Section 2. Vaginitis and Cervicitis

A 39-year-old woman presented to her physician with a malodorous vaginal discharge. On exam, a thin white discharge was seen covering the introitus (Figure 80-1). A speculum exam revealed a thin whitish gray discharge and a distinct fishy odor. The pH of the discharge was 4.6, and 40% of the epithelial cells on her wet prep were clue cells (Figure 80-2). She was diagnosed with bacterial vaginosis and treated with oral metronidazole.

Vaginal discharge is a frequent presenting complaint in primary care. The three most common causes are bacterial vaginosis, candidiasis, and trichomoniasis. However, a significant number of patients with vaginal discharge will have some other condition, such as atrophic vaginitis. Providers must refrain from “diagnosing” a vaginitis based solely on the color and consistency of the discharge, as this may lead to misdiagnosis and may miss concomitant infections.1

The reported rates of chlamydia and gonorrhea are highest among females ages 15 to 19 years. Adolescents are at greater risk for sexually transmitted diseases (STDs) because they frequently have unprotected intercourse, are biologically more susceptible to infection, are often engaged in partnerships of limited duration, and face multiple obstacles to utilization of health care.1

• The quantity and quality of normal vaginal discharge in healthy women vary. Physiologic leukorrhea refers to generally nonmalodorous, mucousy, white or yellowish vaginal discharge in the absence of a pathologic cause. It is not accompanied by signs and symptoms, such as pain, pruritus, burning, erythema, or tissue friability. However, slight malodor and irritative symptoms can be normal for some women at certain times.2 Physiologic leukorrhea is usually a result of estrogen-induced changes in cervicovaginal secretions.
• Noninfectious causes of vaginitis include irritants (e.g., scented panty liners, spermicides, povidone-iodine, soaps and perfumes, and some topical drugs) and allergens (e.g., latex condoms, topical antifungal agents, chemical preservatives) that produce hypersensitivity reactions.
• Before starting an examination, determine whether the patient douched recently, because this can lower the yield of diagnostic tests and increase the risk of pelvic inflammatory disease.3 Patients who have been told not to douche will sometimes start wiping the vagina with soapy washcloths, which also irritates the vagina and cervix and may cause a discharge. Douching is associated with increases in bacterial vaginosis and acquisition of sexually transmitted infections when exposed. However, recent studies indicate that douching with plain water once a week or less did not disturb normal flora.4,5
• There are many causes of vaginitis in humans. Infectious causes include bacterial vaginosis (40% to 50% of cases) (see Figures 80-1 and 80-2), vulvovaginal candidiasis (20% to 25%), and trichomonas (15% to 20%) (Figure 80-3).6 Less common causes include atrophic vaginitis, foreign body (especially in children), cytolytic or desquamative inflammatory vaginitis, streptococcal vaginitis, ulcerative vaginitis, and idiopathic vulvovaginal ulceration associated with HIV infection.
• Rarer noninfectious causes include chemicals, allergies, hypersensitivity, contact dermatitis, trauma, postpuerperal atrophic vaginitis, erosive lichen planus, collagen vascular disease, Behçet syndrome, and pemphigus syndromes.

Clinical Features

• Examine the external genitalia for irritation or discharge (see Figure 80-2). Speculum examination is done to determine the amount and character of the discharge (Figure 80-4). A chlamydia and gonorrhea test should always be done in sexually active females with a vaginal discharge. Look closely at the cervix for discharge and signs of infection, dysplasia, or cancer (Figure 80-3). Bimanual examination may show evidence of cervical, uterine, or adnexal tenderness. Table 80-1 shows diagnostic values for examination of vaginitis.
• Vaginal pH testing can be helpful in the diagnosis of vaginitis. The pH can be checked by applying pH paper to the vaginal sidewall. 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.
• Wet preps are obtained by applying a cotton-tipped applicator to the vaginal sidewall and placing the sample into normal saline. A drop of the suspension is then placed on a slide and examined for the presence and number of white blood cells (WBCs), trichomonads, candidal hyphae, or clue cells (Figure 80-1).
• A 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 to 15 minutes (faster if the slide is warmed briefly) and allows easier visualization of candidal hyphae. The use of KOH with DMSO allows for quicker lyses of the epithelial cells and immediate examination of the smear.
• Another diagnostic procedure is the “whiff” test, which is performed 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. The “whiff” test is positive if the fishy amine odor is detected during the exam and it is then not necessary to add KOH and “whiff” again.

Laboratory Testing (Include Ancillary Testing Too)

• Nucleic acid amplification tests are highly sensitive tests for Neisseria gonorrhoeae, Chlamydia, and Chlamydia trachomatis that can be performed on genital specimens or urine. Urine screening for gonorrhea, chlamydia, or both using nucleic acid amplification test can be used successfully in difficult-to-reach adolescents.7

• Management is based on the identification of the causative agent.
• Treatment for physiologic leukorrhea is unnecessary.
• Management of vaginal irritants and allergens involves identifying and eliminating the offending agents. However, irritants and allergens can often be difficult to identify.
• Health food store lactobacilli are the wrong strain and do not adhere well to the vaginal epithelium. Ingestion of live-culture, nonpasteurized yogurt does not significantly change the incidence of candidal vulvovaginitis or bacterial vaginosis. 8

Patient Resources

• Centers for Disease Control and Prevention. Sexually Transmitted Diseases page—http://www.cdc.gov/std/.
• Planned Parenthood—http://www.plannedparenthood.org/cameron-willacy/images/South-Texas/What_Every_Woman_Needs_to_Know_English.pdf.
• Illinois Department of Public Health. Vaginitis—www.idph.state.il.us/public/hb/hbvaginitis.htm.

Provider Resources

• Centers for Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases—http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf.
• Centers for Disease Control and Prevention. Self-Study STD Module-Vaginitis—www2a.cdc.gov/stdtraining/self-study/vaginitis.asp.
• Centers for Disease Control and Prevention. Vaginitis slides—http://www2a.cdc.gov/stdtraining/ready-to-use/Manuals/Vaginitis/vaginitis-slides-2010.pdf.
• eMedicine—http://emedicine.medscape.com/article/257141-overview.
• American Family Physician—http://www.aafp.org/afp/20000901/1095.html.

A 60-year-old woman with vaginal dryness and irritation is seen to follow-up on an inflammatory Pap smear. She denies discharge, odor, douching, and sexually transmitted disease (STD) exposure. She does admit to some postcoital bleeding. Her cervix has atrophic changes and an endocervical polyp (Figure 81-1). The polyp was removed easily with a ring forceps and no dysplasia was found on pathology.

Vaginal atrophy caused by estrogen deficiency is common and usually is asymptomatic except for vaginal dryness.

Vaginal atrophy, vulvovaginal atrophy, urogenital atrophy, senile vaginitis.

• The average age of menopause is 51 years in the United States.
• Approximately 5% of women experience menopause after age 55 years (late menopause), and another 5% experience the transition between the ages of 40 and 45 years (early menopause). This means that in the United States, most women will live a significant portion of their lives during menopause. Women who in menopause have surgical menopause or have ovarian suppression without estrogen supplementation (progestin-only contraceptives) are susceptible to atrophic changes in their lower genital tract.
• Vaginal dryness occurs in approximately 3% of women of reproductive age, 4% to 21% of women in the menopausal transition, and 47% of women 3 years postmenopause.1 Internationally, 39% of women experience menopause-related vaginal discomfort.2

• After menopause, circulating estrogen levels dramatically decrease to a level at least one-sixth their premenopausal levels.3 Changes that occur in the vaginal and cervical epithelium include proliferation of connective tissue, loss of elastin, thinning of the epithelium (Figure 81-2), and hyalinization of collagen.
• A long-term decrease in estrogen is generally necessary before symptoms become apparent. Genital symptoms include decreased vaginal lubrication, dryness, burning, dyspareunia, leukorrhea, itching, and yellow malodorous discharge.
• Urinary symptoms, such as frequency, hematuria, urinary tract infection, dysuria, and stress incontinence, are usually late symptoms. Over time, the lack of vaginal lubrication often results in sexual dysfunction.
• Cervical polyps (Figure 81-1) are pedunculated tumors that usually arise from the endocervical canal mucosa, and are common in patients with atrophic vaginitis. Many will show squamous metaplasia, and they may develop squamous dysplasia. Polyps are most commonly asymptomatic unless they bleed.
• Menopause is the most common cause of atrophic vaginitis. In premenopausal women, radiation therapy, chemotherapy, immunologic disorders, and oophorectomy may greatly decrease production of ovarian estrogen and lead to atrophic vaginitis. Antiestrogen medications may also result in atrophic vaginitis. Women who are naturally premenopausally estrogen deficient, smoke cigarettes, or have not given vaginal birth tend to have more severe symptoms.3

• Age.
• Family history of early menopause.
• Bilateral oophorectomy.
• Spontaneous premature ovarian failure.
• Antiestrogenic medications effects, such as tamoxifen, danazol, medroxyprogesterone acetate.
• Gonadotropin-releasing hormone agonists (leuprolide, nafarelin, goserelin), or antagonists (ganirelix).
• Prolactin elevation as a result of hypothalamic-pituitary disorders with secondary reduction of estrogen secretion.
• Certain chemotherapeutic agents.
• Pelvic radiation therapy.
• Severe systemic lupus erythematosus or rheumatoid arthritis (because of hypothalamic hypogonadism or primary ovarian insufficiency) combined with glucocorticoid therapy cause combined suppression of ovarian and adrenal activity.

Clinical Features

• Diagnosis is clinical, based upon characteristic symptoms and findings. Many women with symptoms of vaginal atrophy do not discuss their condition with a health care provider because they believe their symptoms are a normal part of the aging process.4
• Atrophic vaginal and cervical epithelium appears pale, smooth, relatively dry, and shiny (Figure 81-2). Inflammation with patchy erythema, petechiae, and friability is common in more advanced cases. The external genitalia may demonstrate diminished elasticity, turgor of skin, sparsity of pubic hair, dryness of labia, erythema (Figure 81-3), and fusion of the labia minora.5

Laboratory Testing

• Laboratory tests to confirm hypoestrogenic findings are typically not necessary.
• Serum estradiol levels of less than 20 pg/mL support a clinical diagnosis of a low-estrogenic state. However, values are very laboratory dependent and most assays are neither sufficiently sensitive nor reliable for diagnosis of hypoestrogenic states without clinical signs and symptoms.
• A serum follicle-stimulating hormone (FSH) level greater than 40 mIU/mL is diagnostic of menopause.
• A Papanicolaou smear can confirm the presence of urogenital atrophy. Cytologic examination of smears from the upper one-third of the vagina shows an increased proportion of parabasal cells and a decreased percentage of superficial cells.
• An elevated vaginal pH level (>5), monitored by a pH strip in the vaginal vault, may also be a sign of vaginal atrophy.3

Imaging

• Testing for associated osteoporosis should be considered if not previously performed.

• Atrophic vaginitis symptoms can be mimicked or exacerbated by coinfection of candidiasis, trichomoniasis, or bacterial vaginosis. These can be identified by wet prep, pH, and whiff test (see Chapter 82, Bacterial Vaginosis).
• Sexually transmitted diseases, including gonorrhea, trichomonas, and chlamydia, also may coexist with or mimic atrophic vaginitis. Cultures or nucleic acid amplification tests can identify these infections. It is important not to assume a diagnosis of solely atrophic vaginitis in the postmenopausal patient who presents with urogenital complaints. (Chapter 80, Overview of Vaginitis).
• Contact dermatitis because of environmental agents (e.g., perfumes, deodorants, soaps, panty liners, perineal pads, spermicides, lubricants, or tight fitting/synthetic clothing) may cause erythema, itching, burning, or pain. (Chapter 146, Contact Dermatitis).
• Vulvovaginal lichen planus, which may produce labial fusion. (Chapter 154. Lichen Planus).
• Lichen sclerosus et atrophicus (LSEA) does produce atrophy of the vulva and can be mistaken for the atrophy of estrogen deficiency. It can be recognized by the hour-glass configuration of the atrophy around the vulva and perianal region (Figure 81-4). LSEA is treated with a high-potency steroid ointment rather than estrogen.

Nonpharmacologic

• Nonhormonal local vaginal moisturizers and lubricants may be used to help maintain natural secretions and comfort during intercourse. Sexual activity has been shown to encourage vaginal elasticity and pliability, and the lubricative response to sexual stimulation. One open-label study indicated that Replens, a bioadhesive vaginal moisturizer, was a safe and effective alternative to estrogen vaginal cream, with both therapies exhibiting statistically significant increases in vaginal moisture, vaginal fluid volume, and vaginal elasticity.6 SOR A
• Water-based vaginal lubricants include:
  • Slippery Stuff (polyoxyethylene, methylparaben, propylene glycol, isopropanol).
  • Astroglide (glycerin, methylparaben, propylparaben, polypropylene glycol, polyquaternium, hydroxyethylcellulose).
  • K-Y Jelly (glycerin, hydroxyethylcellulose, parabens, and chlorhexidine).
  • Pre-Seed (hydroxyethylcellulose, arabinogalactan, paraben, and Pluronic copolymers), which is promoted for women who are trying to conceive.
• Silicone-based:
  • ID Millennium (cyclomethicone, dimethicone, and dimethiconol).
  • Pjur Eros (cyclopentasiloxane, dimethicone, and dimethiconol).
  • Pink (dimethicone, vitamin E, aloe vera, dimethiconol, and cyclomethicone.
• Oil-based:
  • Elégance Women's Lubricant.
  • Natural oils (such as olive oil).
• Water-based and silicone-based vaginal lubricants are compatible with condom use. Oil-based lubricants may damage latex-based condoms.
• Patients should stop smoking, as women who smoke cigarettes are relatively estrogen-deficient.7 SOR A

Medications

• Estrogen replacement therapy relieves menopausal symptoms including atrophic vaginitis.8 SOR A Routes of administration include oral, transdermal, and intravaginal. Risks associated with estrogen use include breast cancer, coronary heart disease, stroke, and venous thromboembolism.
• A Cochrane review found that estrogen creams, pessaries, vaginal tablets, and the estradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy.8 SOR A One trial found significant side effects following conjugated equine estrogen cream administration when compared to tablets causing uterine bleeding, breast pain, and perineal pain. Another trial found significant endometrial overstimulation following use of the conjugated equine estrogen cream when compared to the estrogen vaginal ring. Women appeared to favor the estradiol-releasing vaginal ring for ease of use, comfort of product, and overall satisfaction.8 SOR A
• The amount of estrogen and the duration of time required to eliminate symptoms depend on the degree of vaginal atrophy, and varies among patients. Progestin therapy should be considered in any woman with an intact uterus to avoid causing endometrial cancer. When oral estrogen is used at typical doses, atrophic symptoms will persist in 10% to 25% of patients.9
• Topical administration of estrogen is an excellent treatment for genitourinary symptoms of atrophy, because exposure of other organs can be minimized if low doses of topical estrogens are used. Absorption rates with topical therapy increase with treatment duration because of the enhanced vascularity of the epithelium.
• Vaginal estrogen therapy available in the United States are conjugated estrogens cream (0.625 mg conjugated estrogens/g, 0.5 g of cream intravaginally twice weekly) and estradiol cream (100 mcg estradiol/g of cream, 2 to 4 g of cream intravaginally administered daily for 2 weeks, then decreased to 1 g of cream 1 to 3 times per week), tablet (10 mcg estradiol/tablet intravaginally daily for 2 weeks then twice weekly), and ring (0.5 mcg estradiol/day, released over 90 days). In Europe and some other countries, estriol cream is also available.
• Vaginal estrogen therapy results in some estrogen absorption into the circulation, although to a lesser degree than oral or transdermal estrogen treatment. In one study, systemic absorption was 30% lower in a study of vaginal versus conjugated estrogen therapy.10 SOR B
• Progestin therapy is probably not necessary to protect against endometrial hyperplasia in women treated with the low-dose ring or intravaginal tablet when used as approved. The systemic estrogen absorption with use of the vaginal creams is difficult to quantify, so some experts recommend use of an opposing progestin for women treated with vaginal estrogen cream.11 SOR C

• Follow-up is needed for all patients placed on estrogen therapy to monitor for estrogen-related side effects. Otherwise, follow-up can be as needed.

• Discuss the risks and benefits of estrogen replacement therapy with patients interested in the use of estrogens. Vaginal lubricants (nonprescription) may safely help prevent pain during intercourse.

Patient Resources

• NCBI. Atrophic Vaginitis—www.ncbi.nlm.nih.gov.
• MedlinePlus. Atrophic Vaginitis—www.nlm.nih.gov/medlineplus/ency/article/000892.htm.
• Harvard Medical School. Atrophic Vaginitis—www.health.harvard.edu/fhg/updates/update0703c.shtml.

Provider Resources

• eMedicine. Vaginitis—http://emedicine.medscape.com/article/257141.
• eMedicine. Vulvovaginitis in Emergency Medicine—http://emedicine.medscape.com/article/797497.
• Bachmann GA, Nevadunsky NS. Diagnosis and treatment of atrophic vaginitis. Am Fam Physician. 2000;61(10):3090-3096.—http://www.aafp.org/afp/2000/0515/p3090.html.
• American Family Physician—http://www.aafp.org/afp/20000515/3090.html.

A 31-year-old woman presents with a malodorous vaginal discharge for 3 weeks. There is no associated vaginal itching or pain. She is married and monogamous. She admits to douching about once per month to prevent odor but it is not working this time. On examination, her discharge is visible (Figure 82-1). It is thin and off-white. Wet prep examination shows that more than 50% of the epithelial cells are clue cells (Figure 82-2). The patient is treated with oral metronidazole 500 mg bid for 7 days with good results.

Bacterial vaginosis (BV) is a clinical syndrome resulting from alteration of the vaginal ecosystem. It is called a vaginosis, not a vaginitis, because the tissues themselves are not actually infected, but only have superficial involvement. Women with BV are at increased risk for the acquisition of HIV, Neisseria gonorrhoeae, Chlamydia trachomatis, and herpes simplex virus (HSV)-2, and they have increased risk of complications after gynecologic surgery.1

BV is associated with adverse pregnancy outcomes, including premature rupture of membranes, preterm labor, preterm birth, intraamniotic infection, and postpartum endometritis. However, the only established benefit of BV therapy in pregnant women is the reduction of symptoms and signs of vaginal infection.1

• Vaginal bacteriosis.
• Corynebacterium vaginosis/vaginalis/vaginitis.
• Gardnerella vaginalis/vaginosis.
• Haemophilus vaginalis/vaginitis.
• Nonspecific vaginitis.
• Anaerobic vaginosis.

• BV is estimated to be the most prevalent cause of vaginal discharge or malodor in women presenting for care in the United States. However, more than 50% of women with BV are asymptomatic.1 It accounts for more than 10 million outpatient visits per year.2 The worldwide prevalence is unknown.

• Hydrogen peroxide-producing Lactobacillus is the most common organism composing normal vaginal flora.1 In BV, normal vaginal lactobacilli are replaced by high concentrations of anaerobic bacteria such as Mobiluncus, Prevotella, Gardnerella, Bacteroides, and Mycoplasma species.1,2
• The hydrogen peroxide produced by the Lactobacillus may help in inhibiting the growth of atypical flora.
• The odor of BV is caused by the aromatic amines produced by the altered bacterial flora in the vagina. These aromatic amines include putrescine and cadaverine—aptly named to describe their foul odor.

• Multiple male or female partners.1,3
• A new sex partner.1
• Douching.4
• Lack of condom use.1
• Lack of vaginal lactobacilli.1
• Prior BV infection.1

Clinical Features

• Symptomatic patients present with an unpleasant, “fishy smelling” discharge that is more noticeable after coitus (the basic pH of seminal fluid is like doing the whiff test with KOH). There may be pruritus but not as often as seen with Candida vaginitis. The physical examination should include inspection of the external genitalia for irritation or discharge. Speculum examination is done to determine the amount and character of the discharge. A nucleic acid amplification test for N. gonorrhoeae, Chlamydia, and/or C. trachomatis (or similar test) should be performed on genital specimens (urethral or cervical) or urine.
• BV is usually clinically diagnosed by finding three of the following four signs and symptoms:
  • Homogeneous, thin, white discharge that smoothly coats the vaginal walls (Figure 82-3 and 82-4).
  • Presence of clue cells on microscopic examination (Figure 82-2).
  • pH of vaginal fluid >4.5.
  • A fishy odor of vaginal discharge before or after addition of 10% KOH (i.e., the whiff test).1

Laboratory Testing

• Vaginal pH testing can be very helpful in the diagnosis of vaginitis. The normal vaginal pH is usually 3.5 to 4.5. A pH above 4.5 is seen with menopausal patients, Trichomonas infection, or BV. A small piece of pH paper is touched to the vaginal discharge during the exam or on the speculum. Do not test a wet-prep sample if saline has been added because the saline alters the pH.
• Wet preps are obtained using a cotton-tipped applicator applied to the vaginal sidewall, placing the sample of discharge into normal saline (not water). Observe for clue cells, number of white blood cells, trichomonads, and candidal hyphae. Clue cells are squamous epithelial cells whose borders are obscured by attached bacteria. More than 20% to 25% of epithelial cells seen in BV should be clue cells (Figure 82-2).
• A proline aminopeptidase test card (Pip Activity Test Card), a DNA probe-based test for high concentrations of G. vaginalis (Affirm VP III), and the OSOM BVBLUE test have shown acceptable performance characteristics compared with Gram stain (gold standard).1 However, they are more costly than traditional testing without clear advantages.
• Although a test card is available for the detection of elevated pH and trimethylamine, it has low sensitivity and specificity and is not recommended by the Centers for Disease Control and Prevention (CDC).1
• Culture of G. vaginalis is not recommended as a diagnostic tool because it is not specific.
• Pap tests are not useful for the diagnosis of BV because of their low sensitivity.1

• Trichomonas also may have the odor of aromatic amines and, therefore, easily confused with BV at first glance. Look for the strawberry cervix on examination and moving trichomonads on the wet prep (Chapter 84, Trichomonas Vaginitis).
• Candida vaginitis tends to present with a cottage-cheese-like discharge and vaginal itching (Chapter 83, Candida Vulvovaginitis).
• Gonorrhea and chlamydia should not be missed in patients with vaginal discharge. Consider testing for these sexually transmitted diseases (STDs) based on patients' risk factors and the presence of purulence clinically and white blood cells on the wet prep (Chapter 85, Chlamydia Cervicitis).

• Treatment is recommended for women with symptoms.
• Treatment of male sex partners has not been beneficial in preventing the recurrence of BV.1 SOR A

Medications

• The established benefits of therapy for BV in nonpregnant women are to (a) relieve vaginal symptoms and signs of infection and (b) reduce the risk for infectious complications after abortion or hysterectomy.1 SOR A Other potential benefits might include a reduction in risk for other sexually transmitted infections (STIs).1 SOR B  Table 82-1 shows CDC recommended treatments.
• Metronidazole 2 g single-dose therapy has the lowest efficacy for BV and is no longer a recommended or alternative regimen. Clindamycin cream is oil-based and might weaken latex condoms and diaphragms for 5 days after use. Topical clindamycin preparations should not be used in the second half of pregnancy.1 Multiple studies and metaanalyses have not demonstrated an association between metronidazole use during pregnancy and teratogenic or mutagenic effects in newborns.1 SOR A
• The only established benefit of therapy for BV in pregnant women is to relieve vaginal symptoms and signs of infection.1 SOR A Additional potential benefits of therapy include (a) reducing the risk for infectious complications associated with BV during pregnancy and (b) reducing the risk for other infections (e.g., other STDs or HIV). Multiple studies and metaanalyses have not demonstrated an association between metronidazole use during pregnancy and teratogenic or mutagenic effects in newborns.5
• One randomized trial for persistent BV indicated that metronidazole gel 0.75% twice per week for 6 months after completion of a recommended regimen was effective in maintaining a clinical cure for 6 months.6 SOR B
• Limited data suggest that oral nitroimidazole followed by intravaginal boric acid and suppressive metronidazole gel for those women in remission might be an option in women with recurrent BV. SOR B7
• Intravaginal clindamycin cream has been associated with adverse outcomes if used in the latter half of pregnancy.1

Complementary and Alternative Therapy

• Extended ingestion of live culture, nonpasteurized yogurt may theoretically increase colonization by lactobacilli and decrease the episodes of BV.8 SOR C However, health food store lactobacilli are the wrong strain and are not well-retained by the vagina.
• The efficacy of exogenous lactobacillus recolonization with probiotic lactobacilli vaginal gelatin capsules has been reported in two small trials.9,10

• Avoidance of risk factors is recommended, although asymptomatic BV is common.
• The evidence is insufficient to assess the impact of screening for BV in pregnant women at high risk for preterm delivery.1

• Follow-up visits are unnecessary in nonpregnant women if symptoms resolve.1
• Treatment of BV in asymptomatic pregnant women who are at high risk for preterm delivery might prevent adverse pregnancy outcomes. Therefore, a follow-up evaluation 1 month after completion of treatment should be considered to evaluate whether therapy was effective.1 SOR C
• If symptoms do recur, consider a treatment regimen different from the original regimen to treat recurrent disease.1 SOR C

• Avoid consuming alcohol during treatment with metronidazole and for 24 hours thereafter. Women should be advised to return for additional therapy if symptoms recur because recurrence of BV is not unusual.

Patient Resources

• Centers for Disease Control and Prevention. Bacterial Vaginosis Fact Sheet—http://www.cdc.gov/std/BV/STDFact-Bacterial-Vaginosis.htm.
• Family Doctor.org from the AAFP—http://familydoctor.org/234.xml.
• MedicineNet.com—http://www.medicinenet.com/bacterial_vaginosis/article.htm.

Provider Resources

• Centers for Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases—http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf.

A 35-year-old woman presents with severe vaginal and vulvar itching. She also complains of a thick white discharge. Figure 83-1 demonstrates the appearance of her vagina and vulva while Figure 83-2 shows her cervix. Figure 83-3 shows her wet prep. Treatment with a nonprescription intravaginal antifungal preparation was successful.

Vulvovaginal candidiasis (VVC) is a common fungal infection in women of childbearing age. Pruritus is accompanied by a thick, odorless, white vaginal discharge. VVC is not a sexually transmitted disease. On the basis of clinical presentation, microbiology, host factors, and response to therapy, VVC can be classified as either uncomplicated or complicated.1 Uncomplicated VVC is characterized by sporadic or infrequent symptoms, mild-to-moderate symptoms, and the patient is nonimmunocompromised. Complicated VVC is characterized by recurrent (four or more episodes in 1 year) or severe VVC, non-albicans candidiasis, or the patient has uncontrolled diabetes, debilitation, or immunosuppression.1

Yeast vaginitis, yeast infection, candidiasis, moniliasis.

• VVC accounts for approximately one third of vaginitis cases.1
• Candida species are part of the lower genital tract flora in 20% to 50% of healthy asymptomatic women.2
• Seventy-five percent of all women in the United States will experience at least one episode of VVC. Of these, 40% to 45% will have two or more episodes within their lifetime.3 Approximately 10% to 20% of women will have complicated VVC that necessitates diagnostic and therapeutic considerations.
• It is a frequent iatrogenic complication of antibiotic treatment, secondary to altered vaginal flora.
• Nearly half of all women experience multiple episodes, and up to 5% experience recurrent disease.1
• Recurrent vulvovaginal candidiasis (RVVC) is defined as four or more episodes of symptomatic VVC in 1 year. It affects a small percentage of women (<5%).4 Recurrent yeast vaginitis is usually caused by relapse, and less often by reinfection. Recurrent infection may be caused by Candida recolonization of the vagina from the rectum.5

• Most vulvovaginal Candidiasis is caused by Candida albicans (Figure 83-3).1,6 Candida glabrata now causes a significant percentage of all Candida vulvovaginal infections. This organism is resistant to the nonprescription imidazole creams. It can mutate out of the activity of treatment drugs much faster than albicans species.7
• The disease is suggested by pruritus in the vulvar area, together with erythema of the vagina and vulva (Figures 83-1 and 83-2). The familiar reddening of the vulvar tissues is caused by an ethanol by-product of the Candida infection. This ethanol compound also produces pruritic symptoms. A scalloped edge with satellite lesions is characteristic of the erythema on the vulva.
• VVC can occur concomitantly with sexually transmitted diseases (STDs).
• The pathogenesis of recurrent VVC is poorly understood, and most women with these recurrences have no apparent predisposing or underlying conditions.1

• Diabetes mellitus.8,9
• Recent antibiotic use.
• Increased estrogen levels.
• Immunosuppression.
• Contraceptive devices (vaginal sponges, diaphragms, and intrauterine devices).
• Genetic susceptibility.
• Behavioral factors—VVC may be linked to orogenital and, less commonly, anogenital sex.
• Wearing diapers.
• Spermicides are not associated with Candida infection.
• There is no high-quality evidence showing a link between VVC and hygienic habits or wearing tight or synthetic clothing.

Clinical Features

• The diagnosis is usually suspected by characteristic findings (Figures 83-1 and 83-2). Typical symptoms include pruritus, vaginal soreness, dyspareunia, and external dysuria. Typical signs include vulvar edema, fissures, excoriations, or thick, curdy vaginal discharge.1

Laboratory Testing (Include Ancillary Testing Too)

• Vaginitis solely caused by Candida generally has a normal vaginal pH of less than 4.5.
• The wet prep, KOH smear, or Gram stain may demonstrate yeast and/or pseudohyphae (Figures 83-3 and 83-4). Wet preps may also demonstrate white blood cells, trichomonads, candidal hyphae, or clue cells.
• 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 to 15 minutes (faster if the slide is warmed) and allows easier visualization of candidal hyphae or yeast.1 Swartz-Lamkins stain (potassium hydroxide, a surfactant, and blue dye) may facilitate diagnosis by staining the yeast organisms a light blue.10
• Rapid antigen testing is also available for Candida. The detection of vaginal yeast by rapid antigen testing is feasible for office practice and more sensitive than wet mount. A negative test result, however, was not found to be sensitive enough to rule out yeast and avoid a culture.6 SOR A
• Fungal culture with Sabouraud agar, Nickerson medium, or Microstix-Candida medium should be considered in patients with symptoms and a negative KOH because C. glabrata does not form pseudohyphae or hyphae and is not easily recognized on microscopy. If the wet mount is negative and Candida cultures cannot be done, empiric treatment can be considered for symptomatic women with any sign of VVC on examination.1 SOR C Asymptomatic women should not be cultured as 10% to 20% of women harbor Candida sp. and other yeasts in the vagina.1 SOR A
• Vaginal cultures should be obtained from patients with RVVC to confirm the clinical diagnosis and to identify unusual species, including non-albicans species, particularly C. glabrata (C. glabrata does not form pseudohyphae or hyphae and is not easily recognized on microscopy).1 SOR B C. glabrata and other non-albicans Candida species are observed in 10% to 20% of patients with RVVC.1
• Given the frequency at which RVVC occurs in the immunocompetent healthy population, the occurrence of RVVC alone should not be considered an indication for HIV testing.1 SOR C

• Trichomoniasis can be confused with candidiasis because patients may report itching and a discharge in both diagnoses. Look for the strawberry cervix on examination and moving trichomonads on the wet prep (Chapter 84, Trichomonas Vaginitis).
• Bacterial vaginosis can be confused with candidiasis because patients may report a discharge and an odor in both diagnoses. The odor is usually much worse in bacterial vaginosis and the quality of the discharge can be different. The wet prep should allow for differentiation between these two infections (Chapter 82, Bacterial Vaginosis).
• Gonorrhea and Chlamydia should not be missed in patients with vaginal discharge. Consider testing for these STDs based on patients' risk factors and the presence of purulence clinically and white blood cells on the wet prep (Chapter 85, Chlamydia Cervicitis).
• Cytolytic vaginosis, or Döderlein cytolysis, can be confused with candidiasis. Cytolytic vaginosis is produced by a massive desquamation of epithelial cells related to excess lactobacilli in the vagina. The signs and symptoms are similar to Candida vaginitis, except no yeast are found on wet prep. The wet prep will show an overgrowth of lactobacilli. The treatment is to discontinue all antifungals and other agents or procedures that alter the vaginal flora.

Nonpharmacologic

• VVC is not usually acquired through sexual intercourse; treatment of sex partners is not recommended but may be considered in women who have recurrent infection. Some male sex partners might have balanitis (Chapter 136, Candidiasis) and might benefit from treatment.1 SOR A
• Any woman whose symptoms persist after using a nonprescription preparation or who has a recurrence of symptoms within 2 months should be evaluated with office-based testing as they are not necessarily more capable of diagnosing themselves even with prior diagnosed episodes of VVC and delay in the treatment of other vulvovaginitis etiologies can result in adverse clinical outcomes.1 SOR A

Medications

• Women with typical symptoms and a positive test result should receive treatment. Short-courses of topical formulations effectively treat uncomplicated VVC (Table 83-1).1 SOR A Topical azole drugs are more effective than nystatin, and result in clinical cure and negative cultures in 80% to 90% of patients who complete therapy. SOR A The creams and suppositories in Table 83-1 are oil-based and might weaken latex condoms and diaphragms.1
• The cure rates with single-dose oral fluconazole and all the intravaginal treatments are equal.11 Fluconazole (Diflucan) 150-mg single dose has become very popular, but may have clinical cure rates of approximately only 70%. SOR A Systemic allergic reactions are possible with the oral agents.
• The oral agents fluconazole, ketoconazole, and itraconazole also appear to be effective.1 SOR B
• VVC frequently occurs during pregnancy. Only topical azole therapies, applied for 7 days, are recommended for use among pregnant women.1 SOR C
• The optimal treatment of non-albicans VVC remains unknown. Options include longer duration of therapy (7 to 14 days) with topical therapy or a 100-mg, 150-mg, or 200-mg oral dose of fluconazole every third day for a total of 3 doses.1 SOR C
• Severe VVC (i.e., extensive vulvar erythema, edema, excoriation, and fissure formation) is associated with lower clinical response rates in patients treated with short courses of topical or oral therapy. Either 7 to 14 days of topical azole or 150 mg of fluconazole in two sequential doses (second dose 72 hours after initial dose) is recommended.1 SOR C

Complementary and Alternative Therapy

• If recurrence VVC occurs, 600 mg of boric acid in a gelatin capsule is recommended, administered vaginally once daily for 2 weeks. This regimen has clinical and mycologic eradication rates of approximately 70%.1 SOR B
• Lactobacillus acidophilus does not adhere well to the vaginal epithelium, and it does not significantly change the incidence of candidal vulvovaginitis.5,12
• There is no evidence from randomized trials that other complementary and alternative (CAM) therapies, such as garlic, tea tree oil, yogurt, or douching, are effective for the treatment or prevention of VVC caused by C. albicans.13,14

Maintenance Regimens

• Oral fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months is the first line of treatment. If this regimen is not feasible, some specialists recommend topical clotrimazole 200 mg twice a week, clotrimazole (500-mg dose vaginal suppositories once weekly), or other topical treatments used intermittently.1 SOR C
• Suppressive maintenance antifungal therapies are effective in reducing RVVC.1 SOR A However, 30% to 50% of women will have recurrent disease after maintenance therapy is discontinued. Routine treatment of sex partners is controversial. C. albicans azole resistance is rare in vaginal isolates, and susceptibility testing is usually not warranted for individual treatment guidance.

• Women with underlying debilitating medical conditions (e.g., those with uncontrolled diabetes or those receiving corticosteroid treatments) do not respond as well to short-term therapies. Efforts to correct modifiable conditions should be made, and more prolonged (i.e., 7 to 14 days) conventional antimycotic treatment is necessary.1 SOR C
• Symptomatic VVC is more frequent in HIV-seropositive women and correlates with severity of immunodeficiency. In addition, among HIV-infected women, systemic azole exposure is associated with the isolation of non-C. albicans species from the vagina. According to the available data, therapy for VVC in HIV-infected women should not differ from that for seronegative women.1 SOR C

• Patients should be instructed to return for follow-up visits only if symptoms persist or recur within 2 months of onset of initial symptoms.1

• Studies show that women who were previously diagnosed with VVC are not necessarily more likely to be able to diagnose themselves.1 Any woman whose symptoms persist after using an nonprescription preparation, or who has a recurrence of symptoms within 2 months, should be evaluated with office-based testing. Explain that unnecessary or inappropriate use of nonprescription preparations can lead to a delay in the treatment of other vulvovaginitis etiologies, which can result in adverse clinical outcomes.1

Patient Resources

• FamilyDoctor.org from AAFP. Yeast Infections—http://familydoctor.org/online/famdocen/home/women/reproductive/vaginal/206.htm.
• MedicineNet. Vaginal Yeast Infection (Yeast Vaginitis)—http://www.medicinenet.com/yeast_vaginitis/article.htm.
• WebMD. Vaginal Yeast Infections—http://women.webmd.com/tc/vaginal-yeast-infections-topic-overview.
• Womenshealth.gov. Vaginal Yeast Infections Fact Sheet—http://www.womenshealth.gov/publications/our-publications/fact-sheet/vaginal-yeast-infections.cfm.
• MedLinePlus. Yeast Infections—http://www.nlm.nih.gov/medlineplus/yeastinfections.html.
• eMedicine Health. Candidiasis—http://www.emedicinehealth.com/candidiasis_yeast_infection/article_em.htm.

Provider Resources

• Centers for Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases—http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf.
• American Family Physician. Management of vaginitis. Am Fam Physician. 2004;70:112125-2132.—http://www.aafp.org/afp/20041201/2125.html.
• eMedicine. Candidiasis—http://emedicine.medscape.com/article/213853-overview.
• eMedicine. Vulvovaginitis in Emergency Medicine—http://emedicine.medscape.com/article/797497-overview.

A 27-year-old woman presents with a vaginal itching, odor, and discharge for 1 week. She has one partner who is asymptomatic. Speculum examination shows a strawberry cervix seen with Trichomonas infections (Figure 84-1). This strawberry pattern is caused by inflammation and punctate hemorrhages on the cervix. There is a scant white discharge with a fishy odor. Wet mount shows trichomonads swimming in saline (Figures 84-2 and 84-3). The trichomonads are larger than white blood cells (WBCs) and have visible flagella and movement. She is diagnosed with trichomoniasis and treated with 2 g of metronidazole in a single dose. The patient is tested for other sexually transmitted diseases (STDs) and her partner is treated with the same regimen.

Trichomonas vaginitis is a local infection caused by the protozoan Trichomonas vaginalis that is associated with vaginal discharge. The woman often has an itch and an odor along with the discharge but may be asymptomatic.

Trichomoniasis, trich, tricky monkeys.

• An estimated 3 to 5 million cases of trichomoniasis occur each year in the United States.1
• The worldwide prevalence of trichomoniasis is estimated to be 180 million cases per year; and these cases account for 10% to 25% of all vaginal infections.2

• Trichomonas infection is caused by the unicellular protozoan T. vaginalis.3
• The majority of men (90%) infected with T. vaginalis are asymptomatic, but many women (50%) report symptoms.4
• The infection is predominantly transmitted via sexual contact. The organism can survive up to 48 hours at 10°C (50°F) outside the body, making transmission from shared undergarments or from infected hot spas possible although extremely unlikely.
• Trichomonas infection is associated with low-birth-weight infants, premature rupture of membranes, and preterm delivery in pregnant patients.5
• In a person coinfected 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 two-fold.6

• New or multiple partners.3
• A history of STDs.
• Exchanging sex for payment or drugs.
• Injection drug use.

Clinical Features

• The physical examination should include inspection of the external genitalia for irritation or discharge. Speculum examination is done to determine the amount and character of the discharge and to look for the characteristic strawberry cervix (Figures 84-1 and 84-4).
• Typically, women with trichomoniasis have a diffuse, malodorous, yellow-green discharge (Figure 84-5) with vulvar irritation.3 Vaginal and vulvar itching and irritation are common.
• It should be determined whether the patient douched recently, because this can lower the yield of diagnostic tests. Patients who have been told not to douche will sometimes start wiping the vagina with soapy washcloths to “keep clean” as an alternative. This greatly irritates the vagina and cervix, lowers test sensitivity, and may cause a discharge.

Typical Distribution

• In women, Trichomonas vaginalis may be found in the vagina, urethra, and paraurethral glands of infected women. Other sites include the cervix and Bartholin and Skene glands.

Laboratory Testing

• Because of the high prevalence of trichomoniasis, testing should be performed in women seeking care for vaginal discharge. Screening should be considered for women with risk factors.3
• Wet preps are obtained using a 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 coverslip, and carefully examined with the low-power and high-dry objective lenses. Under the microscope, observe for motile trichomonads, which are often easy to visualize because of their lashing flagella (Figure 84-2).
• Wet prep has a sensitivity of only approximately 60% to 70% and requires immediate evaluation of wet preparation slide for optimal results.3
• The OSOM Trichomonas Rapid Test and the Affirm VP III are FDA-cleared for trichomoniasis in women. Both tests are performed on vaginal secretions at the point of care and have a sensitivity greater than 83% and a specificity greater than 97%. The results of the OSOM Trichomonas Rapid Test are available in approximately 10 minutes, and results of the Affirm VP III are available within 45 minutes. False-positive tests might occur, especially in populations with a low prevalence of disease.3
• An FDA-approved polymerase chain reaction (PCR) assay for detection of gonorrhea and chlamydial infection (Amplicor, manufactured by Roche Diagnostic Corp.) has been modified to test for T. vaginalis in vaginal or endocervical swabs and in urine from women and men, with sensitivity ranges from 88% to 97% and specificity from 98% to 99%.7
• APTIMA T. vaginalis Analyte Specific Reagents (ASR; manufactured by Gen-Probe, Inc.) also can detect T. vaginalis RNA using the same instrumentation platforms available for the FDA-cleared APTIMA Combo2 assay for diagnosis of gonorrhea and chlamydial infection. Published validation studies found sensitivity ranging from 74% to 98% and specificity from 87% to 98%.8
• A vaginal pH above 4.5 is seen with menopausal patients, Trichomonas infection, or bacterial vaginosis.4
• Culture is a sensitive and highly specific method of diagnosis. In women in whom trichomoniasis is suspected but not confirmed by microscopy, vaginal secretions should be cultured for T. vaginalis.3
• A nucleic acid amplification test for Neisseria gonorrhoeae, and/or Chlamydia trachomatis should be performed on all patients with Trichomonas.

• Bacterial vaginosis and Trichomonas may have the odor of aromatic amines, and therefore may easily be confused with each other. Look for clue cells and trichomonads on the wet prep to differentiate between the two (Chapter 82, Bacterial Vaginosis).
• Candida vaginitis tends to present with a cottage-cheese-like discharge and vaginal itching (Chapter 83, Candida Vaginitis).
• Gonorrhea and Chlamydia and should not be missed in patients with vaginal discharge. Consider testing for these STDs based on patients' risk factors and the presence of purulence clinically and WBCs on the wet prep (Chapter 85, Chlamydia Cervicitis).

Medications

• Table 84-1 shows treatments for T. vaginalis infections. Metronidazole 2 g orally as a single dose, or 500 mg bid for 7 days (including pregnant patients) are the best treatments by Cochrane analysis.9 SOR A
• Tinidazole (Tindamax), a second-generation nitroimidazole, is indicated as a one-time dose of 2 g for the treatment of trichomoniasis (including metronidazole-resistant trichomoniasis).3 SOR A It is effective therapy in nonresistant and resistant T. vaginalis.10,11 The contraindications (including ethyl alcohol [ETOH]) to the use of tinidazole are similar to those for metronidazole.
• Pregnant women may be treated with 2 g of metronidazole in a single dose. Metronidazole is pregnancy category B. Vaginal trichomoniasis is associated with adverse pregnancy outcomes, particularly premature rupture of membranes, preterm delivery, and low birth weight. Unfortunately, data do not suggest that metronidazole treatment results in a reduction in perinatal morbidity and treatment may even increase prematurity or low birth weight.3 Treatment of T. vaginalis might relieve symptoms of vaginal discharge in pregnant women and might prevent respiratory or genital infection of the newborn and further sexual transmission. The Centers for Disease Control and Prevention (CDC) recommends that clinicians counsel patients regarding the potential risks and benefits of treatment during pregnancy.3
• Some strains of T. vaginalis can have diminished susceptibility to metronidazole. Low-level metronidazole resistance has been identified in 2% to 5% of cases of vaginal trichomoniasis. These infections should respond to tinidazole or higher doses or longer durations of metronidazole. High-level resistance is rare.
• Metronidazole gel is 50% less efficacious for the treatment of trichomoniasis than oral preparations and is not recommended.3

• Patients should be instructed to avoid sex until they and their sex partners are cured (i.e., when therapy has been completed and patient and partner[s] are asymptomatic).3
• Spermicidal agents such as nonoxynol-9 reduce the rate of transmission of Trichomonas.12
• The risk of acquiring infection can be reduced by consistent use of condoms and limiting the number of sexual partners.

• Because of the high rate of reinfection among patients in whom trichomoniasis was diagnosed, rescreening at 3 months following initial infection can be considered for sexually active women.3

• Sexual partners of patients with Trichomonas should be treated. Patients can be sent home with a dose for a partner when it is believed that the partner will not come in on his own.

Patient Resources

• Centers for Disease Control and Prevention information—http://www.dpd.cdc.gov/dpdx/HTML/Trichomoniasis.htm.
• Medline-plus—http://www.nlm.nih.gov/medlineplus/ency/article/001331.htm.
• Centers for Disease Control and Prevention. STDs:Trichomoniasis— http://www.cdc.gov/std/trichomonas/default.htm.
• PubMed Health. Trichomoniasis—http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002307/.
• MedLinePlus. Trichomoniasis—http://www.nlm.nih.gov/medlineplus/trichomoniasis.html.
• eMedicine Health. Trichomoniasis—http://www.emedicinehealth.com/trichomoniasis/article_em.htm.

Provider Resources

• http://emedicine.medscape.com/article/230617.
• Trichomoniasis in Emergency Medicine—http://emedicine.medscape.com/article/787722.
• Centers for Disease Control and Prevention. 2010 Guidelinesfor Treatment of Sexually Transmitted Diseases—http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf.

A 17-year-old girl presents to the sexually transmitted disease (STD) clinic because her boyfriend was diagnosed with a Chlamydia urethritis. Both she and her boyfriend admit to having had sexual partners in the past before starting to be sexually active with each other. On physical examination, there is ectopy and some mucoid discharge (Figure 85-1). The cervix bled easily while obtaining discharge and cells for a wet mount and genetic probe test. The wet mount showed many white blood cells (WBCs) but no visible pathogens. The patient was treated with 1 g of azithromycin taken in front of a clinic nurse. She was sent to the laboratory for rapid plasma reagin (RPR) and HIV tests and given a follow-up appointment in 1 week. The genetic probe test was positive for Chlamydia and all the other examinations were negative. This information was given to the patient on her return visit and safe sex was discussed.

Chlamydia trachomatis causes genital infections that can result in pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. Asymptomatic infection is common among both men and women so healthcare providers must rely on screening tests to detect disease. The Centers for Disease Control and Prevention (CDC) recommends annual screening of all sexually active women ages 25 years and younger, and of older women with risk factors, such as having a new sex partner or multiple sex partners.1

• A very common STD, Chlamydia is the most frequently reported infectious disease in the United States (excluding human papillomavirus [HPV]).1 An estimated 1.2 million cases are reported to the CDC annually in the United States.2
• The World Health Organization (WHO) estimates there are 140 million cases of Chlamydia trachomatis infection worldwide every year.3
• 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.4
• It is common among sexually active adolescents and young adults.5 As many as 1 in 10 adolescent girls tested for Chlamydia is infected. Based on reports to the 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%.4

• C. trachomatis is a small Gram-negative bacterium with unique biologic properties among living organisms. Chlamydia is an obligate intracellular parasite that has a distinct life-cycle consisting of two major phases: The small elementary bodies attach and penetrate into cells, and the metabolically active reticulate bodies that form large inclusions within cells.
• It has a long growth cycle, which explains why extended courses of treatment are often necessary. Immunity to infection is not long-lived, so reinfection or persistent infection is common.
• 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% to 16% develop pneumonia.1
• Chlamydia infections may lead to reactive arthritis, which presents with arthritis, conjunctivitis, and urethritis (Chapter 155, Reactive Arthritis). Past or ongoing C. trachomatis infection may be a risk factor for ovarian cancer.6,7
• 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.4

• Adolescents and young adults.1,2,8
• Nonwhite populations.
• Multiple sexual partners.
• Poor socioeconomic conditions.
• Single marital status.
• Nonbarrier contraceptive use.
• History of prior STD.

Clinical Features

• The cervix is inflamed, friable, and may bleed easily with manipulation. The cervix may show ectopy (columnar cells on the ectocervix). The discharge is usually mucoid or mucopurulent (Figure 85-1).
• Swab test—A white cotton-tip applicator is placed in the endocervical canal and removed to view. A visible mucopurulent discharge constitutes a positive swab test for Chlamydia (Figure 85-2). This is not specific for Chlamydia as other genital infections can cause a mucopurulent discharge, and is not recommended for diagnosis.

Laboratory Testing

• A significant proportion of patients with Chlamydia are asymptomatic, providing a reservoir for infection. All pregnant women and sexually active women younger than 25 years of age should be screened with routine examinations. A wet prep is usually negative for other organisms. Only WBCs and normal flora are seen.
• Chlamydia cannot be cultured on artificial media because it is an obligate intracellular organism. Tissue culture is required to grow the live organism. When testing for Chlamydia, a wood-handled swab must not be used, as 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.1
• The enzyme-linked immunosorbent assay (ELISA) technique (Chlamydiazyme) has a sensitivity of 70% to 100% and a specificity of 97% to 99%.5 Fluorescein-conjugated monoclonal antibodies test (MicroTrak) has a sensitivity of 70% to 100% and a specificity of 97% to 99%.5
• C. trachomatis can be detected using nucleic acid amplification techniques (NAATs) on swabs or voided urine specimens. These tests are often used for testing to detect gonorrhea and Chlamydia. Nucleic acid amplification tests have been used successfully in difficult-to-reach adolescents (“street kids”) as well as in pediatric emergency departments and school-based settings.9,10 Screening in school-based settings was associated with significant reduction in Chlamydia rates during a 1-year period. Self-collected vaginal swab specimens perform at least as well as with other approved specimens using NAATs.11
• Rectal and oropharyngeal C. trachomatis infection in persons engaging in anal or oral intercourse can be diagnosed by testing at the site of exposure. Although not FDA-cleared for this use, NAATs have demonstrated improved sensitivity and specificity compared with culture for the detection at rectal sites12 and at oropharyngeal sites in men.13
• Certain NAATs have been FDA-cleared for use on liquid-based cytology specimens, although test sensitivity using these specimens might be lower.14
• Persons who undergo testing for Chlamydia should be tested for other STDs as well.1

• Gonorrhea frequently coexists with Chlamydia and should be tested for when a patient is thought to have Chlamydia. The discharge of gonorrhea may be more purulent but this is not always the case (Chapter 215, Gonococcal Urethritis)
• Bacterial vaginosis—The aromatic amine odor and clue cells help to distinguish between these infections (Chapter 82, Bacterial Vaginosis).
• Trichomoniasis—Look for the strawberry cervix and Trichomonas on the wet prep. There may also be a positive whiff test (see Chapter 84, Trichomonas Vaginitis).

Nonpharmacologic

• Patients diagnosed with Chlamydia cervicitis should be tested for other STDs.1

Medications

• Table 85-1 shows CDC recommended treatments for Chlamydia. Azithromycin (Zithromax) 1000 mg one-time dose is easy and may be directly observed in the clinic.1 SOR A It is the first-line therapy for Chlamydia during pregnancy.
• Other treatments include doxycycline 100 mg PO bid × 7 days.1 SOR A Avoid dairy products around time of dosing.
• Erythromycin might be less efficacious than either azithromycin or doxycycline, mainly because of the frequent occurrence of GI side effects that can lead to nonadherence.
• Ofloxacin (Floxin) 300 mg po bid × 7 days is an alternative that should be taken on an empty stomach.1 SOR A It is contraindicated in children or pregnant and lactating women, but may also cover Neisseria gonorrhoeae infection. Levofloxacin 500 mg orally for 7 days is another fluoroquinolone alternative.1 SOR A
• A metaanalysis of 12 randomized clinical trials of azithromycin versus doxycycline for the treatment of genital chlamydial infection demonstrated that the treatments were equally efficacious, with microbial cure rates of 97% and 98%, respectively.15
• Partners need treatment. If concerns exist that sex partners will not seek evaluation and treatment, then delivery of antibiotic therapy (either a prescription or medication) to their partners is an option.1
• Medications for chlamydial infections should be dispensed on site and the first dose directly observed to maximize medication adherence.1

Referral or Hospitalization

• With evidence of complications such as a tuboovarian abscess or severe PID.

• Individuals who are sexually active should be aware of the risk of STDs and that ways of avoiding infection include mutual monogamy and appropriate barrier protection.

• Treatment failures with full primary therapies are quite rare. Reinfection is very common and is related to nontreatment of sexual partners or acquisition from a new partner.

• Test-of-cure (repeat testing 3 to 4 weeks after completing therapy) is not recommended for persons treated with the recommended or alterative regimens, unless therapeutic compliance is in question, symptoms persist, or reinfection is suspected. However, test of cure is recommended in pregnant women.1

• To minimize transmission, persons treated for Chlamydia should be instructed to abstain from sexual intercourse for 7 days after single-dose therapy or until completion of a 7-day regimen.
• To minimize the risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all of their sex partners are treated.1

Patient Resources

• eMedicine Health. Cervicitis—http://www.emedicinehealth.com/cervicitis/article_em.htm.
• eMedicine Health. Chlamydia—http://www.emedicinehealth.com/chlamydia/article_em.htm.
• CDC patient information—http://www.cdc.gov/std/Chlamydia/STDFact-Chlamydia.htm.

Provider Resources

• CDC. Sexually Transmitted Diseases (STDs) 2010: Diseases Characterized by Urethritis and Cervicitis—http://www.cdc.gov/std/treatment/2010/urethritis-and-cervicitis.htm.
• Chlamydial Genitourinary Infections—http://emedicine.medscape.com/article/214823-overview.
• Cervicitis—http://emedicine.medscape.com/article/253402.