Sexually Transmitted Diseases

Sexually Transmitted
Diseases
Elizabeth D. Hermsen, Pharm.D.
Infectious Diseases Research Fellow
University of Minnesota
College of Pharmacy
Objectives
• List signs and symptoms associated
with each STD
• Recognize disease-specific diagnostic
tests
• Identify complications associated with
each STD
• Recommend treatment measures for
each STD
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Overview
• Non-HIV STDs
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Chlamydia
Gonorrhea
Syphilis
Chancroid
Trichomoniasis
Vaginal infections
Pelvic inflammatory disease (PID)
Epididymitis
Pediculosis and scabies
Genital warts and human papillomavirus (HPV)
Genital herpes
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Overview (cont.)
• Most common reportable communicable
diseases in the U.S.
• Higher reported incidence in men –
more frequent and severe complications
in women
• 2/3 of all STD cases each year occur in
teens and twenties
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Overview (cont.)
Ulcers
Papules Vesicles Diffuse
Crusts Misc.
and
erythema
Bullae
HSV,
syphilis,
trauma,
chancroid,
gonorrhea,
trichomoniasis
Warts,
scabies,
molluscum
syphilis
HSV,
syphilis
Trauma,
contact
dermatitis
HSV,
scabies
Tracts:
scabies.
Nits/Blue
spots:
lice
Images available at www.healthac.org
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Chlamydia: Epidemiology
• Causative organism – Chlamydia trachomatis
• Ocular disease
• 500 million worldwide affected
• 7-9 million worldwide blind
• Genital tract infections even more prevalent
• CDC estimate of 4 million cases annually (US)
• Predominantly found in young women (15 – 19
y.o.)
• Co-infection occurs in up to 60% of those
with gonorrhea
• More C. trachomatis shedding in co-infected
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Chlamydia: Pathogenesis
• Sites
– Genital tract (NGU)
– Ocular
– Lung (pneumonia)
• Spread via lymph system / multiply inside
mononuclear phagocytes
• Asymptomatic partner – less likely
transmission
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Chlamydia: Clinical findings
• Often asymptomatic
– Male – dysuria, urinary frequency, mucoid urethral
discharge occurring 7-21 days post-exposure
– Female – endocervicitis with mucopurulent
discharge (dysuria and frequency are uncommon)
• Perinatal
• Infant conjunctivitis
• Infant pneumonia
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Chlamydia: Clinical findings (cont.)
• Ocular trachoma
• Chronic follicular conjunctivitis
• Scarring
blindness
• Lymphogranuloma venereum (LVG)
• Primary stage: painless ulceration at site of inoculation
• Secondary stage: painful inguinal lymphadenitis
(unilateral), inflammatory masses (buboes)
• Third stage: genital abscesses, proctocolitis, lymphatic
obstruction (elephantitis)
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Chlamydia: Clinical findings (cont.)
• Other ocular/genital infections
– Ocular manifestations similar to early trachoma, but
without serious complications
– Genital infections
» Urethritis (NGU)
» Epididymitis and prostatitis
» Proctitis and proctocolitis
» Sexually reactive arthritis
» Cervicitis
» Endometritis
» PID
» Pregnancy issues
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Chlamydia: NGU
• Usually asymptomatic
– Yet 30-50% NGU due to C. trachomatis
• Others: 10-20% Ureaplasma urealyticum,
Trichomonas vaginalis
Gonococcal urethritis
Chlamydia NGU
7-14 day incubation
4 day incubation
Purulent discharge
White/clear/gray discharge
• Diagnosis
- Gram stain of secretions demonstrating ≥ 5 WBCs per
oil immersion field
- Positive leukocyte esterase also indicative
- Lack of N. gonorrhoeae ‡ NGU
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Chlamydia: Complications
• Pregnancy problems
– Largest published study
• Analysis of pregnancy outcomes in 1110 women
(infected but not tx’d), 1323 (tx’d with erythromycin),
9111 uninfected (untx’d) women
• Significant association in premature membrane rupture
(odds ratio 0.56)
– ectopic pregnancy, infertility
• Cancer risk
• Longitudinal, nested case-control study (530,000
women)
• 128 cases of squamous cell carcinoma
• Risk for SCC development linked to IgG Abs of C.
trachomatis
JAMA. 2001;285:47-51.
Am J Obstet Gynecol. 1990;162:34-39.
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Chlamydia: Diagnosis
• Laboratory findings
– Isolate of C. trachomatis
– Nucleic acid amplification tests
– Cytologic examination (intracytoplasmic
inclusions)
– Enzyme immunoassay (EIA), DNA
hybridization probe, direct fluorescence
monoclonal antibody (DFA) test
• Clinical presentation
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Chlamydia: Treatment
• Uncomplicated genital infection
– Doxycycline 100 mg PO BID x7d
– Azithromycin 1 g x1
– Erythromycin base 500 mg PO QID x7d or EES
800 mg PO QID x7d
– Ofloxacin 300 mg BID x7d or levofloxacin 500 mg
QD x 7 d
• Pregnant women
– Erythromycin base 500 mg QID x7d
– Amoxicillin 500 mg TID x7-10d
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Gonorrhea: Epidemiology
• Causative organism – Neisseria
gonorrhoeae
• Approximately 600,000 new infections
annually in U.S.
• Underreported (? Undertreated)
• Resistance
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Gonorrhea: Clinical findings
• Genital infections
– Urethritis
• Typically in males
• Dysuria, frequency, profuse purulent discharge
• Untreated spontaneous resolution in few weeks
– Cervicitis
• Most common gonococcal infection in females
• Dysuria, frequency, vaginal discharge, uterine bleeding
• Typically asymptomatic until complications (PID)
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Gonorrhea: Clinical findings (cont.)
• Other manifestations
– Oropharyngeal
• Typically asymptomatic
• More common in females and MSM
• Mimics pharyngitis or tonsillitis
– Rectal
• Typically asymptomatic
• More common in females and MSM
• Constipation, itching, rectal pain, rectal discharge
– Conjunctivitis
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Gonorrhea: Complications
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Pelvic inflammatory disease (PID)
Epididymitis, prostatitis
Opthalmia neonatorum
Premature rupture of membranes
– 1st trimester
• Disseminated infections
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Dermatitis
Arthritis
Endocarditis
Meningitis
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Gonorrhea: Diagnosis
• Gram stain
– G (-) intracellular diplococci
• Culture
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Gonorrhea: Treatment
• Uncomplicated infections
3rd
gen. ceph or FQ
PLUS anti-chlamydial
Cefixime 400 mg PO X1
Ceftriaxone 125 mg IM X1
Ciprofloxacin 500 mg PO X1
Levofloxacin 250 mg PO x 1
Ofloxacin 400 mg PO X1
Azithromycin 1 gm X1
Doxycycline 100 mg PO
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BID X7
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Gonorrhea: Treatment (cont.)
• Disseminated infections
– Also to be given with anti-chlamydial tx
– Ceftriaxone 1 g IM/IV q24h
– Alternatives
• Cefotaxime 1 g IV q 8h
• Ceftizoxime 1 g IV q 8h
• b-lactam allergic
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Levofloxacin 250 mg IV q24h
Ciprofloxacin 400 mg IV q 12h
Ofloxacin 400 mg IV q 12h
Spectinomycin 2g IM q 12h
– Continue IV for 1-2 days post clinical
improvement, then switch to PO
• Cefixime, levofloxacin, ciprofloxacin, ofloxacin
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Gonorrhea: Treatment (cont.)
• Gonococcal meningitis and endocarditis
– Ceftriaxone 1-2 g IV q 12 h
– 10-14 days for meningitis
– Minimum 4 weeks for endocarditis
• Opthalmia neonatorum prophylaxis
– Silver nitrate 1% soln. X1
– Erythromycin 0.5% ointment X1
– Tetracycline 1% ointmentX1
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Syphilis: Epidemiology
• Causative organism – Treponema
pallidum
• Approx 100,000 cases annually
• Strong association with HIV infections
• Crosses placenta (any time)
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Syphilis: Clinical findings
• Primary syphilis
– Painless lesion
chancre
• Incubation period average 3 weeks
• Dull, red macule
papule
erosion and ulceration
• Resolves spontaneously in 1-8 weeks
• Secondary syphilis
– Symmetrical papular eruption (palms/soles of feet
+ mucous patches in mouth)
– Systemic symptoms
• Malaise, fever, HA, anorexia, lymphadenopathy
– All symptoms disappear in 4-10 weeks (w/out
treatment), but may recur
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Syphilis: Clinical findings (cont.)
• Latent syphilis
– Serologic evidence without manifestations
– Early latent: <1 year since onset
• Infectious
– Late latent: > 1 year since onset
• Non-infectious
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Syphilis: Clinical findings (cont.)
• Tertiary (late) syphilis
– 20-30% of patients progress to this point
– Skeletal system
• Gummas
– CV
• Aortic insufficiency, aortitis, aortic aneurysm
• Neurosyphilis
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Meningitis
Strokes
Seizures
Blindness
Deafness
Dementia
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Syphilis: Diagnosis
• Early syphilis
– Darkfield examination of ulcer exudate
– Direct fluorescent antibody test (DFA-TP)
• Later stages
– Non treponemal (VDRL slide test and RPR card
test)
• Detection of reagin
– Treponemal (FTA-ABS)
• Detection of antibody to T. pallidum
• Remains positive in latent syphilis
• Cross reactive with Lyme disease
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Syphilis: Treatment
• Primary, secondary, and early latent syphilis
– Benzathine PCN G 2.4 million units IM X1
• Late latent
– Benzathine PCN G 2.4 million units IM q week X3
• Neurosyphilis
– Aqueous crystalline PCN G 3-4 million units IV
q4h X 10-14d
– Alternative: procaine PCN 2.4 mu IM/d +
probenecid 500 mg PO QID for 10-14d
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Syphilis: Treatment (cont.)
• Non-pregnant PCN allergic
– Primary, secondary, and early latent
syphilis
• Doxycycline 100 mg PO BID or TCN 500 mg
PO QID X 2 weeks
– Late latent or tertiary syphilis
• Doxycycline 100 mg PO BID or TCN 500 mg
PO QID X 4 weeks
– Ceftriaxone, azithromycin???
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Syphilis: Treatment (cont.)
• Pregnant women
– PCN is the ONLY recommended Tx
• Skin testing and desensitization are indicated if
allergic
• Jarisch-Herxheimer
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Chancroid: Epidemiology
• Causative organism – H. ducreyi
• Endemic in many areas in US
• Occurs as outbreaks
– Commonly co-infection with syphilis or
HSV
• Cofactor for HIV transmission
– Test for HIV at baseline and at 3 mos.
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Chancroid: Clinical findings
• Painful genital lesions
• Tender inguinal lymphadenopathy
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Chancroid: Diagnosis
• Special culture media
– 80% sensitivity
• Exclusion diagnosis + ulcers not typical
of HSV
– Negative darkfield exam serological test for
syphilis
– Ulcer exudate is negative for HSV
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Chancroid: Treatment
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•
•
•
Azithromycin 1g PO x1
Ceftriaxone 250 mg IM x1
Ciprofloxacin 500 mg PO BID x3d
Erythromycin base 500 mg PO TID x7d
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Trichomoniasis
• Causative organism – Trichomonas vaginalis
• Nonsexual transmission possible
• Clinical Findings
– Typically asymptomatic
• 90% men
• 50% women
– Symptoms in women
• Profuse, frothy,malodorous, yellow-green/grayish
discharge
• Itchy, irritation
• Dysuria
• Worsen during menstruation
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Trichomoniasis (cont.)
• Complications
– Weak association with PID
– Weak association with preterm labor
– Bacterial overgrowth (bacterial vaginosis)
• Diagnosis
– Culture
– Wet mount examinations of secretions
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Trichomoniasis (cont.)
• Treatment
– Metronidazole 2g PO X1
• Alternative: Metronidazole 500 mg BID X 7d
– Pregnant women
• ? Don’t treat in 1st trimester
• Treat after 1st trimester if symptoms continue
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Vaginal infections
• Characterized by vaginal discharge and/or
vulvar itching and irritation
• Trichomoniasis, bacterial vaginosis, and
candidiasis
• Role of sexual transmission is unimportant in
vulvovaginal candidiasis and unclear in
bacterial vaginosis
– Sulfa creams and other “broad spectrum” vaginal
preparations not reliable
– Douching not effective for prevention or treatment
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Vaginal infections:
Bacterial vaginosis
• Normal Lactobacillus spp. replaced typically
by
– Gardnerella vaginalis, Mycoplasma hominis,
Mobiluncus spp., or Prevotella spp.
• Associated with having multiple sex partners
and douching
– Unclear whether BV is sexually transmitted
• Complications
– Premature labor
– Delivery complications
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Vaginal infections:
Bacterial vaginosis (cont.)
• Diagnosis
– Gram stain
– A homogeneous, white, noninflammatory
discharge that smoothly coats the vaginal walls
– The presence of clue cells on microscopic
examination
– A pH of vaginal fluid >4.5
– A fishy odor of vaginal discharge before or after
addition of 10% KOH (i.e., the whiff test)
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Vaginal infections:
Bacterial vaginosis (cont.)
•
Treatment
– Metronidazole 500 mg PO BID X7d
– Metronidazole gel (.75%) 5 g
intravaginally QD X5d
– Clindamycin cream (2%) 5 g
intravaginally qHS X7d
– Pregnant women
•
•
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Metronidazole 250 mg PO TID x7d
Clindamycin 300 mg PO BID x7d
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Vaginal infections:
Vulvovaginal candidiasis (VVC)
• Causative organism – Candida spp. (usually
C. albicans)
• NOT usually sexually transmitted
• ~75% of women will have at least one
episode
• Clinical findings
– Pruritus, vaginal discharge, vaginal soreness,
vulvar burning, dysuria
• Diagnosis
– Gram stain
– culture
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Vaginal infections: VVC (cont.)
• Uncomplicated
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• Complicated
Sporadic, infrequent
Mild-to-moderate
C. albicans
immunocompetent
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Recurrent
Severe
Non-albicans
Diabetes, pregnant,
and/or
immunosuppressed
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Vaginal infections: VVC (cont.)
Treatment
• Uncomplicated
• Complicated
– Many topical OTC
preparations for 1-7d
(butoconazole,
clotrimazole,
miconazole,
tioconazole, nystatin)
– Fluconazole 150 mg
PO x1
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– Recurrent, severe,
immunocompromised –
same therapy, longer
duration
– Non-albicans -- ???;
longer duration with a
non-fluconazole azole
– Pregnant – topical
agents only (7d)
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Pelvic inflammatory disease
(PID):
Epidemiology
• Estimated 1 million cases annually
• Risk factors
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–
–
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Youth
Multiple sex partners
IUD use
? Douching
• Spectrum of inflammatory disorders
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Endometritis
Salpingitis
Tubal ovarian abscesses
Pelvic peritonitis
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PID: Epidemiology (cont.)
• Causative organisms
– C. trachomatis
– N. gonorrhoeae
– G. vaginalis, anaerobes, enteric GNB, S.
agalactiae
– Others
• CMV, M. hominis, U. urealyticum
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PID: Clinical issues
• Clinical findings
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–
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Variable
Lower abdominal tenderness (often bilateral)
General aches
Vaginal discharge
• Complications
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Tubal damage + scarring‡ ectopic pregnancy
Sepsis
Chronic pelvic pain
Recurrence
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PID: Diagnosis
• Minimal criteria
– Lower abdominal/uterine tenderness
– Tenderness with motion of cervix
• Additional criteria
– Fever, leukocytosis
– Abnormal cervical or vaginal discharge
– Elevated ESR and CRP
• Laparoscopy
• Endovaginal ultrasound
• Endometrial biopsy
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PID: Treatment
• Broad coverage for likely pathogens
• Hospitalize select patients
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Possibility of surgical emergency (e.g., appendicitis)
Suspected pregnancy
Ectopic pregnancy
Pelvic abscess
HIV (+)
Severe illness, nausea & vomiting, or high fever
Clinically unresponsive to oral therapy
Unwilling/unable to tolerate outpatient treatment
72-h follow-up cannot be guaranteed
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PID: Treatment (cont.)
• Oral
– Ofloxacin 400 mg PO BID or levofloxacin
500 mg PO QD ± metronidazole 500 mg
PO BID x 14d
– Ceftriaxone 250 mg IM x1 or cefoxitin 2 g
IM and probenecid 1 g PO x1 plus
doxycycline 100 mg PO BID x 14d ±
metronidazole 500 mg PO BID x 14d
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PID: Treatment (cont.)
• IV
– Cefoxitin 2 g IV q6h PLUS doxycycline 100 mg
IV/PO q12h
– Cefotetan 2 g IV q12h PLUS doxycycline 100 mg
IV/PO q12h
– Clindamycin 900 mg IV q8h plus gentamicin
– Alternative
• Ofloxacin or levofloxacin ± metronidazole or
ampicillin/sulbactam plus doxycycline
– Continue IV for at least 24 hours after clinical
improvement, then PO doxy or clinda for 14-d total
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Conclusion
–Chlamydia
–Gonorrhea
–Syphilis
–Chancroid
–Trichomoniasis
–Vaginal infections
–PID
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Questions???
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Genital warts and Human
Papillomavirus (HPV)
• Most common STD
– 10 – 20% of sexually active individuals (15
– 49 y.o.) showing evidence of infection
– 60% show evidence of prior infection
• Most asymptomatic and self-limiting
– Minority develop anogenital warts
– ~10% develop chronic infection
Most used
• Predisposed to anogenital cancer
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Genital warts and HPV (cont.)
• External genital warts
– Typically HPV type 6 or 11
• Dysplasia of cervix, anus, genital skin
– Typically HPV 16, 18, others
– HPV DNA has been detected in
association with up to 93% of cervical
cancers
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Genital Warts and HPV (cont.)
• Treatment
– No form of treatment shown to eradicate
virus or modify risk for cancer
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–
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–
–
Spring 2004
Trichloracetic acid
Podophyllin
Cryotherapy with liquid nitrogen or cryoprobe
Imiquimod 5%
Podofilox 0.5% soltn.
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Genital herpes (HSV):
Epidemiology
• 2 serotypes
– HSV-1: herpes labialis, herpes keratitis,
herpetic encephalitis
– HSV-2: genital herpes and neonatal herpes
• Recurrent, incurable
• Incidence increasing
– > 50 million people in the US
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HSV: Clinical findings
• Up to 50% HSV-2 asymptomatic
• Prodromal symptoms
– Tingling
– Itching
– Burning
• Lesions
– Multiple, widely-spaced, bilateral, midline,
ulcerative, painful
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HSV: Clinical findings (cont.)
• Systemic
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–
–
–
HA
Fever
Malaise
Flu-like symptoms
• Infective period
– 10-14 days after onset (viral shedding)
• Complications
– Spontaneous abortion, malformation, pre-term labor
– Neonatal infection
– ? Cervical CA
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HSV: Diagnosis
• Clinical presentation
• Viral culture
– Sensitivity declines as lesions heal
• Type-specific serology
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HSV: Treatment
• 1st clinical episode
– Acyclovir 400 mg PO TID x7-10 d
– Acyclovir 200 mg PO 5x/d x7-10 d
– Famciclovir 250 mg PO TID x7-10 d
– Valacyclovir 1 g PO BID x7-10 d
May extend duration if healing is incomplete
after 10 days
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HSV: Treatment (cont.)
• Recurrent
(Initiate within 1 day of lesion onset or during
prodrome)
– Acyclovir 400 mg PO TID x 5d
– Acyclovir 200 mg PO 5x/d x 5d
– Acyclovir 800 mg PO BID x 5d
– Famciclovir 125 mg BID x 5d
– Valacyclovir 500 mg PO BID x 3-5d
– Valacyclovir 1000 mg PO QD x 5d
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HSV: Treatment (cont.)
• Daily suppressive therapy
– Reduces frequency of infection by > 75%
in patients with recurrence >6X/yr.
•
•
•
•
Acyclovir 400 mg PO BID
Famciclovir 250 mg PO BID
Valacyclovir 500 mg PO QD
Valacyclovir 1000 mg PO QD
– DOES NOT eliminate viral shedding
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HSV: Treatment (cont.)
• Severe disease
– Acyclovir 5-10 mg/kg IV q 8h x 2-7 d or until
resolution, followed by PO therapy to complete 10
days of therapy
• Immunocompromised (HIV)
–
–
–
–
Acyclovir 400 mg PO TID x5-10 d
Acyclovir 200 mg PO 5x/d x5-10 d
Famciclovir 500 mg PO BID x5-10 d
Valacyclovir 1 g PO BID x5-10 d
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HSV: Treatment (cont.)
• Pregnant
– 1st episode near term: systemic acyclovir
advocated
– Recurrence near term: ???
– ? Safety – no major teratogenic effects
have been documented, but data are
insufficient
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HSV: Resistance
• Strains resistant to acyclovir also
resistant to valacyclovir and mostly
resistant to famciclovir.
– Foscarnet 40 mg/kg IV q8 hr
– Cidofovir gel 1% QD x 5d
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