Transcript Genital Ulcer Disease in Women, Part I

Welcome to I-TECH HIV/AIDS Clinical Seminar Series
Sexually Transmitted Diseases, Part II:
Genital Syndromes in Women
Dr. Devika Singh, MD, MPH
June 4, 2009
Slides generously borrowed from mentor Jeanne M. Marrazzo, MD, MPH
STD as a Cause of Cervicitis
and Ulcerative Disease
• Endocervicitis: ‘classic’ STD pathogens
– Gonorrhea
– Chlamydia trachomatis
• Ectocervicitis: often associated w/ vaginitis:
– Trichomoniasis
• Discrete lesions/Genital ulcerative disease/myriad
–
–
–
–
–
Herpes simplex virus
Syphilis
Chancroid
Human papillomavirus
LGV
Things to Consider
• Age of patient
• Change in discharge: increased,
malodorous, bloody, purulent
• Associations: sexual
activity/partnerships, cleaning the
vagina (including douching/irrigation)
• Co-infections: HIV or non-HIV
• Epidemiology/exposures
Case I
22 yo woman presents to your clinic. She
endorses no particular symptoms.
One male partner who is asymptomatic.
Condoms used “sometimes”
On no hormonal contraception
Examination:
• Bimanual examination reveals no
tenderness
Differential?
Differential?
•
•
•
•
•
•
•
Chlamydia trachomatis
Neisseria gonorrhoeae
HSV
HPV
Trichomoniasis
Syphilis
Pregnancy
Chlamydia trachomatis
Epidemiology
• Most common bacterial STD worldwide,
with approximately 90 million cases
each year
– Uro-genital disease
– Ophthalmologic
– Invasive (Lymphogranuloma Venereum)
http://www.who.int
Clinical Syndromes Caused by C. trachomat
Conjunctivitis
Women
Urethritis
Endometritis
Infertility
Cervicitis
Salpingitis
Proctitis
Perihepatitis
Ectopic
pregnancy
Chronic pelvic
pain
Infants
Conjunctivitis
Pneumonia
Pharyngitis
Rhinitis
Chronic lung disease
(?)
C. trachomatis
Cervical Infection
 Classic cause of endocervicitis
 Mucopurulent discharge
 Friability
 Edematous ectopy
 Cervical signs occur in
minority of patients (10-20%)
 Most (80-90%) infected women
have normal cervix / no signs
General Characteristics of Chlamydia
 Superficial, mucosal: epithelial cells
 Often no (or minimal) signs or symptoms
 Chronic in women (months to years)
 Chronic inflammatory response
 Serious reproductive sequelae in
women
 Reinfection common
www.pasante.com
Normal
Fallopian
tubes by
Scanning EM
Photos
courtesy of
Dorothy
Patton, PhD
Fallopian
tubes by EM
after C.
trachomatis
infection
Photos
courtesy of
Dorothy
Patton, PhD
Chlamydia Tests

Cell culture

Antigen Detection

Direct Fluorescent Antibody (DFA)

Enzyme Immunoassay (EIA)

Unamplified DNA Probe (Gen Probe PACE2)

Signal Amplification Tests (Digene Hybrid Capture)

Nucleic Acid Amplification (NAAT)

Rapid Point of Care Tests
What is the recommended treatment for a pregnant
woman with chlamydia?
1. Erythromycin 500 mg po QID x 7 days
2. Doxycycline 100 mg po BID x 7 days
3. Azithromycin 1 g po x 1 dose
4. Levofloxacin 500 mg po daily x 7 days
Chlamydia Treatment in Pregnancy
2006
• Recommended regimens
• Azithromycin 1 g PO x 1
• Amoxicillin 500 mg PO TID x 7 d
• Alternative regimens
• Erythromycin base 500 mg PO QID x 7 d
• Erythromycin base 250 mg PO QID x 14 d
• Erythro ethylsuccinate 800 mg PO QID x 7 d
• Erythro ethylsuccinate 400 mg PO QID x 14 d
2006 CDC STD Treatment Guidelines:
Uncomplicated Chlamydial Infection
• Recommended
– Azithromycin 1 g PO, single dose, directly
observed
– Doxycycline 100 mg PO BID x 7 d
• Alternatives
– Ofloxacin 300 mg PO BID or
levofloxacin 500 mg PO qD x 7 d
– Erythromycin 500 mg PO QID x 7 d
Counseling as Part of Chlamydia Treatment
 Abstain for at least 7 days
and until partner(s) treated
 Consistent condom use
 Get your partner treated
 Return if not improved over
next 7-14 days
A Word about Screening
UNITED STATES

<24 years old: screen all sexually active women
annually

25 and older: Annual testing if ‘at increased risk’


Defined liberally: inconsistent condom use, new or
multiple partners, prior STD or CT, sex work,
certain demographics
If pregnant:

<24 years old  screen

25 and older – only screen if “at increased risk”
Chlamydia
Proctitis
•
•
•
•
•
Severity
Extent
Sigmoidoscopy
Biopsy
Comp-fix AB
LGV strains
Severe
Proctocolitis
Blood, ulcers, pus
Granulomas
Increased (>1/64)
Non-LGV
Mild
Proctitis
Normal, pus
PMNs
Normal
LGV (Serovars L1, L2, L3 of
Chlamydia) Proctitis
Biopsy showing crypt destruction by
diffuse histiocytic and lymphocytic
infiltrate
• Settings: developing context traditionally, but trend
recently has included West (MSM)
• Diagnosis
– Cell culture OK if available
– NAAT not cleared by FDA for rectal specimens
– Can be used if validated by local laboratory
– ID of LGV serovars requires culture serotyping or NAAT genotyping; neither
widely available
– Serologic tests: recommended, but @ reference laboratories; titers not
well-defined for LGV proctocolitis and not highly predictive of infection
Ratelle; Liu 2006
www.cdc.gov/std/lgv
LGV (Serovars L1, L2, L3 of Chlamydia)
Proctitis
• Consider presumptive treatment
• Doxycycline 100 mg bid PO x 21 d
Ratelle; Liu 2006
www.cdc.gov/std/lgv
Chronic lymphogranuloma venereum in female.
Genital elephantiasis
Case II
• 33 yo woman presents with change in
vaginal discharge.
• One new male sex partner for past
three months. Previously was with one
steady male partner x four years.
Regardless…
• ALWAYS do an examination
• Presumptive treatment is inappropriate
Next step is gram stain
Diagnosis?
Neisseria gonorrhoeae
Purulent cervicitis
When seen, tends to be MOST likely
– C. trachomatis
– N. gonorrhea
Gonorrhea
Treatment,
2007
Recommended regimens:

Ceftriaxone 125 mg IM x 1

Cefixime 400 mg PO x 1

Ciprofloxicin 500 mg PO x 1

Ofloxacin 400 mg PO x 1

Levofloxacin 250 mg PO x 1
Alternative regimens:
 Cefpodoxime 400 mg po x 1
 Cefuroxime 1 g po x 1

Spectinomycin 2 g IM x 1: not available

Single-dose injectable cephalosporin regimens

Single-dose oral quinolone regimens
Co-treat for chlamydia unless ruled out with highly sensitive
test (NAAT)
MMWR April 13, 2007; 56 (14)
Case III
• 37 yo woman presents with pain while
having intercourse with her husband.
• She denies any vaginal discharge.
• He is asymptomatic.
Physical exam
Anatomy
Bartholin’s abscess
Aerobic organisms
Neisseria gonorrhoeae
Staphylococcus aureus
Streptococcus faecalis
Escherichia coli
Pseudomonas aeruginos
Chlamydia trachomatis
Anaerobic organisms
Bacteroides fragilis
Clostridium perfringens
Peptostreptococcus species
Fusobacterium
Treatment
• Placement of Word catheter
• Culture/analysis fluid to ensure no coinfection or other findings (rarely, malignancy)
• Treatment is generally broad-spectrum
(including for C. trachomatis and N.
gonorrhea)
Case IV
24 y.o. woman presents with increased,
malodorous vaginal discharge for 5 days.
She has two sex partners: one man and
one woman
She practices no safe sex precautions
Vaginal examination
Cervical examination
Microscopy reveals
Diagnosis?
Trichomoniasis
• Single-celled protozoan parasite,
Trichomonas vaginalis.
• The vagina is the most common site of
infection in women, and the urethra
(urine canal) is the most common site of
infection in men.
http://www.cdc.gov/STD/Trichomonas
Trichomoniasis
• The parasite is sexually transmitted
through penis-to-vagina intercourse or
vulva-to-vulva contact with an infected
partner.
• Women can acquire the disease from
infected men or women, but men
usually contract it only from infected
women.
http://www.cdc.gov/STD/Trichomonas
Trichomoniasis
• Signs or symptoms of infection which include
a frothy, yellow-green vaginal discharge with
a strong odor.
• May cause discomfort during intercourse and
urination, as well as irritation and itching of
the female genital area. In rare cases, lower
abdominal pain can occur. Symptoms usually
appear in women within 5 to 28 days of
exposure.
Trichomoniasis Treatment 2006
Recommended regimen:
– Metronidazole 2 g PO x 1
– Tinidazole 2 g po x 1
Alternative regimen:
– Metronidazole 500 mg PO BID x 7d
•
•
•
Metronidazole safe at all stages of pregnancy; tinidazole
Category C (don’t use)
Vaginal therapy is ineffective
Treat sex partner(s): male and female
Case V
28 y.o. woman comes to your clinic because
she has noted increased, malodorous vaginal
discharge for about a week.
No history of known STD.
In your history you note that she washes her
vagina with a “special rinse” every month
She has been monogamous with a male
partner, who is asymptomatic, for 1 year.
Case V
She and her sex partner do not use condoms
on most occasions but practice “withdrawal”
method.
What do you advise?
1)
2)
3)
4)
She probably has a yeast infection
because she is at low STD risk
She probably has trichomoniasis, and
you’ll call in a prescription for
tinidazole/metronidazole.
Come in for examination.
Stop irrigating vagina
Rationale for office visit

While most women with malodorous discharge have
either BV or trichomoniasis, management of these
two processes differ
–
–
–

Both are treated with metronidazole, but need to know
whether or not to treat partner(s)
Therefore, specific diagnosis is useful
Overall, BV most common
Unfortunately, syndromic diagnosis of abnormal
vaginal discharge is poorly predictive of the actual
cause
–
Examination required (vaginal pH at a minimum)
Bacterial Vaginosis:
An Ecosystem Out of Balance

Overgrowth of commensal anaerobic flora (classically
defined as G. vaginalis, Prevotella, Mobiluncus, M.
hominis) relative to H2O2-producing lactobacilli that
predominate in the healthy vaginal ecosystem
Gram stain of normal vaginal fluid:
many lactobacilli, normal epithelial cells
Gram stain of BV: no lactobacilli,
many other bacteria, and clue cells
Nugent Score: 0
Nugent Score: 10
Bacterial Vaginosis
Wet Prep:
Clue Cell
Vaginal
Discharge
Diagnosis of Bacterial Vaginosis
• Gram stain findings (Nugent scale):
based on number of lactobacilli and
other bacterial morphotypes
• 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)
BV Complications in NonPregnant Women
PID
Post-abortal PID
Post-hysterectomy infection
BV and Adverse Outcomes in Pregnancy
• Data support that BV promotes:
– postabortal infections
– preterm labor and delivery*
– premature rupture of membranes
– intramniotic infection
– histological chorioamnionitis
– postpartum endometritis
– spontaneous abortion in first trimester (IVF)
*infection implicated in up to 10% of cases
2006 CDC STD Treatment Recommendations
Bacterial Vaginosis
Nonpregnant Women
 Recommended
- Metronidazole 500 mg PO bid x 7 d
- Metronidazole gel 0.75% intravag qHS x 5 d
- Clindamycin cream 2% intravag qHS x 7 d
 Alternatives*
- Clindamycin 300 mg PO bid x 7 d
- Clindamycin ovules 100 g intravag qHS x 3 d
* Metronidazole 2 g PO, single dose deleted
Normal Vaginal pH is Important!



pH <4.7 favors growth of acidophilic organisms,
inhibits growth of other organisms (residents and
invaders)
Maintained primarily by human Lactobacillus that
produce hydrogen peroxide
Elevated vaginal pH associated with:




loss of H2O2-producing lactobacilli
bacterial vaginosis, trichomoniasis
enhanced transmission of HIV
acquisition of gonorrhea
Case VI
23 yo woman with HIV (last CD4 310) comes to
see you with complaint of vulvar pain. She
has no prior history of this.
She has one male sex partner (also HIV
positive). They have been together for about
3 months.
They do not use condoms.
Physical exam
Differential?
Differential for Genital Ulcerative
Manifestations in Women
•
•
•
•
•
HSV
Syphilis
Chancroid
CMV
HPV
What about non-STI causes for
genital ulcers?
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Behcet’s syndrome
Crohn’s disease
Erosive lichen planus
Pemphigus
Trauma
What is most likely in this
patient?
HSV
HSV: Clinical Features
 Many patients recognize subtle or nonulcerative symptoms when educated (vulvar
fissures; vulvitis; urethral irritation)
 Genital herpes due to HSV2 
 More severe primary infections, when they occur
 More likely to recur
 Persistent subclinical shedding months-years postinfection
 Genital-genital transmission usual route of
acquisition
HSV: Clinical Features
 Genital herpes due to HSV1 
 Most don’t recur (1 at most); subclinical shedding
does not persist
 Oral-genital probably important route of transmission
Recurrent Genital
Herpes lesions
Cervical exam
Cervical exam
 Seroprevalence strongly associated
with increasing lifetime nos. of sex
partners, female sex, black race
HSV-2
Seroprevalence
in the U.S.
Xu, JAMA 2006
Significance of Genital Herpes
• Physical and psychological concerns
• HSV-2 infection increases the risk of HIV-1 infection
by 2-fold
• Source of transmission to uninfected partners
– 89% expressed concern about transmitting to a
partner in one study
1. CDC Sexually Transmitted Diseases Guidelines. 2002.
2. Wald A, Link K. J Infect Dis. 2002;185:45-52.
3. Catotti DN et al. Sex Transm Dis. 1993;20:77-80.
4. Brown Z et al. JAMA. 2003;289:203-209.
Significance of Genital Herpes
• Transmission of herpes to newborn during pregnancy or
delivery
– Occurs in 1 per 3,200 live births
– May lead to serious complications such as seizures,
blindness, psychomotor retardation, spasticity,
learning disabilities, and death
1. CDC Sexually Transmitted Diseases Guidelines. 2002.
2. Wald A, Link K. J Infect Dis. 2002;185:45-52.
3. Catotti DN et al. Sex Transm Dis. 1993;20:77-80.
4. Brown Z et al. JAMA. 2003;289:203-209.
Which of the following statements is
correct regarding diagnosis of genital
herpes?
1.
Direct viral culture of a genital lesion can
determine whether HSV-1 or HSV-2 is the etiology.
2.
Cytology (Tzanck versus Pap) is one of the most
useful methods of HSV testing.
3.
The odds of getting a positive herpes test from a
genital lesion increase the older the lesion gets.
Diagnostic Tests for HSV
• Culture: usual test of choice
– Widely available, relatively inexpensive
– Distinguishes HSV-1 and HSV-2
– Sensitivity declines as lesions age
• Polymerase chain reaction (PCR)
– Most sensitive
• Antigen tests, e.g. direct FA
– Sensitivity similar to culture
– Only direct FA distinguishes HSV-1 from HSV-2
Diagnostic Tests for HSV
• Cytology (Pap, Tzanck preparation)
– Insensitive, nonspecific; no role in clinical
management
• Serology
– Detects serum antibody
Uses of Herpes Serology

Definite Indications:
–
Diagnosis of genital ulcers or lesions, especially when
lesions cannot be sampled or are unlikely to yield virus
–
Management of sex partners of persons w/ herpes
•
–
Implications for counseling, antiviral therapy in infected partner
Screen persons at risk for HIV transmission (HIV+)
Guerry CID 2005,
Strick CID 2006
Uses of Herpes Serology

Other Uses:
–
–
–
Pregnant women and partners
Patient request
Not clear whether all sexually active persons should
be screened (cost vs. benefit)
BUT AVAILABILITY/COST are issues
Guerry CID 2005,
Strick CID 2006
Genital Herpes: Prevention of Sexual Transmission,
2006 CDC STD Treatment Guidelines
• Antiviral treatment: valacyclovir 500 mg PO QD
• Indications may include:
– Discordant couples (the only evidence-based
indication)
– Persons with multiple partners
– Men who have sex with men
– HIV-infected
• Reassess discordant partner annually for
seroconversion
• Counsel regarding condoms, disclosure,
abstinence
2006 CDC STD Treatment Guidelines
Genital Herpes: First Episode
HIV- and HIV+
•
•
•
•
Acyclovir 400 mg TID x 7-10 d
Acyclovir 200 mg 5x/d x 7-10 d
Famciclovir 250 mg TID x 7-10 d
Valacyclovir 1.0 g BID x 7-10 d
HHH-1117 3/20/1998
www.cdc.gov/std
2006 CDC STD Treatment Guidelines
Genital Herpes: Episodic Treatment of
Recurrences
HIV-infected:
• Acyclovir 400 mg TID x 5-10 d
• Famciclovir 500 mg bid x 5-10 d
• Valacyclovir 1 gm bid x 5-10 d
HHH-1118 3/20/1998
* 5x daily acyclovir regimen deleted
2006 CDC STD Treatment Guidelines
Genital Herpes: Episodic Treatment of
Recurrence
HIV-negative:
• Acyclovir 400 mg TID x 5 d
• Acyclovir 800 mg BID x 5 d
• Acyclovir 800 mg TID x 2 d*
• Famciclovir 125 mg BID x 5 d
• Famciclovir 1 g BID x 1 d
• Valacyclovir 500 mg BID x 3 d
• Valacyclovir 1 g qD x 5 d
HHH-1118 3/20/1998
* 5x daily acyclovir regimen deleted
2006 CDC STD Treatment Guidelines
Genital Herpes: Suppressive Therapy
HIV-infected
• Acyclovir 400-800 mg bid/tid
• Famciclovir 500 mg bid
• Valacyclovir 500 mg bid
HIV-negative:
• Acyclovir 400 mg BID
• Famciclovir 250 mg BID
• Valacyclovir 500 mg qD
• Valacyclovir 1.0 g qd (if >10 episodes /year)
HHH-1119 3/20/1998
Management of Patients
• Consider daily suppressive therapy for patients who:
– Are bothered by their outbreaks, regardless of their relationship
status
– Are sexually active with an uninfected partner*
– Are newly diagnosed and concerned about transmitting genital
herpes to their partner*
• Consider episodic therapy for patients who:
– Are not sexually active and not concerned about their outbreaks
– Are sexually active with a partner who has genital herpes
* Studied in immunocompetent heterosexual adults
Subclinical Shedding: Key
Points
• Frequency of shedding is not related to the
frequency of symptomatic outbreaks (8% vs 7% of
days by culture in people with 0-3 vs. 4-9 annual
outbreaks, respectively)
• Up to 70% of transmission occurs during subclinical
shedding periods (Mertz 1992)
Condoms Reduce HSV2 Transmission
• 528 monogamous couples discordant for
HSV2 infection followed for 18 mos.
– Condom use for >25% of sex acts associated
with 92% reduction in HSV2 acquisition for
women
• 1862 people in HSV2 vaccine study
followed over 18 mos.
– Condom use for >65% of sex acts associated
with 34% reduction in HSV2 acquisition in
women and 41% in men
Wald 2001
A complete STD screen for a young,
sexually active woman includes:
• All women:
– External genital and
speculum exam
– Vaginal pH, KOH
whiff
– Cervical Pap if not
done recently
– Chlamydia test
– HSV serology
– HIV serology
– Pregnancy test
• Selected patients
– Bimanual exam
– Vaginal fluid
microscopy
– Gonorrhea test
– Syphilis serology
A complete STD screen for a young,
sexually active woman includes:
Information on
PREVENTION and
CONTRACEPTION!
Acknowledgments
• Jeanne Marrazzo
• Hunter Handsfield
• Matthew Golden
Thank you!
Next session: June 11, 2009
Listserv: [email protected]
Email: [email protected]
Thank you!
Next session: June 11th, 2009
Jose Jeronimo
New Tools for Cervical Cancer Prevention