Adolescent Health Care: A Practical Guide

Chapter 55

Vaginitis and Vaginosis

Loris Y. Hwang

Mary-Ann B. Shafer

Vagina: Normal State

The vagina is a dynamic ecosystem extending from the vulva to the cervix uteri. Embryologically, the upper four fifth of the vagina is derived from the müllerian ducts and the lower one fifth from the urogenital sinus. The vagina is lined with epithelial cells that are estrogen dependent. Before puberty and after menopause, the cells are thin, leading to heightened susceptibility to infection. During puberty, there is an involution of the squamocolumnar junction such that squamous epithelial cells gradually replace the columnar epithelial cells that line the ectocervix during childhood.

Vaginal Flora

Before the onset of puberty, the vagina is colonized with various bacterial species ranging from fecal flora to skin flora, resulting in a vaginal pH of >4.7. After puberty, the estrogen-stimulated epithelial cells produce more glycogen, and lactobacilli become predominant, comprising >95% of the normal flora. Metabolism of glycogen to lactic acid by the lactobacilli contributes to the lowering of the vaginal pH to <4.5 and helps to maintain a vaginal environment that appears to protect the individual from colonization by more pathogenic organisms. Some lactobacilli also produce hydrogen peroxide, a potential microbicide.

Vaginal Secretions

Vaginal secretions are a normal result of the changing hormonal milieu of the menstrual cycle. Six to 12 months before menarche, there may be a physiological increase in secretions arising from the adnexa, uterus, cervix, or vaginal epithelium itself. These secretions may be copious but are not associated with odor or pruritus.

Changes during the menstrual cycle include the following:

  1. After menses, there is little secretion.
  2. As estrogen levels increase, a cloudy, sticky, white secretion develops.
  3. Just before ovulation, the cervical secretions become clear and profuse.
  4. After ovulation, progesterone stimulates a thick and sticky cervical secretion.
  5. Before menses, a watery cervical secretion develops again.

These normal, odorless secretions are composed primarily of mucus, with occasional squamous cells from the vaginal wall.

Defense Mechanisms of the Vagina

Normal defense mechanisms in the postpubertal teen include the following:

  1. Acid pH level of 3.8 to 4.4
  2. Protective thick epithelium
  3. Estrogen support
  4. Physiological mucous secretion

Vulvovaginitis in Prepubertal Females

Vulvar skin in prepubertal girls is more susceptible to irritation because of the lack of “estrogenization” and the absence of protective labial hair and fat. The hypoestrogenic vaginal mucosa is also thin and has an alkaline pH. Most vulvovaginitis in this group is related to poor hygiene, obesity, tight clothing, or nonabsorbent underpants. Usually, the organisms involved are either normal flora (i.e., lactobacilli, diphtheroids, streptococci, and Staphylococcus epidermidis) or gram-negative enteric organisms (i.e., Escherichia coli). Current evidence suggests that patients should be counseled regarding hygienic measures, and antibiotics should be prescribed only if a single or predominant organism is identified by culture of secretions (Joishy et al., 2005). All sexually transmitted diseases (STDs) can also be associated with vaginitis in prepubertal females. Neisseria gonorrhoeae and Chlamydia trachomatis in prepubertal females infect the vagina and not the cervix. Therefore, vaginal cultures are sufficient. The identification of sexually transmissible agents in prepubertal children beyond the neonatal period suggests sexual abuse (Centers for Disease Control and Prevention, 2002). The significance of the identification of a sexually transmitted agent in such children as evidence of possible child sexual abuse varies by pathogen. Postnatally acquired gonorrhea; syphilis; and nontransfusion, nonperinatally acquired human immunodeficiency virus (HIV) are usually diagnostic of sexual abuse. Sexual abuse should be suspected in the presence of genital herpes, as well.

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Vulvovaginitis and Vaginosis in Pubertal Females: General Approach

Prevalence

The three most common types of vaginitis are vulvovaginal candidiasis (VVC) (20%–25%), trichomoniasis (15%–20%), and bacterial vaginosis (BV) (40%–45%). (BV is not a true “vaginitis” as it does not cause a major inflammatory reaction of the vaginal mucosa, but from a clinical standpoint is included here.) The prevalence of VVC, trichomoniasis, and BV is not well-known because these entities are not reportable, but it is estimated that approximately 75% of women experience VVC during their lifetime, with most first episodes occurring during adolescence. Patients may notice a change in vaginal discharge, and vulvar irritation, itching, vaginal odor, dyspareunia, and/or dysuria. Other causes of discharge include birth control pills (estrogen effect), stress (psychophysiological), chemical irritants, foreign bodies (i.e., tampons), trauma, allergies, and poor hygiene. To the patient, vaginal discharge secondary to cervicitis from N. gonorrhoeae or C. trachomatis can be indistinguishable from discharge secondary to vaginitis.

Evaluation

History

The history in an adolescent with vaginitis should include questions regarding the following:

  1. Type, duration, and extent of symptoms
  2. Location of any pain: Vulva, introitus, or deep vagina. Internal pain may occur with either urinary tract infection or vaginitis, whereas external pain with urination is usually associated with vaginitis
  3. Relationship of symptoms to the menstrual cycle
  4. Sexual activity: Frequency, type, number of sexual partners, and recent changes in partners
  5. Previous STDs
  6. Contraceptive history
  7. Changes in diet, exercise, stress, and medications including antibiotics, steroids, use of spray deodorants, soaps, lubricants, or douches
  8. Family history of diabetes mellitus

Physical Examination

The physical examination in a teen with vaginitis includes the following:

  1. Inspection of color, texture, origin (vaginal or cervical), adherence, and odor of the vaginal discharge
  2. Inspection of the perineum, vulva, vagina, and cervix for erythema, swelling, lesions, atrophy, and signs of trauma
  3. Palpation of the introitus for tenderness
  4. Palpation of the uterus and adnexa for tenderness or masses
  5. Inspection for foreign bodies, such as forgotten tampon

Laboratory Evaluation

The office evaluation should include the following:

  1. pH value of vaginal secretions: The normal pH value of the vagina is <4.5 (3.8–4.4). The pH should be sampled from the anterior vaginal fornix or lateral vaginal wall. Cervical mucus should not be used (typical pH ~7.0) as sample.
  2. Saline wet mount preparation for microscopic evaluation: A drop of saline is placed on a glass slide and then the swab of vaginal discharge is applied to the saline area. Alternatively, the swab of vaginal discharge is placed in a test tube together with 0.5 to 1 mL of saline and then the suspension is swabbed onto a glass slide. A coverslip is applied. Microscopic examination under dry high-power must look for the following:
  3. White blood cells (WBCs): The normal wet prep should have <5 to 10 WBCs per high-power field or ≤1 WBC per epithelial cell.
  4. Presence of trichomonads, may be motile: Motility of trichomonads decreases with time (Kingston et al., 2003), therefore immediate inspection of the sample is advised. Preservation of the sample at a temperature as close to body temperature as possible until time of viewing may also help preserve motility.
  5. Type of background bacterial flora: Normal long lactobacilli versus pleomorphic coccobacilli.
  6. Presence of “clue cells”: Epithelial cells with indistinct borders, intracellular debris, and covered with bacteria.
  7. Potassium hydroxide (KOH) 10% preparation for microscopic evaluation: A swab of vaginal discharge is applied to a glass slide and a drop of KOH 10% solution is added.
  8. Amine or “whiff test”: Presence of a fishy, amine odor on addition of the KOH solution, before application of cover slip
  9. Microscopic examination under dry high-power: Presence of pseudohyphae or budding yeast forms
  10. Testing for trachomatisand N. gonorrhoeae: To rule out endocervical infection that is causing the discharge.

Other laboratory tests as indicated include:

  1. Gram stain of vaginal or cervical secretions
  2. Urinalysis and urine culture
  3. Pregnancy test
  4. Culture systems (InPouch TV) and polymerase chain reaction (PCR) tests for Trichomonas vaginalis
  5. Amine/pH test cards to assist in the diagnosis of BV

Vulvovaginal Candidiasis

VVC is a common form of vaginitis in girls. A major issue in diagnosis is distinguishing true infection from nonpathogenic colonization.

Etiology

VVC is usually caused by Candida albicans (85%–90% of clinical cases) and occasionally by other Candida sp, Torulopsis sp, or other yeasts. C. albicans has greater adherence to vaginal epithelium than the other species of Candida.

Epidemiology

  1. Prevalence: The overall prevalence of VVC is unknown, but there appears to be increased incidence in the second decade of life and on initiation of sexual activity.

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Candida species is isolated from 20% of healthy asymptomatic females presumably indicating a commensal relationship of the candidal species with other vaginal flora. However, an estimated 75% of women experience at least one episode of VVC during their lifetime, and 40% to 45% will have two or more episodes (Centers for Disease Control and Prevention, 2006).

  1. Transmission: Although VVC is usually not sexually acquired or transmitted, evidence exists that sexual contact plays a role in transmission in some patients. Approximately 20% of male partners have asymptomatic penile colonization. Symptomatic male partners might present with balanitis.
  2. Predisposing factors:
  3. Immunosuppressive states: Diabetes mellitus, HIV infection, or therapy with steroids or immunosuppressive agents
  4. Estrogen exposure (enhances adherence of Candidaorganisms to vaginal epithelium) including pregnancy and estrogen-containing oral contraceptives. While oral contraceptives have been suspected as a predisposing factor, epidemiological study results are conflicting.
  5. Antibiotic therapy: Often reported by some women, but studies do not show an association (Glover and Larsen, 2003; Wilton et al., 2003)
  6. Behavioral factors: Orogenital sex, douching
  7. Innate host factors: Genetic predispositions, decreased local vaginal immune responses (i.e., nonsecretors of Lewis antigens, impaired Candidaantigen-specific immunity)

Clinical Manifestations

  1. VVC is usually accompanied by intense burning, vulvar pruritus, erythema, vaginal discharge, soreness, and external dysuria that may worsen before the onset of menses, but these symptoms are nonspecific
  2. Occasional dysuria or dyspareunia
  3. Discharge
  4. Onset: May worsen before menses
  5. Consistency: Usually described as thick, curd-like, “cottage cheese” appearance
  6. Color: Milky, white
  7. Odor: Usually none
  8. Often accompanied by a history of risk factors as described in the preceding text
  9. Examination reveals the following:
  10. Normal or erythematous vulva, fissures, excoriations, satellite lesions including skin folds and thighs, especially in obese females
  11. Vulvar edema
  12. Thick, white, cheesy, adherent discharge

Diagnosis

  1. A wet prep with saline or KOH shows budding yeast with pseudohyphae. Yeast is more readily visualized with the use of KOH, which lyses epithelial cells. The KOH prep has a sensitivity of 40% to 80%.
  2. The pH range is usually <4.5 (normal range).
  3. On gram stains, yeast cells appear as gram-positive oval masses, and pseudohyphae appear as long gram-positive tubes. Gram stain sensitivity is 70% to 100%.
  4. Rapid in-office tests for Candidaantigens in vaginal discharge are commercially available, but their use in the clinical setting has not been well studied. They are not currently recommended.
  5. Cultures may be useful in cases of recurrent VVC, but are not used for routine diagnosis because asymptomatic colonization is common.
  6. The diagnosis can be made in the presence of signs and symptoms of vaginitis with evidence of yeast on wet prep or KOH prep. VVC is further classified as “uncomplicated,” with sporadic/infrequent episodes, mild-to-moderate symptoms, albicansspecies, nonimmunocompromised women; or “complicated,” with recurrent VVC (four or more episodes in 12 months), severe symptoms, non-albicans species, immunocompromised women or pregnant women. Women who have the presence of yeast on laboratory testing but are asymptomatic should not be treated.

Therapy

  1. Regimens for uncomplicated cases in nonpregnant patients:
  2. Topical, intravaginal agents: Short-course topical formulations (i.e., single dose and regimens of 1–3 days) effectively treat uncomplicated VVC, and topical azoles are more effective than nystatin (Centers for Disease Control and Prevention, 2006). Azoles have a clinical cure rate of 80% to 95%, whereas nystatin agents have a cure rate of 70% to 90%. Relief of symptoms and negative cultures are seen in 80% to 90% of patients who complete therapy. If symptoms are more consistent with vaginitis than vulvitis, suppositories are superior to creams with increased cure rates (Carr et al., 1998). Regimens recommended by the Centers for Disease Control and Prevention (CDC) are listed below (Centers for Disease Control and Prevention, 2006). Self-medication with over-the-counter (OTC) formulations is common, but a recent study indicates that self-diagnosis is unreliable, even in women who have had prior diagnoses of VVC (Ferris et al., 2002). The creams and suppositories listed here are oil-based, and may weaken a latex condom or diaphragm.
  • Butoconazole 2% cream (Mycelex-3 OTC) 5 g intravaginally for 3 days or Butoconazole 2% cream sustained release, single intravaginal application, or
  • Clotrimazole 1% cream (Gyne-Lotrimin 7, Mycelex-7 OTC), 5 g intravaginally for 7 to 14 days, or
  • Clotrimazole 100-mg vaginal tablet (Gyne-Lotrimin 7, Mycelex-7 OTC) for 7 days, or
  • Clotrimazole 100-mg vaginal tablet, two tablets for 3 days, or
  • Miconazole 2% cream (Monistat-7 OTC), 5 g intravaginally for 7 days, or
  • Miconazole 200-mg vaginal suppository (Monistat-3 OTC), one suppository for 3 days, or
  • Miconazole 100-mg vaginal suppository (Monistat-7 OTC), one suppository for 7 days, or
  • Miconazole 1,200 mg vaginal suppository, one suppository for 1 day, or
  • Nystatin 100,000-unit (U) vaginal tablet for 14 days, or
  • Tioconazole 6.5% ointment (Monistat 1-day OTC), 5 g intravaginally in a single application, or
  • Terconazole 0.4% cream (Terazol 7), 5 g intravaginally for 7 days, or
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Terconazole 0.8% cream (Terazol 3), 5 g intravaginally for 3 days, or

  • Terconazole 80-mg suppository (Terazol 3), one suppository for 3 days
  1. Oral agent: Fluconazole 150-mg oral tablet, one tablet in a single dose
  2. Patients often prefer single-dose oral therapy over intravaginal therapy because of convenience and ease of use. Treatment choice should take into account patient preference, the severity of disease, the history of recurrent vaginitis, and the existence of any immunosuppressive state (see subsequent text).
  3. Management of sex partners: Because VVC is not considered an STD, partners are not routinely treated unless the male partner has symptoms and signs of balanitis. Partner treatment may be considered in cases of recurrent VVC.
  4. Side effects to therapy: Topical azole medications do not usually cause systemic side effects, but occasional problems with local irritation or burning can occur. Oral azole agents can cause nausea, abdominal pain, headaches, and rarely an elevation in liver enzymes. Assessment for drug interactions should be performed before oral agents are prescribed.
  5. Follow-up: Follow-up is not necessary for individuals who become asymptomatic after treatment. If symptoms occur four or more times in a year (recurrent VVC), an evaluation should be performed for the predisposing conditions listed earlier.
  6. Pregnancy: Topical azole medications can be used during pregnancy, but oral agents should be avoided. Seven-day therapy is preferred during pregnancy. Several treatments have been approved for use during pregnancy, including topical butoconazole, clotrimazole, miconazole, and terconazole.
  7. Severe VVC, or immunocompromised host: Cases with severe symptoms and signs have lower clinical cure rates with short-course medications. Treatment with either 7 to 14 days of topical azoles or fluconazole 150 mg once and then again in 3 days is advised.
  8. HIV infection: Treatment of VVC in adolescents with HIV infection does not differ from treatment in those without HIV infection. However, cases of clinically severe VVC may be treated as discussed in the preceding text. Prompt treatment of VVC in HIV-infected patients is especially advised because of potential for increased transmission of HIV to their sexual partners in these cases. HIV should be considered in cases of recurrent VVC, although routine HIV screening in adolescents with otherwise low risk for HIV is not routinely recommended because recurrent VVC often occurs in immunocompetent adolescents as well.
  9. Recurrent VVC (four or more episodes per year) is seen in <5% of women.
  10. Eliminate or reduce risk factors
  • Minimize the estrogen dose in oral contraceptives
  • Avoid broad-spectrum antibiotics
  • Minimize steroid use
  • Improve control of diabetes
  • Avoid constricting clothing, and wear cotton underwear
  • Avoid douching and vaginal sprays
  1. Obtain vaginal cultures and treat accordingly
  • Individual episodes caused by C. albicansusually respond well to the typical short courses of topical or oral azole regimens as above for uncomplicated VVC, but some experts recommend longer courses, that is, 7 to 14 days of topical treatment, or fluconazole 150 mg PO once and repeated in 3 days (Centers for Disease Control and Prevention, 2006).
  • Non-albicans Candidaspecies appear to respond to boric acid 600 mg gelatin capsule PO once daily for 14 days, or flucytosine vaginal cream 5 g once nightly (Sobel et al., 2003).
  1. Partner treatment: Routine treatment of all sex partners has not been shown to clearly benefit women with recurrent VVC. However, examination and treatment of partners with candidal balanitis is warranted.
  2. Consider HIV testing if other risk factors are present, as discussed in the preceding text.
  3. Long-term maintenance regimens: Several studies have shown decreased recurrences with maintenance regimens, although 30% to 50% of women experience recurrence after medication is discontinued. Regimens have included the following:
  • Fluconazole 150 mg PO once each week for 6 months
  • Clotrimazole 500-mg vaginal tablet each week for 6 months
  • Itraconazole 400 mg PO once monthly, or 100 mg PO once daily for 6 months
  • Ketoconazole 100 mg PO once daily for 6 months. Oral ketoconazole has a risk of mild reversible hepatitis of 5% to 10% and a risk of serious, potentially life-threatening hepatitis of 1 in 15,000. Ketoconazole should therefore be reserved only for resistant, recurrent VVC. Patients require monitoring for hepatotoxicity.
  • For non-albicans Candidaspecies, a maintenance regimen of flucytosine vaginal cream 5 g once nightly for 6 to 8 weeks may be helpful (Sobel et al., 2003).

Trichomoniasis

Etiology

  1. vaginalisinfection of the vaginal epithelium is caused by protozoa with four anterior flagella and one posterior flagellum.

Epidemiology

  1. Prevalence: T. vaginalisis not a reportable STD, but is estimated to be one of the most common treatable STDs, with an estimated 5 million cases annually in the United States and as many as 180 million cases worldwide (Cates, 1999). The peak prevalence rates are between the ages of 16 and 35 years. Prevalence in adolescent females is 10% to 20%, depending on the population examined and diagnostic test used.
  2. Transmission: The organism is almost always sexually transmitted. Because the organism can survive for approximately 1.5 hours on a wet sponge and up to 24 hours on a wet cloth, transmission can possibly occur through sharing of washcloths, communal bathing, or during routine child care.
  3. Incubation period: 4 to 28 days.
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Sites of colonization: Trichomonads can infect sites in addition to the vagina, for example the urethra (82.5% of cases) and periurethral glands (98% of cases).

  1. Predisposing factors: Multiple sex partners, lower socioeconomic status, prior history of STDs, inconsistent condom use.

Clinical Manifestations

  1. Up to 25% to 50% of females are asymptomatic. Nonspecific symptoms include pruritus, dysuria, dyspareunia, lower abdominal pain, and postcoital bleeding. Most males are asymptomatic.
  2. Discharge (50% of cases)
  3. Onset: Any time during the menstrual cycle
  4. Consistency: Classically diffuse, bubbly or frothy
  5. Color: Yellow or greenish
  6. Odor: Only 10% of women complain of malodorous discharge
  7. Examination
  8. Edema and excoriation of the external genitalia
  9. Frothy, foul-smelling vaginal discharge
  10. Erythematous, edematous, and granular vaginal walls
  11. Cervicitis (“strawberry cervix”): May have erosions or petechiae of the cervix (colpitis macularis), seen only in 2% of cases
  12. Bartholinitis
  13. Urethritis
  14. Rarely, abdominal tenderness and symptoms that may be consistent with pelvic inflammatory disease (PID)
  15. Complications: Trichomoniasis does not cause disseminated disease. However, emerging evidence now links trichomonas infection to sequelae such as increased HIV acquisition and transmission, perinatal morbidity, infertility, and cervical cancer. It is postulated that identification and treatment of T. vaginalisinfection would substantially decrease HIV acquisition (Sorvillo et al., 2001).

Diagnosis

  1. Wet prep: At least 10 microscopic fields are examined for the presence of trichomonads which appear as flagellated pear-shaped motile organisms similar in size to polymorphonuclear leukocytes. This is the most frequently used diagnostic method due to its low cost, ready availability, and immediate results. However, the sensitivity is 60% to 70% at best and is dependent on the examiner technique and number of organisms viewable in the sample. The slide must also be viewed as soon as possible because the motility of the trichomonads decreases with time (Kingston et al., 2003). Preservation of the sample at a temperature as close to body temperature as possible until time of viewing may also help preserve motility.
  2. KOH prep: Malodorous whiff is noted
  3. pH: Usually >4.5
  4. Gram stains: More time consuming and lower sensitivity than wet preps
  5. Cultures: Culture is the most sensitive and specific commercially available method of diagnosis. In women in whom trichomoniasis is suspected but not confirmed by microscopy, vaginal secretions should be cultured for T. vaginalis(Centers for Disease Control and Prevention, 2006). Cultures are more time consuming, expensive, and less readily available than wet preps, but require lower concentrations of organisms for diagnosis and can be useful in cases of treatment failure or recurrence of symptoms. Broth culture of a vaginal sample has traditionally been considered to be the gold standard for diagnosis, although newer techniques appear to have better sensitivity, as discussed in the subsequent text.
  6. Rapid point-of-care tests: There are two U.S. Food and Drug Administration-approved methods for rapid testing of vaginal samples (Centers for Disease Control and Prevention, 2006). The OSOM Trichomonas Rapid Test yields results in 10 minutes, and the Affirm VP III yields results in 45 minutes. Sensitivity is >83% and specificity is >97%, compared to culture. These tests are more sensitive than the wet prep, but are more expensive, and false positives occur in low prevalence populations (Briselden and Hillier, 1994; DeMeo et al., 1996; Huppert et al., 2005).
  7. DNA-based techniques: PCR tests have not been FDA-approved, are expensive, and have limited availability through commercial laboratories. Compared to reference standards that incorporate both culture and PCR, wet prep and culture demonstrate sensitivities of only 36% and 70% respectively whereas PCR demonstrates sensitivity of 97% (Madico et al., 1998). The specificity is 98%.
  8. Papanicolaou smear: Trichomonads are seen in Pap smears, but Pap smears are unreliable for the routine diagnosis of T. vaginalisinfection. The sensitivity to detect T. vaginalisby Pap smear is only approximately 50% when compared against culture. The sensitivity is even lower in populations in which rates of trichomonal infections are <20% (Wiese et al., 2000).
  9. Urine sediment: Trichomonads are occasionally seen in the urinary sediment. Microscopic examination of urine sediments in conjunction with wet preps has been shown to increase sensitivity (Blake et al., 1999). Urinary samples can be useful in males in whom urethral secretions are difficult to obtain.

Therapy

  1. Regimens for nonpregnant patients (Centers for Disease Control and Prevention, 2006)
  2. Recommended: Metronidazole 2 g PO in a single dose, or Tinidazole 2 g orally in a single dose.
  3. Alternative: Metronidazole 500 mg PO twice a day for 7 days.
  4. Both regimens of metronidazole have a cure rate of 90% to 95%. The single-dose regimen is preferred to increase compliance. Treatment of asymptomatic girls is advisable.
  5. Intravaginal metronidazole gel has not been shown to be effective (<50%) and therefore is not recommended.
  6. Revised CDC treatment guidelines now include recommendations for the use of tinidazole (Centers for Disease Control and Prevention, 2006). Randomized controlled trials comparing single 2 g doses of metronidazole and tinidazole suggest that tinidazole is equivalent to, or superior to, metronidazole in achieving parasitological cure and resolution of symptoms (Forna and Gulmezoglu, 2003).
  7. Side effects of therapy: Oral metronidazole can cause nausea, vomiting, and a metallic taste. Disulfiram-like

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effects occur if alcohol is ingested. All patients should be advised to avoid alcohol during treatment and until 24 hours after completion of metronidazole.

  1. Management of sex partners: Routine treatment of partners is recommended. Patients should also avoid sexual contact until the patient and all partners have completed medications and are asymptomatic.
  2. Allergy: Patients with allergy to nitroimidazole should receive desensitization because no alternative medication classes are effective for T. vaginalis.
  3. Follow-up: Follow-up is not necessary for individuals who become asymptomatic after treatment.
  4. Treatment failure: If failure occurs with either regimen, the adolescent should be retreated with metronidazole 500 mg twice daily for 7 days. If failure occurs again, the teen can be treated with metronidazole 2 g PO daily for 3 to 5 days. Some T. vaginalisstrains demonstrate decreased susceptibility to medications, but high-level resistance is rare. Any suspicions of resistance to metronidazole should be reported to the CDC for discussion of further susceptibility, testing, and recommendations (Centers for Disease Control and Prevention, 2006).
  5. Pregnancy: Published data have notshown an association between teratogenicity and metronidazole during pregnancy; it is safe to be used during all stages of pregnancy (Medical Letter, 1999). Recommended treatment includes 2 g of metronidazole PO in one dose.
  6. HIV infection: Same treatment regimens as above.

Bacterial Vaginosis

Bacterial vaginosis (BV), also known as Gardnerella vaginitis, “clue cell” vaginitis, Haemophilus vaginitis, or Corynebacterium vaginitis, is not a true vaginitis as it is not characterized by a marked inflammatory response at the vaginal mucosa. The current term BV was adopted to reflect the syndrome that is characterized by the presence of diverse bacteria without signs of vaginal mucosal inflammation. It is the most frequent cause of abnormal vaginal discharge and odor in postpubertal females.

Etiology

The syndrome consists of the replacement of normal lactobacilli in the vagina with Gardnerella vaginalis, anaerobic bacteria (i.e., Bacteroides sp, Mobiluncus sp), and Mycoplasma hominis. In most females without BV, the dominant vaginal organism is Lactobacillus sp (>95% of all vaginal organisms), whereas in females with BV, lactobacilli are often not found or found with decreased bacterial counts (100-fold to 1,000-fold decrease).

As discussed earlier, lactobacilli help maintain an acid pH level that prevents the growth of G. vaginalis and anaerobic bacteria. In BV, there is loss of lactobacilli, an elevated pH level, and high concentrations of G. vaginalis, anaerobes such as Bacteroides and Mobiluncus sp, and genital mycoplasmas. The sequence of this disruption is not well understood.

Epidemiology

  1. Prevalence: BV is the most common cause of abnormal vaginal discharge. However, BV is not a reportable disease, and prevalence varies widely (10% to 50%), depending on the population sampled.
  2. Transmission: The mechanism of transmission of BV is unresolved. Sexual transmission is suggested by the age and sexual experience of the infected patients (Shafer et al., 1985), and by the isolation of the organism from the urethras in 70% to 90% of male partners. Although rarely isolated from nonsexually active individuals, it is not an exclusive STD (Yen et al., 2003). G. vaginalis, Mobiluncussp, and M. hominis have been isolated from the rectum of females with BV and indicate a potential source of autoinfection (Catlin, 1992).
  3. Predisposing factors: BV is more common in women who have new sex partners, female sex partners, or multiple sex partners in the last 6 months, women who douche, and African-American women. Nansel et al. (2006), in a 1-year longitudinal study of 3,614 women, found that psychosocial stress was associated with increase in overall prevalence and incidence of BV.

Clinical Manifestations

  1. Symptoms can include vaginal pruritus and vaginal discharge. Up to 50% of cases are asymptomatic.
  2. Vaginal discharge
  3. Onset: May be more noticeable after vaginal intercourse or after menses
  4. Consistency: Thin, homogeneous
  5. Color: Grayish white
  6. Odor: Often patients note a “fishy” odor, particularly in the presence of semen. The combination of G. vaginalisand anaerobes produces organic acids and several amines. In the presence of an elevated vaginal pH level, these products volatilize to the malodorous compounds of putrescine and cadaverine. Trimethylamine may also contribute to the odor.
  7. Examination
  8. Thin gray-white discharge, adhering to the vaginal walls
  9. Usually no vulvar or vaginal wall changes
  10. Possibly a pungent “fishy” odor
  11. Complications: There is growing evidence that BV is linked to serious sequelae including PID, increased HIV acquisition and transmission, infertility, and postsurgical/postabortal infection. Obstetric complications include chorioamnionitis, premature rupture of membranes, preterm labor, and postpartum endometritis.

Diagnosis

Variations of the Amsel criteria are commonly used for the clinical diagnosis of BV. Three of the following four clinical symptoms and signs are required:

  1. The presence of a homogeneous, white, noninflammatory discharge that smoothly coats the vaginal walls.
  2. The presence of “clue cells” (epithelial cells that appear granular and stippled with indistinct cell borders due to adherence of bacteria and cellular debris between cells) on wet prep examination. Clue cells should comprise at least 20% of the epithelial cells examined.
  3. The vaginal pH level is >4.5.
  4. The vaginal discharge has a positive result on whiff test, a fishy odor before or after the addition of 10% KOH.

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Gram stain is also sometimes available as a diagnostic tool and is indicative of BV if the relative concentration of bacterial types shows the characteristic altered flora. Gram stains are classified according to the Nugent criteria, which designate a score of 0 to 10 based on the proportion of bacterial morphotypes, with a score of more than 7 considered as BV (Nugent et al., 1991). Table 55.1 outlines the Nugent scoring system. Culture is currently not recommended as a diagnostic test because of its questionable specificity. Finally, a number of newer commercial probe tests that detect vaginal pathogens including G. vaginalis DNA are under study.

TABLE 55.1
Nugent Scoring System for Gram-Stained Vaginal Smears

Score

Lactobacilli Morphotypes per Oil Immersion Field

Gardnerella Morphotypes per Oil Immersion Field

Curved Bacteria (Mobiluncus) per Oil Immersion Field

0

>30

0

0

1

5–30

<1

<1–4

2

1–4

1–4

>5

3

<1

5–30

 

4

0

>30

 

Final Total Score

Conclusion

0–3

Normal flora

4–6

Intermediate flora

7–10

Bacterial vaginosis

Therapy

  1. All women with symptomatic BV should be treated, regardless of pregnancy status. The primary goal of treatment is to relieve symptoms and signs. Screening and treatment of asymptomatic women found to have BV before surgical procedures or other intervention is also recommended by many experts. Treatment of BV with metronidazole has been shown to reduce postabortion PID rates.
  2. Regimens for nonpregnant patients (Centers for Disease Control and Prevention, 2006)
  3. Recommended
  • Metronidazole 500 mg PO twice daily for 7 days, or
  • Clindamycin cream 2% one full applicator (5 g) intravaginally each night for 7 days, or
  • Metronidazole gel 0.75% one full applicator (5 g) intravaginally twice daily for 5 days

Cure rates for these recommended regimens are comparable (75%–85%). All patients treated with metronidazole should be advised to avoid alcohol during treatment and until 24 hours after completion of medication. (See “side effects” in the “Trichomoniasis” section in the preceding text.) Clindamycin cream may weaken latex condoms but offers the advantage of lack of systemic side effects.

  1. Alternative (Centers for Disease Control and Prevention, 2006)
  • Clindamycin 300 mg PO twice daily for 7 days
  • Clindamycin ovules 100 g intravaginally once at bedtime for 3 days

Metronidazole 2 g single-dose therapy has the lowest efficacy for BV and is no longer a recommended or alternative regimen (Centers for Disease Control and Prevention, 2006). The FDA has also approved the use of metronidazole extended release 750 mg PO once daily for 7 days, and metronidazole gel 0.75% intravaginally once daily for 5 days, but efficacy data are not published.

  1. Patients should be advised to avoid douching and reduce the number of sex partners.
  2. Management of sex partners: Treatment of male partners is not routinely recommended because it does not alter the female patient's response rate or the rate of recurrence. However, female sex partners should be evaluated and treated if BV is found.
  3. Follow-up: Follow-up is not necessary if the patient becomes asymptomatic. Adolescents with recurrent or persistent infections should be reevaluated for other infections.
  4. Recurrent BV: Recurrence occurs in 20% to 30% of cases within 3 months. The cause of recurrence is poorly understood and management is controversial. Studies have not shown exogenous lactobacillus and yogurt therapies to be effective. Maintenance regimens are under study.
  5. Pregnancy
  6. All symptomatic pregnant women in any trimester should be treated. Recommended regimens for pregnant women are as follows (Centers for Disease Control and Prevention, 2006):
  • Metronidazole 500 mg orally twice a day for 7 days
  • Metronidazole 250 mg PO three times daily for 7 days, or
  • Clindamycin 300 mg PO twice a day for 7 days
  1. Optimal screening and treatment of asymptomatic pregnant women is unclear. Because BV is associated with adverse pregnancy outcomes, asymptomatic pregnant women at high risk (i.e., those with history of premature delivery) may be screened during early second trimester. Screening of asymptomatic pregnant women at low risk is not recommended.
  2. HIV infection: Same treatment regimens as above.

Other Causes of Vaginal Discharge

  1. Physiological discharge: A normal overall increase in vaginal secretions occurs 6 to 12 months before menarche. Vaginal and cervical secretions also vary depending on the hormonal state—estrogen induces a more profuse discharge, whereas progesterone induces a thicker discharge. At the time of ovulation or just before menses, vaginal secretions tend to increase. Physiological discharge is characterized by:
  2. Lack of offensive odor
  3. Lack of pruritus or burning
  4. Lack of vulvar, vaginal, or cervical erythema
  5. Possible brown stain on the underwear
  6. Lack of polymorphonuclear leukocytes on wet mount
  7. P.730


Extravaginal disease: Extravaginal lesions may cause staining of the underwear, leading to the perception of a discharge. These lesions include the following:

  1. Perineal lesions: Herpes, syphilis, intertrigo
  2. Bartholin gland abscess
  3. Proctitis
  4. Bleeding hemorrhoids
  5. Enterobius vermicularis: Pinworms
  6. Irritant vaginitis: Vaginal discharge can result from irritation associated with agents such as chemical douches, vaginal deodorants, vaginal sprays, tampons or pads, colored or perfumed toilet paper, bubble bath, laundry detergents, fabric softeners, swimming pools or hot tubs, powders, soaps, spermicides, or medications used by male partners that remain on the penis.
  7. Foreign bodies: Vaginal discharge may be caused by items such as forgotten tampons, intrauterine devices (uterine discharge), and objects for masturbation.
  8. Vulvodynia or vulvar vestibulitis: Clinical manifestations include pain with penetration during intercourse and small inflamed areas at 5 and 7 o'clock positions on the perineum that are exquisitely tender to touch. The vaginal examination results (including pH, flora, and wet prep) are normal. A course of topical steroids may be helpful.
  9. N. gonorrhoeae: See Chapter 61. Gonorrhea generally infects the endocervix and not the vaginal walls. Most females are asymptomatic, although approximately 25% experience a foul-smelling cervical discharge that may be perceived as vaginal discharge.
  10. P.731

  11. trachomatis: See Chapter 62. Cervical infections are common, and cervical discharge may be perceived as vaginal discharge.

Table 55.2 outlines the treatment of vaginitis in adolescents.

TABLE 55.2
Vaginal Discharge in the Adolescent

Condition

Signs and Symptoms

Diagnosis

Treatment

Physiological discharge

Clear gray discharge
No offensive odor
No burning or itching

Wet prep: Epithelial cells with no or few polymorphonuclear cells; no pathogens

Reassurance and explanation

Vulvovaginal candidiasis (VVC)

Curd-like discharge
Intense burning, pruritus
Usually no odor
Often associated vulvitis

KOH: Budding yeast and pseudohyphae

Numerous acceptable regimens listed in text

Trichomoniasis

Pruritus Malodorous,
frothy, yellow-green discharge
Dysuria Rarely, abdominal pain

Wet prep: Pear-shaped organism with motile flagella

Metronidazole: 2 g single dose or 500 mg b.i.d. for 7 days
Treat and evaluate partner

Bacterial vaginosis

Homogeneous, malodorous, gray-white discharge
Usually mild or no pruritus or burning

Wet prep: Epithelial cells covered with gram-negative rods
Few polymorphonuclear leukocytes
pH >4.5

Metronidazole: 500 mg b.i.d. for 7 days, or metronidazole gel 0.75% one applicator b.i.d. for 5 days, or clindamycin cream 2% one applicator (5 g) intravaginally for 7 days
Alternative regimens listed in text
Evaluate female partners and treat accordingly

N. gonorrhoeaeinfection

Majority asymptomatic
Gray-white cervical discharge

Culture
Gram stain can be used, but a negative smear must be confirmed by culture

Ceftriaxone 125 mg IM once, or cefixime 400 mg once; plus azithromycin 1 g orally once, or doxycycline 100 mg orally b.i.d. for 7 days

C. trachomatisinfection

Majority asymptomatic
Yellowish cervical discharge
Cervicitis

Nucleic acid amplification test or culture
Exclusion of other organisms in a girl with cervicitis

Azithromycin 1 g once, or doxycycline 100 mg PO b.i.d. for 7 days

Retained tampon

Malodorous discharge
Local discomfort

History and physical examination
History of exposure to deodorant spray or scented tampons

Removal of tampon

Irritant vaginitis

Vaginal discharge, erythema

Other agents listed in text

Cessation of irritant agent

Web Sites

For Teenagers and Parents

http://kidshealth.org/teen/sexual_health/. Teen-oriented Web site from the Nemours Foundation, including information on STDs and vaginitis.

http://www.nichd.nih.gov/health/topics/vaginitis.cfm. Vaginitis information from the National Institutes of Health.

http://www.health.state.mn.us/divs/idepc/diseases/vaginitis/. Vaginitis information from the Minnesota Department of Health, includes patient handouts in various languages (pdf files).

http://www.mayoclinic.com/invoke.cfm?id=DS00255. Vaginitis information from the Mayo Clinic.

http://www.ashastd.org/learn/learn_vag_trich.cfm. American Social Health Association Web site on vaginal infections and other STDs.

http://www.mckinley.uiuc.edu/Handouts/vaginal_discharge.html. Information on vaginal discharge from the University of Illinois student health center.

For Health Professionals

http://www.cdc.gov/nchstp/dstd/Whats_New.htm. Updates from the CDC regarding STDs.

http://www2a.cdc.gov/stdtraining/self-study/default.asp. Self-study modules from the CDC that include vaginitis and STD topics.

http://www.emedicine.com/EMERG/topic631.htm. E-medicine site on vaginitis.

http://www.aafp.org/afp/20041201/2125.html. American Academy of Family Physicians article on vaginitis, includes patient handouts.

References and Additional Readings

Ament LA, Whalen E. Sexually transmitted diseases in pregnancy: diagnosis, impact, and intervention. J Obstet Gynecol Neonatal Nurs 1996;25:657.

Amsel R, Totten PA, Spiegel CA, et al. Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14.

Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal complaints. JAMA 2004;29:1368.

Augenbraun M, Bachmann L, Wallace T, et al. Compliance with doxycycline therapy in sexually transmitted diseases clinics. Sex Transm Dis 1998;25:1.

Blake D, Duggan A, Joffe A. Use of spun urine to enhance detection of Trichomonas vaginalis in adolescent women. Arch Pediatr Adolesc Med 1999;153:1222.

Briselden AM, Hillier SL. Evaluation of affirm VP microbial identification test for gardnerella vaginalis and Trichomonas vaginalis. J Clin Microbiol 1994;32:148.

Burtin P, Taddio A, Ariburnu O, et al. Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol 1995;172: 525.

Caliendo AM, Jordan JA, Green AM, et al. Real-time PCR improves detection of Trichomonas vaginalis infection compared with culture using self-collected vaginal swabs. Infect Dis Obstet Gynecol 2005;13:145.

Carey JC, Klebanoff MA, Hauth JC, et al. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. N Engl J Med 2000;342:534.

Carr P, Felenstein D, Friedman R. Evaluation and management of vaginitis. J Gen Intern Med Clin Rev 1998;13:335.

Cates W Jr. Estimates of the incidence and prevalence of sexually transmitted diseases in the United States. American Social Health Association Panel. Sex Transm Dis 1999; 26(4 Suppl):S2.

Catlin BW. Gardnerella vaginalis: characteristics, clinical considerations, and controversies. Clin Microbiol Rev 1992;5(3):213.

Centers for Disease Control and Prevention, Division of STD Prevention. Sexually transmitted disease surveillance, 2003. Atlanta: Department of Health and Human Services, 2004.

Centers for Disease Control and Prevention. Sexually transmitted diseases: treatment guidelines, 2002MMWR 2002:51 (RR-6):1.

Centers for Disease Control and Prevention. Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006;4;55(RR-11):1.

Chernesky MA. Nucleic acid tests for the diagnosis of sexually transmitted diseases. Fems Immunol Med Microbiol 1999;24:437.

Ciemins EL, Flood J, Kent CK, et al. Reexamining the prevalence of Chlamydia trachomatis infection among gay men with urethritis: implications for STD policy and HIV prevention activities. Sex Transm Dis 2000;27:249.

Cohen CR, Plummer FA, Mugo N, et al. Increased interleukin-10 in the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission? AIDS 1999;13:327.

DeMeo LR, Draper DL, McGregor JA, et al. Evaluation of a deoxyribonucleic acid probe for the detection of Trichomonas vaginalis in vaginal secretions. Am J Obstet Gynecol1996;174:1339.

Dun E. Antifungal resistance in yeast vaginitis. Yale J Biol Med 2000;72:281.

Farrington PF. Pediatric vulvo-vaginitis. Clin Obstet Gynecol 1997;40:135.

Ferrer J. Vaginal candidosis: epidemiological and etiological factors. Int J Gynaecol Obstet 2000;71(Suppl 1):S21.

Ferris DG, Nyirjesy P, Sobel JD, et al. Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 2002;99:419.

Fiori PL, Rapelli P, Addis MF. The flagellated parasite Trichomonas vaginalis: new insights into cryopathogenicity mechanisms. Microbes Infect 1999;1:149.

Forna F, Gulmezoglu AM. Interventions for treating trichomoniasis in women. Cochrane Database Syst Rev 2003;(2): CD000218.

Forsum U, Hallen A, Larsson PG. Bacterial vaginosis–a laboratory and clinical diagnostics enigma. Apmis 2005;113:153.

Forsum U, Holst E, Larsson PG, et al. Bacterial vaginosis–a microbiological and immunological enigma. Apmis 2005;113:81.

Gardner HL. Haemophilus vaginalis after twenty-five years. Am J Obstet Gynecol 1980;137:385.

P.732

 

Glover DD, Larsen B. Relationship of fungal vaginitis therapy to prior antibiotic exposure. Infect Dis Obstet Gynecol 2003; 11:157.

Hammerschlag MR. Sexually transmitted diseases in sexually abused children: medical and legal implications. Sex Transm Infect 1998;74:167.

Heine RP, Wisenfeld HC, Sweet RL, et al. PCR Analysis of distal vaginal specimens less invasive strategy for the detection of trichomonas. Clin Infect Dis 1997;24:985.

Hillier S, Holmes KK. Bacterial vaginosis. In: Holmes KK, Mardh PA, Sparling PF, et al. eds. Sexually transmitted diseases, 3rd ed. New York: McGraw-Hill, 1999.

Holmes KK, Stamm WE. Lower genital tract infection in women. In: Holmes KK, Mardh PA, Sparling PF, et al. eds. Sexually transmitted diseases, 3rd ed. New York: McGraw-Hill, 1999.

Huppert JS, Batteiger BE, Braslins P, et al. Use of an immunochromatographic assay for rapid detection of Trichomonas vaginalis in vaginal specimens. J Clin Microbiol2005;43:684.

Hwang L, Shafer MA. Chlamydia trachomatis infection in adolescents. Adv Pediatr 2004;51:379.

Joishy M, Ashtekar CS, Jain A, et al. Do we need to treat vulvovaginitis in prepubertal girls? Br Med J 2005;330:186.

Kingston MA, Bansal D, Carlin EM. ‘Shelf life’ of Trichomonas vaginalis. Int J STD AIDS 2003;14:28.

Krieger JN, Alderete JF. Trichomonas vaginalis and Trichomoniasis. In: Holmes KK, Mardh PA, Sparling PF, et al. eds. Sexually transmitted diseases, 3rd ed. New York: McGraw-Hill, 1999.

Krohn MA, Hillier SL, Nugent RP, et al. Vaginal Infection and Prematurity Study Group. The genital flora of women with intraamniotic infection. J Infect Dis 1995;171:1475.

Larsen B. Vaginal flora in health and disease. Clin Obstet Gynecol 1993;36:107.

Madico G, Quinn TC, Rompalo A, et al. Diagnosis of Trichomonas vaginalis infection by PCR using vaginal swab samples. J Clin Microbiol 1998;36:3205.

Mardh PA. The vaginal ecosystem. Am J Obstet Gynecol 1991;165:1163.

McGregor JA, French JI. Bacterial vaginosis in pregnancy. Obstet Gynecol Surv 2000;55:S1.

Medical Letter. Drugs for sexually transmitted infections. Med Lett 1999;41:1062.

Merchant J, Oh K, Klerman L. Douching: a problem for adolescent girls and young women. Arch Pediatr Adolesc Med 1999;153:834.

Metzger GD. Laboratory diagnosis of vaginal infections. Clin Lab Sci 1998;11:47.

Mitchell H. Vaginal discharge–causes, diagnosis, and treatment. Br Med J 2004;328:1306.

Nansel TR, Riggs MA, Yu KF, et al. The association of psychosocial stress and bacterial vaginosis in a longitudinal cohort. Am J Obstet Gynecol 2006;194:381.

Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 1991;29:297.

Nyirjesy P. Vaginitis in the adolescent patient. Pediatr Clin North Am 1999;46:733.

Nyirjesy P, Sobel JD. Vulvovaginal candidiasis. Obstet Gynecol Clin North Am 2003;30:671.

Ohlemeyer CC, Hornberger LL, Lynch DA, et al. Diagnosis of Trichomonas vaginalis in adolescent females. In Pouch TV culture versus wet-mount. J Adolesc Health 1998;22:205.

Peipert JF, Montagno AB, Cooper AS, et al. Bacterial vaginosis as a risk factor for upper genital tract infection. Am J Obstet Gynecol 1997;177:1184.

Petrin D, Delgaty K, Bhatt R, et al. Clinical and microbiological aspects of Trichomonas vaginalisClin Microbiol Rev 1998; 11:300.

Plummer PA, Simonsen JN, Cameron DW, et al. Co-factors in male-female sexual transmission of human immunodeficiency virus type 1. J Infect Dis 1991;163:233.

Shafer MA, Sweet RL, Ohm-Smith MS, et al. Microbiology of the lower genital tract in postmenarchal adolescent girls: differences by sexual activity, contraception, and presence of nonspecific vaginitis. J Pediatr 1985;107:974.

Sobel JD. Vulvovaginal candidiasis. In: Holmes KK, Mardh PA, Sparling PF, et al. eds. Sexually transmitted diseases, 3rd ed. New York: McGraw-Hill, 1999.

Sobel JD. What's new in bacterial vaginosis and trichomoniasis? Infect Dis Clin North Am 2005;19:387.

Sobel JD, Brooker D, Stein GE, et al. Fluconazole Vaginitis Study Group. Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitisAm J Obstet Gynecol 1995;172:1263.

Sobel JD, Chaim W, Nagappan V, et al. Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. Am J Obstet Gynecol 2003;189:1297.

Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance Fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med 2004;351:876.

Sorvillo F, Smith L, Kerndt P, et al. Trichomonas vaginalis, HIV, and African-Americans. Emerg Infect Dis 2001;7:927.

Spinillo A, Pizzoli G, Colonna L, et al. Epidemiologic characteristics of women with idiopathic recurrent vulvovaginal candidiasis. Obstet Gynecol 1993;81:721.

Sweet RL. Role of bacterial vaginosis in pelvic inflammatory disease. Clin Infect Dis 1995;20(Suppl 2):S271.

Sweet RL. The enigmatic cervix. Dermatol Clin 1998;16:739.

Swygard H, Sena AC, Hobbs MM, et al. Trichomoniasis: clinical manifestations, diagnosis and management. Sex Transm Infect 2004;80:91.

Syed TS, Braverman PK. Vaginitis in adolescents. Adolesc Med Clin 2004;15:235.

Van Der Pol B, Williams JA, Orr DP, et al. Prevalence, incidence, natural history, and response to treatment of Trichomonas vaginalis infection among adolescent women. J Inf Dis2005; 192:2039.

Vermillion ST, Holmes MM, Soper DE. Adolescents and sexually transmissible diseases. Obstet Gynecol Clin North Am 2000;27:163.

Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod Health 2004;36:6.

Wiese W, Patel SR, Patel SC, et al. A meta-analysis of the Papanicolaou smear and wet mount for diagnosis of vaginal trichomoniasis. Am J Med 2000;108:301.

Wilton L, Kollarova M, Heeley E, et al. Relative risk of vaginal candidiasis after use of antibiotics compared with antidepressants in women: postmarketing surveillance data in England. Drug Saf 2003;26:589.

Yen S, Shafer MA, Moncada J, et al. Bacterial vaginosis in sexually experienced and non-sexually experienced young women entering the military. Obstet Gynecol 2003;102 (5 Pt 1):927.