Bacterial Vaginosis, Related Syndromes, and Less Common Sexually Transmitted Diseases

Geographic Distribution and Magnitude of Disease Burden

BV is the most common cause of vaginal discharge in the United States and has a worldwide presence. The prevalence of BV varies by the population studied; reports of the occurrence of BV in college students of 5% to 25% compared with 12% to 35% among STI clinic patients have been published. Estimates from the Centers for Disease Control and Prevention (CDC) 2001–2004 National Health and Nutrition Survey indicate that as many as one in three women of reproductive age are affected at any given time. African American and Hispanic women had significantly higher prevalence (33.2% and 30.7%, respectively) than Caucasian or Asian groups (22.7% and 11.1%, respectively). The occurrence of BV in our global population can range from 23% to 29%.

Risk Factors

BV is more common in women with a new sexual partner or many sexual partners, in those who have frequent intercourse, when there is a lack of condom use, and in those who practice douching. Studies of women who have sex with women (WSW) have found concordance between BV diagnosis and the prevalence of BV-associated bacteria (BVAB); digital-vaginal and digital-anal sex practices significantly increased the incidence of BV. BV has not been considered an STI, but recent studies support the idea that BVAB exchange between sexual partners is related to the occurrence of BV. Additionally, male circumcision also can reduce the risk of BV in women. These data suggest that BV is sexually transmitted; however, the definite etiology remains unclear. The use of an intrauterine device (IUD)—particularly copper IUDs (thought to increase BVAB colonization)—has been associated with an increased risk of BV; interestingly, women using hormonal contraception had no BV prevalence change. In pregnancy, BV has been associated with preterm delivery and premature rupture of membranes. BV can increase susceptibility to STIs, including Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Mycoplasma genitalium , human papillomavirus (HPV), and herpes simplex virus type-2. Several of these bacteria may lead to the development of pelvic inflammatory disease (PID), postoperative infections after gynecologic procedures, and HIV infection—the latter is thought to be associated with vaginal dysbiosis, even without BV, which may increase susceptibility to HIV.

Clinical Features

In BV, vaginal dysbiosis results from replacement of healthy, hydrogen peroxide and lactic acid-producing Lactobacillus spp. with high concentrations of facultative and strict anaerobic bacteria (i.e., Gardnerella vaginalis , Prevotella spp., Atopobium vaginae , and many others) which alters the vaginal pH and is associated with the occurrence of BV. That said, lactobacilli may not be the predominant species in all women without symptoms. A growing spectrum of species form the “normal” microbiome in women of different ethnicities. In addition, different periods of the menstrual cycle with hormonal status and immune variations may play a role.

Women with apparent microbiologic dysbiosis may or may not be symptomatic. BV is occasionally characterized by mucosal inflammation that may produce irritation, itching, or burning, but the most common symptom is a vaginal discharge that may be malodorous (often described as “fishy”) and acquired more commonly after unprotected sexual intercourse or during their menses. On vaginal speculum examination, a homogeneous, milky discharge that is adherent to the walls of the vagina is commonly present ( Fig. 61.1 ). BV may occur concomitantly with other causes of vaginitis, including trichomoniasis (discussed in Chapter 54 ) and vulvovaginal candidiasis.

Diagnostic Approach

Evaluating patients with suspected BV is dependent on physical examination of the vagina, microscopic examination of the discharge, and pH determination. The amount, consistency, and location of the discharge within the vagina should be noted.

The diagnosis of BV is accomplished by using clinical criteria (Amsel criteria) or a Gram stain of the vaginal discharge. Clinical criteria diagnosis requires three of the following symptoms or signs: (1) a homogeneous, thin, white discharge that smoothly coats the vaginal walls; (2) a fishy odor from the vaginal discharge before or after addition of 10% potassium hydroxide (KOH; i.e., the amine or “whiff” test); (3) a pH of vaginal discharge fluid greater than 4.5; or (4) the presence of clue cells (vaginal epithelial cells with adherent coccobacilli best recognized at the edge of the cell accounting for at least 20% of the epithelial cells on microscopic examination). A comparison of these criteria with characteristics of other common causes of vaginitis is shown in Table 61.1 .

A Gram stain of a vaginal discharge sample for Nugent scoring is considered the gold standard for BV laboratory diagnosis because it shows the relative concentrations of bacteria in the vaginal ecosystem—including the reduction of lactobacilli and the increase of bacteria associated with BV, including gram-negative and gram-variable rods and cocci morphotypes. Performing a vaginal Gram stain for Nugent score is time consuming and usually not a point-of-care (POC) test. White blood cells are not usually present in vaginal fluid from a patient with BV; the presence of neutrophils in vaginal fluid suggests the potential of a co-infection at either the cervical or vaginal sites. Cervical Papanicolaou (Pap) testing is not recommended for the diagnosis of BV because of low sensitivity.

Saline wet mount, OSOM BV Blue test (which detects vaginal sialidase activity), FemExam card (detects metabolic by-products of G. vaginalis ), and the Affirm VP assay (oligonucleotide probe test detecting high concentrations of G. vaginalis ) are POC tests with varying sensitivities and specificities; no new POC tests for BV have emerged in the past few years. There are currently five commercially available NAATs for BV diagnosis in symptomatic women; two are US Food and Drug Administration (FDA) approved and the other three are laboratory-developed tests (LDTs), which need to be internally validated prior to their use. These three NAATs have very good sensitivity and specificity similar to FDA-approved assays, and include LabCorp NuSwab VG, MDL OneSwab BV Panel PCR w/ Lactobacillus Profiling by qPCR, and Quest Diagnostics SureSwab BV. FDA-approved assays include the BD MAX Vaginal Panel and Hologic Aptima BV; both NAATs perform nearly as well as Nugent scoring with the BD MAX also reporting Candida ssp. and T. vaginalis detection results. Advantages of NAAT tests over POC tests for BV diagnosis are that they do not require microscopy, are objective, are able to detect fastidious bacteria, provide quantitation, and are ideal for self-collected vaginal swabs. However, Amsel criteria and the Nugent score still remain useful for the diagnosis of symptomatic BV with their lower cost and ability to provide a rapid diagnosis.

Clinical Management and Treatment

In nonpregnant women, BV treatment is intended to relieve vaginal signs and symptoms of infection and reduce the potential for infectious complications associated with abortion or hysterectomy as well as the potential reduction in the risk of acquiring HIV and other STIs. Because of the increased risk of BV postoperative infectious complications, some providers screen for and treat women with BV before performing elective surgical abortion or hysterectomy. All women with symptomatic disease should be offered treatment and screened for STIs at appropriate intervals depending on their sexual risk behaviors.

The 2015 CDC-recommended treatment for BV ( Box 61.1 ) includes using oral metronidazole, 500 mg twice a day for 7 days; 0.75% metronidazole gel, one full applicator (5 g) intravaginally once a day for 5 days; or 2% clindamycin phosphate cream, one full applicator (5 g) intravaginally at bedtime for 7 days. Three additional FDA-approved BV treatments are available in the United States, all using a single dose: secnidazole 2 g oral granules, metronidazole 1.3% vaginal gel, and clindamycin phosphate 2% vaginal cream (a sustained-release formulation). Research involving biofilm-disrupting agents is underway; studies evaluating the clinical and microbiologic efficacy of using intravaginal suppositories of a human-derived strain of Lactobacillus ( Lactobacillus crispatus strain CTV-05) given as adjunctive therapy in managing BV were inconclusive. There are no data supporting the use of douching for treatment or relief of BV symptoms, and the use of vaginal probiotics is currently not recommended. Prior recommendations suggested patients should avoid alcohol ingestion during metronidazole treatment and for 24 hours after treatment; however, a 2014 systematic review of the literature revealed no in vitro studies, animal models, reports of adverse effects, or clinical studies provided any evidence of a disulfiram-like interaction between alcohol and metronidazole. Clindamycin cream is oil-based and might weaken latex condoms and diaphragms for 5 days after use.

Adverse outcomes associated with BV during pregnancy include premature rupture of the membranes, preterm labor, preterm birth, intra-amniotic infection, and postpartum endometritis. Past studies indicate that treatment of pregnant women with BV at high risk for preterm delivery (women who previously delivered a premature infant) might reduce their risk for additional prematurity. Clinicians should consider the evaluation and treatment of high-risk pregnant women with asymptomatic BV. A meta-analysis of metronidazole use during pregnancy failed to identify any associated adverse events. The treatment of asymptomatic BV in women with low- or average-risk pregnancies is controversial and not currently recommended.

Prognosis and Recurrence

When recommended therapies are used, cure rates for BV are 70% to 80%. Recurrences with BV are common; up to 66% of women experience a recurrence within 12 months of treatment. A different treatment regimen from the original management may be considered to control recurrent disease; however, optimal management strategies for women with persistent or recurrent BV is unclear. In one trial, after completion of a recommended BV regimen, metronidazole gel 0.75% used topically twice per week for 6 months as suppressive management was effective in maintaining a clinical cure for 6 months. Additional studies using high-dose intravaginal metronidazole 750 mg in conjunction with 200 mg miconazole as well as the compound astodrimer 1% vaginal gel, a dendrimer-based microbicide, looks promising. The utility of yogurt therapy, acidifying agents, or exogenous oral Lactobacillus treatment is disappointing.

There are no data suggesting that BV should be treated differently in HIV-infected women. Additionally, treatment of male sexual partners of women with BV remains not recommended based on data from prior male partner treatment trials. There are currently no data on whether treatment of female sexual partners of women with BV improves outcomes.