Symptoms caused by infections of the lower female genital tract are some of the most common gynecologic complaints. This section reviews infections of the vulva, parasitic infections, vaginitis, ulcerative lesions, and cervicitis.
Vulvar Infections
Human Papillomavirus
Human papillomavirus (HPV) is the most common STI in the US. The prevalence of an HPV genital infection is approximately 40% of US adults aged 18 to 59 years old and is highest among teens and young adults. There are over 120 different types of HPV, with approximately 40 types causing a lower genital infection. Most infections are transient and spontaneously resolve within 2 years of initial infection; however, the ability to clear the infection is inversely related to the patient's age.
There are two main types of HPV infections: oncogenic, high-risk HPV (eg, HPV-16, HPV-18), and nononcogenic, low-risk HPV (eg, HPV-6 and HPV-11). Persistent infection with the high-risk HPV is associated with cervical, vulvar, anal, and oropharyngeal squamous cell cancer and some adenocarcinomas. HPV 16 and 18 account for over 66% of cervical cancers in the US, and approximately 25% of the low-grade and 50% of high-grade cervical dysplasia. The low-risk HPV types HPV 6 and 11 are associated with 90% of condyloma acuminata (genital warts) and low-grade dysplasia. Risk factors for HPV infection include number of sexual partners, history of other STIs, smoking, immunodeficiency (eg, HIV infection), use of immunosuppressive medications (eg, chronic steroid use), or solid organ transplant recipient.
Clinical manifestations. Genital warts can be single or multiple and may be soft, sessile, verrucous, filiform, fleshy, flat, or raised lesions. Warts are typically asymptomatic but may be associated with itching, burning, bleeding, or pain.
Diagnosis.Genital warts are diagnosed based on physical examination. A biopsy should be considered if any lesions appear hyperpigmented, indurated, fixed, ulcerated, bleeding, or atypical, particularly if patient is postmenopausal. Also, biopsies are warranted if the patient does not respond to treatment nor has worsening symptoms despite treatment. Condyloma lata from secondary syphilis should be considered in the differential diagnosis, and serologic testing is recommended.
Treatment is indicated for cosmetic or symptomatic relief. Options for treatment include surgical excision, topical cytotoxic or keratolytic agents, immune modulators, and cytodestructive techniques (see Table 28-1). No single treatment modality has been proven to be most effective; therefore, treatment modality should be individualized. The choice of treatment depends on anatomic location, size, morphology, and number of lesions. Treatment cost, convenience, and treatment side effects are also considered.
| Therapy | Application | Use in Pregnancy |
|---|---|---|
| Patient Applied | ||
| Imiquimod 3.75% or 5% cream | Apply three times a week at bedtime for up to 16 wk. Wash area with soap and water 6–10 h after application. | Contraindicated |
| Podofilox 0.5% solution or gel | Apply BID for 3 d, no treatment for 4 d, repeat cycle up to four times. Do not exceed 0.5 mL volume per day. | Contraindicated |
| Sinecatechins 15% ointment | Apply three times daily for up to 16 wk. Do not use in immunosuppressed or those with genital herpes. | Contraindicated |
| Provider Administered | ||
| Topical trichloroacetic acid (80–90% solution) | Apply a small amount weekly until the wart sloughs off. Typical course is six treatments. Can be used to treat vaginal warts | Permitted |
| 5-Fluorouracil epinephrine gel | Intralesional injection weekly for up to 6 wk | Contraindicated |
| Interferons | Inject 0.5–1.5 million IU per lesion two to three times weekly for up to 3 wk. Requires local anesthesia. Can be used to treat vaginal warts. | Not recommended |
| Podophyllin resin at 25% in benzoin | Apply weekly for up to 6 wk. Do not exceed 0.5 mL volume per day | Contraindicated |
| Excisional procedure | Electrocautery or sharp excision | Only if obstructing vaginal delivery |
| Cryotherapy with liquid nitrogen or nitrous oxide | Can be repeated weekly until resolved | Permitted |
| CO2 laser or plasma energy ablation | May require special privileges and equipment. Can be used to treat vaginal warts. | Not recommended |
Lesions may spontaneously regress and recur, and many lesions will resolve within 3 months in immunocompetent patients. However, recurrence rates range from 30% to 70%, and a combination of treatment modalities may be required. Patients need to be counseled that treatment does not completely eradicate the virus, and that it remains unclear whether treatment reduces the risk of further transmission.
Complications from treatment with ablation or immune modulators include hypo- or hyperpigmentation of treated areas. Rarely, abnormal scarring or chronic pain can occur.
See Chapter 51 for discussion regarding vulvar intraepithelial neoplasm (VIN).
Prevention. A 9-valent HPV (9vHPV) prophylactic vaccine, known commercially as Gardasil 9, is protective against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and is available in the US. Over 90% of HPV-related cancers are caused by one of the seven oncogenic types covered in the 9vHPV vaccine. The HPV vaccine is recommended for patients 9 to 26 years, and permissible in adults aged 27 to 45 years. See Chapter 51 for further discussion about the HPV vaccine and HPV prevention.
Parasites
Pediculosis Pubis
Pthirus pubis (pubic lice) is an ectoparasite that infects the pubic, perineal, and perianal areas, but may also involve the eyelids and other body parts. The louse deposits eggs at the base of a hair follicle. The incubation period is 1 week, and the louse can live for up to 6 weeks with adequate blood supply from the host. Transmission occurs through sexual contact or shared bedding and clothing.
Clinical manifestations. Symptoms include intense pruritus at the site of infection, which may be accompanied by a maculopapular rash. If numerous lesions occur over a short period of time, systemic symptoms may be present, including fever, malaise, and myalgia.
Diagnosis is made by direct visualization of the lice, larvae, or nits in the pubic hair, or microscopic identification of the crablike louse under oil.
Scabies
Scabies is caused by the mite Sarcoptes scabiei var. Hominis and is highly contagious. It is transmitted via close contact and may infect any part of the body, especially flexural surfaces of the elbows, wrists, finger webs, axilla, breast, genitals, and buttocks. Fomite transmission is also possible through clothing, bedding, or towels. The adult female burrows beneath the skin, lays eggs, and travels quickly across the skin.
Clinical manifestations. Scabies often presents with insidious onset of severe intermittent pruritus approximately 3 to 6 weeks after the initial exposure. Subsequent infections can become symptomatic within 24 hours of reinfection. The intense pruritus may worsen at night and involve most of the body. The characteristic lesion is the burrow, a 1- to 10-mm curving track that serves to house the mite, though other lesions may be present (eg, papules, vesicles).
Diagnosis. The appearance of a pruritic eruption with the characteristic lesion along the typical distribution is diagnostic. Skin scraping can be obtained, which will reveal the presence of mites, eggs, or feces under oil-immersion microscopic examination.
Treatment of pediculosis pubis and scabies. The first step in management is decontamination of clothing and bed linens with machine washing and drying on high heat cycle. Treat pruritus with antihistamines. Other topical treatments are listed in Table 28-2. Retreatment can be considered 2 weeks after initial regimen. All household and sexual contacts should also be treated.
| Treatment | Instructions | Special Considerations |
|---|---|---|
| Pediculosis Pubis | ||
| Permethrin (Nix) 1% cream | Apply to affected areas and wash off after 10 min. Comb the infected areas with a fine-tooth comb | Safe in pregnancy |
| Pyrethrins with piperonyl butoxide | Apply to affected area and wash off after 10 min | Safe in pregnancy |
| Ivermectin | 250 μg/kg PO, repeated in 1–2 wk | Not recommended in pregnancy |
| Malathion | 0.5% lotion applied for 8–12 h then washed off | Caution with breastfeeding |
| Scabies | ||
| Permethrin (Nix) 5% cream | Applied to affected area of the body from the neck down. Wash off after 8–14 h | Safe in pregnancy |
| Malathion | 0.5% lotion applied for 8–12 h then washed off | Caution with breastfeeding |
| Ivermectin | 200 μg/kg PO, repeated in 2 wk | Not recommended in pregnancy |
| Crusted Scabies | ||
| 25% topical benzyl benzoate OR 5% permethrin cream
AND PO ivermectin | Topical treatment: applied to entire body from neck down, applied daily for 7 d, then twice weekly until resolution Ivermectin: 200 μg/kg on days 1, 2, 8, 9, and 15 |
Genital Ulcers
The most common infectious causes of genital ulcers in sexually active women are genital herpes and syphilis. Less common causes include chancroid and donovanosis. Consider the diagnosis of Lipschütz ulcers in young women, particularly if not yet sexually active.
Genital Herpes
Genital herpes is caused by herpes simplex virus (HSV), a highly contagious DNA virus that infects one in six people between the ages of 14 and 49 years in the US. There are an estimated 800,000 new cases annually. There are two types of genital HSV: types 1 and 2. The virus is spread by direct contact with a herpes ulcer, saliva, and genital secretions. HSV-1 is classically associated with orolabial cold sores but can spread from the mouth to the genitals through oral sex. HSV-2 typically accounts for recurrent genital herpes, though HSV-1 is estimated to account for 50% of first-episode genital infections.
Clinical manifestations. Genital herpes classically presents as multiple painful, vesicular, or ulcerative lesions. However, some may have mild, subclinical, or asymptomatic presentations. The incubation period is typically 4 days (range of 2 to 12 days).
Outbreaks can last up to 6 weeks following primary infection. Primary infection is typically associated with the most severe symptoms, including flu-like symptoms, tender lymphadenopathy, local pain and itching, headaches, and dysuria. Multiple vesicles then appear that may coalesce into painful ulcerations. Outbreaks are self-limiting, and lesions heal without scar formation.
Recurrent outbreaks are less symptomatic and of shorter duration, lasting up to 7 days. They are classically proceeded by prodromal symptoms of localized genital pain, tingling, or shooting pain, which may occur hours to days before the outbreak of herpetic lesions. The number of recurrent symptomatic outbreaks often decreases over time.
Complications include herpes encephalitis (a rare but potentially life-threatening infection of the brain), aseptic meningitis, pneumonitis, disseminated infection, and urinary tract infections (which can cause severe pain and urinary retention).
Diagnosis. Clinical suspicion is based on history and the appearance of lesions; however, it is insensitive and nonspecific. Obtain laboratory confirmation with type-specific virology and serologic testing.
Cell culture and polymerase chain reaction (PCR) nucleic acid amplitude testing (NAAT) are the preferred methods for confirmatory diagnosis. The sensitivity of cell culture is low, however, especially with recurrent lesions or those that have begun to heal. NAAT is more commonly employed due to its increased sensitivity. Viral isolates should be typed to determine HSV-1 or HSV-2 as that assists in prognosis and counseling. Because viral shedding is intermittent, a negative culture or NAAT does not eliminate the diagnosis of HSV.
Type-specific IgG serology can confirm clinical suspicion when culture and NAAT are negative. Type-specific IgG serologic assays that differentiate HSV-1 from HSV-2 are recommended. Antibodies develop within weeks of infection and persist indefinitely. False negatives may occur in the early stages of infection. Therefore, if there is a high clinical suspicion, the test should be repeated 12 weeks later. Importantly, IgM antibody testing is not useful and not recommended. The CDC recommends type-specific serologic testing in certain scenarios: (1) recurrent or atypical symptoms with negative HSV NAAT or culture; (2) clinical diagnosis of genital herpes without laboratory confirmation, (3) patient whose partner has genital herpes, (4) persons living with HIV. Routine serologic screening for HSV is not recommended.
Treatment. If untreated, most lesions will heal without scarring and spontaneously regress in 2 to 3 weeks. Systemic antiviral therapy for HSV may reduce symptoms and complications of infection (Table 28-3). Topical antiviral therapy has not been shown to be efficacious and is not recommended. Regardless of treatment, the virus cannot be completely eradicated and remains latent in the cell bodies of the sacral nerves S2–S4.
| Stage | Recommended Treatment Regimens | Duration |
|---|---|---|
| Primary outbreak | Acyclovir 400 mg PO TID Famciclovir 250 mg PO TID Valacyclovir 1 g PO BID | 7–10 d Treatment can be extended if not resolved after 10-d course |
| Episodic recurrences (begin treatment with onset of prodromal symptoms or within 1 d of lesion outbreak) | Acyclovir 800 mg TID Acyclovir 800 mg BID Famciclovir 125 mg BID Famciclovir 1 g BID Valacyclovir 1 g qd Valacyclovir 500 mg BID | 2 d 5 d 5 d 1 d 5 d 3 d |
| Suppressive therapy | Acyclovir 400 mg BID Valacyclovir 500 mg qd* Valacyclovir 1 g qd Famciclovir 250 mg BID | Per day *Valacyclovir 500 mg once a day can be less effective for those with frequent recurrences (>10 episodes/y) |
| Severe disease | 5–10 mg/kg IV acyclovir q8h Followed by PO antiviral therapy | 2–7 d or until clinical improvement. Then oral antivirals for total of 10-d course |
| Persons with HIV, daily suppressive therapy | Acyclovir 400–800 mg BID or TID Valacyclovir 500 mg BID Famciclovir 500 mg BID | |
| Persons with HIV, episodic infection | Acyclovir 400 mg TID Valacyclovir 1 g BID Famciclovir 500 mg BID | 5–10 d |
| Suppression in pregnancy | Acyclovir 400 mg TID Valacyclovir 500 mg BID | Starting at 36 wk and continuing until delivery |
Adapted from Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2021. MMWR. 2021;70(No. RR-4):1–137.
Prevention. Patients should be counseled to remain abstinent from the onset of prodromal symptoms until complete reepithelialization of the lesions. Couples should discuss the role of suppressive therapy in decreasing transmission risk. It should be stressed that condoms can reduce but do not eliminate the risk of transmission, as shedding can occur in areas not covered by the condom. There is a two- to fourfold increase in acquiring HIV, even without the presence of physical lesions.
Special populations
HIV. HSV lesions in persons infected with HIV may be more severe and painful and appear atypical. In addition, HSV shedding is increased. Therefore, daily suppressive antiviral therapy should be considered in this population. See Table 28-3.
Pregnancy. All pregnant patients should be screened for a personal history of HSV. Pregnant women with an HSV outbreak should be treated. Suppressive therapy, beginning generally at 36 weeks' gestation, is recommended for all women with a history of genital HSV, as cesarean section is recommended if a patient reports prodromal symptoms or has an active outbreak at the time of delivery. See Chapter 10.
Syphilis
Syphilis is a systemic infection caused by the spirochete Treponema pallidum. Transmission is by direct contact with a mucocutaneous lesion, including a chancre, condyloma lata, or mucosal lesion. The incubation period is from 10 days to 3 months.
Clinical manifestations. The disease is divided into stages, which may overlap in temporal sequence: primary, secondary, tertiary, and latent syphilis. Patients typically present with primary or secondary syphilis.
Primary syphilis is characterized by the appearance of a highly infectious, hard, painless, well-circumscribed solitary chancre on the vulva, vagina, cervix, or anus. Regional lymphadenopathy is frequently present. The primary chancre usually resolves spontaneously within 3 to 8 weeks.
Secondary syphilis reflects hematogenous spread of the spirochete, usually 4 to 10 weeks after primary infection. This stage is characterized by generalized nonpruritic papulosquamous rash typically on the back, chest, palms, and soles, mucous patches, patchy alopecia, condyloma lata, generalized lymphadenopathy, and systemic symptoms.
Latent syphilis is defined by seropositivity without clinical manifestations. Latent syphilis documented as acquired during the previous year is referred to as early latent. All other latent syphilis is either late latent or latent syphilis of unknown duration.
Tertiary syphilis develops in up to one third of the untreated or inadequately treated patients. It is characterized by gummas, locally destructive lesions of the bone, skin, or other organs. Cardiovascular involvement in tertiary syphilis includes aortic aneurysm and aortic valve insufficiency.
Neurosyphilis occurs when T. pallidum invades the central nervous system (CNS) and can occur during any stage of syphilis. Neurologic symptoms that may present in the first few weeks to years following infection include cranial nerve palsy, meningitis, stroke, and auditory and ophthalmic abnormalities. Late neurologic signs may not be evident for 10 to 30 years after initial infection and include tabes dorsalis and general paresis.
Diagnosis. Definitive diagnosis of syphilis is made by identifying the spirochete through dark field microscopy or by direct fluorescent antibody tests of lesion exudate or tissue. Most labs make the diagnosis using a combination of nontreponemal serologic tests and treponemal tests. Nontreponemal tests include the Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) that measure antibodies against lipoidal antigens like cardiolipin and lecithin. They are not specific to T. pallidum and biologic false-positive nontreponemal tests are associated with HIV infection, older age, pregnancy, autoimmune disorders, chronic active hepatitis, intravenous drug use, febrile illness, and immunization. Therefore, a positive VDRL or RPR test requires confirmatory testing with treponemal testing. Treponemal tests include fluorescent treponemal antibody absorbed test (FTA-ABS), T. pallidum passive particle agglutination assay (TP-PA assay), enzyme immunoassays (EIA), and chemiluminescent immunoassays (CIA). Serologic tests become positive 4 to 6 weeks after exposure, usually 1 to 2 weeks after the appearance of the primary chancre.
Nontreponemal test antibody titers may correlate with disease activity and are used to follow treatment response. A fourfold change in titer of the same nontreponemal test, such as from 1:16 to 1:4, is considered necessary to demonstrate clinical significance.
The nontreponemal tests may become nonreactive after treatment; however, for some individuals, these antibodies may persist, a phenomenon referred to as “serofast reaction.” The FTA-ABS test often remain positive indefinitely, regardless of treatment, although may become nonreactive after 2 to 3 years.
Most laboratories have begun using a reverse syphilis screening algorithm where the treponemal tests (eg, EIA, CIA) are done first, followed by a nontreponemal test (eg, RPR). Treponemal tests will be positive in individuals with previously treated syphilis as well as in those with untreated or incompletely treated syphilis. A positive treponemal test result must be followed by a nontreponemal test with titer. If the nontreponemal test is negative, a different treponemal test should be performed to verify the results of the first test. If the second treponemal test is positive, patients without a history of prior treatment should be offered treatment for late latent syphilis.
All patients with tertiary syphilis or any stage syphilis with clinical evidence of CNS involvement should have a lumbar puncture for cerebrospinal fluid (CSF) analysis. The diagnosis of neurosyphilis cannot be made with a single test but requires a combination of reactive serologic tests, CSF white blood cell count and protein, and reactive VDRL-CSF. Additional testing with a CSF treponemal test (FTA-ABS) may be performed in unclear cases.
The diagnosis of syphilis should prompt HIV and other STI testing.
Treatment. Parenteral benzathine penicillin G is the preferred treatment for all stages of infection. See Table 28-4. Penicillin G is the only treatment with documented efficacy in pregnancy. Therefore, pregnant patients with a penicillin allergy should be desensitized and treated with penicillin. After initiation of treatment, patients may experience Jarisch–Herxheimer reaction, an acute reaction characterized by headache, myalgia, and fever. This reaction most commonly occurs following treatment of early syphilis secondary to the high bacterial load and is caused by an inflammatory reaction induced by lysis of the spirochete.
| Stage | Recommended Regimen | Duration |
|---|---|---|
| Primary and Secondary Syphilis | ||
| Primary and secondary syphilis | Benzathine penicillin G 2.4 million units IM | Single dose |
| Retreatment of primary or secondary syphilis | Benzathine PCN G 2.4 million units IM | Weekly dose for 3 wk |
| Nonpregnant primary or secondary infection with PCN allergy | Doxycycline 100 mg BID Tetracycline 500 mg QID Ceftriaxone 1 g daily IM or IV | 14 d 14 d 10–14 d |
| Latent Syphilis | ||
| Early latent syphilis | Benzathine PCN G 2.4 million units IM | Single dose |
| Late latent or syphilis of unknown duration | Benzathine PCN G 2.4 million units IM | Weekly dose for 3 wk |
| Nonpregnant latent syphilis with PCN allergy | Doxycycline 100 mg BID Tetracycline 500 mg QID | 28 d 28 d |
| Tertiary Syphilis | ||
| Tertiary syphilis with normal CSF examination | Benzathine PCN G 2.4 million units IM | Weekly dose for 3 wk |
| Neurosyphilis | ||
| Neurosyphilis and ocular syphilis | Aqueous crystalline penicillin G 18–24 million units daily | Administered as 3–4 million units IV every 4 h or continuous infusion for 10–14 d |
| Alternative regimen (if compliance can be assured) | Procaine penicillin G 2.4 million units IM daily PLUS Probenecid 500 mg PO QID | Both for 10–14 d |
CSF, cerebral spinal fluid; HIV, human immunodeficiency virus; IM, intramuscular; IV, intravenous, PCN, penicillin; BID, two times a day; TID, three times a day; QID, four times a day.
Adapted from Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2021. MMWR. 2021;70(No. RR-4):1–137.
Follow-up
Primary or secondary syphilis. Serologic and clinical evaluation should be repeated at 6 and 12 months after treatment (or at 3, 6, 9, 12, and 24 months if HIV positive). Failure of titers to decline fourfold or greater within 12 months (or 24 months if HIV positive) after therapy for primary or secondary syphilis may be due to treatment failure or reinfection.
Latent syphilis. Quantitative nontreponemal serologic testing should be repeated at 6, 12, and 24 months (or at 6, 12, 18, and 24 months if HIV positive). CSF examination may be indicated.
Neurosyphilis. Normalization of serum RPR titer predicts normalization of abnormal CSF parameters in immunocompetent patients and patients with HIV who are on effective antiretroviral therapy.
Other Ulcerative Lesions
Chancroid is a rare infection in the US caused by H. ducreyi; however, it may still occur in regions of Africa and the Caribbean. Chancroid is a risk factor for HIV transmission. Patients often present with one or more extremely painful 1- to 2-cm genital ulcers with an erythematous base and clearly demarcated borders. The base of the ulcer typically has a gray or yellow purulent exudate, which bleeds when scraped. Some may present with tender inguinal lymphadenopathy, which may undergo liquefaction and develop fluctuant buboes at risk of spontaneous rupture. Definitive diagnosis is with detection of H. ducreyi on special culture media (not widely available). Some laboratories have developed locally validated PCR tests. Recommended treatment is azithromycin 1 g PO single dose, ceftriaxone 250 mg IM single dose, ciprofloxacin 500 mg PO BID for 3 days, or erythromycin 500 mg PO TID for 7 days.
Granuloma inguinale (donovanosis) is another rare cause of genital ulcers in the US but is endemic in some tropical and developing areas. The genital ulcer is caused by the intracellular bacterium Klebsiella granulomatis. The disease is a slowly progressive ulcerative lesion on the perineum or genitals without regional lymphadenopathy. The lesion is highly vascular and subcutaneous granulomas may occur. The diagnosis is made by dark stain and visualization of Donovan bodies. Extragenital infection can occur with extension to the pelvis and dissemination to abdominal organs, bones, or the mouth. Treatment stops progression of the lesion, but relapse can occur. The first-line treatment regimen is azithromycin 1 g PO weekly or 500 mg daily for a minimum of 3 weeks, until all lesions have completely healed.
Lymphogranuloma venereum (LGV) is caused by Chlamydia trachomatis serovars L1, L2, or L3. The typical manifestation is tender unilateral inguinal or femoral lymphadenopathy. A self-limiting ulcer or papule may occur at the initial site of inoculation; however, this lesion typically resolves by the time they seek care. Diagnosis is based on clinical suspicion, epidemiologic information, and exclusion of other etiologies. Chlamydial testing of genital and lymph node specimens by culture, direct immunofluorescence, or NAAT may be used to confirm the diagnosis. Further NAAT-based genotyping to differentiate LGV from non-LGV C. trachomatis serovars is not widely commercially available. The recommended treatment regimen is 100 mg doxycycline BID for a total of 21 days. Azithromycin or erythromycin can be used as second-line therapy, particularly in pregnancy.
Vaginitis
Vaginitis is characterized by pruritus, dyspareunia, and malodorous discharge. The vaginal microbiota is diverse, and may include lactobacilli (eg, L. cripatus, L. gasseri, and L. jensenii), diphtheroids, Candida albicans, Gardnerella vaginalis, Escherichia coli, mycoplasmas, and group B streptococci. The physiologic pH is approximately 4, which is primarily influenced by lactic acid produced by L. cripatus, inhibiting the overgrowth of pathologic bacteria. Physiologic vaginal fluid is typically white, odorless, and seen in dependent areas of the vagina on exam.
The most common types of vaginitis are bacterial vaginosis (BV), trichomoniasis, and candidiasis (Table 28-5). A focused history should include information regarding symptoms, duration, relationship to menstrual cycle, use of prior treatment, douching, and sexual history. Physical examination should start with inspection of the vagina and include collection of samples for vaginal pH, amine (“whiff”) test, saline wet mount, and potassium hydroxide (KOH) microscopy. The diagnosis is confirmed by microscopic examination of the discharge, including saline wet mount and KOH microscopy, vaginal pH, and commercially available molecular tests.
| Bacterial Vaginosis | Trichomoniasis | Vulvovaginal Candidiasis | |
|---|---|---|---|
| Vaginal pH | >4.5 | 5.0–7.0 | 4.0 |
| Discharge characteristics | Thin, grayish, adherent, fishy odor with KOH application (whiff test) | Thin, frothy, white/gray/yellow-green, copious | Thick, white, curd like |
| Wet prep | Clue cells | Trichomonads, WBCs | Hyphae, pseudohyphae, budding yeast (KOH prep) |
Bacterial Vaginosis
BV is the most common cause of vaginitis, although most women are asymptomatic. BV is polymicrobial, not caused by a single specific species of bacteria, but rather a shift in the normal vaginal flora. The shift is characterized by a change in the vaginal microflora from predominance of lactobacilli to anaerobic bacteria, especially Gardnerella vaginalis, Mycoplasma hominis, Bacteroides, Peptostreptococcus, and Fusobacterium. BV is associated with multiple male and female partners, a new sex partner, lack of condom use, douching, increased risk of pelvic inflammatory disease (PID), and postprocedural gynecologic infections. BV increases the risk of acquisition of STIs including HIV, N. gonorrhoeae, C. trachomatis, and HSV-2.
Clinical manifestations. The most common symptom is malodorous discharge.
Diagnosis. BV is diagnosed by the presence of at least three of four Amsel's clinical criteria: (1) homogeneous thin discharge coating the vaginal walls; (2) vaginal pH greater than 4.5; (3) greater than 20% clue cells on microscopic examination; and (4) fishy odor before or after the addition of 10% KOH to the sample (whiff test). Commercially available molecular PCR tests are also now available. Care should be used when interpreting the results of PCR tests that include only a single organism (eg, G. vaginalis), as G. vaginalis may be present in women without BV. Instead, multiplex PCR assays that detect multiple organisms are preferred. Some commercially available PCR assays detect BV, vulvovaginal candidiasis (VVC), and trichomoniasis.
Treatment. Treatment of BV is recommended for symptomatic pregnant and nonpregnant patients (Table 28-6). Partner treatment is not recommended.
Special populations. BV in pregnancy has been associated with spontaneous abortion, low birth weight, premature rupture of membranes, and preterm delivery. Although antibiotic therapy has been shown to effectively treat BV, treatment trials among asymptomatic women have not shown a reduction in preterm birth risk. Thus, ACOG does not recommend routine screening and treatment of asymptomatic BV; however, treatment is recommended if symptomatic. See Chapter 10.
Recurrence. The rate of recurrence of BV is as high as 30% within 3 months, and more than 50% within 12 months. If a recurrence occurs, or if symptoms persist despite treatment, retreatment with the same recommended regimen is an acceptable approach. If three separate episodes occur in 12 months, suppressive therapy should be considered. Suppressive therapy commonly begins with an induction regimen that consists of 0.75% metronidazole gel or an oral nitroimidazole for 7 to 10 days, followed by twice weekly dosing of gel for 4 to 6 months. Alternatively, vaginal boric acid 600 mg suppositories for 30 days can be added. Monthly oral metronidazole 2 g, given with prophylactic oral fluconazole 150 mg, is also an option.
Trichomoniasis
Trichomoniasis is the most prevalent nonviral STI in the US, with an estimated 2.6 million new infections annually. Infection is caused by the unicellular protozoan Trichomonas vaginalis, the incubation period for which is 4 to 28 days. Like other STIs, trichomoniasis is associated with an increased risk of PID and HIV acquisition.
Clinical manifestations. Patients report malodorous, yellow-green, copious vaginal discharge that may be associated with vulvar pruritus. Other common complaints include dyspareunia, dysuria, postcoital bleeding, and lower abdominal pain and cramping. However, many patients can be asymptomatic.
Diagnosis. Clinical exam findings can include frothy, malodorous discolored vaginal discharge or a friable, erythematous cervix (“strawberry cervix”). Saline wet mount may reveal flagellated, motile protozoon; however, the sensitivity is only 55% to 70%. NAAT assays, from vaginal, endocervical, or urine specimens, are the recommended diagnostic test for T. vaginalis and have sensitivity 3 to 5 times greater than a wet mount.
Treatment. Treatment should be considered for all symptomatic pregnant and nonpregnant women (Table 28-7). While trichomoniasis in pregnancy has been associated with perinatal morbidity (low birth weight, preterm delivery, preterm rupture of membranes), treatment of trichomoniasis in pregnancy has not been shown to decrease the risk of these outcomes. Metronidazole gel has not been shown to be effective, and therefore is not recommended. Patients with an allergy to metronidazole can be referred for desensitization and subsequent treatment with metronidazole. Tinidazole is more expensive than metronidazole; however, it has been shown to reach higher concentrations in the genitourinary tract with fewer gastrointestinal side effects. All patients with recently diagnosed trichomoniasis should be counseled to refrain from intercourse until the patient and her partner have completed treatment. All sexual partners in the past 60 days should be referred for evaluation and presumptive treatment. Some states allow for expedited partner therapy (EPT) for T. vaginalis infection.
Follow-up. A test-of-reinfection is recommended 3 months after treatment. Most organisms respond well to standard treatment, but relative resistance to metronidazole has been documented for 4% to 10% of vaginal trichomoniasis. If treatment failure occurs and reinfection has been excluded, then either metronidazole or tinidazole 2 g orally for 7 days can be considered.
Special populations. Up to 53% of women with HIV are also infected with T. vaginalis. Treatment of symptomatic and asymptomatic, pregnant and nonpregnant women with HIV is recommended, as treatment is associated with decreased genital-tract HIV viral load and decreased viral shedding.
Vulvovaginal Candidiasis
The most common species associated with VVC is Candida albicans; however, other species of Candida or yeast may also cause symptoms. The lifetime incidence of VVC is 75%, with 40% to 45% of women having repeated infections. Complicated VVC occurs in 5% of women affected by VVC. See Table 28-8 for the distinction between complicated and uncomplicated VVC.
| Uncomplicated VVC | Complicated VVC |
|---|---|
| Sporadic or infrequent episodes AND Mild-to-moderate VVC symptoms AND Likely to be Candida albicans AND Immunocompetent | Recurrent VVC (≥4 episodes in year) OR Severe VVC symptoms OR Nonalbicans candidiasis (eg, C. glabrata) OR Diabetes, HIV, immunocompromise, debilitation, immunosuppression, chronic corticosteroid therapy |
VVC, vulvovaginal candidiasis.
Adapted from Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2021. MMWR. 2021;70(No. RR-4):1–137.
Clinical manifestations. Women often present with vaginal itching, burning, irritation, dyspareunia, external dysuria, and a thick white vaginal discharge.
Diagnosis. Signs of VVC include vulvar fissures, excoriations, and vulvovaginal erythema, and edema. The vaginal pH is typically normal, between 4 and 4.5. The diagnosis of uncomplicated VVC may be made based on the clinical signs and symptoms, in addition to the presence of hyphae or spores on saline or 10% KOH wet prep, Gram stain of vaginal secretions is positive for yeast, hyphae, or pseudohyphae, or fungal culture is positive. Molecular assays may also be used when microscopy is not readily available. Diagnosis should be classified as uncomplicated or complicated VVC to guide treatment. Culture should be performed in women not responding to treatment, in cases where nonalbicans species is suspected, or in recurrent VVC to establish species and to test for azole sensitivity.
Treatment. All symptomatic patients, including those who are pregnant, should be treated. Empiric treatment of women with clinical signs and symptoms of VVC, but with a negative wet mount, can be considered.
Treatment of uncomplicated VVC is listed in Table 28-9. Azole-resistant C. albicans is rare; however, it should be considered in women with prolonged azole exposure. If symptoms persist or recur within 2 months after treatment, patients should return for reevaluation.
| Drug | Formulation | Dosage | Duration |
|---|---|---|---|
| Clotrimazole (OTC) | 1% cream | 5 g daily | 7–14 d |
| 2% cream | 5 g daily | 3 d | |
| Miconazole (OTC) | 2% cream | 5 g daily | 7 d |
| 4% cream | 5 g daily | 3 d | |
| 100 mg vaginal suppository | 100 mg daily | 7 d | |
| 200 mg vaginal suppository | 200 mg daily | 3 d | |
| 1200 mg vaginal tablet | 1200 mg daily | Once | |
| Ticonazole (OTC) | 6.5% ointment | 5 g | Once |
| Butoconazole | 2% cream | 5 g daily | Once |
| Terconazole | 0.4% cream | 5 g daily | 7 d |
| 0.8% cream | 5 g daily | 3 d | |
| 80 mg vaginal suppository | 80 mg daily | Once | |
| Fluconazole | 150 mg oral tablet | 150 mg once | Once |
For severe cases of VVC (fissure formation, extensive vulvar erythema or edema), extended treatment with topical azoles for up to 14 days or two to three doses of fluconazole 150 mg, 72 hours apart, is recommended. For recurrent cases of VVC, recommend extended azole treatment, followed by oral fluconazole (150 mg) weekly for 6 months as maintenance. If patients are unable to take oral fluconazole, can consider prolonged therapy with topical agents such as clotrimazole 500 mg weekly or 200 mg twice weekly. Maintenance therapy is effective in reducing recurrence in up to 50% of women.
Nonalbicans (eg, C. glabrata) VVC optimal treatment remains undefined. The current first-line therapy for nonalbicans is a 7- to 14-day course of a nonfluconazole topical or oral azole. If recurrence occurs, can consider 600 mg boric acid in gelatin capsule vaginally once daily for 3 weeks.
Treatment of partners is not indicated unless the partner is symptomatic.
Cervicitis
Cervicitis is defined by the presence of mucopurulent cervical discharge or cervical bleeding induced with gentle manipulation of the cervix. If symptomatic, patients often complain of abnormal vaginal discharge, intermenstrual bleeding, or postcoital bleeding. Cervicitis may be a manifestation of an upper genital tract infection, and therefore should also be evaluated for PID. Cervicitis is most commonly caused by Chlamydia trachomatis or Neisseria gonorrhoeae infection. Other etiologies include T. vaginalis, Mycoplasma genitalium, and HSV infections; however, in a majority of patients, no infectious etiology is found.
Chlamydia
Chlamydia is the most frequently reported bacterial STI in the US and is typically asymptomatic. The infection is caused by the obligate intracellular pathogen Chlamydia trachomatis, which preferentially infects the columnar cells in the cervix, urethra, pharynx, or rectum. The CDC recommends annual screening of all sexually active women less than 25 years old. Screening is also recommended for older women with risk factors, including a new sex partner, more than one concurrent sexual partner, a sex partner with concurrent partners, or the diagnosis of a recent STI infection in the patient or her partner. Chlamydia infection is associated with PID, and evidence suggests that screening programs have reduced the occurrence of PID.
Clinical Manifestations. Chlamydial cervicitis is asymptomatic in approximately 75% of cases. Symptomatic complaints include abnormal, yellow-colored vaginal discharge, mild dysuria, or postcoital bleeding.
Diagnosis. Chlamydial infections are diagnosed primarily by NAAT. Vaginal swabs are preferred, collected either by patient or clinician. NAAT can also be performed on a first-catch urine sample. All women who present with symptoms of cervicitis also should be evaluated for gonorrhea and trichomoniasis.
Treatment. Treatment is recommended upon diagnosis to prevent adverse sequelae. The recommended treatment regimens are listed Table 28-10. Presumptive therapy can be initiated based upon clinical findings and STI risk assessment.
| Regimen | Duration |
|---|---|
| Recommended Regimen | |
| Doxycycline 100 mg PO | Two times a day for 7 d |
| Alternative Regimens | |
| Azithromycin 1 g PO | Single dose |
| Levofloxacin 500 mg PO | Once a day for 7 d |
| Pregnancy | |
| Azithromycin 1 g PO (preferred) | Single dose |
| Amoxicillin 500 mg | Three times a day for 7 d |
Adapted from Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2021. MMWR. 2021;70(No. RR-4):1–137.
Patients should abstain from intercourse for 7 days after treatment to avoid reinfection. A test of cure, 3 to 4 weeks following treatment, is not necessary unless symptoms persist or patient is pregnant. The NAAT may continue to be positive for up to 3 weeks following treatment. Test of reinfection is recommended 3 months after treatment. Patients who seem to fail therapy are most likely to have been reinfected by a sexual partner. All patients with the diagnosis of chlamydia should also be tested for other STIs.
All of a patient's sexual partners for the 60 days prior to the onset of symptoms should seek medical advice for evaluation and presumptive treatment. EPT can be considered if allowed by state law.
Pregnancy. Women younger than 25 and at increased risk of Chlamydia infection should be screened at initial prenatal visit and in the third trimester. Preferred treatment regimen is Azithromycin 1 g PO once, as doxycycline is contraindicated in the second and third trimesters. Test of cure should be performed 4 weeks following completion of treatment.
Gonorrhea
Gonorrhea is the second most reported bacterial STI in the US. The infection is caused by Neisseria gonorrhoeae, a Gram-negative intracellular diplococcus, which has an incubation period of usually 3 to 5 days, but it can be as long as 14 days. The most infected site is the endocervix; however, pharyngeal, urethral, and rectal sites can be infected as well. Rarely, disseminated infections may occur. The CDC recommends annual screening of all sexually active women less than 25 years old. Screening is also recommended for older patients with risk factors for STIs.
Clinical manifestations. Symptoms often go unrecognized, and patients may not present until they develop sequelae of PID. If symptoms do arise, patients may complain of purulent vaginal discharge, dysuria, or intermenstrual bleeding.
Diagnosis. FDA-approved NAATs are available for endocervical, vaginal, and urine samples. NAAT has greater sensitivity than culture analysis. Vaginal swabs are preferred, collected either by the patient or clinician. Culture should be used when antibiotic sensitivity testing is indicated, especially if treatment failure is suspected.
Treatment. See Table 28-11. Treatment of gonococcal infections is complicated by the ability of Neisseria gonorrhoeae to develop resistance to multiple antimicrobials. The CDC recommends ceftriaxone 500 mg intramuscular and no longer recommends the routine addition of azithromycin. Concurrent treatment with doxycycline (100 mg orally twice a day for 7 days) is only recommended if chlamydia infection has not been excluded.
| Infection | Recommended Regimen |
|---|---|
| Uncomplicated infections of the cervix, urethra, or rectum | Ceftriaxone 500 mg IM single dosea,b |
| If ceftriaxone is not available, alternatively: Cefixime 800 mg oral single dose | |
| If cephalosporin allergy, alternatively: Gentamicin 240 mg IM single dose AND Azithromycin 2 g oral single dose | |
| Disseminated gonococcal infection (arthritis–dermatitis syndrome) | Ceftriaxone 1 g IM or IV q24hb |
| Pregnancy | Ceftriaxone 500 mg IM single dosea |
aIf the patient weight is greater than 150 kg, recommend 1 g Ceftriaxone IM single dose.
bIf chlamydial infection has not been ruled out, treat for chlamydia with 100 mg doxycycline twice daily × 7 days.
IM, intramuscular; IV, intravascular.
Patients should be counseled to abstain from intercourse for 7 days following treatment, and until all sexual partners are adequately treated, to reduce the risk of transmission. All patients with the diagnosis of gonorrhea should also be tested for other STIs. All patients should undergo a test of reinfection 3 months after treatment. Patients who seem to fail therapy are most likely to have been reinfected by a sexual partner. If treatment failure is suspected, however, then culture and antimicrobial susceptibility testing should be performed.
All of a patient's sexual partners for the 60 days prior to the onset of symptoms should seek medical advice for evaluation and presumptive treatment. EPT should be considered if allowed by state law.
Pregnancy. Women at increased risk should be screened at initial prenatal visit and in the third trimester. Preferred treatment regimen is ceftriaxone 500 mg IM, as gentamicin has risk of ototoxicity and nephrotoxicity to the fetus. Test of cure should be performed approximately 4 weeks following completion of treatment.
Disseminated gonococcal infection (DGI) often presents with a petechial or pustular rash, asymmetric polyarthralgia with or without purulent arthritis, tenosynovitis, or oligoarticular septic arthritis. It may be complicated by perihepatitis and rarely osteomyelitis, vasculitis, endocarditis, or meningitis. Diagnosis may be confirmed with NAAT of genital sites, in addition to specimens obtained from sites of infection, such as joint aspiration, blood, or from a lumbar puncture. All gonococcal isolates should be tested for antimicrobial susceptibility. Treatment should involve inpatient admission and consultation with an infectious disease specialist. Treatment of arthritis–dermatitis syndrome is listed in Table 28-11. Transition to a PO regimen may be considered 24 to 48 hours after clinical improvement and should continue for at least 7 days.
Mycoplasma Genitalium
Mycoplasma genitalium is increasingly recognized as a causative agent of cervicitis and PID in women. M. genitalium lacks a cell wall, and therefore is not amendable to Gram staining. It is also the smallest known self-replicating bacterium and is extremely difficult to culture, requiring up to 2 months to grow. For these reasons, it was only recently recognized as a major causative agent of cervicitis and PID. It is estimated that as many as 1% of reproductive-age adults may be infected with M. genitalium, which would make it more prevalent than gonorrhea.
Clinical manifestations.M. genitalium infection is associated with mucopurulent cervicitis; however, many of those infected may not endorse any symptoms. Other symptoms can include vaginal itching, dysuria, and pelvic discomfort. The infection can ascend to the upper genital tract, resulting PID.
Diagnosis. Due to the unique properties of the organism, traditional microbiologic assays, such as culture and staining, are not applicable. NAAT assays are FDA approved for urine, urethral, endocervical, and vaginal swabs.
Treatment.M. genitalium has demonstrated high rates of resistance to macrolides. As such, resistance-guided therapy is recommended if available. If resistance testing shows the infection to be macrolide sensitive, treatment is doxycycline 100 mg twice daily for 7 days followed by azithromycin 1 g once and 500 mg daily for 3 days thereafter. If found to be macrolide resistant or if resistance testing is not available, treatment is doxycycline 100 mg twice daily for 7 days followed by moxifloxacin 400 mg daily for 7 days.