dose to give to their part under. they don't need to come in.

so that's allowed now in several states except state of maryland, district of columbia don't allow this yet but got an exception because our rates are so high. i think if you staw the district of columbia rates you would think it should be done there as well.

this is very very important and just recently showed how it can be utilized to lower the partner rates of infection very effectively. i just thought i don't know how many clinicians are in the room here but since i presented a case of pvid i thought i would

share with you the treatment for pid is much more complicated because we have to treat the anaerobes. it requires that we use intramuscular treatment or even id treatment for these women because this can be life threatening and it can cause

sterility in these women so very very important. this was proposely treated and again all their sex partners need to be treated as well. let me present a second case that i actually saw when i was an infect scious disease fellow out in seattle.

and actually we published this in the new england journal of medicine because it was so unique. it was an hiv infected gay man. he actually had a diagnosis of aids back then. we didn't ma it was h i v positive but he was 23 year old

and he came in with severe rectal pain and he admitted to receptive anal sex and oralsex. he had no lesions but tenderness on rectal anoscopy visualized severe inflammatory proctol -- which is highly invasive. and actually millics crohn's disease.

and this individual who had been seen by gas troent recall gist who is treating him for toirdz with crohn's disease at the but fortunately we were able to make the diagnosis. we did a study and identified 13 cases within four months of so it was epidemic at the time.

there are other causes of procto colitis and rule out viral causes in these individuals that could be sexually transmitted or could be a part of their immunosuppression. we serial typed these called l 1, l2 or l3. this is called the groove sign.

rectal exposure does lead to this severe procto colitis. if you biopsy it they have granulomas. we need to treat these individuals. i'm going to shift to another std for a couple minutes because this is now a huge public health

threat to our nation and to the this is a 22 year old commercial sex worker who presented with one week of treatment of gonnococchal -- presented in the baltimore clinic. we did pcr if you will and some of the other ones we used. her symptoms did not get better

after she was treated. she had a history of seven sex partners since her last visit and on exam she did have a discharge coming from the cervical -- and she was still positive for gonorrhea. our debate did she fail -- or did she go out and get

reinfected. we went and took the isolate and were able to show that it was in fact resistance to -- which is an oral dose that was the standard for treatment for gonorrhea. so what is the situation of gonorrhea in the u.s.?

we have a case rate in the u.s. that's the highest of any industrialized country. 50 times higher than sweden, eight times higher than our neighbor canada. we did see it decline down towards 1996 but now has been level for the last 15 years and

in fact is doubling in men who has sex with men and we're starting to see more drug resistance. this is the epidemic curve of gonorrhea, and it's always fascinating to look at this. here's 1941. we're in the middle of world war

two and you can see the rates coming up and then it chopperly declines with penicillin. that was the advent penicillin. they made specific guidelines that the military were the first to get it after the congressmen needed it. and it did start to come down.

but it didn't go any lower than what it was before. and then it became epidemic during the love years if you will. free sex free love and so forth. and you can see it became really extremely high rate. 500 per hundred thousand

population. but then we mounted public health efforts to screen everyone for gonorrhea and get them treated. and you can see we did succeed but then since then, since 96 it's really been level. and if you start to look at

again here are the women, here are the men, their case rates. it's a little bit more equal women slightly higher. but what's fascinating when you go in to look at antibiotic and this is looking at -- resistance which was a standard for a while.

now recommendations i do not use -- you can see there was full susceptibility that -- you until 2000 and then the resistance started going up quite dramatically and has remained up. but when you look at the population in which it got

resistant, it was men who had sex with men. instead of men who had sex with so it happened to be because we were using this antibiotic more frequently and because of other problems in the gonorrhea developed resistance. again, high disparities

resulting in these individuals. and this again reflects the opening remarks that irwin talked about and that is these bugs keep generating resistance. and now gonorrhea's now classified as the super bugn terms of resistance. much like multiple drug

resistent tb. so first developed resistance in the 40's. in the 50's it developed resistance to penicillin in the 60's developed resistance to tetracycline. you saw the data on the floor quinn loans and now

unfortunately it's developing resistance to -- and the cephalosporin. whenever we get a new antibiotic within a decade it develops resistance and that's what is shown in this particular article. if you're interested, it is a

very interesting historical article showing that the -- that all of the. stds with is one of the brightest bugs in terms of how to acquire resistance. we now see erythromycin resistance in san diego and hawaii.

cephalosporin resistance in japan, norway, canada. in the u.s., this is showing again the development of resistance, both to -- and -- again msm is the group we worry about the most because that's where the resistance appears to be showing up.

and baltimore, the case that i was discussing in november was our very first cephalosporin resistent strain. these are the mics and the mbcs. it's still sensitive to -- but the oral drugs we can no longer use.

we were able to treat her with im treatment. it's a chromosomal mediated plasma transmitted resistance. there's multiple regions on the chromosome of the -- that encodes for the resistance. we don't have time to go through them all but a fascinating story

of how the organism can actually pick up these resistent plasmids and then pass it on to the chromosomes that develop so brand new guidelines for gonorrhea that we need to follow. first line treatment now is a two-drug regimen.

so you don't treat gonorrhea with one drug anymore. you got to use two drugs. that's -- it doesn't matter whether you got chlamydia or not. two drug regimen, the ultimate to be -- but we don't recommend you use that because we've seen

resistance now. if you see -- treatments you have to go through very step wise algorithm using -- and two grams of azithromycin. two grams is a lot to take. that's about 20 to 30%. they vomited. so we need to be very careful

now in terms of treatment of that organism. i'm going to close out with the gentle ulcer diseases leading up to dr. cohen's presentation which will focus solely on herpes simplex virus which is one of the very most common gentle transmitted viruses.

so let me just mention that when a person presents with a gentle ulcer there's a differential diagnosis we all have to go through. everyone in the clinic, clinician wise needs to think about is it herpes. it's usually painful.

is it syphilis, it's usually painless -- is a little more painful, lgb painless and gran yew low ma very rare in the u.s. but common in india and in tropical areas. we call that -- and that could be actually quite painful. flourish let's start with

this helped us with medicine in its myriad ways. again going back to world war ii, syphilis was epidemic. about the same rates that you were seeing with gonorrhea almost. penicillin came along and wow, did that stuff work.

and then look what happens. we really get into a situation where it starts to level off and then starts to go up in the 90's. a lot of people ask what is going on here. very interesting investigations leading to cocaine and trading

sex for drugs. and commercial sex workers and smsm not fearing aids were coming down with this disease. we mounted public health efforts, will go through this cycle. we've done this with malaria. you mount a massive response

things start to look good like here and then you back off. you can't back off with these diseases because everyone in normal adulthood is going to be sexually active and these bugs are these bugs are easy to transmit. this i find the most interesting

graphic that i'm showing you today because for the other diseases, i was showing you they were more common in women than in men. when it comes to syphilis, it's more common in men than it is with women and it is men who have sex with men which are at

extremely high risk for getting this particular infection. so this is the men over here, this is the rates in women. and part of this is shown on this graphic shown from 2007 to 2011, you can see it's going up in the msm. why is it going up with msm when

we have an epidemic of hiv threatening the msm population. it's called anti-retroviral drug therapy. it works. it's taken the fear out some of these individuals that put themselves back at risk. not everyone.

can't generalize to the spire population of msm but the bath houses reopened up. there's through the internet anonymous donors and you start to see the result of that. so syphilis is a marker to control sexual behavior to limit hiv transmission is failing.

because that's the group that's at higher risk. so what's in your neighborhood? how does it look for the state of maryland. you're in montgomery county, i'm in baltimore. here we are syphilis primary and secondary rates and congenital

cases of malaria. so shown in the blue are the congenital cases. these are infants being born with syphilis. that's inexcusable. every single pregnant woman with premaitle -- prenatal careneeds to be screened before she

delivers her baby. we're doing that for hiv but we seem to be forgetting the other stds. and this shows you the rate in these are the congenital cases and this is the rate in men who have sex with men shown in red. well, we rank number three in

the country at this state, okay. 452 cases of syphilis. it's really a shame to see this. but some of you work in the district of columbia, what's it look like there? it's worse. for the district of columbia, it's the highest case rate of

any urban center in the country, higher than any other industrialized city. it's as high as anywhere i've seen worldwide. and here it is in msm going sky skyrocketing in the mid to third decade of the 21st century. now it's leveling off.

we've got to see this coming down or we're just failing these people. you've seen these photographs. this is a dark field with use of a mono -- from a gentile ulcer. that's called primary infection. if not diagnosed and treated can present as secondary infection

which is usually a skin rash in the palms and soles. and we always look for this in all of our patients. and of course the tertiary infections we see rarely because we're usually now do screen all individuals at some point with sero logic diagnosis trying to

get them treated. this is secondary syphilis. you know syphilis and you know all of medicine is actually interesting because we actually see quite a bit of secondary syphilis in our hiv population and men who have sex with men. you can occasionally see these

oral lesions as well. so after primary and secondary, the trip mean goes into what's called the latent phase. it's still there, there's still an immune response. they usually have a positive serology. if the diagnosis was made within

the first year then it's called early latent syphilis. if they don't know when they got their primary infection that we usually clftd them in late late and that's usually a year after, more than a afterwards. after these early latent cases can relapse after secondary

cases. after four years that's no longer infections and -- it can either be asymptomatic or symptomatic if this is in the early phases of neurologic it can present as meningitis in the first year of infection but later on it's usually

asymptomatic but in a rare population you see vascular diseasor parenchymal disease. if they are hiv infected and positive serology in the latent phase we recommend you do a spinal tap. we've changed the testing for it's now done by eia.

the eia which is highly sensitive but not very specific but just the positive eia doesn't mean they have syphilis. you need the reflux it to a more specific -- test. and go through a confirmatory test. and the same is true with the --

if you do a spinal test. and then of course this is mandatory reporting. the good news about syphilis is penicillin still works. we have to use higher doses than we did during world war ii but basically 2.4 million units of long acting benzene penicillin

work. if they have -- we can treat them with tetracycline. if they have latent syphilis more than one year we have to treat them for a longer period of time f they have neurosyphilis this doesn't get into the csf so now we got to go

to iv. there are multiple steps that we go through in the treatment of i'm going to close with [indiscernible] papilloma virus. so we have some time to talk about herpes. i bring this up. i only have two slides on this.

there's two types that cause infection but there are four actually that cause cervical cancer but in the u.s. there are primarily two, hpv type 16 and 18. but we also see six and 11 that's extremely common. so a vaccine was developed

against these called the quadrivalent ones because these cause 70% of serve cull cancer. these two probably cause 80% of all the benign warts. but they can go on to cause the low grade dysplasia. the single biggest risk factor for dysplasia is persistence of

the infection and it can last for quite a long time. these are some of the risk factors and we are concerned once between with co-infection with hiv because of the this is an m.hains survey. this is for people with high risk or low risk hpv.

this is extremely common for both low risk and high risk. and it was on the basis of these data that the fda and the preventive recommendations public health recommendations promoted that all individuals within an age group be given the hpv vaccines.

it's now approved for both girls and boys. it's highly efficacious. one of the best vaccines we have. we recommended a nine year old girls to 26 year olds and the same for boys now. the up take is 35% in girls.

only 35%, leaving 65% at risk for developing cervical cancer because someone didn't get them vaccinated. so as a parent, this is something i made sure my daughter got vaccinated. it is very very efficacious. and it should be applied for

boys. in australia, 95% of all girls are vaccinated. 95%. it's truly a failure of our healthcare system that we only have a 35% uptake in women and a 5% uptake in boys. not good signs at all.

it's not therapeutic so once you get cervical cancer, you're not going to be getting this vaccine at that point. so on to dr. cohen who is going to talk about hermes. one in five adults in the u.s. has been infected with the herpes simplex virus but only

10% of that population who are infected are even aware they have this virus. they cause primarily gentle disease but also oral infections which you'll hear about and there's intermittent asilt matt ig sheddings. it's life long and

intermittently shedding it even though there's no symptoms with infect people. the good news as you'll hear is that we do have very good anti-virals. they're not a hundred% in suppression but they are very high and i'll let jeff go into

much more detail about these treatments. so, these are the different drugs that we use and i will be glad, maybe we'llaa takequestions after jeff has had a chance to talk since i went a little bit longer. thank you.

[applause] >> thank you very much. we can have a couple questions if you have something you would like to ask at this point. there's a microphone in the center here. >> yes, so i just have a question about you have the most

common sti's like the four you listed. i was wondering how many of them are like co-infected because you have siferl of them that had over a hundred million cases every year. i was just wondering like those are not separated infections.

>> it can be counted twice. you mean in other words could a person have chlamydia and >> yes, because i think thosal are quite high, right. >> they are high and they're just estimates from the world health organization and you can pull it up on your computer.

and they tell you how they tried to get this. but yes, so there were 105 chlamydia, 106 gonorrhea. probably an overlap of about 10%. where they had -- and they're listed in that 105. but it's know that much higher

than that. >> okay, thank you. >> yes. >> i read a couple articles in the popular press recently the idea there are viruses kind of akin to hiv, there are places where hiv originated -- i was wondering if you had any

comments about that. >> so this is looking at some of the simian viruses and so forth? so some are retro viruses and some are others. there are groups working in west africa preferentially is where a lot of this is being picked up. and maybe jeff might want to

address some of this as well. as far as i know, none quite fits the picture of either hiv or some of these stds that i've been talking about. but we're continually screening and looking. there's the department of defense funds an initiative that

is looking at the emergence of new diseases and new infections. but none that quite fit the picture of hiv at this point. jeff, did you want to comment on that? no, okay. >> thank you. we'll have more time for

discussion after dr. cohen. i'm going to be talking on herpes simplex virus. show a little bit about the epidemiology of the disease, talk to you a little bit about treatment and talk to you about the state of vaccines for herpes simplex virus.

so as a disclaimer, i do have a collaborative research agreement with -- to study an hsv2 vaccine. as mentioned it was described in the 80's "time" magazine as a social plague because this virus can be transmitted by others from people who don't even know

they visit. here we have a modern day cluster print and i guess -- so in the united states, in the worldwide, you can see that hv infects over 500 million persons and in the united states it's estimated that 50 million persons are infected with hsv.

once infected of course people are infected for life. you can see here in the united states, this is the problems in it's roughly 21 to 30%. but in other countries, particularly in areas of africa, it's greater than 50%. in men, these rates are about 5%

higher. and as tom mentioned, most individuals infected with hsv two are asymptomatic or the infection is recognized. these are prevalence rates from the cdc from hsv2. certain ethnic groups particularly black,

non-hispanics have much higher rates of hsv2 than other ethnic groups. and you can see here also that individuals that are 14 to 19 years old have relatively low rates of hsv2 but these rapidly increase as individuals get older.

so this is important for in terms of who we would vaccinate with an h. sv2 vaccine. and we really think about targeting the same groups that get the hpv vaccine. now gentile herpes was thought to be predominantly hsv2 and

more revent studies show hsv 1 has an increasing role for gentile herpes. this is a study from madison wisconsin at the university there and you can see the percentage of hsv1 is the cause of gentle herpes. it was well under 50% in the

early 1990's but in both women and in men that has increased such that hsv1 is the predominant cause of gentile herpes in young women. this is in the year 2001 and a recent vaccine study. it was shown also that hsv1 was the predominant cause of gentile

herpes. we have to think about hsv1 and 2. when we think about a vaccine for gentile herpes it has to protect against hsv1 and 2. why do we need that vaccine? to try to prevent gentile herpes and they can transmit the

disease to the neo notes which is difficult to treat in the young child. causes severe disease in patients with aids and in transplant recipients. as tom mentioned hsv2 causes a three fold increase risk of acquisition of hiv as well

increased risk for transmitting hiv. we do have some anti-virals able -- even,000 you can reduce the transmission rate, it does not affect the hiv acquisition rate in persons with herpes simplex. so anti-viral therapy for hs2 is

not the solution to reduce the rate of transmission of hiv. so what happens in terms of the pathogenesis. individuals get infected with gentle herpes on the mucosa in women or on the skin of penis and men. the virus travels up thesensory

nerve alongside the spine here. there the virus establishes a latent infection for life. it stays there for the lifetime of the individual and then the virus can come back down the same nerve and reactivate to cause gentile herpes reactivation.

this is a very frequent, react valuations are much more frequent than was originally thought. so this was the study done in seattle by -- group. in the study they took individuals who generally had asymptomatic disease.

these patients swab themselves four times a day and pcr was performed to look at shedding of virus. most of the patients were asymptomatic when the swabs were performed and when they looked any time of the day and you look at the number of positive swabs

over the total number of swabs, one out of five swabs was positive. so one out of five time these people were shedding hsv dna from the gentile area or from the male. this sort of changes the bear dime.

we used to think of this virus latent, getting act valuations one to six or five react valuations a year. but it turns out people are shedding this virus quite a bit of the time. and unfortunately even when people are asymptomatic and

shedding the virus they can't transmit the virus to their partner. so hsv often does not remain latent. we look at the cellular level here, we can see again the virus infects the skin or the mucosa, the virus replicates inside

these cells and the virus then is trafnls mitted to -- transmitted to the axonal -- again you get replication here with shedding of virus. so i'm going to focus a little bit on this box right here in replication and tell us and sort of say why it's important to

study this and how it teaches us about treatment of disease because for the treatment of gentle herpes we focus on the replication aspect of things and we really don't have drugs to affect latency right now. so when the virus replicates it makes 84 different proteins.

these are called the immediate early protein which regulate expression of other viral genes. the early proteins which are the targets of every anti-viral we have for herpes simplex virus. and the late proteins which are structural components and this is what's been the target of

vaccines. so why do we study the immediate to early proteins? well, there are new compounds coming down the pike and actually tom christy here at the nih has been studying gene expression of herpes virus. he's found new compounds that

regulate expression of these immediate early protein. and they reduce replication and they can rules reactivation from latency. so one of the one that he's discovered in his laboratory which effects the histones which are important for controlling

gene expression, if he takes mice and infects them with herpes simplex virus it's latent in the ganglia. if you take the ganglia out of the mouse, the virus replicates -- if you remove the -- it does replicate. with some of these newer

compounds -- they also inhibit replication. so these are new targets and new targets are important because the drugs that we have right now all act on the same step of the these are immediate early genes. in terms of early proteins there are a large number of them but

the ones that are particularly of interest are the herpes sym pleaks -- and the herpes simplex prim race. we give it to patients the kinase phosphorylates and puts a single phosphate group on to the apsych veer and the cell with two additional phosphates so you

have the sigh -- and inhibits viral replication. so these drugs are incredibly safe because they are only phosphorylated, this initial phosphorylation event only occurs inside infected cells and as a result psych veer and other drugs are quite safe.

where did anybody get the idea for giving apsych veer. it turn out -- elliott and george hitchens who shared the nobel prize for development of apsych veer and some other drugs basically took gun seen which is one of the building blocks of dna and modified it just a bit.

this guanine base is the same here but the rival sugar here is broken open. this used to be called acyclo gun gun seen because this structure is missing and it was renamed acyclo veer so you can see it looks -- inhibits the viral dna plain race.

we have other drugs including the -- which is a more active form and what was done to take the end of this molecule and just put a valine amino acid on it and that increases the ability of the body to absorb the drug so it gets absorbed much better.

but in the intestine the valine comes off so what's in the blood stream is actually apsych veer. we get the same thing in the blood stream but a higher level giving valley psych veer. the third drug we often use for treating herpes simplex is -- and again this is a pro drug

just like -- it gets converted into the body into -- and you can see the sick veer again has this guanine base here and has a tail coming off of it. so all three of these molecules are very very similar. by studying dna and by studying the structure of dna, a number

of anti-virals have been discovered. what about treatment of hsv two. so again eye psych clear and we can error treat acute or recurrent disease. if you look at the duration of symptoms of an individual, are the first episode individuals

typically have about a 12 day course of symptoms, it takes a full 20 days for the healing to with recurrences, they are usually shorter, usually about nine days of symptoms. if we give any of these three drugs, it reduces the time to resolution of the first episode

by only about two days. and recurring episodes by about one day. reduces the time of healing of lesions by about four days or one day and reduces the time of duration of shedding by seven days or two days. without treatment there's about

12 days of shedding. so we can modify the disease in this case, and it's recommended particularly for this first episode which tend to be more severe to treat with apsych career. recurrent episodes as we'll talk about the treatment can vary

depending on how many recurrences people have. now there's also suppressive therapy and if people have greater than six recurrences a year or if they're in a relationship where their partner is not infected with herpes simplex virus many clinicians

recommend suppressive therapy where you take one of these compounds every day. when that's done, 70-80% of the recipients are recurrence free after taking the drug for four and there's an 80-90% reduction in the number of days with asymptomatic shedding based on

culture by taking suppressive and in the absence of pressive therapy, about 38% of people will have six or more recurrences a year. the mean rekurnlings rate is about four per year. and this is the hsv2. with hsv1 the recurrence rates

are lower -- so there are drugs to treat. these drugs are not cures for they do rules symptoms. they can reduce shedding but the herpes is still there. this is an electron micro graph of a herpes virus. you can see the core here that

has the dna inside of it. there's an envelope and it's like proteins, they stab the envelope and many lie co-proteins are what scientists target for development of these glyco proteins are the major target for antibodies against herpes simplex virus and

they're important for the virus to attach to cells and to fuse with cells. so in terms of developing vaccines, we try to learn from nature first. ant body is transmitted across the placenta. it protects the neonates from

developing severe disease. it would rules antibody responses. however, amount bodies is not prevent recurrences. what's more important for recurrences are t cells. another arm of the immune system or t lymphocytes.

if you look at people who don't make antibody or people with t cell immune deficiencies they have really severe hsv2 disease. t cells are important for limiting severity of the and both the cd4 cells and the cd8 cells are important for limiting disease severity.

so we think that both antibody and t cells will be important for a vaccine and there's only one licensed vaccine per herpes virus which is the chicken pox vaccine and the shingles this is a live attenuated vaccine and induces both antibody and t cell immunity.

based on that paradigm we think of herpes vaccine to induce both antibody and t cell responses. so again in terms of t cells, this is a slide from actually a human ganglia from a person who died. not of herpes virus but the person had latent herpes virus

in their ganglia. in the herpes virus you can see here are these black speckles here in the glue creas which are probed with a marker to herpes what you can see are these t cells surrounding the graduate law which you think are poised there to try to prevent

now the group in seattle spent a number of studies in women and this is actually a biopsy of a gentile mu coast awe from a woman who has herpes. what you can see here by staining for t cells and for staining for hsv2 uses what's called tetra-- located in the

epidermal junction here. they're poisepoised to try to kill virus infected cells when the virus is reactivating here. so there are lots of t cells in the gentle area poised to kill the virus infected cells but still virus shedding occurs. so in terms of preventing hsv2

we know that condoms with reduce transmission. and we also recommend if we wanted to reduce transmission both condoms as well as chronic daily psych clear, a study from the seattle group showed it reduced the shed ongoing of dna by 72% and more importantly

reduced the transmission of hsv2 to susceptible partners by 50%. so you do get a reduction but only 50%. and we think that newer drugs on top of -- might reduce this rate but really a cure for herpes would really require a vaccine to prevent infection or prevent

disease and shedding. so again for developing vaccine, the most of the research so far has been glycoprotein d. this is on the outside of the it's the most abundant protein on virus infected cells and on the outside of the virus. it is the major target or i

should say a major target for neutralizing antibody. it's also a target for the t cells which are important for controlling reactivation and it's the protein known to bind receptors on the cell. if you could block dplie co-protein d binding from

receptors you could block the virus from getting into cells. so thus far there have been four randomized double blinds placebo controlled trials of a prophylactic simplex virus vaccine which are good clinical end points. the first was done in 1990.

glyco proteins were obtained from infected cells. they were given to one partner who is in a stable relationship with another partner who has hsv2. unfortunately the outcome showed no difference in time to hsv2 accusation and they were

relatively low levels of antibody to gd. so later on, re-- given to individuals in stable relationships or individuals in a sexually transmitted disease clinic. but unfortunately there was no time of difference in

acquisition throughout for the end point of study but when they looked very early on in the study there was a trend towards lower rates of hsv2 acquisition but they didn't really hold up. back to back papers were published in the new england journal -- using lipid a and

discordant couples. the primary end point of the study was protection against gentile hermes and it was not met with only a 38% efficacy. but subgroup analyses were done. it turned out when they looked at women and not men but looked at women with zero negative the

vaccine had a 73 to 74% efficacy for gentle herpes virus disease. so because of this substudy, the fda requires a study where the primary end point would be gentile herpes virus disease in just these individuals. and thi was the herpes vax study.

it was the group it looked like worked here. to everyone's surprise this vaccine in this group had only a 20% efficacy for gentile herpes which is why the fda in their wisdom says you can't license something based on the substudy you have to do, you have a

primary end point here. just to look at this study a little bit more, this was published last year. the double blind placebo controlled study phase three study the nih participated in this study. 8,000 women at 50 different

sites in the united states and canada are really enormous again women with zero negative for both hsv1 and 2 got three doses of this glycoprotein -- the placebo group got hepatitis a vaccine. the follow up was 20 months, the primary end point was gentile

disease be it hsv1 or 2. these are the outcomes. only 20% efficacy for gentile hsv disease which you see here but if you look at hsv1 gentile disease there was redukion compared to the control group. if you look at hsv2 disease the vaccine did a little bit worse

than the control group. so this is for disease. what about infection preventing infection. just about the same rates here. the vaccine really has very low rate for protecting against hsv open fection. little bit better for s shvment

s1 nothing for hsv2. they looked at shedding because if you had a vaccine to prevent a disease but individuals still shed, that's not going to help public health because people will be going around shedding the vaccine did not rules the rate of shegd of hsv.

the vaccine induced antibody responses but fell rapidly and by 16 months of the study the antibody response were undetectable. the vaccine induced -- cd4t cells but not cd8t cells. so this was a very humbling possible reasons why it didn't

work, insufficient levels of apartment body to hsv dplie co-protein lack of reducing -- the only herpes protein in the vaccine was glycoprotein dnd perhaps other herpes virus proteins would have been improve the immune response. and we really don't know what

the immune response was at the site of infection in the general file tract. so although they measured apartment bodies and t cells in the peripheral blood which is probably more important is the apartment bodies and t cells at the site of infection, the

gentile tract. where is it going from here? a number of other subunit vaccines are under development. a group in seattle is looking at multiple hsv2 peptides, short proteins of the herpes simplex virus complex to what are called heat shock proteins and a

different -- and these heat shock proteins allow this vaccine to induce both cd4 and cd8 responses which were seen in most of these individuals in a phase one trial. no idea how efficacious this would be. another group is looking at

glycoprotein d and an immediate early protein and their -- and this is, this study's just under way in clinical trials.gov is absolutely no data on it at this point. another group has done mouse and guinea pig studies with glycoprotein d and c.

dna vaccine expressing -- this induces some t cell responses and minority of individuals in this particular study. there's an -- activated hsv2 in -- has been tested and looks good at least in animals. now in addition to subunit vaccines, they are live

attenuated and replication effected vaccines under development. there's a group in great britain that has taken the genome, deleted several immune -- genes which i'll talk about in a minute and this virus seems to be attenuated.

it doesn't inhibit the cellular immune responses. this trial is ongoing, there's no data available for it at the time moment. group in philadelphia -- looks promising in mouse and guinea pig models. i'm going to briefly mention

later on has mutated glycoprotein d and i'll talk about that in a few minutes. there's a replication vaccine that's deleted for two essential genes that can infect cells but not spread. so in terms of this replication defective vaccines that's

probably sort of next on the clinical trial list. david -- deleted two essential genes in herpes simplex virus ul5 and ul29 which are required for the virus to grow. if you take this virus which lacks these two essential genes, you can grow the virus in the

cell that expresses ul5 and ul29. the virus grows perfectly fine. virus comes out of the cell and that virus can infect normal cells when it infect normal cells that don't have ul5 or ul29 the virus makes immediate early and late proteins but the

virals dna can't replicate so no virus was produced. but this normal cell will make most of the immunogenic proteins of the virus. excuse me. so why might this vaccine be more effective in glycoprotein d, it should induce t cells --

the immune system and the glycoprotein is being expressed with other membranes of the cell and as a result it may be a more physiologic confirmation than the soluble glycoprotein d that make it different. however this virus still encodes these immune genes that inhibit

the immune response and herpes simplex virus is a difficult virus for a vaccine and encodes a protein that down regulates class one molecules that blocks cellular immunity and encodes a protein that blocks antibody responses encodes a protein that blocks -- responses.

so these viral proteins which block the immune system are still in this vaccine. so how do we test herpes vaccine in the laboratory? we test them in mice and in guinea pigs. in the mouse model and the guinea pig model we can tell

whether the vaccine can prevent primary disease, whether the vaccine can reduce shedding, reduce latent infections, reduce whether the vaccines can induce antibody responses. we use mice because we have reagents that look at t cell responses in mice and we use

guinea pigs because unlike mice guinea pigs undergo spontaneous recurrences of herpes simplex. this is a slide from a paper we wrote a few years ago where we compared -- as well as a more potent -- with dl529. what you can see is the guinea pigs that got the dl529 vaccine

and these open triangles had less shedding of virus after challenge so the animals get each of these different groups of the animals get a different vaccine and the animals are challenge the intravaginally with hsp2. so you see decrease shedding of

the virus, you see decrease lesion scores in these animals because the guinea pigs do get gentile lesions. we see decrease number of occurrences with ld529 versus dplie co-protein d. if we look at latent virus in the dorsal ganglia of the

animals we see latent virus in the animals that got dl529. at least in the guinea pig it looks like this vaccine may be more effective than glycoprotein d. so in coninvestigate compared to glycoprotein, i didn't have time to show you -- higher levels of

cdat cell responses and it intends to reduce both acute disease as well as the number of occurrences. a company right now is currently making this vaccine for phase one clinical study in humans. so we are also in our laboratory looking at a replication

competent vaccine because we think this might even be better than a replication defective recall that the only vaccine that works for herpes virus is the shingles and -- and these vaccines are live attenuated vaccines so we're interested in making a live attenuated

and what we've done is try to engineer a virus that can grow in epithelial cells but not in neurons. so the idea you've seen this before is we have a virus, if it replicates in the epithelial cells and can induce a good immune response but not get

transferred to the neuron, gets blocked at this stage, it can't induce a latent infection and shouldn't reactivate. so you should get the immune response and initial potential rash but then it would be all over at that point. so we've taken advantage of the

fact that glycoprotein d is the major glycoprotein that's important for binding to receptors. one of the receptors is -- also winds to another receptor called herpes virus intermediator -- binding these receptors are essential for the virus to

infect cells. and what's been known now by crystallography is if you look at the structure of nectin complex to herpes simplex virus glycoprotein d there's an interface here where nexten binds. this is magnified here and there

are certain amino acids which are these letters here this important for glycoprotein d to interact three of which are shown in boxes here and arginine even these three amino acids with the idea of hsv when we need these amino acids should not be ae to bind in nect it n

one shown by other individuals but we made a recall informant viruses that has mutations in the amino acids and it shouldn't be able to bind or enter through nectin one. to go through this again different receptors are needed for different binding to cell

sites. we made a virus that has these three amino acids change because of changing the nucleotide sequence error. it can't bind to nectin so -- but neurons are thought to only use nectin1 so they shouldn't bind to neurons and shouldn't be

able to enter neurons. we've taken epithelial cells, neuronal cells infected with wild type virus. it replicates the high titers in those cells and infect epithelial cells just nine but doesn't infect neuronal cells in culture.

if we change them back the virus grows perfectly fine. this is in cell culture. what about in animals. so in mice, if we infected the mice intramuscularly with wild type virus the ganglia become infected with herpes simplex but we infect with ten times the

dose of our mutant virus the ganglia don't seem to get infected at all. so we've just done some preliminary experiments on immunizing mice intermuscularly with our vaccine virus or mock immunization and then challenge the animals with very high doses

of wild type virus. you can see the animals they get the vaccine protected whereas the animals that got the mock vaccination all died. so the last slide just to conclude studies of hsv2 proteins i think are very important for developing new

anti-virals to treat both acute disease and hopefully to rules reactivation and importantly better reduce shedding. while an hsv2 vaccine is not currently available we think that new approaches to vaccine development beyond the glycoprotein d are promising.

with this late note i'll stop there and see if we have time for questions. these are the members of my laboratory group that have been working on the hsv vaccine and steve straus -- and david -- developed the dl529 vascular is an.

so i'll stop there. >> if you have questions, go to the microphone. how long do you think it will take to evaluate the current vaccine that you're working on? just so we get an appreciation. >> since dl529 was first developed in the laboratory it's

taken literally a decade for us to get the, it's thought because we're really all that lazy but it's taken a decade to get an industrial partner on board to commit to the millions of dollars it takes to make a gmp grade vaccine. now we hope to be doing a phase

one study, hopefully a phase one study will be done in the future and from there, you could see the herpes vac study was a decade from the time that gd was first into humans to get to a phase three licensable study so these studies take really a long period of time.

i would say it's still a decade off unfortunately. and part of that is just because again the, as tom has mentioned, there's the public doesn't perceive a tremendous need for a so you can see what's happened with hiv vaccines which has taken a while to undergo but

finally we're getting vaccines from the pipeline. hsv is even much slower. >> do you think that where do you think we will be at five years from now? in the treatment of sexually transmitted diseases. are there other reasons for

brightness in the horizon or are we going to be -- >> there are some new anti-virals for hsv that work at a completely different step than what i showed you. think if you combine them with the new current anti-virals you can reduce shedding by another

50% and even more and potentially that could help to reduce the spread of herpes in terms of taking someone already infected and avoiding, curing them from hsv and having absolutely no virus in them i think we're a long ways off. tom can talk about some of the

other. >> so if you look back over the last decade and-a-half, it's been revolutionary in terms of using molecular diagnostics to identify those people who are infected. and i would say within the next few years we will have

diagnostics for the vast majority of these stds. so before you leave the clinic you'll be told whether you got chlamydia, gonorrhea, herpes, hepatitis c, etcetera etcetera. and i actually think early diagnosis and trying to get that part of mainstream medical care

could really make a major advance in limiting the spread of these diseases. we're not there yet but i think we will. in terms over effective drugs, the bug i worry about is i do think resistance is going to continue to grow.

most of that resistance doesn't come from the u.s., it comes from other countries where the antibiotics are unregulated. and we're starting to see that with malaria. we see it with tuberculosis. i think we're going to see this with gonorrhea and some of the

others. so i worry about that. i hope we don't go down that road. but i can tell you most of the std meetings, there is session after session after session is about gonna caulkal resistance to antibiotics.

>> may i ask a question what is known about the transport mechanism for the biernldz up and p and down the axon? >> how the virus is transported along the axon. it's pretty clear the envelope of the virus comes up --

transporters up along the axon using the same machinery that these neurons use to transport things. it's an effect where when people label the virus with glean fluorescent protein you don't see sort of a graduate transport, it goes in sputters

and stuff along the pathway but it's using the same molecular machinery that the cell uses to transport. and there's really that's something else that one could potentially block but the problem is you need something specific for the virus and it

wouldn't interfere with transmission of signals in the >> i'm curious, i haven't gotten married lately but when i did, you had to have a blood test for does that still exist or are there any premarital tests that are required by law? >> not that i'm aware of.

they tried to do that for hiv and it didn't get implemented because they said it was too costly. so they always analyze cost effective before they implement one of these public health policies. syphilis which is the one you

referred to, once those rates came down, yes, it's very level and low. i mean it's still bad in the district and few others. it's an msm. it's a different population. so to mandate it for everyone, which is what you'd have to do

would not be cost effective. and that's why the policy makers don't implement that. interesting. >> okay. well listen, thank you both very very much. it was very exciting. i appreciate it.

by the way, next week we go back to building 50. this is an exception today of