STI Guidelines: New Treatment, New Challenges


ELIZABETH LIEBOW:
Good afternoon, I’m Elizabeth Liebow with the
Maryland Department of Health and Mental Hygiene, specifically
the Center for STI Prevention. And I’d like to
welcome you all here today to our sixth annual
Sexual and Reproductive Health Webinars Series. I’d like to welcome
you also on behalf of our two other
cosponsoring organizations– the STD, HIV Prevention
Training Center at Johns Hopkins and the
mid-Atlantic Public Health Training Center at
Johns Hopkins, which is hosting and webcasting
this event today. For those of you who
are watching online, if you click on the
link on your screen, you can email questions to
our presenters throughout the entire webcast, or you
can send any email questions to M-A-P-H-T-C at
J-H-S-P-H dot edu. That’s the mid-Atlantic
Public Health Training Center at the Johns Hopkins
School of Public Health. Dr. Anne Rompalo, who’ll
be speaking today, should have her
PowerPoint slides up on this website by this
Friday, this coming Friday. And within the next two weeks,
the archives’ recorded webinar will be available as well. I’m going to turn this over
to Barbara Conrad, the chief of the Center for STI
Prevention at the State Health department, who will
introduce our speaker today, Dr. Anne Rompalo. BARBARA CONRAD: Welcome, I’m
so glad you can join us today. Dr. Anne Rompalo is a
professor of medicine at the Johns Hopkins
University School of Medicine, Division
of Infectious Disease, with joint appointments in
the Department of Obstetrics and Gynecology at
the Departments of Epidemiology, Population,
Family, and Reproductive Health, and the Department
of International Health at the Bloomberg
School of Public Health. She is a noted provider in the
field of infectious diseases and is an
internationally-recognized expert in the field of
sexually-transmitted infections, STIs. So we’re very glad
to today to be able to have Dr. Rompalo
give us an update on the STI guidelines, new treatments,
and new challenges. Dr. Rompalo? ANNE ROMPALO: Good afternoon– [SHATTER NOISE] — Oooh, dear. Well, this is a good way to
start– one and all, both here and on the web. I’m going to go
through a lot of data. I didn’t think there would
be a lot of updates going on with the new
treatment guidelines, but, in actuality, there are. So we’re going to
start by reminding you this is the email. If you have questions,
please do use that. And we will try to get
to them and answer them. I have no disclosures. And this lecture was
adapted from a lecture that was shared with me from
Dr. Kim Moore Koski, who is professor of
medicine in Emory, and who works for the CDC in
pushing forth these guidelines every four years. So the overview of what
we’re going to talk about within this hour is, quickly,
the guidelines process, some screening updates– particularly, the United States
Preventive Services Task Force, recommendations for screening
of chlamydia and GC. I’m going to spend some time
talking about STIs in men who have sex with men. And then I’m going to focus
on some new directions in the guidelines, which would
be emerging issues, those with mycoplasma and
genitalium, a touch on HCV, some treatment concerns focusing
on gonorrhea and chlamydia. I’m going to talk on
syphilis, specifically under simplest
definition, and just touch upon the reverse
testing algorithm. I’m going to spend
a second on HPV management and,
also, on trichomonas. This is what the current
MMWR STD treatment guidelines look like. It is authoritative. We spend a lot of time
accruing evidence. It is all evidence-based. It talks about diagnosis,
evaluation, and treatment, as well as prevention
and vaccinations that should be part of prevention. There is a lot of information
in this 270 page document. However, you can
get wall charts, pocket guides, mobile apps for
your Apple or Droid devices. And I will say that the updated
guidelines has been revised, and it’s waiting
for CDC clearance. It would have been out earlier,
except for the Ebola outbreak, which took precedence,
as it should. So let’s start with clinical
prevention guidelines. Everyone who comes in,
who is sexually active, should have an evaluation, both
behavioral and biological risk factor assessment. And that’s the five
P’s, asking people about their partners,
their practices. If it’s a woman, is she
trying to prevent pregnancy? What’s being used for
protection against STDs? And what’s the past
history of STDs? These are the infamous
five P’s, and that should be part of your
regular assessment. The United States Preventive
Services Task Force, in this document, also
talks about high intensity behavioral counseling. And I suggest, when it
comes out, you read it. It’s great, but we
don’t have enough time to talk about that today. There will be a section on
pre-exposure vaccinations. And HPV hepatitis A and
hepatitis B vaccines should be available and given. There are sections about
male latex condoms. Also on female condoms, male
circumcisions, microbicides, emergency contraception. A lot of information here, and
now the new kid on the block is pre-exposure
prophylaxis for HIV. Very important that we
all know, as providers, who to talk to about this
and how to prescribe it. And then there’s a section
on retesting after treatment, which I will touch upon. So I’m going to focus on
chlamydia and gonorrhea screening. This might be a
review, but that’s OK– for many of you. There should be annual screening
of all sexually active women, who are 25 years
old and younger. You can screen older
women, certainly, if they’re at increased
risk, which is listed here. But screening older
women at low risk, really, is not recommended. Chlamydia screening
for sexually active men is always and will
continue to be an issue. However, there is
insufficient evidence– remember this is an
evidence-based document for general screening. So you should consider screening
men, sexually active men, who are in high
prevalence situations, such as adolescent clinics
corrections or STD clinics. And generalized screening
for gonorrhea in men is not recommended. Now there are sections
specifically zooming into special populations,
and they’re listed here. I’m sure many of you are
already aware of this, but the new kid on
the block is there is discussion about
transgender men and women and the new
treatment guidelines. So I suggest, if you
see this sub-population, please take a look at the
guidelines with that regard. I’m going to spend
more time, though, focusing on what’s written on
screening for men who have sex with men, because there
is a lot of documentation now, in the past 10
years, about an increase in recent or concurrent STI
among HIV-infected individuals. There are increases in
MSM of early syphilis, and you can see there’s various
and sundry references here. There are increases in rectal
gonorrhea and chlamydia infections that
have been reported. There’s increases
in substance abuse and much documentation about an
increase in sexual practices, such as multiple anonymous
partners and, in particular, sex partners who you meet
through the internet. And here’s some data
to illustrate this. This is the SSuN data, which
is the STD surveillance network data from 2012. And it’s the proportion of
MSM attending STD clinics with primary and secondary
syphilis, gonorrhea, or chlamydia by HIV status. And the dark blue
reflects HIV-negative, and the light blue
reflects HIV-positive. You can see, whether it’s
primary or secondary syphilis, gonococcal infection of
your urethra, pharynx, or rectal area, or your urethral
chlamydia or rectal chlamydia, HIV-positive patients
are much higher. So this is an issue,
and we can speak an hour about the co-infections
of STIs and HIV and increased HIV
acquisition and transmission. But the bottom line
is this is important, and we need to be screening. So what the CDC and the
new treatment guidelines recommend is that if we have
a sexually active man who has sex with other men, whether
he’s positive or negative, he should get syphilis
serology screening every year, at least yearly, and gonorrhea
and chlamydia testing using NAATs– Nucleic Acid Amplification
Test– and this says urine– every year. If he performs receptive
oral intercourse, he should get a
gonococcal NAATs, or culture of the throat. And if he performs
receptive anal intercourse, he should be tested with
NAATs chlamydia and gonorrhea. And I will say that the
State of Maryland has– if all of you from the State
of Maryland who are listening. The lab is now doing NAATs
for chlamydia and gonorrhea of the rectum. If they haven’t gotten
vaccinated for hepatitis A and B, there should
be yearly screening– if they were negative the
last time you saw them. And you should consider
screening them for hepatitis C if they’re at risk. Now– listen– more frequent
STI screening should be done depending on the risk. That is– remember, a
couple of slides ago, I talked about the five
P’s– you need to talk to your patients
about ongoing risk. Because if they’re at
risk, they need screening. They don’t have to have symptoms
to be infected with STIs, just remember that. And that should be every
three to six months if the risk is there. Now, the proposed new sections. Emerging issues– there is going
to be a section on mycoplasma genitalium. There is evidence that
mycoplasma genitalium has a role in
non-gonococcal urethritis. 20% of non-gonococcal
urethritis infections are caused by this
in several studies, and I’ll show you some data. And there is a role of M
genitalium also causing cervicitis and PID. Now here’s the
problem, there are no commercially-available
tests that we have that are blessed currently. There are in-house
nucleic acid amplification tests that are out
there, but there’s no commercially-available
test yet. So that puts us in a bind. However, there are
treatment implications, because men who have
NGU, for example, respond much better to
Azithromycin treatment than they do Doxycycline. There’s conflicting
data, however, whether you use a single
dose of the Azithromycin, and if that’s good enough, or if
we have to use extended doses. And, unfortunately, we’re
seeing emerging resistance to Azithromycin. So here’s some data that was
put together at the treatment guidelines and presented. There’s observational studies. So, listen, it’s
observational studies. They are not randomized
controlled trials. So these are the
data we’re working with– seven with Doxycycline
and about 14 with Azithromycin. And the microbiologic
cures are shown here– for Doxycycline, seven
to nine day course. The microbiological cure using
that course is about 37%. And the range is shown here,
according to the studies. For Azithromycin,
it’s much better. But the range, again,
is also shown here. And here is a randomized
controlled trials that haven’t been done. There’s three listed here. And you can see with
M. gent, the cure rate for Azithromycin is
much better, no matter what study you go to for
M. gent with Azithromycin versus Doxycycline. Now also look at this. As the time has
been marching along, the efficacy of Azithromycin
is not consistently high. And over time, it
seems to be declining. So this is an example
of what do we use next? And you don’t have to read
every single one of these, and nor will I. But this is
the efficacy of Moxifloxacin. Now Moxifloxacin
has been given– if you look at this–
anywhere from a seven day course to a 14 day course. And these are the cure
rates, specifically focusing on M. gent gentalium. And they look pretty good,
but the most recent one, which is by Manhart in
2013, showed a decline with Moxifloxacin. Now Moxifloxacin is an
expensive drug right now. So there’s a lot
more information we need on this as the cause of
NGU, as a diagnosis, and then, finally, what’s
the best treatment? Other emerging issues–
there is a section talking about sexually-acquired
HCV, hepatitis C virus. It’s associated with
unprotected, receptive anal intercourse among– in particular,
these studies MSM. It may be due to rough
or poorly lubricated, unprotected anal
penetration, also fisting. And it’s associated with
any type of ulcerative STIs in the rectum,
proctocolitis that can be caused by lymphogranuloma
venereum, which is LGV, and, or syphilis. So it’s recommended that
MSM, whether they’re positive or negative,
have annual screening. And that could be yearly or,
actually again, more frequently according to the risk, such as
the HCV prevalence among MSM population in your area. There is high risk behavior. Or the individual
has an ulcerative STI or an STI-related
proctitis or proctocolitis. So remember that acute HCV
may be HCV antibody negative, if the CD4 count in the
individual is less than 200. So an HCV RNA should be done if
you see elevated liver function tests. Let me spend a
second on urethritis. And this is just a list
of the percentages. And look, there’s a big
vacillation on how much urethritis is caused by,
for example, chlamydia. But the bacteriam and viruses
and other entities that can cause you urethritis– and
this is particularly in men– is gonorrhea, chlamydia, M.
gent, as we talked about. Ureaplasma is there, but
it’s anywhere from 0% to 20%. Trichomoniasis is considered,
herpes can cause it. Adenoviruses, enteric
bacteria– and Candida has even been involved in this. So there’s a big garbage
bag, if you will, full of causes for urethritis. How do you diagnose it? Well, look at the discharge. If there’s discharge there,
and you have no other tests– so the syndromic approach–
than that’s what you use. However, there are POC, point
of care, tests available. And these include gram stains or
methylene blue or jentz violet stains of the
urethral discharge. It used to be said– and this is new
data– that if you had greater than or equal
to five white cells per oil immersion field, then that
was a diagnosis of urethritis. And if you had gram negative
intracellular diplococci, that was NGU. But if you didn’t, then that
was non-gonococcal urethritis. But now with the use
of NAATs testing, we decreased the criteria to
greater than or equal to two white blood cells for
those of you that use this. If you don’t have a point
of care test available, then those who meet at least one
criteria for your urethritis– that would be discharge,
pain with urination– they should have
NAATs testing done for gonorrhea and chlamydia,
and you should treat them right there for both. If I have symptoms– I’m a guy and have symptoms–
but I don’t have any signs of inflammation– you
don’t see any discharge, there is white cells there– then NAATs testing may
identify an infection. And if you have that
available, you can use that. However, you may want to
consider treating them if they’re there for
gonorrhea and chlamydia. And you should do that if you
think there’s a high risk, and they’re unlikely to
come back for test results. Let men move to gonorrhea. Just a review– the
recommendations from gonorrhea are not taken lightly. There is the GISP, which
is gonococcal isolates surveillance program. I’m going to show you a slide
of where these are located, but it’s about 29
different clinics who collect specimens to
send to localized labs, who do extensive culture
sensitivity patterns on this. The CDC treatment
guidelines will not change the recommendations
unless there is anti-microbial
resistance greater than 5% to a particular antibiotic. Also, when you pick out
these antibiotics that appear in this guideline,
the antibiotics that are chosen
to treat gonorrhea have to be 95%
[INAUDIBLE] efficacious. And the lower 95% confidence
interval used to be 90%. But, in 1995, it was
bumped up to 95%. So you have to have, at least,
95% efficacy for these drugs to make it into the guidelines. You also consider
pharmacokinetics, pharmacodynamics, and some
of these are listed here. And the CDC, when we get
together and talk about this, think about the mechanism
of action, the side effects, and safety. How much does it cost? All of these are factored
into recommendations that appear in this document. And this is an example
of the GISP sites and the regional laboratories. The regional laboratories–
traditionally, there were four that are listed here. They’re adding Austin,
if they haven’t already. And the clinical sites are
peppered throughout the United States. This is a great way to
monitor gynecoccal resistance in the US. And we’re lucky to have it. This just shows cefixime,
what happened with cefixime. The percentage of isolates
with elevated cefixime minimal inhibitory concentration. And I’m going to say
that for those ID folks that are sitting in the
audience or at home. This is a lower MIC than
you would necessarily use, because they want to know
a harbinger of resistance. And what happened when the
2010 treatment guidelines came along, dual therapy
was recommended, and cefixime was still in that
ceftriaxone plus azithromycin or doxycycline. But then, because it
stayed high, in 2012, there was an MMWR that said
cefixime was no longer first recommended for this therapy. Over time, it’s
gone down, but I’ll talk about the new
guidelines now. This reflects isolates
for ceftriaxone. Ceftriaxone, again, the level
that we’re looking at– the MIC is low. But it’s a harbinger
of things to come, so we want to know
what’s happening. And again, this is pretty good. It’s still the drug of choice. I will say, however, that in
other countries, particularly Japan, Australia– the MIC for ceftriaxone
is creeping up. And there have been resistant
gynococcal infections to ceftriaxone that
have been reported. Particularly, one
sentinel event was from a woman with a
gynococcal isolate from her throat in Japan that
had high-level resistance to ceftriaxone. So we are very aware of that
and watching it carefully. The recommendations for
uncomplicated gynococcal infection of the
cervix, the urethra, or the rectum are
ceftriaxone 250 in a single, intra-muscular dose,
plus azithromycin– 1 gram orally. If you can’t get your
hands on ceftriaxone, well then cefixime
is an alternative, but they’d rather you get
your hands on ceftriaxone. Now some people think
well, you can go back to the old drugs, right? You haven’t used them forever. But gonorrhea is a very– I know I’m
anthropomorphizing, but it’s a smart, little bacterium. And once it picks up resistance,
it remembers resistance. So this is just
showing tetracycline hasn’t been used to treat
gonorrhea in forever. But still, the isolates
remember that it’s resistant, and we can’t use it. So that’s what a theory is. You can use the old drugs. Doesn’t work with GC. Azithromycin, you can see here,
still has really good efficacy for gyncoccoal infection. But, also, other countries
have been showing that the MICs are creeping up. So GC treatment– there are
no clinical data right now to support increasing the
dose of ceftriaxone from 250, say, to 500, or azithromycin
as part of the dual therapy that we’re recommending. Now listen, higher
ceftriaxone doses and, or azithromycin doses are
recommended outside the US, in, for example,
the UK and Japan. But that’s based on modeling
data, not clinical data. So the CDC is sticking
to its guns on this. Ceftriaxone treatment
failures have occurred, but not in the United States. Azithromycin monotherapy
is effective. I’m not saying
it’s not effective, but it’s not recommended. Monotherapy with
azithromycin is not recommended because of
the ease of resistance. So can you use it if your
back is against the wall– probably, but it’s
not recommended. Test of cure is not needed. You don’t have to
do a test of cure if you treat urogenital
or rectal infections with the recommended or
alternative therapies. But if you use anything
except ceftriaxone and Azithromycin
for pharyngeal GC, you do have to do
a test of cure. So if you use
anything outside of the recommended or alternative
treatment for pharyngeal GC, you do. Why– because GC of
the throat shares a lot of information with other
organisms in the throat. And usually that’s
where resistance first pops up, because they
like to share resistance. So there is a paragraph,
in the treatment guidelines that are coming out, that
discusses possible treatment options. There was an NIH-sponsored,
randomized controlled trial by Kirkaldy at the
CDC, and it was published in CID, Clinical
Infectious Disease in 2014, looking at gentamicin, 250 IM,
plus azithromycin, two grams oral, or gemifloxacin,
320 milligrams, plus azithromycin, two grams. And there are data in vitro. In vitro is like
in the test tube that says there’s an
additive effect of gentamicin and azithromycin. It’s not in humans,
but it’s in vitro. And gemmafloxacin
is the other drug that was combined
with azithromycin, and it’s has more activity
against the ciprofloxacin resistanting gonorrhea
that have these mutations, and, thus, confer resistance
to the ciprofloxes. And then that’s GyrA and ParC. And these are the
data here, and I won’t go through them for time. But if you want to look– all I will say is there’s a lot
of patients in these studies that have urethral and cervical
infections, but not too many that have pharyngeal or rectum. So just be aware of that. These are expensive
drugs or with gentamicin it’s not it’s a shot
that’s not unpainful, if I can say it that way. So if you suspect
treatment failure, then one thing to remember
is most treatment failure is due to reinfection. So if treatment
failure is suspect, then you should
indeed obtain culture, find who’s doing culture,
and send that culture to either the state or your
laboratory if they’re doing it. And the request
susceptibility testing. So treat. If you think that
reinfection is likely and you treat it with
ceftriaxone, and azithromycin, then you can give it again,
same dose, same regimen. If you treat it with
cefixime, the oral cefixime and azithromycin,
then you should treat with a shot of ceftriaxone
and the azithromicin. If treatment failure
is suspected, and you know, you run
out of options, then what we talked about in
the previous slide is, if you can get your
hands on it is available, you need to report this to
the local or state health department. And you need to
do a test of cure with a culture in
seven to 14 days. Make sure that
partners too do it. Let me go on to chlamydia. Now, this is
something to remember. It’s not new data. But it’s data that’s
kind of gotten forgotten. The effectiveness
of azithromycin to treat chlamydia infections
is less than doxycycline. In other words, doxycycline is
better for treating chlamydia than azithromicin. There are several trials
that are out there. And there are several
rectal infection studies that have been done
and we’ll talk about that. There is doxycycline that we
have delayed release, which is called Doryx,
and that’s going to be on the treatment
guidelines, 200 milligrams every day, instead of
doxy, 100 milligrams twice a day for a week. Amoxicillin has been removed
as an alternative regimen in pregnant women because,
for several reasons. In-vitro studies demonstrate the
penicillin, which amoxicillin is a type of penicillin, induces
persistent viable noninfectious chlamydia forms that can
revert to infectious forms after you stop the penicillin. Earlier amoxicillin
treatment studies in chlamydia in pregnancy, they,
the ones that we’re basing on, they had major limitations. So you know, on this finally
a randomized controlled trial by Kacmar and associates
showed higher test of cure using a NAATs test,
LCR lygase chain reaction with azithromicin
versus amoxicillin. So amoxicillin has
fallen to the wayside. Azithromycin versus doxycycline,
these are three trials. This is the efficacy,
and you can see early on, doxy was a little bit better. But as we march
through time it looks as if doxycycline does
better than azithromycin when you’re looking at chlamydia. And these are some
of the studies. And again, I put
this slide up there for you to look at for data. Syphilis. Syphilis is back. And it’s back big time. And it’s back among men
who have sex with men. Here’s a primary and
secondary stage syphilis reported from the 2012
data by stage, sex, and sexual behavior. And looking at primary and
secondary, primary being dark blue, secondary
being light blue. Look at MSM. We have a lot of it is
what I’m trying to say. Look for it. Now listen, there
is no test, there is no magic bullet
for this diagnosis. There’s a magic
bullet for treatment, but there’s no magic
bullet for diagnosis. There are no treponema pallidum
detection tests available now. So we’re stuck with serology. OK? Now, serology you
want to see an RPR, a VDRL, the titer
decline fourfold in a specified amount of time. Well, syphilis doesn’t
always read this textbook. So, according to stage,
if you have earlier stage disease, primary, secondary,
maybe even early latent, they’re more likely to read the
textbook and decline fourfold after treatment. That titer, if it’s
a low titer, it may be less likely to decline
and then a higher titer. So we have to grapple with this. This has not changed. This is the same. The time between penicillin
doses is also an issue. If I have primary or secondary
or even if you can diagnose me with early latent, one
dose, 2.4 million units of long acting bicillin, and
benzothene penicillin is great. Once you get into syphilis
of unknown duration, or latent early
syphilis, you have to give three doses
theoretically a week apart. OK, the last
treatment guidelines said that if you miss a week,
and you’re not pregnant, OK. These data that looked
at this more closely said actually, less than
nine days is best based on pharmacokinetic data. Meaning that you try to
get them in every week. If you get to nine days, OK. Once it gets past nine days,
it’s a little bit shaky. Best, nine days between
the three shots. Seven days in pregnant
women, done and done. Miss a dose, have to
start all over again. That’s non-negotiable. OK. The treatment algorithm, or I
should say diagnosis algorithm. We used to traditionally do
a non-treponemal test, which was a VDRL or a rapid
protein reagent test, RPR. RPR you do right there,
read it with your naked eye. VDRL, you have to
send it to the lab. It’s a flocculation test. They look at it
under the microscope. And then if it
was positive, we’d confirm it with a specific
treponemal tests, like the FTA, TPP, et cetera. Well, you know
these tests take– one tech has to do one
test for every person. And that’s time and
cost inefficient. So there’s new tests which
are enzyme immunoassay or chemiluminescent
assays, where you can run 100 serologies
in a card in one go. And this is much more, I’d say
cost beneficial to the labs. So this is a new algorithm. I just want you
to pay attention. You have an EIA or CIA. These are the new screening
test that if they’re negative, everything stops, done, stop. You don’t have syphilis. If it’s positive, then you
need to do an RPR or VDRL, and if that’s positive, then
it’s up to the clinician. Yes, you have syphilis. Now, where are you in
the stage of syphilis? Are you a treated old infection? Are you a new infection? Where are you in the staging? You’re not left out of that. You have to figure that out. If it’s RPR negative however,
another treponemal test needs to be done. So that could be
a TPPA or an FTA. When that test, that TPPA, is
negative, syphilis is unlikely. Again, look at your patient. Look at your patient. If that you think that they
may be at risk for syphilis or in an incubation
stage, then you know what? These tests may not have
caught up with the infection. If it’s TPPA positive, you
got [INAUDIBLE] positive, RPR negative, TPPA
positive, you have to figure out where that person
is in the stages of syphilis. Now if that sounds
complicated, it is. And there’s a half an hour
lecture I can give on that. But this is how we’re kind
of, not everyone’s doing this, but we’re moving more and
more toward it, so be aware. All right. Treatment is the same. There’s no difference. For penicillin
alternatives, you have doxycycline and ceftriaxone. Quite frankly that’s
been the same. Now azithromycin was mentioned
a couple of treatment guidelines ago. But the problem is
that azithromycin, the treponema
pallidum has come up with a mutation that
allows it to laugh in the face of azithromycin. So it’s more common in
men who have sex with men. And we do not use it therefore
in these populations, particularly. And we don’t use
it in pregnancy. So honestly,
azithromycin in the US is frowned upon for the
treatment of syphilis. OK. Evaluation of central
nervous system involvement, neurosyphilis. Listen, for sake
of time, anyone who has syphilis, serologic
evidence of syphilis, or signs or symptoms
of syphilis, and has neurologic
signs or symptoms, whether that be a facial droop,
blindness, decrease– and we’re having more reports of
blindness with syphilis in HIV positive
and negative men, auditory findings,
meningitis, stroke, anyone who has neurologic signs
or symptoms needs a spinal tap. We’re just going to stop there. Neurosyphilis diagnosis
is, is it’s difficult. There is no one way to
diagnose neurosyphilis. And it’s written here. CSF test, cell count or
protein, a reactive CSF VDRL, with reactive– you
have any of these, and you also have
reactive blood test, peripheral blood test that
shows the person has syphilis. And you may or may not have
neurologic signs or symptoms. Again, what I said, LP. Anyone who has a blood test
positive for syphilis or signs or symptoms and also has
neuro-ocular symptoms needs an LP. If you think there
is serologic failure, they haven’t declined
their titer fourfold in the requisite amount of time,
or they have tertiary syphilis, they need a spinal tap. Now there are some
data that say, some studies and mostly in
Dr. Christina [INAUDIBLE] from Seattle, in HIV positive
patients, many of them showed abnormalities, CSF
abnormalities if they had a CD4 count less
than 350 and/or RPR titer greater than 132. So some experts
recommend if you have a HIV positive patient
with these indicators, they need a spinal tap. However, other data
say that unless you have neurologic
signs or symptoms, we don’t know the
value of an LP. So, yes, there are
some debate about this. But this is how
the guidelines are going to stand on this topic. A mention of lymphogranuloma
venereum, and remember LGV is a type of chlamydia. It’s sero variety, L1, L2, L3. It tends to cause
nasty protocolitis. And there have been some
outbreaks in men or women who have receptive rectal sex. But there have been outbreaks
in the past 10 years of proctocolitis
being caused primarily by LGV among HIV positive MSM. And so MSM who present
with this proctocolitis signs or symptoms, bloody
discharge, diarrhea, rectal pain, they
should be tested with a rectal nucleic
acid amplification test for chlamydia. Now listen, you can do
PCR based genotyping, looking specifically for
LGV versus non LGV strains. But you’re not going to get
these results in real time. And you have to find
the laboratory that actually does that. So proctocolitis plus or
minus perianal ulcers, you have a patient that
comes in with that, you think it’s
sexually transmitted, you should presumptively
treat for LGV. And instead of one
week of doxycycline twice a day, it’s
actually 21 days. Painful perianal only, perianal
ulcers are mucosal ulcers that you see on an
anoscopy, you should think about herpes for that and
syphilis, whether it’s painful or not. Syphilis always and always
in the differential diagnosis with ulcers. OK, let me speak
on genital herpes. Now quite frankly,
there are not a lot of new data on genital herpes. Points to remember, however,
increasing proportion of anogenital
infections are indeed due to herpes type one, as
opposed to herpes type two. Most genital, anogenital
infections are herpes type two. But we are seeing
more HSV 1, and it could be related to oral sex. It’s both in young
females and in MSM. Don’t bother with an IGM test
because right now, the IGM tests are not useful. There are serologic
tests that you can use. They are listed here. There is HerpeSelect, for HSV-2
ELISA, and for HSV-1 ELISA. But mind you, they’re
not 100% perfect. There could be false positives. And this is that
a low index value. So if the lab is
using low indexes to call this test
positive, you may be getting more false positives
and you need to let them know. And for herpes,
HerpeSelect HSV-1 ELISA, it can be insensitive actually. So if you’re relying
on these two tests, it could be problematic. There is a paper
that is circulating that compares all of these
in different populations. I’m one of the authors. But don’t blame me. I don’t know where the paper is. I think it’s in CDC clearance. I’m not sure. But it’s great. And when it comes
out it will show the difference between tests
among different populations. So I think the 2015 treatment
guidelines may come out before this paper does. There’s no change in
recommended therapy. OK, a word on HPV. Now if you haven’t heard,
I think in February, 2015, the new 9-valent HPV vaccine
has become available. It’s FDA blessed. Not every clinic has it. It’s not rolled
out completely yet. And I can’t tell you the cost. So right now, what you
have is ACIP HPV vaccine recommendations from 2014 and
they have not been updated. I will tell you, I just
listened to a webinar that was conducted by the CDC. And basically, if you
are starting someone on the HPV vaccine,
which is the 9-valent, and you get your hands on,
or I’m sorry the 4-valent, and you get your hands on the
9-valent, then the next time if you shoot up someone with
the 4, and they come in, and the 9-valent is available,
then give them the 9-valent. Otherwise I cannot comment on
booster doses or catch up doses or anything like that,
because it wasn’t discussed in the webinar. And I don’t think they’re
ready to change the vaccine recommendations yet. So, the only thing
that you have to be aware of with HPV treatment,
and honestly, everyone should get vaccinated and
prevent the possibility of even having to be treated. But what is out is
the podophylin resin. We no longer recommend
it, because there have been cases of
serious systemic toxicity, including death with this. And there’s no clear efficacy
benefit when you compare it to the podophylotoxin of old. Imiquimod is great. It’s the 3.7% you can
apply every night. Patient can apply it
themselves to the genital wart, for I think a week or two. There have been
some case reports, and there are a few, of
inflammatory responses to this imiquimod, but
these are in patients that usually have some
sort of skin condition that they’re applying
this medication. OK, word on risk to
healthcare workers who treat genital warts. HPV DNA actually can be
found in the smoke plumes after laser or electrosurgical
therapy of extragenital warts, CIN, or common warts. There’s two case reports
of laryngeal papillomas that were reported in
healthcare workers who were exposed to the smoke
plumes when they were treating. So if you’re doing
this, if you’re freezing or doing any of the
electrocautery or CO2 laser, you should wear a
protective mask, which is usually a full mask. Or if you’re using ablation,
and you’re going after CIN, then perhaps you should use one of
the local exhaust ventilation smoke evacuators. Depends on your practice,
in our RSCD clinic, we usually have the head masks
that there are plastic shields that protect from plumes. Anal cancer screening. Listen, HPV vaccination
of MSM should be routine and hopefully, we won’t be
talking about this, please. But right now, there are
some clinical centers who perform anal cytology
in high risk populations. And if you happen to have
one of these centers, then it’s a good idea maybe
to do this and then refer. But if you don’t have
any place to refer, then that’s a conundrum. And you need to think
about whether you want to do screening or not. The data are insufficient to
recommend routine anal cancer screening with anal cytology. We need more evidence. We need safety in response
to treatment data. And the CDC says,
you have to think about the programmatic
considerations of your particular program
if you’re going to do this. High risk HPV tests are
not clinically useful for anal cancer screening
as of this rendition of the guidelines because of
the high prevalence of anal HPV infection. So vaccinate and let’s
try to eradicate this. Now I’ll spend a
second on trichomonas. Trichomonas is a
very interesting bug. These are data that
was published in 2012 in the Journal of Clinical
Microbiology using NAATs test to determine the prevalence
of trichomonas, chlamydia, gonococcal infection in among
7,600 almost, US women who are 18 to 89 years of age. And I believe this
is the NHANES group. And if you look here,
look, what you expect, chlamydia is in the
light white bars. And that declines over time. And gonorrhea is not
as high as chlamydia, and again, that
declines over time. But look at trichomonas. You get it and you
get it and you get it and you supposedly get more. It’s very interesting. I think this is an interesting
thing to keep in mind. And again, remember
this is using nucleic acid amplification
testing, not wet prep. So it’s much more sensitive. So something to keep in
the back of your mind. Consequently, here’s what the
guidelines are going to say. Consider screening of
those receiving care in high prevalence settings like
the STD clinic or corrections or in asymptomatic persons
at high risk of infection, those that come in say they
have multiple partners. We lack data on
screening and treatment however, to reduce
the adverse events and to reduce disparities in
the prevalence of the diseases. Screening decisions are
informed by the epidemiology. Now, if you want to do
the best test available, then nucleic acid amplification
testing is the way to go. There are several types
that are available. I’m not saying that
they’re inexpensive. I can’t tell you
the exact price. But actually, it’s much
more sensitive to use these than to use any other method. So, if you have someone– this is new. If you have someone that
you treat for trichomonas, you really need to retest
them for trichomonas in three months, just like you
do for gonorrhea and chlamydia. Trich is now added. Mind you, it’s not
a test of cure. It’s a retest. Because many women who
have any of these three get reinfected in the next three
months after you treat them, because they go right
back into a sexual network where the prevalence of
these infections are high or they get re-infected from
a partner that wasn’t treated. The treatment is the same. Is there a resistance to either
of these nitroimidazoles. Well, it’s been reported and
here is two reports here, that it’s between 4% and 6%. Now, the reason why we’re
talking a little bit about this is because of the really tight
association of trich and HIV infection. And this slide illustrates that
trich is an independent risk factor for HIV acquisition. So if you look at any
of these three studies, you’ll see that the odds
ratio for acquiring HIV, for having HIV if you have
trich, or for getting HIV is two and above, 2.1 to 2.7. The maternal trichomonas
vaginalis infection is a risk factor for
vertical transmission of HIV also to the neonates. So we are paying close
attention to trich and we would love
to get rid of it. So there is a section
about how to deal and treat trichomonas in HIV infection. We know that women
with HIV infection should receive screening when
they come in for HIV care. They enter the continuum
of care and annually if they’re sexually active. It has been associated with PID,
although this is an old study. And there have
been data that show that if you treat trichomonas
and the woman also has HIV, it does decrease
genital HIV shedding. That’s a good thing. However, if you’re
going to treat, you’re going to treat
with a longer course. You need to give metronidazole,
500 milligrams twice a day for seven days, not two. Or you can give
tinidazol for longer. Factors that may influence
whether the woman clears her trick or not
could be whether she has concominant BV infection. Is she on adequate ARVs,
anti-retroviral therapy? What else is going on
in the vaginal ecology? Now, that’s great. This is HIV infection in women. We don’t have enough data
to make any suggestions and extend these
recommendations to men. But again, you should retest. After you treat someone, you
should retest in three months. BV. Nothing’s really new right
now on BV as far as treatment. But there is a nice section on
recurrent bacterial vaginosis, which I know plagues a lot of
women and their clinicians. And these are the listed
things that we talk about. And I’ll just highlight some. Bi-weekly suppression
with metronidazole gel, and that was a
randomized controlled trial. And that was given
for four to six months and it seemed to be working. And then it’s a
combination of either metronidazole or tinidazol
gel or oral tablets for extended periods. And you can read about
this in the guidelines. We are awaiting data that
will inform us about treatment and how good it is with regard
to if the woman is vitamin D deficient or if it has
anything to do with her BV risk or what contraceptive
she’s taking. And there is an
L.crispatus vaginal capsule which would be really
great for BV prevention. But that’s in process and
we don’t have data yet to recommend any of that. In sexual assault in adults,
well, the initial examination, you always have to
individualize it. But you should think about
NAATs testing for gonorrhea, chlamydia, and NAATs or
point of care test for trich. Always think about HIV
screening, syphilis and hepatitis B
screening if they haven’t gotten the vaccine. And the prophylaxis
is written here. Empiric treatment for
gonorrhea, chlamydia, trich. Think about and give
emergency contraception if it’s appropriate. Post-exposure hepatitis B
vaccination, if she hasn’t been or he hasn’t been
vaccinated, HPV vaccination, and think about HIV
post-exposure prophylaxis according to the risk. And the CDC has a brilliant
algorithm that you can go to or have, I would suggest have on
hand if the situation comes up. This is the motley
crew that we’re all here down at the CDC
that met in Atlanta to review these guidelines. And if you have
any problems, call any of these people except me. OK, these are the resources. The Maryland DHMH, Department
of Health and Mental Hygiene has the 2010 guidelines
available for you. And hopefully we will
have the 2014 or 15, however they call
them guidelines up as soon as they come out. And there’s some
information if you need more from the state of
Maryland with your questions. And remember, if
you have questions that we need to discuss, you
can email this [email protected] And I’m going to try to
take some questions now. AUDIENCE: Are
there any questions from the live audience here? No, Barbara Conrad,
our [INAUDIBLE] for the Center for
STI Prevention at DHMH has several questions
and will meet you the podium in one minute, Anne. DR. ANNE ROMPALO: OK. Let’s hope I can
answer your questions. I’ll do them justice. BARBARA CONRAD: Trich questions? DR. ANNE ROMPALO: Yep. BARBARA CONRAD: Trich
questions as in trichomonas? DR. ANNE ROMPALO: Yep. BARBARA CONRAD: All right. DR. ANNE ROMPALO: Is that on? BARBARA CONRAD: I think– DR. ANNE ROMPALO: Is this on? Well, talk to me and
I’ll repeat the question into this live mic. BARBARA CONRAD: It says it’s on. Does trich in a co-infected
patient, co-infected with HIV, also increase the risk for
transmitting HIV to partners? DR. ANNE ROMPALO: Yes. There have been data both ways,
transmission and acquisition. So, the mere fact that
if you treat a woman, and I think no, actually
it’s women and men. If they have trichomonas and
you treat them and their HIV infected treatment decreases
the HIV, the amount of HIV in the secretion, and
for both men and women. Most of these studies
were done in Africa. And I believe the first
study that was done in men was done by Mike
Cohen and a cohort. And I can’t remember
the country, but it was an African
study, great study. BARBARA CONRAD: Regarding the
increase in vaginal trichomonas in women as they
age, could this be related to changes in pH
or other biome factors? DR. ANNE ROMPALO:
Great question. I personally have arguments with
Charlie [INAUDIBLE] about this. I wonder, OK, first and
foremost, trichomonas loves hormones. There are studies done
by several investigators, one in Texas, Dr. Alderete,
looking at trichomonas growth factors. And it loves to grow in
the presence of estrogens and in the presence of blood. So pregnant women
tend to have a really lot of trichomonas
during pregnancy if they are infected at all. But one wonders if
women start to use– and this is a wonder. This is all it is. I have no data to back this up. If some of the spikes in
infection in older women are not necessarily
as tightly bound to new sex partners
or sexual activity, but indeed pH and
vaginal or microbiome changes as a woman
goes through menopause or as she uses estrogen
creams topically. So I don’t know. And the data are out. But it is fascinating. BARBARA CONRAD: What are
the new recommendations about including gonorrhea in
expedited partner therapy? DR. ANNE ROMPALO: Ha, ha. Expedited partner therapy. I didn’t put a slide up there
because actually it stands. So I know it is a
state by state issue. Some states say
yes, you can treat for both gonorrhea and chlamydia
expedited partner therapy. We just had a bill
passed here in Maryland. Elizabeth is sitting
here who knows. What are we talking
about in that? We definitely do chlamydia. And we do gonorrhea if you know
that the patient’s partner is not going to come in. And remember, expedited
partner therapy is based on re-infection
in decreasing the prevalence of disease. Ideally, you would love
to have people come in or get tested someplace
to see if they have it or not, but that doesn’t
necessarily always work. So some states say both for
gonorrhea and chlamydia. Other states like New
York says chlamydia only. It’s a state by state issue. BARBARA CONRAD: Thank you. What is the treatment
recommendation for treating oral gonorrhea? DR. ANNE ROMPALO: What is
the treatment recommendation for treating oral gonorrhea? It is ceftriaxone 250
plus azithromicin. Alternate is the same. But if you have to
go with cefixime, then you have to
go with cefixime. But if you do anything except
those two recommendations, you’ve got to do a test to cure. Now the problem with
oropharyngeal gonorrhea remember, and it has
its own section– they’re watching me for time,
let me know if I’m going over –is that it’s asymptomatic
most of the time. You need to screen
according to risk. And finally, it historically
or been difficult to treat. I mean all this stuff,
ceftriaxone is great. Cefixime has been great. But we just want
to be very careful. So as it comes out,
unless things change, it’s almost the same. It is the same,
except they talk more about the alternative therapies
in the treatment guidelines. BARBARA CONRAD: OK thank you. Any further audience audiences
from the questions, right. Any questions from the audience? No? And nothing else coming in
on line, so I think we’re– DR. ANNE ROMPALO: OK. Well thank you one and all
for coming and listening. And those of you that
listen in the near future when this is put up, if
you have any questions, then hopefully maybe we can
send them to DHMH and Elizabeth LeBeau will shoot them to me. I just volunteered her. BARBARA CONRAD: Yes. DR. ANNE ROMPALO: All right. Thank you very
much, one and all. We appreciate it. And remember April is
STD Awareness Month. Get yourself tested. Get yourself treated. Get yourself talking about STDs. BARBARA CONRAD: Yes. So thank you Dr.
Rompalo and thank you all for participating. Just to remind you, today’s
PowerPoint presentation will be posted on the website
the next couple of days and the webcast
archive should be available in about two weeks. Thank you. DR. ANNE ROMPALO: Thanks again. [APPLAUSE]

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