Vaginitis and STDs

Objectives

Introduction
  1. Sexually transmitted diseases (STDs) are a common problem in adolescents. Chlamydia trachomatis is the most prevalent bacterial STD in the United States, with the highest rates reported among adolescents. 1
  2. Vaginal discharge is a frequent presenting complaint. The three most common diseases associated with vaginal discharge are trichomoniasis, bacterial vaginosis, and candidiasis. 2 However, a significant number of patients with vaginal discharge will have some other condition. Physicians must refrain from the temptation of "diagnosing" a vaginitis based solely on the color and consistency of the discharge, since this may lead to misdiagnosis of relatively common conditions such as cytolytic vaginosis, and may miss concomitant infections. 3 A complete examination - including assays or cultures, wet preps, pH evaluation, and examination - should be performed if reasonably possible.
  3. Adolescents present a special challenge. The reported rates of chlamydia and gonorrhea are highest among females aged 15 to 19 years, and young adults are also at highest risk for HPV infection. In addition, surveillance data indicate that 9% of adolescents who have acute HBV infection either have had sexual contact with a chronically infected person or with multiple sex partners or report their sexual preference as homosexual. Younger adolescents (i.e., persons aged <15 years) who are sexually active are at particular risk for infection. Adolescents at especially high risk for STDs include youth in detention facilities, STD clinic patients, male homosexuals, and injection-drug users. Adolescents are at greater risk for STDs because they frequently have unprotected intercourse, are biologically more susceptible to infection, are engaged in partnerships often of limited duration, and face multiple obstacles to utilization of health care. 3
  4. It should also be determined whether the patient douched recently, because this can lower the yield of diagnostic tests. Vaginal douching has also been found to increase the risk of pelvic inflammatory disease and ectopic pregnancy. 4 Patients who have been told not to douche will sometimes start wiping the vagina with soapy wash-cloths as an alternative to "keep clean." This greatly irritates the vagina and cervix and may cause a discharge.
  5. The physical exam should include inspection of the external genitalia for irritation or discharge from the introitus. Speculum exam is done to determine the amount and character of the discharge. A chlamydiazyme and culture for gonorrhea should always be done on any appreciable discharge in sexually active females. Newly available sensitive and specific urine tests for chlamydia (polymerase chain reaction [PCR] and ligase chain reaction [LCR]) provide alternative ways of screening at-risk adolescents. Bimanual exam may show evidence of cervical, uterine, or adnexal tenderness, indicating more extensive involvement of infection. Table 1 shows diagnostic values for examination of vaginitis. Although these tests are greater than 90% sensitive and specific, many physicians do not employ them in dealing with women with vaginal discharge. 5
    1. Vaginal pH testing can be very helpful in the diagnosis of vaginitis. The normal vaginal pH is usually 3.5 to 4.5. Estrogen causes deposition of glycogen in mature epithelial cells, which is then converted by bacterial enzymes to glucose. The glucose is anaerobically fermented to lactic acid, which gives the vagina a pH of 3.5 to 4.5. Apply pH paper to the vaginal side-wall. Do not place water on the glove or speculum, since it alters pH. Cervical mucus has higher pH than vagina, so do not place the pH paper in contact with the cervical mucus. A pH above 4.5 is seen with menopausal patients, trichomonas infection, or bacterial vaginosis. Gjerdngen, et al., found that when vaginal pH was routinely checked in pregnant patients, there was a significantly higher detection of bacterial vaginosis (BV) and Trichomonas vaginitis. 6

       

    6. Table 1. Diagnostic Values for Differential Diagnosis of Vaginal Infections.
    Diagnostic Criteria Normal Bacterial Vaginosis Trichomonas Vaginitis Candida Vulvovaginitis
    Vaginal pH 3.8 - 4.2 > 4.5 4.5 < 4.5 (usually)
    Discharge White,thin, flocculent Thin, white, gray Yellow, green, frothy White, curdy, "cottage cheese"
    Amine odor "whiff" test Absent Fishy Fishy Absent
    Microscopic Lactobacilli, epithelial cells Clue cells, adherent cocci, no WBCs Trichomonads, WBCs >10/hpf Budding yeast, hyphae, pseudohyphae

     

  6. Laboratory work usually includes a chlamydiazyme and GC culture (or urine tests), wet prep, and KOH prep (or "whiff test").
    1. 1Wet preps are obtained using a second cotton-tipped applicator applied to the vaginal side-wall, placing the sample of discharge into normal saline (not water). A drop of the suspension is then placed on a slide, covered with a cover-slip, and carefully examined with the low-power and high-dry objective lenses. Under the microscope, observe for presence and number of white blood cells (WBCs), trichomonads, candidal hyphae, or clue cells. Trichomonads are motile, pear-shaped organisms with active flagella, larger than a WBC but smaller than epithelial cells, that are usually seen swimming or thrashing around in the wet prep. Clue cells are epithelial cells that have bacteria adhered to their surface, obscuring their borders and causing a stippled appearance. Yeast or hyphae also may be seen on the wet prep.
    2. The KOH prep is made by adding a drop of KOH solution to a drop of saline suspension of the discharge. The KOH lyses epithelial cells in 5 to15 minutes (faster if the slide is warmed briefly over a flame) and allows easier visualization of Candidal hyphae. 2 Another diagnostic procedure is the "whiff" test, which is done by placing a drop of KOH on a slide of the wet prep and smelling for a foul, fishy odor. The odor is indicative of anaerobic overgrowth or infection. 2 A KOH slide may be made by adding the KOH to the wet prep slide, provided it does not dry out excessively.
    3. Testing can be simplified using the FemExam® pH and Amines TestCard™ (Matria), which is a credit card-sized device with 2 wells that test for pH and amines. Clinicians use a swab to apply a sample of vaginal discharge to the test area on the card and an easy-to-read plus sign appears to indicate an increase in pH or amine levels. The Osmetech Microbial Analyser is a fully automated device that measures the volatile gases produced from vaginal swabs, which are sealed in glass vials. It is designed for diagnosing and differentiating chlamydia, gonorrhea, and BV vaginal infections.The tests are quick and easy to use but are more costly than traditional testing.
     

      7.  

Chlamydia trachomatis

  1. Background
    1. A very common sexually transmitted disease, chlamydia is the most frequently reported infectious disease in the United States. 7 Though 526,653 cases were reported in 1997, an estimated 3 million cases occur annually. The annual cost of chlamydia and its consequences in the United States is more than $2 billion. The CDC estimates screening and treatment programs can be conducted at an annual cost of $175 million. Every dollar spent on screening and treatment saves $12 in complications that result from untreated chlamydia. 8
    2. It is common among sexually active adolescents and young adults. 7 As many as 1 in 10 adolescent girls tested for chlamydia is infected. Based on reports to Centers for Disease Control and Prevention (CDC) provided by states that collect age-specific data, teenage girls have the highest rates of chlamydial infection. In these states, 15- to 19-year-old girls represent 46% of infections and 20- to 24-year-old women represent another 33%. 8 The infection may be asymptomatic and the onset often indolent. It can cause cervicitis, endometritis, PID, urethritis, epididymitis, neonatal conjunctivitis, and pediatric pneumonia. Of exposed babies, 50% develop conjunctivitis and 10% to16% develop pneumonia. It may also lead to Reiter's syndrome.
    3. Up to 40% of women with untreated chlamydia will develop PID. Undiagnosed PID caused by chlamydia is common. Of those with PID, 20% will become infertile; 18% will experience debilitating, chronic pelvic pain; and 9% will have a life-threatening tubal pregnancy. Tubal pregnancy is the leading cause of first-trimester, pregnancy-related deaths in American women. 8
      Risks factors for Chlamydia 7
      • Lower socioeconomic status
      • Black race
      • Age <24 years
      • New sexual partner within 3 months
      • Multiple sexual partners
      • Nonuse of barrier contraceptives
      • Recent exposure to another STD (especially GC)
    4. Intracellular parasite with a two-stage life cycle: Infectious stage (elementary body) and metabolic-reproductive stage (reticulate or inclusion body).
    5. Prevalence varies widely from 3% to 40%, and it may predispose to preterm and low-birth-weight babies. 9
  2. Diagnosis
    1. Often asymptomatic. Look for urethritis, endometritis, salpingitis, perihepatitis, and mucopurulent cervicitis. Dysuria is a very common complaint.
    2. All pregnant woman should be screened.
    3. Wet prep is usually negative for other organisms - may only see WBCs.
    4. >10 PMNs per high-power field on Gram stain of cervical mucous.
    5. Must NOT use wood-handled swab, since substances in wood may inhibit chlamydia organism . Culture has sensitivity of 70% to 100% and a specificity of almost 100%, which makes it the gold standard against which other tests are measured. The ELISA technique (Clamydiazyme) has a sensitivity of 70% to 100% and a specificity of 97% to 99%. Flourescein-conjugated monoclonal antibodies test (MicroTrak) has a sensitivity of 70% to 100% and a specificity of 97% to 99%. Office-based tests have a sensitivity of 81% to 94% and a specificity of 95% to 99%. 7
    6. Consider culture confirmation for positive test results in low risk patients. 7 False-negative and false-positive rates change with prevalence of disease in population studied.
  3. Treatment: Partners must be treated before unprotected intercourse, or reinfection may occur. PID requires more intensive therapy. 2
    1. Azithromycin (Zithromax) 1000 mg one-time dose. Take on an empty stomach. Not well-tested in nursing mothers. May be used during pregnancy. DO NOT use (4) 250 mg pills - costs more.
    2. Doxycycline 100 mg p.o. BID x 7 days or tetracycline 500 mg BID x 7 days; avoid dairy products around time of dosing. Candida vaginitis is a common sequela.
    3. Ofloxacin (Floxin) 300 mg p.o. BID x 7 days. Take on an empty stomach. Contraindicated in children or pregnant and lactating women. Also covers N. gonorrhea.
    4. Levofloxacin 500 mg orally for 7 days.
    5. Erythromycin base 500 mg QID x 7 days- Preferred treatment in pregnancy.
    6. Erythromycin ethylsuccinate 800 mg QID x 7 days - alternative pregnancy treatment.
    7. Erythromycin base 250 mg QID x 14 days and Erythromycin ethylsuccinate 400 mg QID x 14 days are alternative pregnancy treatments.

Neisseria gonorrhea

  1. Background
    1. Gonorrhea, caused by Neisseria gonorrhoeae, is second only to chlamydial infections in the number of cases reported to the CDC in the United States, with 361,705 reported cases in 2001. 3
    2. The incidence of gonorrhea is highest in high-density urban areas among persons under 24 year of age who have multiple sex partners and engage in unprotected sexual intercourse. 10
    3. N. gonorrhea is a sexually transmitted disease that can lead to salpingitis, tuboovarian abscess, and/or sterility if not treated promptly.
    4. It is a gram-negative diplococcus that most commonly infects the endocervix.
    5. It may produce systemic symptoms: fever, arthritis, dermatitis, pericarditis, endocarditis, and meningitis.
    6. During the 1980s, gonococcal resistance to penicillin and tetracycline became widespread; as a result, CDC recommended using cephalosporins as first-line treatment for gonorrhea. Since 1993, CDC also has recommended using fluoroquinolones for gonorrhea treatment. However, fluoroquinolone-resistant N. gonorrhoeae (QRNG) is being identified more frequently in Hawaii and California, and cephalosporins should be used instead of fluoroquinolones as first-line treatment for gonorrhea acquired in these two states. 10a
  2. Diagnosis
    1. 75% of women have no symptoms.
    2. Mucopurulent discharge: often profuse, yellow, irritating.
    3. May cause urethritis, cervicitis, endometritis, salpingitis, perihepatitis.
    4. The N. gonorrhea culture starts with a sample taken with a cotton-tipped swab from the cervical os and immediately transferred to a selective media (Thayer-Martin) agar plate. The swab should be rolled across the surface since these organisms are extremely delicate and can be killed (i.e., a false negative test obtained) by the simple friction of dragging the applicator across the agar. Cultures should be stored in a low oxygen container (CO2 jar) for transport.
    5. Gram stain from cervix (not vagina) - 70% sensitive.
    6. Wet prep may show many polys (WBCs).
    7. Look for Bartholin's or Skene's glands involvement.
    8. May have systemic symptoms - rash, arthritis, fever.
    9. Routine dual therapy without testing for chlamydia can be cost-effective, because the cost of therapy for chlamydia (e.g., $0.50-- $1.50 for doxycycline) is less than the cost of testing. 3 Consider testing for syphilis and HIV.
  3. Treatment
    1. Quinolone-resistant N. gonorrhoeae is increasing. 3
    2. Cefixime (Suprax) 400 mg orally in a single dose; may be used during pregnancy.
    3. Ceftriaxazone (Rocephin), 125 mg IM one time.
    4. Ofloxacin (Floxin) 400 mg one-time dose (see warnings under 'Chlamydia').
    5. Ciprofloxacin 500 mg orally once.
    6. Levofloxacin 250 mg orally in a single dose.
    7. Alternatives include: Spectinomycin (Trobicin), 2 g IM one time; Ceftizoxime (Cefizox), 500 mg IM one time; Cefoxitin (Mefoxin), 2 g IM one time, plus probenecid, 1 g orally one time; Cefotaxime (Claforan), 500 mg IM one time; Gatifloxacin (Tequin), 400 mg orally one time; Norfloxacin (Noroxin), 800 mg orally one time; Lomefloxacin (Maxaquin), 400 mg orally one time.
    8. Also treat for probable coexistent chlamydia infection.
  4. Treatment - Disseminated Gonorrhea
    1. Manifestations are arthritis, dermatitis, pericarditis, endocarditis, and meningitis
    2. Ceftriaxone 1 gm IV or IM q 24 hr.
    3. Ceftizoxime 1 gm IV q 8 hr.
    4. Spectinomycin 2 gm IM q 12 hr.

Vulvovaginal Candidiasis

  1. Background
    1. 75% of all women in the U.S. will experience at least one episode of vulvovaginal Candidiasis. 2
    2. Nearly half of all women experience multiple episodes, and up to 5% experience recurrent disease. 2
    3. The incidence of the disease appears to be rising.
    4. Frequent iatrogenic complication of antibiotic treatment, secondary to altered vaginal flora.
    5. Most commonly caused by Candida albicans. 2
    6. New species: Candida glabrata and Candida tropicalis now cause one quarter of all Candida vulvovaginal infections. Those organisms are resistant to the OTC imidazole creams. Glabrata and Tropicalis species mutate out of the activity of treatment drugs much faster than Albicans species.
    7. Recurrent yeast vaginitis is usually due to relapse, and only occasionally due to reinfection. Recurrent infection may be due to candida recolonization of the vagina from the rectum. 11 It is defined as four or more episodes of symptomatic disease annually and affects <5% of women. 2 Weekly or daily antifungal treatment for 6 months is recommended. Most women with recurrent infections have high levels of lactobacilli, and yogurt ingestion probably is of no benefit.
  2. Diagnosis
    1. The disease is suggested by pruritis in the vulvar area, together with erythema of the vagina and vulva. The familiar reddening of the vulvar tissues is due to an ethanol by product of the Candida infection. This ethanol compound also produces pruritic symptoms.
    2. A white discharge may or may not be present.
    3. Vaginitis solely caused by Candida generally has a vaginal pH <4.5.
    4. Wet prep or KOH smear may demonstrate yeast or pseudohyphae. KOH is an inherently insensitive test. Some yeast do not form pseudohyphae.
    5. Fungal culture is advised for persistent symptoms despite negative KOH.
  3. Treatment
    1. Although Lactobacillis acidophilus does not adhere well to the vaginal epithelium, extended ingestion of live-culture nonpasteurized yogurt may decrease the episodes of BV. It does not, however, significantly change the incidence of candidal vulvovaginitis. 11
    2. Some experts believe that topical treatment is superior to oral therapy because of better benefit-to-risk ratios. Multiple vaginal formulations are available.
  4. Prescription Intravaginal: All of the following except nystatin may weaken or damage latex condoms and contraceptive diaphragms. Azoles are more effective than nystatin.
    1. Butoconazole (Femstat) 2% cream, 5 g for 3 days.
    2. Clotrimazole (GyneLotrimin) 100 mg vaginal tablet for 7 days, or 2 tablets for 3 days, or 500mg tablet once.
    3. Clotrimazole (GyneLotrimin) 1% cream, 1 applicator hs for 7 days.
    4. Miconazole (Monistat) 100 mg. vaginal suppository for 7 days.
    5. Miconazole (Monistat 3) 200 mg. vaginal suppository for 3 days.
    6. Miconazole, 2% derm. and vag. cream (Monistat Dual-Pak), q.d. x 3 days; for women with prominent involvement of external genitalia.
    7. Terconazole (Terazol) 0.4% cream, 5 g for 7 days.
    8. Terconazole (Terazol 3) 0.8% cream or suppository, hs for 3 days.
    9. Tioconazole 6.5% (Monostat 1, Vagistat 1) 1 applicator (5 grams) hs once.
    10. Nystatin (Mycostatin) 100,000 unit vaginal tablet for 14 days.
  5. Treatment: Over-the-counter intravaginal - many available.
    1. OTC self-medication should be reserved for women with previously confirmed Candida vulvovaginitis with recurrence of the same symptoms. 2 Miconazole (Monistat-7) vaginal cream, 100 mg, 1 application high in the vagina q.d. x 7 nights; may be used during 2nd and 3rd trimesters.
    2. Clotrimazole (Gyne-Lotrimin, Mycelex-G) vaginal cream or 100 mg vaginal tablet, q.d. x 7 to14 nights; may be used during 2nd and 3rd trimesters.
  6. Treatment: Prescription Oral
    1. Cure rates with single-dose oral fluconazole and all the intravaginal treatments are equal. 12
    2. Oral agents fluconazole, ketaconazole, and itraconazole appear to be effective. 2
    3. Fluconazole (Diflucan) 150 mg single dose has become very popular, but may have clinical cure rates of about only 70%. Systemic allergic reactions are possible with the oral agents.
    4. Recurrent Disease: Oral ketaconazole, 100 mg daily for 6 months or less, does prevent symptoms, as does weekly or monthly dosing with oral fluconazole.
    5. Pregnant patients should be treated with a topical azole agent for 7 days. 2

     

Trichomonas Vaginitis

  1. Background
    1. Trichomonas infection is caused by the unicellular protozoan Trichomonas vaginalis.
    2. Decline in incidence since 1970s due to increased knowlege of the disease, effectiveness of metronidazole treatment, treatment of sexual partners, improved diagnosis, and correctly identifying patients.
    3. The majority of men (90%) infected with T. vaginalis are asymptomatic, but many women (50%) report symptoms. 2
    4. Typically, women have a diffuse, malodorous, yellow-green discharge with vulvar irritation. 2
    5. Vaginal itching and irritation are common.
    6. The high levels of zinc in male prostatic fluid enable men to occasionally spontaneously clear the infection, whereas women are rarely able to clear the infection without treatment.
    7. The infection is predominantly transmitted via sexual contact. The organism can survive up to 48 hours at 10 degrees Celsius (50 degrees F), making transmission from shared undergarments or from infected hot spas possible.
    8. Trichomonas infection are associated with low-birth-weight infants, premature rupture of membranes, and preterm delivery in pregnant patients. 2, 13 Compared with whites and Hispanics, T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks. 13 However, it is questionable if treating asymptomatic infections during pregnancy prevents preterm delivery so routine screening is not indicated. 14
    9. In a person co-infected with HIV, the pathology induced by T. vaginalis infection can increase HIV shedding. Trichomonas infection may also act to expand the portal of entry for HIV in an HIV-negative person. Studies from Africa have suggested that T. vaginalis infection may increase the rate of HIV transmission by approximately twofold. 15
  2. Diagnosis
    1. Culture is felt to be the gold standard.
    2. Wet prep is 60% sensitive, Pap smear 56% sensitive, and monoclonal antibody testing is 86% sensitive for detecting the disease. 16
    3. Wet prep demonstrates mobile pear-shaped protozoan with lashing flagella.
    4. The pH generally is 6 to 7 with this infection.
    5. May cause dysuria or abdominal pain.
    6. Cervix is sometimes strawberry red with strawberry spots, and the vagina has burning and itching.
  3. Treatment
    1. Metronidazole 2 gm orally as a single dose (as effective but more side-effects), or 500 mg BID for 7 days (including pregnant patients) are the best treatments by Cocharine analysis. 17
    2. If treatment failure occurs, retreat with 500 mg BID for 7 days. 2
    3. If repeated failure occurs, treat with 2 gm daily for 3 to 5 days. Repeated or increased dosages have been noted to overcome the organism's resistance to the drug. 2
    4. No effective metronidazole alternatives with an indication in U.S. 14 Oral 500 mg QID plus intravaginal 500 mg BID tinidazole works with metronidazole-resistant trichomoniasis but it is not approved for use in the U.S. 18
    5. Topical Clotrimazole and AVC are clinically not effective. 19
    6. Topical metronidazole 0.75% vaginal gel is unlikely to achieve therapeutic levels in the urethra or perivaginal glands, where infection may also be present. 2 Metronidazole vaginal gel is not effective as a single agent for the treatment of trichomoniasis. 20
    7. Partners are also treated for the infection. The patient should be instructed to avoid sex until both are cured. 2
    8. Warn patient about Antabuse effect during treatment (avoid alcohol intake). Warn patient about amber urine and metallic taste. Sexual activity need not be restricted during treatment if both partners are treated at same time.

Bacterial Vaginosis

  1. Background
    1. Bacterial vaginosis (BV) is a clinical syndrome resulting from alteration of the vaginal ecosystem. The condition is the most common cause of vaginal discharge or odor, especially in young women. 2 It accounts for more than 10 million outpatient visits per year. 21
    2. Hydrogen peroxide-producing Lactobacillus is the most common organism comprising normal vaginal flora. 2 It is found in 95% of women with normal flora, versus only 35% of women with bacterial vaginosis. The hydrogen peroxide produced by the lactobacillus may help in inhibiting the growth of atypical flora. In BV, normal vaginal lactobacilli are replaced with high concentrations of anaerobic bacteria such as Mobiluncus, Prevotella, Gardnerella, Bacteriodes, and Mycoplasma species. 2, 21
    3. This is called a vaginosis, not a vaginitis, due to the fact that the tissues themselves are not actually infected, but only have superficial involvement. More than half of women with the disorder are asymptomatic. 2
    4. Historically, this condition has been called Corynebacterium vaginitis, Gardnerella vaginalis vaginitis, Anaerobic vaginosis, and Bacterial vaginosis.
    5. It is uncertain whether BV is sexually transmitted. 2 Arguments for sexual transmission include an association of BV with multiple partners, decreased prevalence in monogamous couples, and a rare occurrence in virgins. Arguments against sexual transmission include a failure to demonstrate benefits in treating sexual partners, lack of persistence in males, and occasional findings in virgins. The CDC guidelines do not recommend treatment of partners. BV organisms have been found concurrently in PID. 21, 22
    6. BV has been associated with adverse pregnancy outcomes including premature rupture of membranes, preterm labor, and preterm birth. 9, 23, 24, 25 It has also been linked to an increased risk of miscarriage in the first trimester, 26 and may predict miscarriage in the second trimester. 26a BV organisms are frequently found in postpartum and postcesarean endometritis. 2 Although the mechanism by which BV causes these obstetric problems is not known, there is some evidence that it may infect the upper genital tract, predisposing to preterm delivery. 23 The presence of normal lactobacillus species has been shown to be negatively associated with preterm delivery. 9 Treatment with metronidazole (250 mg TID X 7d) and erythromycin (333 mg TID X 14d) was performed on 426 women at 22 to 24 weeks' gestation. For those with BV, there was a significant reduction in preterm deliveries. 27, 28 Other studies did not find decreases in preterm labor with treatments of metronidazole (two 2 gms doses) or with vaginal clyndamycin. 29, 30 Inflammatory Pap smears during pregnancy have not been found to predict preterm labor and should not be used as a marker for BV. 31
      Table 2. Association of BV with Adverse Pregnancy Outcomes
      Study
      % Preterm delivery
      OR or RR (Cl)
      BV
      no BV
      Gratacos, '98 16 5 3.1 (1.8, 5.4)
      Hillier, '95 6.3 4.2 1.4 (1.1, 1.8)
      Meis, '95 6.8 2.8 1.69 (1.04, 2.74)
      Hay, '94 7.2 2.9 2.8 (1.1, 7.4)
      McGregor, '94 10.9 3.3 3.3 (1.2, 9.1)
      Joesoef, '93 20.2 11.8 2.0 (1.0, 3.9)
      Kurki, '92 6.8 1.1 6.9 (2.5, 18.8)
      Gravett, '86 17 8 1.9 (0.98, 3.8)
  2. Diagnosis 2
    1. BV can be clinically diagnosed by finding 3 of the following 4 signs and symptoms:
      • A homogeneous, off-white creamy discharge that adheres to the vaginal walls
      • clue cells
      • pH >4.5
      • fishy odor after the addition of 10% KOH (whiff test)
    2. Gram stain may be used for diagnosis by establishing characteristic bacterial morphotypes. 2
    3. Clue cells are squamous epithelial cells whose borders are obscured by attached bacteria. Clue cells should not be confused with vacuolated epithelial cells. Generally, more than 20% to 25% of epithelial cells seen in bacterial vaginosis should be clue cells.
    4. FemExam® pH and Amines TestCard and Osmetech Microbial Analyser
  3. Treatment - The principle goal of treatment is to relieve symptoms. 2
    1. Oral metronidazole 500 mg BID X 7 days (cure rate 95%) or 2 g orally as a single dose (cure rate 84%). 2
    2. Topical metronidazole 0.75% vaginal gel one applicator-full intravaginally BID X 5 days. 2
    3. Topical clindamycin 2% vaginal cream one applicator-full intravaginally at bedtime X 7 days. 2 Note that this preparation may weaken or damage latex condoms and contraceptive diaphragms.
    4. Clindamycin ovules 100 g intravaginally once at bedtime for 3 days.
    5. Resistant cases or pregnant patients can receive clindamycin 300 mg BID for 7 days.
    6. In a multisite study of ambulatory clinic patients comparing oral metronidazole, topical metronidazole, and topical clindamycin, no significant difference was found in the patients' cure rates, but patients receiving intravaginal products reported a higher satisfaction with treatment. 32
    7. Sulfonamides are ineffective. Tetracycline is 13%-65% effective. Ampicillin 50% to 70% effective, but destroys lactobacilli, which slows the return of normal flora.
    8. Health food store lactobacilli are the wrong strain and are not well retained by the vagina. Although Lactobacillis acidophilus does not adhere well to the vaginal epithelium, extended ingestion of live-culture, nonpasteurized yogurt may increase colonization by the bacteria and decrease the episodes of BV. It does not, however, significantly change the incidence of candidal vulvovaginitis. 11
    9. BV will also be present with other infections. Treating the concomitant infection usually causes the non-specific vaginitis to resolve. It is usually not necessary to treat it separately.
    10. The treatment of asymptomatic patients is controversial. Because of the association with postsurgical infections, patients scheduled for invasive surgery, induced abortions or outpatient procedures should first receive a full course of therapy. 2
    11. The CDC does not recommend treatment of sexual partners, although some consider treatment of partners of women with recurrent or intractable bacterial vaginosis. Studies indicate that treatment of sexual partners of women with bacterial vaginosis does not increase the cure rate. 33 A 'Clinical Evidence' evidence based review found that treating the partner of a patient with BV is "likely to be ineffective". 33a
    12. Pregnant patients should be treated, as the infection has been implicated in many pregnancy complications as noted above. High-risk asymptomatic patients (previous preterm birth) should be screened early in the second trimester and all symptomatic patients should be treated. Metronidazole has traditionally been contraindicated in the first trimester, not because of strong evidence of teratogenic risk, but because the drug readily crosses the placenta. Recent reports suggest this drug is not a teratogen and it is now listed as a pregnancy class "B" drug. 34, 35 Oral metronidazole 250mg orally TID for 7 days is the preferred regimen. 2, 27 Alternatives include oral metronidazole 2 g orally as a single dose, clindamycin 300 mg BID for 7 days, or topical metronidazole 0.75% vaginal gel one applicator-full intravaginally BID X 5 days. Clindamycin 2% vaginal cream is not recommended in pregnancy because of the possibility of increased preterm labor. 2 A 'Clinical Evidence' evidence based review found that treating pregnant women with a history of preterm labor is "likely to be beneficial". 33a
    13. Recurrent BV usually recurs within 1 to 2 months of initial improvement following treatment. Many clinicians treat the male sexual partner, although there is no evidence that this reduces recurrence. Weekly intravaginal metronidazole or acidification (Aci-Jel BID to 2X weekly) may be tried.

     

Pelvis Inflammatory Disease (PID)

  1. Background
    1. One million women seek treatment for PID annually. There are approximately 250,000 hospitalizations and 110,000 surgical procedures performed for this problem, at an annual cost of $3.5 billion in the United States.
    2. Possible sequelae include infertility, ectopic pregnancy, TOA, chronic pelvic pain, and TAH-BSO. The infection is usually a polymicrobial ascending infection, with both gonorrhea and chlamydia being present.
  2. Diagnosis
    1. The classic clinical presentation includes lower abdominal pain, fever, and tenderness to uterine and adnexal palpation. Look for the "PID shuffle," where patients slide their feet while walking to avoid jarring the pelvic organs. There is no correlation between severity of symptoms and risk of complications. Must rule out ectopic pregnancy!
      Table 3. Diagnostic Criteria for PID
      Minimum Criteria
      Uterine or adnexal tenderness or Cervical motion tenderness
      Additional Criteria
      Oral temperature >38.3°C (>101°F)
      Abnormal cervical or vaginal mucopurulent discharge
      Presence of WBCs on saline microscopy of vaginal secretions
      Lab documentation of cx gonococcal or chlamydial infection
      Elevated C-reactive protein level
      Elevated erythrocyte sedimentation rate
      Specific criteria
      Endometrial bx with histopathologic evidence of endometritis
      Laparoscopic abnormalities consistent with PID
      Transvaginal U/S or MRI study showing thickened, fluid-filled tubes, with or without free pelvic fluid or tubo-ovarian complex
  3. Uncomplicated Outpatient PID Treatment
    1. Ofloxacin 400 mg orally twice a day for 14 days or Levofloxacin 500 mg orally once daily for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days. (cure rate = 95%) 36
    2. Ceftriaxone 250 mg IM in a single dose or Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose or other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) plus Doxycycline 100 mg orally twice a day for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days.
    3. Rocephin 250 mg IM plus Doxycycline 100 mg bid or erythromycin 500 mg P.O. qid, x 14 days. Re-evaluate in 72 hrs and admit if not improved. (cure rate = 75%) 36
    4. Clindamycin 900 mg IV every 8 hours plus Gentamicin loading dose IV or IM (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing may be substituted.
    5. Cefotetan (Cefotan), 2 g IV every 12 hours, or cefoxitin (Mefoxin), 2 g IV every 6 hours plus Doxycycline (Vibramycin), 100 mg orally or IV every 12 hours.
    6. Ofloxacin (Floxin), 400 mg IV every 12 hours, or levofloxacin (Levaquin), 500 mg IV once daily with or without Metronidazole (Flagyl), 500 mg IV every 8 hours, or ampicillin-sulbactam (Unasyn), 3 g IV every 6 hours plus Doxycycline, 100 mg orally or IV every 12 hours.
      PID Hospitalization Criteria
      • Diagnosis uncertain
      • Surgical emergency not R/O
      • Suspected pelvic abcess
      • Pregnancy
      • Adolescent or noncompliant
      • Unable to eat
      • Temperature > 38o C
      • Outpatient failure or cannot keep f/u
  4. Complicated (TOA or Complex) PID Treatment
    1. Clindamycin 900 mg q 8 hr or Metronidazole 400 mg q 8h + Gentamycin loading + maintenance.

     

Genital Herpes

  1. Background
    1. Herpes viruses are DNA viruses that can lie dormant in sensory neurons after initial infection, then later reactivate and cause disease. Viruses in this family include herpes simplex virus (HSV) and varicella zoster virus (VZV).
    2. HSV infection is the most common cause of genital ulcers in this country. 2 Approximately 45 to 50 million Americans have genital herpes, and an estimated 1 million new cases occur each year. 2 Primary infection occurs mostly in adolescents and young adults.
    3. Two HSV serotypes have been identified in humans. HSV-1 is the most common cause of oral herpes infection, and HSV-2 is the primary pathogen in sexually transmitted genital herpes. Both serotypes can be present at oral or genital sites.
    4. HSV infection can be characterized by episodes of latency, with asymptomatic viral shedding, recurrent activation, and perinatal and sexual transmission. 36f It increases the risk of HIV transmission and is believed to play an important role in the heterosexual spread of HIV.
  2. Diagnosis
    1. 1. The diagnosis of genital herpes is best established by viral culture. In the updated guidelines, the CDC2 also recommends type-specific serologic testing to determine the HSV serotype since recurrent episodes are less likely with the HSV-1 serotype. In addition, type-specific serologic tests may help confirm the diagnosis of genital herpes in patients with recurrent infection or with healing lesions, for which HSV culture results may be false-negative. 2
  3. Treatment
    1. Initial and recurrent episodes of genital HSV can be treated, and recurrent episodes (more than six per year) can be suppressed with antiviral medications. Suppressive treatment is much more effective than episodic treatment.
    2. Acyclovir (Zovirax) is a guanosine analog that inhibits DNA polymerase. It has poor bioavailability and a short half-life. Treatment with daily oral acyclovir decreases episodes from 11.4 to 1.8 per year. 36a, 36b Topical acyclovir is not an effective treatment for episodic genital HSV.
    3. Valacyclovir (Valtrex) is a prodrug that metabolizes to acyclovir. It has better bioavailability and less frequent dosing than acyclovir. After one year of daily treatment with valacyclovir, 40 to 50% of patients are episode free, and the mean rate of occurrence is 0.8 episodes per year. 36c Compared with placebo, valacyclovir decreases the length of episodes and mean healing time by two days. 36d It is as effective as acyclovir for initial and episodic treatment and for suppression of genital HSV.
    4. Famciclovir (Famvir) is a prodrug of penciclovir (Denavir), a purine analog. It has high bioavailability and quickly metabolizes to penciclovir. In episodic treatment of genital HSV, famciclovir decreases time to healing. A study of its use in the suppression of recurrent genital HSV infection showed an average of 1 to 1.8 episodes per year in treated patients versus 5.1 episodes per year in patients who received placebo. 36e Topical penciclovir decreases time to crusting by one day. 36f
    5. Acyclovir, valacyclovir, and famciclovir have similar side effects, which include nausea, vomiting, headache, and diarrhea. When used in high dosages as an intravenous medication, acyclovir can crystallize the renal tubules, causing acute renal failure.
      Table 4. Treatment Regimens for Genital Herpes
      First episode
      Acyclovir (Zovirax), 400 mg orally three times daily for 7 to 10 days, or 200 mg orally five times daily for 7 to 10 days
      Famciclovir (Famvir), 250 mg orally three times daily for 7 to 10 days
      Valacyclovir (Valtrex), 1 g orally twice daily for 7 to 10 days
      Recurrent episode
      Acyclovir, 400 mg orally three times daily for 5 days, or 200 mg orally five times daily for 5 days, or 800 mg orally twice daily for 5 days
      Famciclovir, 125 mg orally twice daily for 5 days
      Valacyclovir, 500 mg orally twice daily for 3 to 5 days, or 1 g orally once daily for 5 days
      Suppressive therapy
      Acyclovir, 400 mg orally twice daily
      Famciclovir, 250 mg orally twice daily
      Valacyclovir, 500 mg orally once daily, or 1 g orally once daily

Human Papillomavirus (HPV)

  1. HPV infects approximately 24 million people in the United States, and there are approximately one million new cases diagnosed each year. 31 Though HPV affects all ages, young sexually active adults account for most office visits. Manifestations range from subclinical infections to multiple hyperplastic exophytic lesions, and cervical malignant potential exists with some genotypes. Infection may be present for many years prior to any clinical demonstration of disease. Male and female condoms may not prevent transmission of HPV, since it is a regional disease affecting the perineum, scrotum, and anal areas, where condoms do not protect.
  2. HPV is most commonly transmitted by sexual intercourse. The incidence is very low in people who have never had sexual activity and increases with an increasing number of sexual partners. Treating HPV in a patient will not affect the partner's course of HPV progression or treatment response.
  3. HPV Virology
    1. Human papillomavirus is a member of the DNA family of papovaviruses. To date, greater than 70 genotypes have been identified via DNA hybridization analysis. Each genotype has specificity for certain types of epithelium and anatomic locations. Various genotypes also have different malignant potentials.
    2. HPV types can be classified into three groups: Those causing benign, low-risk lesions, those with moderate-risk, and those associated with high-risk for oncogenesis. (See Table 5) Multiple viral types may coexist in a patient, and the cancer risk of many HPV types is not established. Research is ongoing into the usefulness of viral typing as an adjunct to the Pap smear.
      Table 5. Malignant Potential of HPV Genotypes
      Low risk - 6, 11, 42, 43, 44
      Intermediate risk - 31, 33, 35, 51, 52
      High risk - 16, 18, 45, 56
    3. HPV Types 16 and 18 have high potential for cervical malignancy. Type 16 has been detected in approximately 50% of invasive cancers and is the most common type in latent viral infections. Type 18 is 2.6 times more common in more rapidly progressive forms of cervical dysplasia. However, even for high-risk genotypes, HPV infection rarely leads to cervical cancer. Only 15% of women infected with HPV will progress to cervical dysplasia, while just 1% will actually develop cervical cancer.
  4. Biology of HPV
    1. Innoculation with the HPV virus usually occurs at sites of mucous membrane microtrauma, most frequently during sexual intercourse. The incubation period is typically 6 weeks to 8 months, but may last many years. Active expression results in the formation of koilocytotic cells that demonstrate chromatin clumping, nuclear atypia, and perinuclear halo on light microscopy.
      Table 6. Things that Affect HPV Expression
      Glucocorticoids more active disease expression and increased relapses and recurrences
      Pregnancy relative immune suppression with more active disease expression
      HIV more expression, progression, and recurrence of HPV related diseases
      Tobacco smoking independent risk factor for cervical dysplasia (probably through immunosuppression)
    2. Infection (or treatment) may be followed by a host-containment or latent phase. The virus may still be present, but there is no active gross or histologic expression of HPV disease. This phase is brought on by activation of the host's immune response, with resultant control of viral expression. Therefore, any activity causing immunosuppression should be avoided if possible. (Table 6) The virus may insert its DNA into the human genome during this phase and replicate with each cellular mitotic division. This DNA insertion is common for HPV types that more often cause malignant transformation within cells.
      Table 7. Problems that May Appear Similar to Genital Condyloma
      INFECTIOUS DISEASES
      • Condyloma lata (syphilis) - broad-based, smooth-surfaced lesion
      • Herpes simplex (HSV) - Vesicular eruption with red bases and ulcerations
      • Moloscum contagiosum - umbilicated yellowish papules with central core
      COMMON BENIGN SKIN LESIONS
      • Seborrheic keratoses - hypertrophic lesions with rough surface
      • Nevi - typical appearance - raised or pedunculated types may occur
      • Pearly penile papules - 1 to 2 mm circumscribed papules, usually over the proximal edge of the glans penis
      NEOPLASMS - BIOPSY REQUIRED IF SUSPECTED.
      • Bowenoid papulosis - carcinoma-in-situ, single or multiple 2 to 4 mm rough papules, flesh-colored to red-brown
      • Malignant melanoma - typical appearance - usually single, may be flat or raised with variable color and shape
      • Giant condyloma or Buschke-Lowenstein tumor - low-grade, locally-invasive malignancy that can appear as a fungating condyloma
  5. HPV Diagnosis
    1. Condyloma acuminata is typically diagnosed by its hypertrophic appearance. The differential diagnosis includes several types of anogenital conditions that are shown in Table 7. HPV infection may involve all genital areas, including the cervix, perianal areas, perineum, and surrounding skin. Single or multiple condylomata may be present, and subclinical infections (requiring acetic acid application to be appreciated) are common. The female perineum, cervix, and vagina are commonly involved, as well as the penile shaft, foreskin, and scrotum in males. HPV lesions may also be found in the anal areas, oral mucosa, larynx, trachea, and rectum. A biopsy with pathological study of any atypical, pigmented, or persistent lesions should be done to rule out malignancy.
  6. Treatment
    1. HPV lesions can be difficult to treat. The primary care physician, however, with his or her broad perspective on disease processes and long-term relationship with the patient, is uniquely equipped to address this problem and its potential ramifications. Careful use of both traditional and newer methods of treatment and appropriate patient education can result in a high level of success.
    2. In 1998, the MMWR published a list of recommended therapies, and new therapies have been developed since then. 37 Treatment should be guided by patient preference. Practitioners should be familiar with at least one patient-applied treatment (imiquimod and podofilox) and one provider-applied therapy. 37
    3. HPV vaccines are being developed that may be able to help protect women from infection and cervical cancer. In a 2002 randomized, double-blind, controlled trial of 2,392 women, administration of a HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia. 37a
  7. HPV Infection in Children
    1. Although not as definite a sign of child abuse as once thought, the possibility of sexual abuse should be strongly considered.
    2. HPV lesions have been found in both girls and boys, and both sexual and nonsexual routes of transmission have been found.
    3. Types of nonsexual transmission that have been documented include gestational, 38 during birth, 39 - 44 and from familial nonsexual contacts. 40, 45, 46, 47
    4. Perinatal transmission rates are not known; they are generally felt to be low, considering the high prevalence of maternal HPV infections and the low rates of perinatal infection. 48, 49
    5. When HPV lesions are found, a good history should be obtained and other sexually transmitted diseases should be tested for. The child should be checked carefully for any sign of abuse.
      1. Examination with a colposcope may be useful in identifying HPV lesions and signs of sexual abuse.
      2. Children with possible HPV infection should be examined and treated with extra care and sensitivity to minimize any psychological trauma.
    6. Condylomata in children are treated the same as in adults, but care should be taken to minimize pain.
    7. Clinicians should be aware that all states in the U.S. require that any suspected child abuse be reported to the appropriate authorities. 45, 50 Factual information, reassurance that the physician will not abandon the family, and an explanation of the need to take action may help preserve the doctor-family relationship. 50
    8. Remember that a child's physical and mental well-being is involved.

References

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36c. Reitano M, Tyring S, Lang W, Thoming C, Worm GM, Borelli S, et al. Valacyclovir for the suppression of recurrent genital herpes simplex virus infection: A large-scale dose range-finding study. International Valacyclovir HSV Study Group. J Infect Dis 1998;178:603-10.
36d. Spruance SL, Tyring SK, DeGregorio B, Miller C, Beutner K. A large-scale, placebo-controlled, dose-ranging trial of peroral valacyclovir for episodic treatment of recurrent herpes genitalis. Valacyclovir HSV Study Group. Arch Intern Med 1996; 156:1729-35.
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36f. Whitley RJ, Roizman B. Herpes simplex virus infections. Lancet 2001;357:1513-8.
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41. Patel R, Groff DB. Condyloma acuminata in childhood. Pediatrics 1972; 50:153-4.
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43. Hajek EF. Contribution to the etiology of laryngeal papilloma in children. J Laryngol 1956; 70:166-8.
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45. Greene I. Therapy for genital warts. Dermatol Clin 1992; 10:253-67.
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47. Stumpf PG. Increasing occurrence of condylomata acuminata in premenarchal children. Obstet Gynecol 1980; 56:262-4.
48. Schwartz DB, Greenburg MD, Daoud Y, Reid R. Genital condylomas in pregnancy: Use of trichloroacetic acid and laser. Am J Obstet Gynecol 1988; 158:1407-16.
49. Shah K, Kashima H, Polk F, et al. Rarity of cesarean delivery in cases of juvenile-onset respiratory papillomatosis. Obstet Gynecol 1986; 68:795-9.
50. Norins AL, Caputo RV, Luckey AW, et al. Genital warts and sexual abuse in children. J Am Acad Dermatol 1984; 11:529-30.
E.J. Mayeaux, MD
updated 8/30/05
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