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Grand Rounds (week 4): Herpes Update

Terri Warren
this lady is THE reigning expert in this field and she is an excellent speaker
over 30 papers about HSV in her name
degrees are in psych and nursing
owner of Westover Heights Clinic x30years

INCIDENCE
HPV is a more incident infx, more people get it per year
HSV is more prevalent because harder to clear, more out there
56% of pop have HSV 1
numbers reducing dt less contact among humans, parents with cold sores know not to kiss kids
30% of women in their 30's in the US has HSV 2, 90% don't know it
women are 2x more likely to be infected than men
teens are getting HSV1 genitally more than ever before, seems to be preventive of HSV2 infx
78% of new genital herpes infx were HSV1 in one college study
auto-innoculation usu occurs with 1st infx only, because then there is an immune response systemically
concern: ocular infx
70% of transmission occurs from people with no sx

MOST INFX ARE MISSED
most infx are subtle, not dramatic, people don't recognize sx until educated
outbreaks in entire boxer shorts area (sacral ganglia)
people attrbute sx to other things: yeast infx, UTI (herpetic urethritis has dysuria but no freq/urge) in females
3% of urethritis is prob herpetic
often misdxd as shingles/VZV by providers (if recurrent much more likley to be simplex than zoster)
existing HSV1 infx amerliorates HSV2 outbreak, mb completely ASX
people aren't being tested

PRESENTATION
50% of recurrence are in same location, 50% in new

DIAGNOSIS
if sx: swab the area, test for zoster and simplex virus
when swabbing use only plastic shaft and dacron/poly tip, no wood or cotton; they inhibit viral growth
be very aggressive, tell pt count to five with me, scrub them, she often draws blood from swabbing
some pts can't handle the pain, but she goes to pt tolerance
break tip off in media
order "HSV PCR with typing" only (4x more sensitive and now FDA approved), the other type of swab test is culture
cannot use IgM to sort old from new infx in HSV, IgG can't tell HSV1 from 2
early antiviral treatment reduces antigen presence and immune response

if no SX order serum IgG type specific antibody test (no crude antigen testing!)
HerpeSelect (Quest) is most used (ELISA, Immunoblot, Express is currently off market)
result is a number .9 and below neg, .9-1.1 equivocal, over 1.1 is positive (96% are neg or pos) there are some false positives
if pos but below 3.5, confirm test with another test , 2-2.5 50% are false pos, over 2.5 almost all confirm, over 5 is pretty sure
you can ask for confirm via Western blot at UWa without having to redraw blood
if your lab doesn't send there, find out what they can do
don't tell someone they have an infx if they may not!

Biokit (in office test)
looks for HSV 2 has pretty good sensitivity and specificity
need moderately complex CLEA cert lab to do it

Captia
another kind of ELISA
pretty commonly used
ranges similar to HerpeSelect

Physical exam is worst way to dx HSV
experienced clinicians wrong 1/5x
miss it far more often than that
most herpes is subtle in presentation

pt thinks she scratched herself or injured via shaving
outbreaks on buttocks last longer (~2x), scar tissue is common
in labia scarring more common, depigmentation more common
if buttock lesion genitalia are contagious even if no sx there

HSV1 usu goes mouth to genitals, can happen in monogamous relationship
HSV1 recurs about .7x/year
HSV2 recurs average 3-5x/year
HSV2 largely protects vs getting HSV1
HSV1 does not protect vs HSV2 though HSV1 genital reduces risk of HSV2 genital infx
person with HSV2 genitally will prob never get HSV1 anywhere

Tx mb different for two
early suppression for new HSV2: daily therapy
may not be necessary for new HSV1
person with HSV1 orally can likely have sex without transmission with the person who has HSV1 genitally (has Abs)

new stat: if no recurrence of HSV1 in first year there's 88% chance it will never recur
HSV1 very benign in genital area

HX
childhood cold sores?
recently onset cold sores?
genital lesion hx?
sex partner hx?

if virus is present on swab but negative in serum => new infx

SCREEN IN
current or previous partner has HSV
negative swab test from lesion that looked like HSV
document 1st in
has been dxd by PE (20% of clinical dx are incorrect)
requsting STD screen
recurrent vague genital sx or dysuria/pyuria
HIV positive pts on HSV suppressive therapy live longer, 70-80% of HIV pts are positive

pts not infected usu have low number
3 weeks 50% seroconvert
6 weeks 70% seroconvert
4 months most everybody seroconverst
confirm 1.1-3.5 possitives
do not use IgM

more false positives in HSV1 pts

IgM present in 35% of recurrences

sensitivity of ELISA
96% for HSV2
90% for HSV1

sensitivity of Western Blot
many pts pos by swab and neg by blot (she would like to know if this happens in our practice with HSV2)

she does herpes consults on the phone with pts from all over the world

case: IgM pos, IgG neg, still neg IgG later, people think they have HSV but they don't

case: HSV2 pos male and HSV1 pos female, new relationship:
(2 is protective vs 1 but not the other way)
ask female: ever had genital lesions or cold sore?
is the relationship meaningful? more willing to take risk if so
doc's guidance:
v imp to discuss virus and have it known in relationship
time to transmission was 240 days in couples when it was known
time to transmission if unknown 60 days
consider daily suppressive therapy

REDUCE TRANSMISSION
condoms reduce by 30%
daily antiviral therapy (vallecyclovir is only one studied) 48% acyclovir probably the same
become aware of sx
knowing

CODES TO USE TO ENCOURAGE INSURANCE COVERAGE
genital itching 689..1
pain with intercourse 625.0
pain with urination 788.1
female with genital pain 625.0
neuralgia 724.3
burning, tingling, numbness, prickling of genital area 782.0

TRANSMISSION RATES
in couple aware that one has HSV2, abstaining from sex with outbreask
not using condoms, not taking antivirals
10% male to female per year transmit
4% female to male per year transmit
varies among studies, this is composite
this is people who didn't transmit in first 3 months

70 million dollar study, lost data when couples broke up, but info was good
not taking antivirals was control group of study
add antivirals gets down to 5 and 1%
add condoms gets down to 2.5 and .5%

in her clinic they've done 4 herpes vaccine trials, all have failed

mc time of transmission is in first 3 months of relationship
more sex, longer sex

LAWSUITS ABOUT TRANSMISSION
common
can only win if documented that person who go it didn't have it yet
or if new infx is swab test pos and antibody negative
did you insist on STD testing prior to having sex with this person?
suing does little for adjustment to HSV

ANTIVIRAL THERAPY

FOR FIRST EPISODE
tx 7-10 days with refills, most use refills
acyclovir 400mg po tid 710d or
famciclovir 250mg po tid 7-10d or
valacyclovir 1g po bid 7-10d
all work equally well when taken as directed, compliance is different, price is different

FOR EPISODIC
Acyc 800mg tid x2d
fam 1g big 1d
vala 2g po then 12 hours later, 2g again in one day
start at the first sign of prodrome-->no outbreak

has no effect on trans

SUPPRESSION
daily therapy for someone with uninfected sex parter, multiple partners, new HSV2, late in preg, high risk for HIV acquisition, wanting fewer outbreaks
ACYClovir 400mg bid
FAMciclovir 250mg bid (tid for preg)
VALAcyclovir 500mg qd OR 1g qd (bid for preg)
take 5d prior to hot date
"episodic suppression"---use it 5d prior to big trip or sex binge
doesn't need suppression: not sexually active, not bothered by infx, couples who decide not to worry about it

sunlight is only known trigger

more likely to shed virus in first 3-4 months of infection
shedding continues even in longterm infections, somewhat less
tests for that via daily home swabbing, sx aren't informative

she doesn't "have good luck teaching people to abstain"

HX: how was it dxd?
if PE: swab and type specific ab
case: she's pos for 1 and having 2 wks of sx /mo-->it's not the HSV
case: she's pos for 2-->put on suppression-->months later no better-->it's not the HSV

HX: sx all the time? not HSV
suppression makes no difference? not HSV
resistance is .03% for those who are not immunocompromised

SHEDDING
there's no day that's safe
HSV2 genital sheds 15% of days
HSV1 oral 9-18% of days
HSV1 genital 5% of days
HSV2 oral 1% of days

HSV2 doesn't like to be on the mouth, doesn't reactivate much

some correlation between shedding and outbreaks but not strong
can have outbreak without much shedding and vv
no proven correlation with menstrual cycle

best resource: American social health org
http://www.ashastd.org/
CDC.org get STD guidelines
pubmed she gets alerts about all HSV articles

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