FEMALE GENITAL TRACT INFECTIONS
From University of California, San Francisco, School of Medicine’s 35th Annual Advances in Internal Medicine
Michael S. Policar, MD, MPH, Associate Clinical Professor, Department of Obstetrics, Gynecology and Reproductive
Sciences, University of California, San Francisco, School of Medicine
| General issues in screening and prevention: current guidelines published by Centers for Disease Control and
Prevention (CDC; 2006) emphasize counseling and prevention; pearls—always tell patients which sexually transmitted
diseases (STDs) they are being screened for (eg, when screening for human papillomavirus [HPV] along with Papanicolaou
[Pap] test); routinely take thorough sexual histories and counsel patients about risk reduction; provide
nonoccupational postexposure prophylaxis for HIV prevention (eg, after sexual assault); provide emergency contraception
and antibiotic therapy for victims of sexual assault; counsel patients to avoid douching and repetitive use of
spermicides (latter increases vaginal inflammation, increasing risk for viral infections)
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Genital Herpes
| Transmission and epidemiology: ≈50 million people in United States infected (most cases asymptomatic and unrecognized);
intermittent asymptomatic shedding of virus accounts for most transmissions; asymptomatic shedding—
most frequent during first year after infection, then decreases over time; likelihood of asymptomatic shedding same in
those who have had clinical symptoms as in those who have never been symptomatic; accounts for most transmission
of herpes simplex virus (HSV)-2 (shedding less common with HSV-1); epidemiologic changes—proportion of genital
infections caused by HSV-1 increasing; increased parental vigilance has decreased childhood exposure to cold sores
(oral infection with HSV-1; builds immunity); these adults at higher risk for acquiring HSV-1 sexually; HSV and risk
for HIV infection—presence of genital ulcers (in men and women) increases risk for infection with HIV
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| Screening: routine screening unnecessary for general population and pregnant women; recommended for—HIV-positive
patients; discordant couples (one partner HSV-positive; status of other partner negative or unknown); patients
who engage in high-risk behaviors; caveat— screen only if counseling provided and patient likely to change behavior
(ie, increase prevention or decrease risky behaviors)
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| Preventing transmission: randomized placebo-controlled trial looked at 1500 discordant couples; half of infected
partners treated with valacyclovir (Valtrex) for 1 yr; transmission—although treatment reduced rate by ≈50% (3.6% vs
1.9%), overall incidence of transmission low (preventing 1.7 cases per 100 couples per year; number needed to treat
[NNT] to prevent one case high [59 couples]); advice for discordant couples—avoid intercourse or touching lesions
during outbreak; consider using condoms (but not 100% effective in preventing transmission); treat outbreaks (reduces
viral load and shedding); consider prophylactic treatment (explain relative and absolute reductions in risk)
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| Treatment: primary outbreak—7 to 10 days of acyclovir (400 mg tid or 200 mg 5 times/day), famciclovir (250 mg tid),
or valacyclovir (1 g bid); recurrence—preferred courses include acyclovir, 800 mg tid for 2 days or famciclovir, 1 g bid
for 1 day; longer courses associated with lower rates of adherence and higher cost; prophylaxis—clinical trials used
Valtrex, but generic acyclovir (400 mg bid) often substituted
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Human Papillomavirus
| Screening: hybrid capture test identifies 13 strains of high-risk HPV; recommended for—primary screening (with Pap
test) for women ≥30 yr of age (too many false-positive results in younger women); triaging women with atypical squamous
cells of undetermined significance (ASCUS) on Pap test (colposcopy if positive; retest if negative); follow-up
for adolescents with biopsy-proven low-grade squamous intraepithelial lesions (LSIL); follow-up after colposcopy or
treatment for dysplasia; not recommended for—triaging adults with LSIL, high-grade squamous intraepithelial lesions
(HSIL), atypical squamous cells when HSIL cannot be excluded (ASCH), or atypical glandular cells (AGC) on Pap
test; screening for STDs in general population; evaluation of sexual partners; evaluation of genital warts; note—never
screen for low-risk strains of HPV, because results have no impact on management
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Vaginal Trichomoniasis
| Diagnosis: point of care tests—performed in office; have high sensitivity and specificity and low cost; not intended as
screening tools
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| Treatment: preferred—single dose of metronidazole (eg, Flagyl; 2 g); single dose of tinidazole (2 g); tinidazole somewhat
more effective but more expensive; alternatives—7-day treatment with metronidazole (500 mg); cost per dose—
generic metronidazole, ≈$1; Flagyl, ≈$15; tinidazole (Tindamax), ≈$12
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 | Tinidazole: advantages—associated with fewer adverse effects (nausea, vomiting, dizziness, cramping) and marginally
higher cure rate than metronidazole; allergy—patients with true allergy to metronidazole (eg, urticaria, anaphylaxis)
also will have reaction to tinidazole; recommended for—patients with history of metronidazole failure or
intolerance
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| Clinical pearls: advise patient that infection may have occurred any time since initiation of sexual activity (patient
may remain asymptomatic during carrier state, which may last many years); evaluate saline suspensions immediately,
because organisms die quickly (cannot diagnose trichomoniasis using microscopy unless organisms alive); use fresh
saline suspensions (hypertonic solutions kill organisms); treat with single-dose metronidazole unless tinidazole indicated
(see above); pregnancy—metronidazole approved for use during all 3 trimesters (no evidence of teratogenicity),
but consider avoiding in women with pregnancy-associated nausea and vomiting
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Bacterial Vaginosis (BV)
| Etiology: pathologic findings—loss of lactobacilli normally present in vagina; overgrowth of anaerobes; in some
women, sexual intercourse decreases vaginal lactobacilli (adhere to sperm); low levels of lactobacilli allow overgrowth
of anaerobes; previously overlooked bacteria (specific to BV) recently identified (may aid in diagnosis and
treatment); sexual transmission—not transmitted sexually between heterosexual partners; among women who have sex
with women (WSW), high rate of concordance between partners suggests horizontal transmission (eg, by sharing sex
toys or through direct contact)
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| Treatment: candidates—symptomatic (nonpregnant) women; pregnant women, especially those at risk for preterm
birth (generally treat at 26th week of pregnancy); women with upcoming pelvic surgery (eg, induced abortion, hysterectomy,
cervical procedure); paradigm shift—BV associated with increased risk of acquiring and transmitting
HIV and increased risk for pelvic inflammatory disease (PID) among young women and urinary tract infections
among all women; therefore, more clinicians treating asymptomatic women without specific indications
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| Treatment regimens: oral—metronidazole 500 mg bid for 7 days; topical—metronidazole gel; clindamycin cream; single
dose of metronidazole (2 g) no longer recommended
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| Recurrent BV: for women with ≥3 episodes/yr, consider suppression therapy with metronidazole gel (twice weekly)
after 1-wk “wash-in” period of daily therapy; counseling—abstain from sexual intercourse during treatment; avoid
douching (increases risk for BV); use condoms (especially during first month after treatment); clean shared sex toys
between uses; avoid vaginal insertion following anal insertion (introduces rectal flora to vagina)
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| Diagnosis: microscopy—clue cells represent ≥20% of epithelial cells; amine test—use vaginal discharge from speculum;
vaginal pH—4.5 to 6.0; culture and Pap test—no role in diagnosis
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Vulvovaginal Candidiasis (VVC)
| Classification: uncomplicated—sporadic; mild to moderate symptoms; most commonly caused by Candida albicans;
occurs in immunocompetent women; responsive to treatment; complicated—resistant to treatment; recurrent or severe;
infection with species other than C albicans; occurs in pregnant women or those with uncontrolled diabetes or
other immune deficiency
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| Treatment for uncomplicated VVC: duration—7-day, 3-day, and 1-day topical treatments available; oral
medication—fluconazole (Diflucan); single tablet (150 mg); efficacy and adverse effects—similar for 3-day and 7-day
topical treatments and fluconazole; recommendations—3-day topical therapy or fluconazole (ask if patient has preference)
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| Severe VVC: findings—erythema; excoriation; fissures
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| Treatment: 7 to 14 days of topical therapy or 150 mg fluconazole, repeated in 3 days; immunocompromised host—conventional
antimycotic therapy for 7 to 14 days or 150 mg fluconazole every 3 days for 3 doses; pregnant women—
topical azoles for 7 days; insufficient data on safety of oral fluconazole during pregnancy
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| Recurrent VVC: defined as ≥4 episodes/yr; most women do not have predisposing condition; partners almost never
source of transmission; data show autoinoculation from gastrointestinal tract main source; many women who think
they have recurrent VVC do not, so CDC recommends obtaining vaginal culture; initial treatment (wash-in period)—7
to 14 days of topical therapy or 150 mg fluconazole every 3 days for 3 doses; maintenance therapy—fluconazole, twice
weekly to begin, reducing to once weekly if well controlled; verification—only ≈33% of women who believe they
have recurrent VVC have candidiasis; diagnosis should be verified; Candida glabrata—accounts for ≈15% of yeast infections;
different presentation (burning more common than itching) and treatment; yogurt—contains different species
of Lactobacillus from vaginal flora, so unlikely to prevent infections
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Chlamydia and Gonorrhea
| Screening tests: nucleic acid amplification test (NAAT; “state-of-the-art”); DNA hybridization test (eg, Genprobe
PACE 2); Chlamydia culture; enzyme immunoassay (Chlamydiazyme) no longer available; note—important to know
which test used, its sensitivity and specificity, and prevalence of chlamydia in practice; positive predictive value
(false-positive or true-positive) affected by specificity and sensitivity of test
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| Routine screening: based on population risk factors; cervical chlamydia—annually in sexually active women <26 yr
of age; cervical gonorrhea—annually in sexually active women <26 yr of age, only when prevalence in practice ≥1%
(otherwise, routine screening not recommended); pregnant women—screen for syphilis, HIV, chlamydia, and hepatitis
B; screening practices—nationally, only ≈50% of women ≤25 yr of age screened annually for chlamydia; similar annual
screening rate among women ≥26 yr of age wrong because with age, target cells (columnar epithelium of cervix)
replaced by squamous epithelium, so exposure generally does not lead to infection; positive predictive value of
screening test decreases; prevalence of chlamydia—3% among women 15 to 19 yr of age; 2.6% among women 20 to
24 yr of age; ≈0.1% among women in late 30s
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| Targeted screening: based on behavioral risk factors; factors associated with increased risk—history of gonorrhea,
chlamydia, or PID within previous 2 yr; \>1 sex partner during previous year; new sex partner within previous 90 days;
sex partner who has other sex partners; women ≥26 yr of age with any of these risk factors should be screened for gonorrhea
and chlamydia; screening for gonorrhea recommended for all sexually active black women ≤30 yr of age living
in urban areas; syphilis and HIV—screening based on sexual history, behaviors and serostatus of sex partners, and local
prevalence of disease; anorectal and oropharyngeal sampling—no CDC recommendation for screening heterosexual
women, heterosexual men, or WSW; among men who have sex with men, screen rectum for gonorrhea and chlamydia
and screen throat for gonorrhea (no screening test available for oropharyngeal chlamydia)
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| Contact testing: for individuals with known or suspected exposure (eg, unprotected sex with person with unknown
sexual history), screen for gonorrhea, chlamydia, syphilis, and HIV; no contact testing (culture) for HSV or HPV; vaccination
recommended over screening for HBV
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| Coinfection testing: infection with one STD increases risk for other STDs; for patients with gonorrhea, chlamydia,
syphilis, or HIV, test for other three; recurrent herpes, trichomoniasis, and external genital warts may indicate long-
standing infection (ie, do not trigger coinfection testing); BV and VVC not considered STDs, so coinfection testing not
warranted
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| Test of cure: testing efficacy of antibiotic treatment; uncommon, unless antibiotic associated with high rate of failure
or poor compliance suspected
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| Repeat screening: patients treated for gonorrhea or chlamydia at high risk for reinfection; retesting 3 mo to 6 mo after
treatment identifies patients at highest risk
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| Treatment: chlamydia—1 g azithromycin preferred; gonorrhea—fluoroquinolones no longer recommended due to
high rates of resistance; intramuscular injection of 125 mg ceftriaxone preferred; acceptable oral regimens include single
doses of cefpodoxime (Vantin) or cefuroxime (eg, Ceftin)
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Pelvic Inflammatory Disease
| Treatment: general principles—overdiagnose and treat rather than underdiagnose; treat early and aggressively; address
gonorrhea, chlamydia, anaerobic bacteria, and BV; regimen A—levofloxacin or ofloxacin (for 14 days); regimen
B—combination of doxycycline with ceftriaxone or cefoxitin; addition to 2006 recommendations—add metronidazole
500 mg bid for 14 days to treat BV or improve coverage of anaerobes; quinolones—acceptable if risk for gonorrhea
low, NAAT negative for gonorrhea, and follow-up likely; use alternative treatment if gonorrhea documented
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Questions and Answers
| Diagnosing trichomoniasis in men: microscopic examination of prostatic fluid has low sensitivity; empirical
treatment of male partners of women with trichomoniasis preferred
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| Horizontal transmission of HSV from asymptomatic carrier to uninfected partner: 1 in 4 men seropositive
for HSV-2; asymptomatic shedding common; 4% annual transmission rate if not treated prophylactically
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| Counseling HPV-discordant couples: HPV infection common among sexually active individuals; focus on prevention
(vaccination in appropriate populations) and early detection
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| LSILs in adolescents: common; indicate transient infection; clearance occurs in \>90% of cases; Pap tests—begin
testing 3 yr after initiation of sexual activity; recheck patients with ASCUS or LSIL in 1 yr (do not refer immediately
for colposcopy)
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Suggested Reading
Czerucka D et al: Review article: yeast as probiotics — Saccharomyces boulardii. Aliment Pharmacol Ther 26:767,
2007; Datta SD et al: Gonorrhea and chlamydia in the United States among persons 14 to 39 years of age, 1999 to
2002. Ann Intern Med 147:89, 2007; Engberts MK et al: Symptomatic candidiasis: Using self-sampled vaginal
smears to establish the presence of Candida, lactobacilli, and Gardnerella vaginalis. Diagn Cytopathol 35:635, 2007;
Hutchinson KB et al: Condom use and its association with bacterial vaginosis and bacterial vaginosis-associated
vaginal microflora. Epidemiology 18:702, 2007; Kershaw TS et al: Using clinical classification trees to identify individuals
at risk of STDs during pregnancy. Perspect Sex Reprod Health 39:141, 2007; Simpson P et al: Real-time PCRs
for detection of Trichomonas vaginalis beta-tubulin and 18S rRNA genes in female genital specimens. J Med Microbiol
56(Pt 6):772, 2007; Spitzer M: Screening and management of women and girls with human papillomavirus infection.
Gynecol Oncol 107(2Suppl):S14, 2007; Stanley M: Prevention strategies against the human papillomavirus: the effectiveness
of vaccination. Gynecol Oncol 107(2Suppl):S19, 2007; Wang SA et al: Antimicrobial resistance for Neisseria
gonorrhoeae in the United States, 1988 to 2003: the spread of fluoroquinolone resistance. Ann Intern Med 147:81, 2007;
Workowski KA, Berman SM: Centers for Disease Control and Prevention sexually transmitted diseases treatment
guidelines. Clin Infect Dis 44(Suppl3):S73, 2007; Zetola NM et al: Syphilis in the United States: an update for clinicians
with an emphasis on HIV coinfection. Mayo Clin Proc 82:1091, 2007.
Educational Objectives
| The goal of this program is to improve identification and treatment of genital tract infections. After hearing and assimilating
this program, the clinician will be better able to:
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| 1. Implement current screening guidelines published by the Centers for Disease Control and Prevention.
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| 2. Identify population-based and behavioral risk factors for acquiring sexually transmitted diseases (STDs).
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| 3. Apply current treatment guidelines and management algorithms for patients with STDs.
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| 4. Educate patients about preventing transmission of STDs.
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| 5. Discuss the role of prophylaxis for recurrent bacterial vaginosis and vulvovaginal candidiasis.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty amd planning committee members
to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified
conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business
or commercial interest. For this program, the faculty and the planning committee reported nothing to disclose.
Acknowledgments
Dr. Policar was recorded at 35th Annual Advances in Internal Medicine, presented by University of California, San Francisco,
School of Medicine, and held May 21-25, 2007, in San Francisco, CA. The Audio-Digest Foundation thanks Dr. Policar and the
University of California, San Francisco, School of Medicine for their cooperation in the production of this program.
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