STD Update
WAPA Winter Conference, 2013
Julie Dombrowski, MD, MPH
Assistant Professor, Medicine/Infectious
Diseases
Medical Director, King County STD Clinic
Overview

Cases highlighting key points

Chlamydia and gonorrhea - gonorrhea resistance

NGU

Syphilis - testing algorithm

Genital Herpes

Vaginitis

Miscellaneous key points

Revisit cases
Case 1
A 22 year-old woman comes to your clinic for “a check-up”.
She is sexually active with her boyfriend and had one other
male partner in the past year. She had a “negative STD
screen” prior to starting her relationship with her boyfriend.
She does not need a Pap test today.
Which is the most appropriate testing in this case?

A) Urine specimen for chlamydia and gonorrhea culture

B) Cervical swab for chlamydia and gonorrhea nucleic
acid amplification test (NAAT)

C) Vaginal swab for chlamydia and gonorrhea NAAT

D) None of the above – she does not need STD
screening
Case 2
A 24 year-old man comes to see you for urethral discharge
and burning with urination x 3 days. He has had 4 female
sex partners in the past year. On exam, you find yellowish
penile discharge. You do not have access to a
microscope, but you plan to send a urine sample for
gonorrhea and chlamydia NAAT.
How will you treat him?





A) No indication for treatment today – await lab results
B) azithromycin 1gram po x 1
C) cefixime 400mg po x 1 + azithromycin 1gram po x 1
D) ceftriaxone 250mg IM + doxycycline 100mg po BID
E) ceftriaxone 250mg IM + azithromycin 1 gram po
Case 3
A 29 year-old new patient comes to see you about “sores
on my penis”. On exam, you see:
What is the most important history
question for diagnosis and
appropriate treatment in this
case?




A) Have you ever had this before?
B) Do you have sex with men, women or both?
C) Did you have tingling before you saw the sores?
D) Are these painful?
Case 4
You are seeing a 26 year-old woman for follow-up after her
first prenatal visit (G0P1), at which she was screened for
syphilis. She and her husband have been monogamous
and married for 3 years. Her test results are:

T. pallidum EIA:
POSITIVE

Rapid plasma reagin (RPR):
NEGATIVE

T. pallidum particle agglutination assay (TPPA): NEGATIVE
What do you tell her?




A) She has syphilis and needs treatment
B) She has syphilis, she needs treatment, and her husband needs
testing and treatment
C) She might have syphilis, she needs treatment, and her husband
needs testing and treatment
D) She does not have syphilis. She has a false positive test result.
Case 5
A 27 year-old woman who requested serologic screening
for herpes has a positive HSV-2 antibody using a FOCUS
EIA assay with a value of 3.8. She has no history of clinical
herpes.
What do you tell her?
A) She very likely has genital herpes caused by HSV-2,
and just never had a symptomatic outbreak
B) The HSV-2 antibody result is probably a false positive
C) She is probably actively seroconverting to HSV-2,
having acquired it from her current partner
D) You need to check a Herpes IgM antibody to clarify the
results
Chlamydia & Gonorrhea
Chlamydia—Rates by Sex, United States,
1991–2011
NOTE: As of January 2000, all 50 states and the District of Columbia have regulations that require the reporting of chlamydia
cases.
2011-Fig 1. SR
Pelvic inflammatory disease — Initial visits to
physicians’ offices by women 15 to 44 years of age:
United States, 1980–2010
500
400
300
200
100
0
0
2
4
6
8
0
2
4
6
8
0
2
4
6
8
0
8
8
8
8
8
9
9
9
9
9
0
0
0
0
0
1
19
19
19
19
19
19
19
19
19
19
20
20
20
20
20
20
SOURCE: National Disease and Therapeutic Index (IMS Health)
Chlamydia Incidence Rates Among Women By County Washington State,
2010
Whatcom
422
Okanogan
San Juan
385
Pend
Ferry
Skagit
Stevens
421
245
Island
334
188
Snohomish
Clallam
371
334
Jefferson
261
Chelan
366
King
Mason
Grays
346
Harbor
Douglas
317
Kittitas
Thursto
n
684
324
237
*
Wahkiakum
524
509
Adams
Whitman
796
421
Lewis
332
Cowlitz
496
Clark
Washington State Department of
Health
Spokane
*
Grant
453
Pacifi
c
Lincoln
407
46
3
Pierce
321
469
Yakima
Franklin
825
726
Garfield
Columbia *
*
Benton
531
Skamania
Walla Walla
420
299
Klickitat
238
STD/TB Services
IDRH Assessment Unit
Oreille
* Rates are not calculated
from 0 to 4 cases because
they are unreliable.
Asotin
Asotin
284
5
County Incidence Rates Per
100,000
Rates not calculable
<300
301-500
>500
Chlamydia



Incidence increasing
Morbidity appears to be decreasing
We need to:
 Improve screening


Improve partner treatment


~57% of eligible women in WA State screened annually
Expedited partner therapy
Improve rescreening

Rescreen all persons diagnosed with chlamydia 3 months
after treatment
Major Clinical Syndromes Caused by C. trachomatis
Syndrome
Anatomic Site
Women
10-20%
Sequellae
Pelvic Inflammatory
Disease
Urethra
Urethritis
Bartholin’s glands
abscess
Cervix
Cervicitis
Ectopic pregnancy
Rectum
Proctitis
Chronic pelvic pain
Infertility
 Most (80-90%) women
infected with chlamydia have
normal cervix / no signs
~24,000
women
per year
in the US
Randomized Trials of Chlamydial
Screening
Author
Population
Design
PID Incidence in
Untested (per 100
person yrs)
RR
Scholes
(1996)
♀ GHC
RCT screening vs.
no screening
2.2
0.44 (0.20.9)
Prevalence 7%
Ostergaard
(2000)
Danish high
school students
Prevalence 5%
RCT Screening vs.
no screening via
mail
4.2
0.50 (0.231.1)
Oakshott*
(2010)
♀ UK Students
RCT screening vs.
specimen collection
but not testing
1.9
0.65 (0.341.22)
Prevalence
5.4%
* 83% reduction in PID among women who tested CT positive at baseline. 79% of
PID cases occurred in women who tested negative for chlamydia at baseline
9.5% of women with CT at baseline who were untreated developed clinical PID
within 1 year
CDC Guidelines 2010:
CT & GC Screening for Women

Annual Chlamydia screening for all sexually active women
age ≤ 25


Older than 25 – screen women at increased risk



Gonorrhea screening recommended also
Multiple partners, drug use, commercial sex work, inconsistent
condom use, previous STDs
Other Criteria – IDU insertion, pregnancy
Above applies to women who have sex with women
Nucleic Acid Amplification Testing (NAAT)

Culture: cultivates live organisms




Not widely available for Chlamydia trachomatis
NAAT: detects genetic material (DNA or mRNA)
More sensitive than culture for GC and CT at all
anatomic sites
Vaginal swabs preferred specimen for screening
women, but urine and cervical also acceptable
Clinician-obtained
Patient-obtained
Partner Notification & Treatment


Sex partners from past 60 days should be evaluated,
tested, and treated
Expedited partner therapy (EPT) for GC/CT


Increases likelihood that partners are treated and decreases
Washington State DOH, 2004: “If treatment is not otherwise
assured, the patient should be provided antibiotics for their
partner(s). These medications must include appropriate written
information for the treated third party.”
Heterosexuals with GC or CT should be routinely offered
medication for their sex partner if you are not confident that
you can otherwise treat the partner(s)
PDPT Individual RCT
Trends in Chlamydia Positivity Among Women Age 15-25 Tested Through IPP Clinics and
Gonorrhea Incidence in WA State Women
Chlamydia Positivity
16
14
Cases/100,000
Percent
10
Gonorrhea Incidence
8
6
4
12
10
8
6
4
0
1
2
Time
3
4
0
1
2
3
Time
P<.001 for both chlamydial positivity and gonorrhea
incidence
Slide courtesy of Dr. Matthew Golden
4
Effect of EPT on Chlamydial Positivity and
Gonorrhea Incidence in Women, Randomized Trial
ITT Analysis
Chlamydial positivity in
women
Gonorrhea incidence in
women
Risk
Ratio
95% CI
.89
.77-1.04
.86
.69-1.08
* Analysis controls for secular trend that may have been ongoing
independent of the study intervention
Slide courtesy of Dr. Matthew Golden
Reporting a Case (WA example)
Step 1: Google “STD case report WA” and click on first link
Case Reports - Washington State Department of Health (DOH) Home Page
Jul 30, 2010 ... Access Washington Logo linking to Access Washington. Notifiable Condition Case
Report Forms for STD, by County. Click on the map to go to the Case Report ...
www.doh.wa.gov/cfh/std/casereports/de... - Cached - Similar
Step 2: Click on your county on this map
Step 3: Fill out this form & fax to the number at the top of the page
(partner instructions on back)
PDPT Packs in WA State
Information provided with
EPT
 Information about
medications & STD
 Advice about
complications and need
for care (e.g. PID)
 Where to seek care
Recurrent Gonorrhea & Chlamydial
Infection*
14
Men
Women
13.3
Percent
12
11.7
10
8
12.6
9.4
6
4
2
0
Gonorrhea
* In absences of PDPT
Chlamydia
Retesting: Test of cure vs. Rescreening

Test of cure for GC & CT?



Not recommended, unless

Pregnancy

Persistent symptoms in patient or partner

Uncertain adherence to treatment
Do not use NAAT sooner than 3- 4 weeks
Rescreen anyone with a positive test 3 months post
treatment

High rates of reinfection (not treatment failure)
Gonorrhea—Rates by Sex, United States,
1991–2011
2011-Fig 17. SR
GC: Tremendous Disparities

By race: Rates in African Americans >20x those in whites

By sexual orientation: MSM rates16x those in heterosexual
men in King County
CDC Guidelines 2010:
CT & GC Screening for Men

Selective male chlamydia screening in high prevalence
settings



Adolescent clinics, correctional facilities, STD clinics, military
MSM

A test for urethral GC and CT if insertive intercourse in past year*

A test for rectal GC and CT if receptive intercourse in past year*

A test for pharyngeal GC if receptive oral sex in past year
Rescreen anyone with a positive test 3 months after
treatment
*regardless of reported condom use
MSM: Extra-genital Screening is Key
 N=6434 men
Site
% of all GC
cases*
% of all CT
cases*
Urethra
21
29
Rectum
15
54
Pharynx
36
7
Rectum & Pharynx
12
4
Rectum & Urethra
6
6
Urethra & Pharynx
5
<1%
All 3 sites
5
<1%
 53% of chlamydia and 64% of gonorrhea cases
would be missed with urethral screening only
Kent CK, et al. CID 2005;41:67-73
NAAT for rectal and pharyngeal testing



>2x sensitivity of culture for rectal and
pharyngeal chlamydia and gonorrhea
Not FDA-approved, but can be done if
laboratory validation is complete (Lab Corp
has done this)
Can use vaginal swab for these sites
Update to CDC’s STD Guidelines, 2010:
Oral Cephalosporins No Longer a
Weekly / Vol. 61 / No. 31 gust 10, 2012Recommended Treatment for
Gonococcal Infections
Uncomplicated genital track or rectal gonorrhea
RECOMMENDED
Ceftriaxone 250 mg IM
PLUS
Azithromycin 1g po x 1 OR doxycycline 100mg po bid x 7d
ALTERNATIVE
Cefixime 400mg po x 1
PLUS
Azithromycin 1g po x 1 OR doxycycline 100mg po bid x 7d
PLUS
Test of Cure in 1 week
Rationale for Treatment
Recommendations
•
Pharyngeal infections
•
•
•
~30% of MSM and women with genital tract gonorrhea
also have pharyngeal infection
Oral cephalosporins have poor penetration
Decreased susceptibility to oral cephalosporins
•
Multi-drug resistant (PCN, quinolones, azithromycin)
•
Ceftriaxone still extremely effective
•
Higher doses of ceftriaxone and dual agent use may
discourage development of resistance
Percentage of N. gonorrhoeae Isolates with Elevated MICs
to Oral Cephalosporins, 2005- June 2011
Source: Gonococcal Isolate Surveillance Project
Distribution of Minimum Inhibitory Concentrations (MICs)
of Ceftriaxone Among Neisseria gonorrhoeae Isolates,
Gonococcal Isolate Surveillance Project (GISP), 2007–
2011
2011-Fig 30. SR
Percentage of PHSKC STD Clinic Patients with Pharyngeal Gonococcal Testing Positive for
N. gonorrhoeae within 180 Day of Treatment
• Patients diagnosed by culture 1993-2009 - Passive follow-up
• Patients treated with cefixime or cefpodoxime 400mg
• 277/817 (34%) patients retested – No variation by treatment regimen
50
Percentage Patients Retesting Positive
P<0.05 Cephalo+AZM vs
Cephalo
40
Alone or with Doxy
31
Percent
30
25
20
10
12
4
0
Cephalo + Cephalo +
AZM
Doxy
N=119
N=62
AZM
Alone
Cephalo
Alone
N=21
N=48
Source: Golden.
ISSTDR 2009
Gonorrhea Treatment Summary

Decreased susceptibility to oral cephalosporins is primarily
a concern for MSM

No gonococci in US are resistant to ceftriaxone (yet)

Decreased susceptibility strains are rare in heterosexuals

Recommendations:

All patients with GC should be treated with ceftriaxone and
azithromycin (preferable to ceftriaxone + doxycycline)

Continue EPT for heterosexuals with oral cephalosporins

MSM should not receive EPT

All patients with GC should be rescreened 3 months after
treatment
Gonorrhea Summary & Treatment Recommendations
• No gonococci in the U.S. are resistant to ceftriaxone
• Decreased susceptibility to cefixime remain very rare
in heterosexuals
• Recommendations:
• Ceftriaxone + Azithro is first choice – NOT doxy
• Cefixime/Azithro is reasonable alternative when
IM therapy is not an option (try to avoid in MSM)
• Test of cure only indicated for:
• Persistent signd/symptoms
• Pharyngeal GC treated with non-ceftriaxone
regimen
• Pregnant women
• EPT recommendations unchanged – NO EPT in
MSM
Non-gonococcal urethritis
ORGANISMS DETECTED in MEN with NGU
Seattle MEGA Trial
(n=524)
NIH Trial (n=305)*
C. trachomatis
26%
43%
M. genitalium
14%
31%
U. ureealyticum-biovar 2
24%
T. vaginalis
2%
21%
Idiopathic
38%
29%
* Birmingham, AL; Baltimore, MD; New Orleans, LA; Durham, NC.
Randomized Trials of Azithromycin vs.
Doxycycline for NGU: Clinical Cure
Doxy
100
Azithromycin
Percent Cured
80
77
81
60
75
78
84
69
40
20
0
Stamm
Schwebke*
Manhart
Manhart L. CDC STD Prevention Conference
Randomized Trials of Azithromycin vs.
Doxycycline for NGU: M. genitalium Microbiologic
Cure
Doxy
100
Percent Cured
80
Azithromycin
87
60
40
67
45
40
31
20
30
0
Mena*
*P<.05
Schwebke*
Manhart
Manhart L. CDC STD Prevention Conference
Persistent NGU Treatment
CDC Approach
Initial Rx: Doxy or Azithro
? Defined etiology, reexposure/partner
treatment
Document evidence of inflammation –
positive GS or urine LE
If positive – Treat with Doxy or Azithro +/Metronidazole
(+/- trich culture)
Seattle Approach
Initial Rx: Doxy or Azithro
? Defined etiology, reexposure/partner
treatment
Document evidence of inflammation –
positive GS or urine LE
If positive – Treat with Moxifloxicin
400mg po qd x 7
? Defined etiology, reexposure/partner
treatment
Document evidence of inflammation –
positive GS or urine LE
If positive – Treat with Moxifloxicin
400mg po qd x 7
Syphilis
Primary and Secondary Syphilis—Rates by Sex and
Male-to-Female Rate Ratios, United States, 1990–
2011
2011-Fig 38. SR
King County: Early syphilis*,
1994-2011
400
376
MSM syphilis**
350
Early syphilis cases
Heterosexual syphilis
300
263
250
200
179 174
188 185
145
140
150
100
32
50
2
16
23 11 5
15
4
60 58 50 60
9
12
77
26
2
3
5
13
10
0
*Reported P, S, and EL syphilis
**Excludes some male cases with unknown MSM status
5
6
9
13
Syphilis – A Brief Refresher
Few hours: lymph ->
bloodstream
Chancre
~ 3 weeks (10-90 days)
spontaneously heals
1-6 weeks later
Syphilis – A Brief Refresher
Few hours: lymph ->
bloodstream
Chancre
~ 3 weeks (10-90 days)
spontaneously heals
1-6 weeks later
15% overlap
3-6 weeks after chancre
Transmission
Risk: ~30% per
sex act
(compared to
0.07-2% per sex
anal sex act for
HIV*)
*Cassels et al, AIDS 2009;23:2497
Reverse Sequence Syphilis Screening Algorithm
•Why? Decreased cost for the laboratory
•Traditional
• Screen with nontreponemal test (RPR or VDRL)
• Confirm with a treponemal specific test (TPPA, MHATP)
•Reverse
•Screen with treponemal specific EIA
•Confirm with RPR
•If conflict: resolve with older treponemal test (TPPA)
EIA Screening Algorithm
Negative
EIA or
CLIA
No
Syphilis
Positive or
Equivocal
RPR
Positive
Negative
TP-PA
Negative
Unlikely syphilis
Probably false positive EIA
But if high suspicion, repeat in 1 month
Syphilis
Positive
Syphilis
-early disease
-past infection (treated)
-untreated, long duration
Reverse Sequence Syphilis Screening
EIA +
RPR- Among EIA+ TPPA- Among
(Old Syphilis or False+) RPR- (False+)
3.4%
57%
32%
Low Prevalence 2.3%
Pops
61%
41%
High Prevalence
14.5%
Pops
51%
14%
Total
MMWR 2011;60:133
Geographical Distribution of Endemic,
Non-venereal Treponematoses
Vaginitis
Key Features of Normal
Vaginal Environment

Normal pH <4.7:



Maintained by dominant vaginal bacteria,
Lactobacillus, that produce lactic acid
Favors growth of lactobacilli and inhibits growth of
other organisms (residents and invaders)
Human lactobacilli


Major species: L. crispatus and L. jensenii
Need to produce hydrogen peroxide (H2O2) for
maximal benefit
Vaginitis


Very common
National Health and Examination Survey (ages 14-49)




28% of women reported symptoms
BV prevalence: 27%
 White women: 23%
 Non-Hispanic black women: 51%
Trichomonas prevalence 3%
 White women: 1%
 Non-hispanic black women: 13%
Top 3 causes



Bacterial Vaginosis
Candidiasis
Trichomoniasis
Koumans, STD 2007
Sutton, Clin Infect Dis 2007
Diagnosis

Lack of specificity in clinical presentation = syndromic
diagnosis doesn’t work
A pH-Based Framework for Evaluating
Common Causes of Vaginitis
Nyirjesy & Sobel, Curr ID Reports 2005
Bacterial Vaginosis: Dx

Typical discharge: homogenous, greyish, adherent to
vaginal epithelium

Clinical findings (Amsel criteria): 3 of the following must
be present:
 homogeneous discharge
 pH >4.5
 clue cells (>20%)
 amine odor on addition of KOH (+whiff test)
PCR amplification of vaginal bacteria
BV negative
BV positive
Fredricks et al. NEJM Nov 2005; 368:1899-1911
Vaginitis Treatment

BV

Metronidazole 500mg po BID x 7 days





Or gel 0.75% vaginally QD x 5 days
Or clindamycin cream 2% vaginally x 7 days
15-20% of women fail initial treatment
~75% recurrence over 1 year
Trichomonas



Metronidazole 2g po x 1
Or tinidazole 2g po x 1 ($)
Nitroimidazole resistance: only useful drug
class
Time to BV Recurrence (ITT), Biweekly MTZ Gel vs.
Placebo
Sobel
AJOG
2006
Herpes
HSV-2 Seroprevalence in U.S.
Prevalence (%)
MMWR 59
(15), 2010
AW-245 8-13-1996
Herpes: Key Points

Most persons with HSV do not know they have it


Do not have or do not recognize symptoms
Most transmission occurs by subclinical genital
shedding

Distinct from unrecognized infection

Suppressive antiviral therapy decreases, but
does not eliminate risk of transmission

Know how to interpret serology results
Genital Ulcers – Exam is non-specific
Sensitivity/Specificity
Incubation
Herpes
2-7 days
Primary
Lesion
Base
Size
Edges
Induration
Pain
≥3 lesions
Erythematous,
serous
1-2mm
Erythematous
None
Tender
63%/64%
Syphilis
9-90 days
Papule
(one)
60%/50%
Smooth,
Non-purulent
5-15mm
Classic herpes triad (≥3 superficial,
tender lesions): 94% specificity, but seen
only in a minority of patients
Elevated,
Demarcated
Firm
Non-tender
47%/95%
67%/58%
DiCarlo RP, CID 1997;25:292
Herpes Testing: Lesions


Test to confirm diagnosis
Highest yield: vesicles,
pustules (early lesions)


Unroof & scrape base
PCR more sensitive than culture (N>36,000 samples)
Sensitivity
False
positive
Viral Culture
24%
76%
PCR
99.9
0.1%
Specificity
100
Ratio PCR:Viral culture positivity
3.1 (presence of lesions)
5.1 (absence of lesions)
Wald et al JID 2003: 188
Slide adapted from Christine Johnston, MD
Herpes Testing: Serology

Type-specific serology tests may be useful:




Median time to seroconversion: 3 weeks


Recurrent/atypical symptoms with negative culture
Clinical diagnosis without lab confirmation
Patients with a partner with genital HSV
Upper limit: 4 months
HSV-2 serologic testing can be offered to
persons presenting for a STD evaluation


Personal health service
Screening for HSV-1 or HSV-2 in the general
population is not indicated.
Type-Specific gG-Based HSV
Serology: Commercial Kits 2012
Sensitivity
Specificity
HerpeSelect-2 ELISA (Focus)
96-100*
97-100
HerpeSelect Immunoblot (Focus)
HerpeSelect Express (Focus)
biokitHSV-2 (biokitUSA )
Cobas-HSV-2 (Roche)
Captia Select-HSV-2 (Trinity)
97-100
86-100
93-100
93
90-92
98
97-100
94-97
98
91-99
• Cost varies; $30-$180
• Western blot assay, considered gold standard, available through University of
Washington
Median time to seroconversion:
3 wk (<4m)
False Positive HerpesSelect: A function of prevalence
Positive Predictive Value (%)
100
89
80
85
78
60
63
98% Specificity
40
20
0
5%
10%
15%
Prevalence
20%
Interpreting Common Serologies


HerpeSelect (Focus) ELISA is commonly used
Although package insert states that an index value
>1.1 should be interpreted as positive, several
experts use a cutoff of 3.5


PPV as low as 38% in college students with very low HSV2
seroprevalence (3.4%) [Mark 2007]
Leads to higher negative predictive value [Golden 2005;
Philip 2008]



Correctly reports uninfected people as uninfected
Fewer false positives
For patients who REALLY want to know, consider
Western blot


Call #206-598-6066 to request HSV Type-Specific Serology
information packet
http://depts.washington.edu/herpes/
Herpes Serology: Limitations

Does not tell






Cannot diagnose a lesion
False positives


How long infected
If person has had or will have symptoms
How likely a person is to shed asymptomatically
Where infected (HSV-1)
Decreased PPV in low prevalence populations
AND in patients with HSV-1 infection
False negatives

77% of patients have antibodies by 6 weeks after
HSV-2 primary infection and 59% after HSV-2
non-primary infection.
Herpes Serology


No role for IgM
No role for non-type specific IgG tests
Which Patients Should Receive
Suppressive Antiviral Therapy?



Frequent recurrences
Psychological distress
Acyclovir – excellent safety for  10 years


Famciclovir and Valacyclovir – safety for 1 year


Higher bioavailability (GI absorption) allows less
frequent dosing)
Consider discontinuation after 1 year



No need to monitor safety labs or to caution women
against getting pregnant while taking it
To observe rate of recurrence
To monitor adjustment to recurrences
No evidence of emergence of resistant strains in
immunocompetent persons
Prevention strategies for HSV-2






Disclosure of serostatus
Avoid sex with lesions (imperfect, but
higher viral load when present)
Condoms
Antiviral therapy
Vaccine (may prevent HSV1 in women;
Belshe NEJM 2012)
Topical microbicides…stay tuned
• Can’t predict with symptoms as guidance (Wald 1995)
• Frequency of shedding higher with history of
symptomatic outbreaks (20% of days), but still 10% of
days in asymptomatic persons (Tronstein 2011)
• Shedding most frequent first year after initial outbreak,
but persists for years after
Asymptomatic Shedding & Transmission
• Most transmissions from persons without clinical
history of genital herpes
• Subclinical Recurrences
• Viral shedding 10% of asymptomatic days
• Suppressive therapy can prevent transmission
Corey et al. N Engl Jour Med 2004; 350 (1): 11-20
Genital HSV-2 Shedding Rate
Percent of swabs with HSV detected
25
Trial 1
IRR=0.05
95% CI=0.03-0.08,
p<0.001
20
15
Trial 2
IRR=0.79
95% CI=0.63-1.00,
p=0.052
10
Trial 3
IRR=0.54
95% CI=0.44-0.66,
p=0<0.001
5
0
No Medication
Estimated
Acyclovir AUC
0
SD-ACV
7.7
SD-VAL
10
HD-ACV
25
SD-VAL
10
HD-VAL
88
Johnston, JAMA 2012
Genital HSV-2 Shedding Rate
Percent of swabs with HSV detected
25
Trial 1
IRR=0.05
95% CI=0.03-0.08,
p<0.001
• Frequent
short bursts of HSV-2 reactivation occur in the
20
presence of both standard dose suppressive antivirals and on
high dose therapy
15
– While shedding frequency and quantity is reduced on high dose
Trial 3
valacyclovir, breakthrough shedding
at a similar IRR=0.54
episode
rate on
Trialoccurs
2
IRR=0.79
95% CI=0.44-0.66,
all
doses
95%
CI=0.63-1.00,
10
p=0<0.001
p=0.052
• Antiviral therapy, though clinically effective, does not alter the
underlying pathobiology of frequent HSV-2 reactivation
5
0
No Medication
Estimated
Acyclovir AUC
0
SD-ACV
7.7
SD-VAL
10
HD-ACV
25
SD-VAL
10
HD-VAL
88
Johnston, JAMA 2012
Counseling the Newly Diagnosed
Patient with HSV2



Consider serologic testing of partner(s)
Recognize risk of subclinical shedding
Discuss value of suppressive antiviral
therapy


Effective in reducing outbreaks, reducing
BUT NOT ELIMINATING days with shedding
Discuss other preventive measure


Condoms
Avoiding sex with outbreaks
Things to You Might Want to Say






I know this must be really hard news for you
to hear
This is a manageable disease, even though
there is no cure yet
You are not alone—1 in 4 adults is infected
with HSV-2
Genital herpes is usually not associated with
serious health issues, including effects on
reproductive health
Give yourself some time to adjust; don’t
expect it to happen overnight
There are a lot of good resources online
Miscellaneous Key Points
HPV Vaccine
Don’t Miss Acute HIV
HIV Testing Regulations
Take-Home Points

Screen women <26 for chlamydia annually

Offer heterosexuals with GC and CT EPT

Treat gonorrhea with ceftriaxone + azithromycin

Rescreen for GC and CT 3 months after treatment

Be vigilant for syphilis among MSM

Social history should include gender of sex partners

Syphilis EIA has high false positive rate in low prevalence
populations

Know how to interpret your herpes serologic test


Index values are key
Most herpes is transmitted through subclinical shedding and
most people with herpes don’t know they have it
Thank You
jdombrow@uw.edu
Acknowledgements
 Jeanne Marrazzo, MD, MPH
 Matthew Golden, MD, MPH
 Devika Singh, MD, MPH
 Sue Szabo, PA
 Christine Johnston, MD, MPH
 Joanne Stekler, MD, MPH
 Caroline Mitchell, MD
 CDC (slides)
STD Web Resources
Herpes Web resources

ASHA patient herpes hotline

University of Washington Viral Diseases Research Clinic (206) 7204340

www.ashastd.org
www.herpeshelp.com
www.westoverheights.com
www.healthcheckusa.com
www.herpesdiagnosis.com
www.herpeshomepage.com





(919) 361-8488
reading materials
Glaxo web site
handbook
order own tests
diagnosis data
posts, pharmacy link