Asymptomatic Bacterial Vaginosis: To Treat or Not to Treat?

Abstract

Purpose of Review:

The purpose of this review is to summarize current evidence for and against the treatment of asymptomatic bacterial vaginosis (BV) in women.

Recent Findings:

Asymptomatic BV is common although its pathogenesis remains incompletely understood. In favor of treating asymptomatic BV is the large body of data supporting that it is sexually transmitted. Along these lines and similar to other STIs, treatment of BV, regardless of symptom status, should be considered to reduce adverse outcomes of infection (i.e. adverse birth outcomes, infertility, post-gynecologic surgery infections, etc.) and prevent further sexual transmission of BV pathogen(s) to sexual partners. One study has found that treatment of women with asymptomatic BV led to a significant reduction in incident chlamydial infections over a 6 month follow-up period, compared to observation-only women. Additionally, some women with asymptomatic BV actually have symptomatic BV but do not recognize these symptoms as an infection. Nevertheless, limitations of the trial regarding treatment of asymptomatic BV as well as the 2020 United States Preventative Task Force recommendation against screening and treatment of asymptomatic BV in pregnant women dampen enthusiasm for recommending treatment in this setting.

Summary:

Treatment of asymptomatic BV remains controversial. Additional studies are needed to further investigate the pathogenesis of BV, which will directly influence advances in its diagnosis, treatment, and prevention.

Introduction

Bacterial vaginosis (BV) is the most common cause of vaginal discharge worldwide, with a global prevalence ranging between 23-29% that is higher in racial and ethnic groups (i.e. African American women 33.2%, Hispanic women 30.7%) (1). It is also common in women of low income (2). BV is characterized by the loss of healthy, hydrogen peroxide and lactic-acid producing Lactobacillus species and high concentrations of facultative and strict anaerobic bacteria (3), which form a polymicrobial biofilm on vaginal epithelial cells (4). Women with BV are at increased risk of acquisition of HIV (5) and other sexually transmitted infections (STIs), including chlamydia (6), gonorrhea (7), trichomoniasis (6), Mycoplasma genitalium (8), human papilloma virus (HPV) (9), and herpes simplex virus type-2 (HSV-2) (10); co-infection with other cervical (11) and vaginal (12) STIs is common. In addition, women with BV are at risk for adverse birth outcomes (preterm delivery, chorioamnionitis, low birth weight, postpartum endometritis, etc.) (13-15), gynecologic complications such as pelvic inflammatory disease (PID), infertility (16), post-hysterectomy infections including vaginal-cuff cellulitis or deep infections (17), and other adverse health consequences (18) (Table 1).

Table 1.

Complications of Bacterial Vaginosis

Complication
Increased risk of HIV acquisition and transmission
Increased risk of acquisition of STIs
Chlamydia
Gonorrhea
Trichomoniasis
Mycoplasma genitalium
HPV infection
HSV-2
Obstetric complications
First trimester miscarriage in women undergoing IVF
Amniotic fluid infections
Chorioamnionitis
Preterm delivery
Low birth weight
Postpartum and post-abortal endometritis
Post-abortal PID
Gynecologic Complications
PID
Tubal infertility
Post-hysterectomy infections
Vaginal cuff cellulitis
Recurrent Infection
Recurrent/persistent BV
Persistent HPV infection

Abbreviations: STI=sexually transmitted infection, HPV=human papilloma virus, HSV=herpes simplex virus, IVF=in vitro fertilization, PID=pelvic inflammatory disease

A clinical diagnosis of BV is made using the Amsel criteria (with 3 out of 4 criteria needed BV diagnosis: homogeneous, thin, grayish-white vaginal discharge, vaginal pH>4.5, positive whiff-amine test, and >20% clue cells/high power field on a wet mount of vaginal secretions) (19). A microbiological diagnosis of BV has traditionally used a vaginal Gram stain to determine the Nugent score [based on differentiating Lactobacillus-dominated vaginal communities from small gram-variable rods (Gardnerella vaginalis morphotypes) and curved Gram-variable rods (Mobiluncus spp. morphotypes)] (20). More recently a definition of “molecular BV” has been proposed to describe non-optimal vaginal microbiota depleted of Lactobacillus spp. with an increased relative or absolute abundance of facultative and strict anaerobic bacteria, as detected by sequencing of the 16S rRNA gene, shotgun metagenomics sequencing, taxon-specific quantitative PCR (qPCR), or metaproteomic analysis (21). With this in mind, several PCR-based nucleic acid amplification tests (NAATs) for BV diagnosis in symptomatic women have recently become commercially available, all of which have excellent sensitivity and specificity. These include the BD MAX™ Vaginal Panel (22) and Hologic Aptima® BV (23), both FDA-approved in the U.S. Additional laboratory-developed tests (LDTs) are the LabCorp NuSwab® VG (24), MDL OneSwab® BV Panel PCR w/ Lactobacillus Profiling by qPCR (25), and Quest Diagnostics™ SureSwab® BV. These LDTs have to be internally validated prior to their clinical use (26). However, because the exact etiology of BV remains unknown, there is a lack of concordance in the bacteria targeted in these tests. Nevertheless, these tests are a promising alternative to microscopy to detect clue cells on wet mount or visualize vaginal Gram stains for Nugent score determination (27) and their widespread use may increase the number of patients diagnosed with BV moving forward.

Currently recommended treatments include multi-dose regimens of oral and intra-vaginal metronidazole (MTZ) or intra-vaginal clindamycin. Alternative treatments include multi-dose regimens of oral clindamycin, oral tinidazole (TDZ), or intra-vaginal clindamycin ovules (28). A single 2 gram dose of oral secnidazole, a 5-nitroimidazole with a longer half-life (17 hours) than MTZ (7-8 hours) or TDZ (12-14 hours) (29), was recently FDA-approved for BV treatment in women (30, 31) and has been added as an alternative BV treatment recommendation in the 2020 ACOG Practice Bulletin on Vaginitis (27). Despite currently available therapies, BV is difficult to treat and has a high recurrence rate in excess of 50% at 6-12 months (32), perhaps due to persistence of the BV biofilm on vaginal epithelial cells (33, 34). Several biofilm-disrupting agents (i.e. intra-vaginal boric acid) have been studied in vitro and in vivo in the treatment of BV, including recurrent disease (35-37), but none are routinely recommended outside of the use of intra-vaginal boric acid in recurrent disease (28).

Asymptomatic BV (i.e. absence of symptoms of vaginal discharge and/or odor) is a very common entity in clinical practice. According to U.S. National Health and Nutrition Examination Survey (NHANES) data which found a BV prevalence of 29.2% among 14-49 year old women (corresponding to 21.7 million women), the large majority of women (84%) reported no symptoms (38). Other studies have found similar results (2). Despite this high prevalence, national guidelines do not currently recommend screening or treatment of asymptomatic BV in women (27, 28), likely due to the lack of rigorous clinical trial data demonstrating significant benefit (i.e. reduction of adverse outcomes of infection in women). For example, the 2015 CDC Sexually Transmitted Diseases (STD) Treatment Guidelines currently state that the established benefits of therapy for BV in pregnant and non-pregnant women are to relieve vaginal symptoms and signs of infection (28). It is currently unknown if asymptomatic BV is a milder form of infection than symptomatic BV and whether their pathogenesis, response to antibiotic therapy, or complication rates differ. Because of this lack of data, there is controversy regarding whether women with asymptomatic BV should be treated. In this manuscript, we review the natural history of asymptomatic BV and summarize current evidence for and against its treatment in women.

Natural History of Asymptomatic BV

The natural history of asymptomatic BV has been infrequently studied. In a 6 month longitudinal study of 270 mostly asymptomatic women (78% had no complaints of vaginal discharge at enrollment) (39), the baseline prevalence of clue cells on wet mount was 5.6% with a 6 month persistence rate of 36%. Symptomatic BV developed in only 1 patient in this group during the study. The authors proposed that therapy is unwarranted for the incidental finding of a positive laboratory indicator for BV in the absence of symptoms. In a small, randomized, double-blind, placebo-controlled trial of metronidazole gel versus placebo in women with asymptomatic BV (40), 18.5% of women in the placebo arm developed symptomatic BV at day 28. In a third study of 568 women with symptomatic BV enrolled in a trial examining the effect of duration of therapy with MTZ and dual therapy with MTZ and azithromycin on BV cure rates (41), 49 women had asymptomatic BV (Nugent score 7-10 and absence of vaginal symptoms) at the first follow-up visit (day 21) (42). Of these 49 women, 41 had no co-existing genital infection and returned for subsequent visits. At the second follow-up visit on days 35-40, 46.3% continued to have asymptomatic BV by Nugent score, 26.8% were asymptomatic with an intermediate Nugent score, 14.6% were asymptomatic with a normal Nugent score, and 12% had progressed to symptomatic BV. By days 95-100 (3-4 months), 43.9% had progressed to symptomatic BV. When BV was defined by the Amsel criteria instead of the Nugent score, 39 women had asymptomatic BV at day 21. By days 35-40, 42% of these women had asymptomatic BV while 15.2% became symptomatic. By days 95-100, 18/36 (36.7%) developed symptomatic BV. Increased vaginal pH was a significant risk factor for development of symptomatic BV in this study while a normal Nugent score was protective (p<0.05). Neither douching nor recent sexual activity was predictive of development of symptomatic, as opposed to, asymptomatic BV. Overall, these data suggest that a relatively large proportion of women with asymptomatic BV subsequently develop symptomatic BV in the absence of therapy within 1 (12-18%) and 4 (44%) months however, additional data with larger samples sizes are needed.

Evidence Supporting Treatment of Asymptomatic BV

A large body of epidemiological and microbiological data suggests that BV is an STI (43-45), although its exact etiology remains controversial (3, 46, 47). Along these lines and, similar to other STIs (28), if BV is sexually transmitted, treatment of infection should be recommended regardless of symptoms to prevent adverse outcomes of infection (i.e. increased risk of acquisition of HIV/STIs and adverse birth outcomes) and reduce transmission of BV pathogen(s) to sexual partners. Asymptomatic infection by other STIs (i.e. chlamydia, trichomoniasis) (48-50) is common and treatment is currently recommended for these infections regardless of symptoms (28). Indeed, the microbiological diagnosis of BV using a vaginal Gram stain to determine the Nugent score is the same whether or not a woman has symptoms (although the Nugent score has been cited as an oversimplification of the actual ecology of BV) (21); the same reasoning could apply to a molecular diagnosis of BV.

In a non-blinded randomized controlled trial (RCT) of women with asymptomatic BV (defined by a Nugent score ≥7 and lack of report of a vaginal odor and/or discharge), women randomized to a 5-day regimen of intra-vaginal MTZ gel followed by twice weekly use for 6 months had a significantly longer time to development of incident STIs (chlamydia, gonorrhea, trichomoniasis, HSV infection, and/or PID) than women in the observation-only group (p=0.02) (51). At 6 months, the incident STI rate was 1.58 per person-year (95% CI 1.29, 1.87) in the MTZ gel group vs. 2.29 per person-year (95% CI 1.95, 2.63) in the observation-only group. This difference in STI rates was primarily driven by a significant difference in the number of incident chlamydial infections (p=0.013). The authors hypothesized that women with BV have an indole-rich environment in their vaginal microbiota (produced by certain BV-associated bacteria [BVAB] such as Prevotella spp.) (52) which promotes the production of tryptophan and enhances the ability of chlamydia to survive in the female genitourinary tract (51). In the absence of an indole-rich environment, the host immune system (i.e. interferon-gamma, a host pro-inflammatory cytokine known for its anti-chlamydia properties) depletes tryptophan which may eradicate chlamydia by tryptophan starvation (52). Treatment of asymptomatic BV and normalization of the vaginal microbiota in the intervention arm of this study potentially contributed to the decrease in incident chlamydial infections by this mechanism.

Regarding sexual transmission of BV, multiple studies have found that the genital microbiota of men’s urethral, urine, and semen specimens contain BVAB also found in the vagina (53-56). Eren et al found strong correlations of G. vaginalis [present in 95-100% of cases of BV (57-60)] oligotypes between genital microbiome specimens of male and female sexual partners, supportive of sexual exchange (56). Zozaya et al found that the penile skin and urethral microbiota of male partners of women with BV were more similar to the vaginal microbiota of their female partners compared to non-partner women with BV (53). A recent prospective study of 252 heterosexual couples found that increasing relative abundance of several BVAB (i.e. Dialister spp., Megasphaera spp., and Brevibacterium spp.) in male penile microbiomes (meatal and/or glans/coronal sulcus) was significantly associated with an increased odds of BV in their female sexual partners (45). In a pilot study of 22 heterosexual couples in which women had symptomatic BV, treatment of male partners with oral MTZ (400 mg twice daily for 7 days) and topical clindamycin cream (2% twice daily for 7 days) resulted in a reduction in the prevalence and abundance of BVAB in the male glans/coronal sulcus at 8 days following treatment, although this effect did not persist at 28 days (61). The investigators hypothesized that BVAB may reside in the prostrate or persist in the male urethra following treatment, subsequently proliferating in its absence. Interestingly, loss of the treatment effect at 28 days did not always lead to re-emergence of BVAB in the vaginal microbiome of the men’s female sexual partners, suggesting that sexual transfer of genital microbiota is not easily measured (61). A phase 3 randomized, double-blinded trial to evaluate the efficacy of oral MTZ 400 mg and topical 2% clindamycin cream applied to the glans penis and upper shaft (under the foreskin if uncircumcised), both twice daily for 7 days, is currently underway (Australia New Zealand Clinical Trials Registry #12619000196145). In addition, a phase 3 multi-center randomized, double-blinded trial to evaluate the efficacy of 7 days of oral MTZ versus placebo for treatment of male sexual partners of women with recurrent BV is also occurring (NCT02209519).

With regards to female-to-female sexual transmission of BV, a high level of concordance of BV status (by Nugent score) has been found in women and their female sexual partners, suggestive of sexual transmission of BVAB (62). A recent prospective study of women who have sex with women (WSW) with normal baseline vaginal microbiota found that, among women who developed incident BV (iBV) compared to those who did not, the relative rate of any sexual activity prior to iBV was 40% higher (p=0.010), sex with a woman was 38% higher (p=0.038), digital-vaginal sex was 57% higher (p=0.005), and digital-anal sex was 5.6 times higher (p<0.001). Sexual activity occurred in 93% of WSW with iBV at a median of 4 days (95% confidence interval, 2-6) prior to BV onset (43). Another recent prospective study of WSW found that specific clades of G. vaginalis were associated with differing sexual behavioral practices, with acquisition occurring through sexual activity (44).

In addition to the strong body of epidemiological and microbiological data supporting the sexual transmission of BV, another potential reason for treating asymptomatic BV is that some women actually have symptomatic BV (i.e. vaginal discharge, odor, etc.) but do not recognize these symptoms as an infection (21). In a large study of 1,063 women with BV (diagnosed by Nugent score ≥7), 372 women (35.1%) denied any genital symptoms upon direct, detailed, and explicit questioning while 148 women (13.9%) reported that their vaginal odor was “pleasant” (2). Additionally, among women with BV but without complaints of vaginal discharge in this study, clinicians noted a thin, homogeneous vaginal discharge on pelvic examination 35% of the time. Thus, there may be a fairly substantial margin of error in women’s report of their lack of vaginal symptoms while being evaluated for BV and other vaginal infections, erroneously leading to a diagnosis of asymptomatic BV when this should have been diagnosed as symptomatic infection.

BV is also known to be associated with surgical site infections such as post-hysterectomy vaginal cuff cellulitis (63). In a randomized trial, preoperative treatment with metronidazole resulted in a significantly lower rate of vaginal cuff infections in women with BV who underwent hysterectomy compared to those who did not receive treatment for BV (64). Screening women for BV prior to hysterectomy and treating patients who are positive, regardless of symptoms, is a cost-effective option for preventing vaginal cuff infections (63, 65). In a cost comparison study comparing 3 strategies for women undergoing elective hysterectomy, “treating all patients for BV” was associated with a vaginal cuff infection rate of 4.0% and a mean cost of $593, “testing all patients for BV and treating if positive” was associated with a 4.2% cuff infection rate and mean cost of $623, and “neither testing or treating patients for BV” was more expensive and less effective than the other strategies (65). Thus, we are in favor of screening and treating asymptomatic BV prior to elective hysterectomy to prevent post-operative complications.

BV is also associated with infertility in women. In a systematic review and meta-analysis published in 2013 (16), the estimated prevalence of BV in infertile women across 12 studies including 3,229 patients was 19% (95% CI 14-25%). BV was significantly more prevalent in women with tubal infertility compared to antenatal women in the same population (odds ratio [OR] 3.32, 95% CI 1.53-7.20). BV was not associated with decreased conception rates (OR 1.03, 95% CI 0.7-1.33). Similarly, none of the studies found an association between abnormal vaginal flora and conception rates following in vitro fertilization (IVF) treatment. BV was associated with a significantly elevated risk of preclinical pregnancy loss (OR 2.36, 95% CI: 1.24-4.51) but not with an increased risk of first trimester miscarriage (OR 1.20, 95% CI 0.53-2.75). These findings suggest that BV may have a role in both the etiology and pregnancy outcomes of infertility patients which provides additional rationale for treating asymptomatic BV. One limitation of this analysis was that the studies included were cross-sectional and do not allow for causal inferences.

In a more recent systematic review published in 2019 (66), the risks associated with BV in IVF patients using meta-analysis was conducted. A total of 12 studies were eligible, comprising 2,980 patients. The prevalence of BV was 16% (95% CI 15-18%) in the general study population and tubal factor infertility was highly prevalent in women with BV compared with normal vaginal microbiota patients (p=0.001). Despite a significant association with early spontaneous abortion [relative risk (RR) 1.68, 95% CI 1.24-2.27], BV did not significantly impact the live birth rate (RR 1.47, 95% CI 0.96-1.57) or the clinical pregnancy rate (RR 0.93, 95% CI 0.75-1.15). However, the quality of evidence in this study was very low and the equivocal results justify the need for further research. Nevertheless, these results suggest that infertile women, including those undergoing IVF, should be screened and treated for asymptomatic BV, due to potential adverse outcomes that may occur.

An additional rationale for treating asymptomatic BV is that menses and sexual activity can lead to fluctuations in vaginal bacterial community composition over time, at times rapidly (67-69). These inciting events may cause women with asymptomatic BV to become symptomatic, thus requiring treatment, however, women may not be able to or not want to access care during these times for diagnosis and treatment. Multiple studies have found that women frequently and erroneously self-treat their vaginal symptoms with over-the-counter (OTC) medications, most commonly anti-fungal medications for vaginal yeast infection, delaying appropriate therapy and adding to subsequent health care costs (70, 71).

With regards to the cost of treatment for asymptomatic BV, MTZ is one of the most affordable medications for any STI (72). As of September 11, 2020, a 7 day course of oral MTZ 500 mg twice daily in the U.S. is only $7.77 (https://www.goodrx.com/metronidazole). In contrast, the estimated annual global economic burden of treating symptomatic BV is U.S. $4.8 (95% CI, $3.7-$6.1) billion ($1.3 billion for symptomatic cases in the U.S.), with more than half of this cost due to recurrent disease. This cost is nearly tripled when including costs of BV-associated preterm births and HIV cases, with African American women bearing a disproportionate burden of this cost (1).

Evidence against Treatment of Asymptomatic BV

Although there is a wealth of evidence in favor of treating asymptomatic BV, there are some limitations to these data. Multiple limitations of the unblinded RCT randomizing women with asymptomatic BV to a 5-day regimen of intra-vaginal MTZ gel followed by twice weekly use for 6 months vs. observation-only to prevent development of incident STIs have been discussed (73). These include the relatively small sample size (n=107 with 53 women in the intervention group vs. 53 in the observation-only group) of only high-risk women (i.e. those seeking care in a STD clinic) limiting generalizability, no use of placebo, no measure of compliance in the MTZ gel group, and a limited follow-up period of 6 months. In addition, the protective effect from incident STI acquisition in the MTZ gel group was limited to the first 3-4 months of the study. It has been suggested that larger, blinded, placebo-controlled studies with inclusion of low-risk women followed for a longer period of time are needed prior to broadly recommending treatment of asymptomatic BV (73).

With regards to screening and treatment of asymptomatic BV in pregnant women to prevent adverse birth outcomes, the U.S. Preventive Services Task Force (USPSTF) recently provided an updated 2020 statement on this topic since their prior 2008 report (74, 75); the updated statement includes a review of 44 studies (from 48 publications) (76). Since the prior 2008 USPSTF recommendation, only 1 large applicable trial (i.e. the PREMEVA trial) has been published (77) and the overarching recommendations in the USPSTF report remain essentially unchanged (78). Overall, among 10 clinical trials reporting findings from general obstetric populations (n=7,953), the evidence continues to suggest no difference in the incidence of preterm delivery and related outcomes for the treatment of asymptomatic BV during pregnancy. Data continue to be inconclusive for women with prior preterm delivery (3 trials showed a significant beneficial effect (79-81), 2 trials showed no benefit (82, 83), and one trial showed harm (84). Maternal adverse events from treatment across 8 trials were infrequent and minor (i.e. vaginal candidiasis) but were slightly more common among treated women compared to women receiving placebo. The evidence on harms from in utero exposure were inconclusive. The USPSTF concluded that additional studies are needed to evaluate screening and treatment of asymptomatic BV in pregnancy, particularly for women at increased risk for preterm delivery (76). Women at increased risk for preterm delivery may include those with cervical insufficiency, multi-fetal gestation, low maternal body mass index (BMI), maternal age (i.e. young or advanced age), and certain race/ethnicities (African American, Native Hawaiian/Other Pacific Islander, or American Indian/Alaska Native) (78). Although not specifically reviewed in the 2020 USPSTF statement, there is some concern that prenatal antibiotic exposure is associated with alterations in the neonatal gut microbiome which may adversely affect the development of the infant immune system and influence post-natal health (85). However, the currently available data are heterogeneous and give insufficient attention to confounding variables.

There are several limitations of the studies included in the 2020 USPSTF report that merit mention (76). These include no data to directly evaluate health benefits and harms of screening for BV in pregnancy. In addition, studies assessing the benefit of treatment of asymptomatic BV in pregnancy were heterogeneous and varied with respect to methodological quality, dose and duration of BV treatment, adherence to treatment, test of cure, and documentation of recurrent disease. With respect to harms, the trials included were underpowered for maternal adverse events. Finally, the trials included was limited to treatment of asymptomatic BV in pregnancy with MTZ and clindamycin and did not include data on other treatments, as they have not been as rigorously studied in pregnant women. There is also concern that the terms “symptomatic” and “asymptomatic” need better definition, especially in pregnancy (78).

With regards to the treatment of BV itself, recurrence rates at 6-12 months are high (in excess of 50%) with the use of currently recommended therapies, reflective of an incomplete understanding of BV pathogenesis and whether current treatments are targeting the appropriate vaginal bacterial communities (32, 86). These high rates of BV recurrence have led investigators to evaluate a wide range of alternative treatment approaches, including extended and suppressive antimicrobial regimens beyond initial therapy in addition to combination first-line regimens and adjunctive intra-vaginal and oral probiotic therapies, as reviewed in (32). To date, there has been limited progress in achieving long-term cure following cessation of any of these treatment regimens (32). Complications of antimicrobial treatment, including gastrointestinal upset and vaginal yeast infection (40), can also occur. In this setting, current treatment of asymptomatic BV is unlikely to lead to a long-term “cure,” which can understandably be frustrating and psychologically taxing for patients and their partners, particularly in the setting of an absence of symptoms. As novel BV therapeutics are developed moving forward, future studies should be conducted to determine if their use in asymptomatic BV is associated with a reduction of the known complications of infection. Vaginal microbiota transplant is a new provocative treatment option for women with BV that is currently being studied (NCT03769688, NCT04046900); a universal donor screening approach was recently

BV may also be a transient temporary situation and the vaginal microbiota may, at times, revert back to a non-BV state in the absence of treatment. A shift from a BV to non-BV state (based on Nugent score) was noted to occur in 4/14 (28.6%) women with incident BV (defined as a Nugent score of 7-10 on at least 2 consecutive days) in a recent prospective vaginal microbiome study of WSW (69). In this study, the spontaneous shift from a BV to non-BV state occurred relatively rapidly across 2-4 days among these women, with 3 of the 4 women (K018, K026, and K028) experiencing this shift after their menses ceased. Along these lines, it may not make sense to treat asymptomatic BV, especially if diagnosed in the context of menses. However, larger studies are needed to confirm and extend these results.

Conclusion

In summary, asymptomatic BV is a highly prevalent condition in women although its natural history has been infrequently studied. It is also unknown if asymptomatic BV is a milder form of infection than symptomatic BV and whether their pathogenesis, response to antibiotic therapy, or complication rates differ. These topics should be active areas of future research. Because of this lack of data, there is controversy regarding whether asymptomatic BV should be treated in women, including those that are pregnant, to prevent adverse outcomes of infection including risk of acquisition of HIV/other STIs and adverse birth outcomes. The cornerstone of this controversy is whether or not BV is an STI. In addition, its pathogenesis and exact etiology remain incompletely understood which directly influences advances in BV diagnosis, treatment, and prevention. Additional studies are needed to further investigate the pathogenesis of BV, its method of transmission (most likely sexual), and the role of the BV biofilm in the high rates of recurrent disease. Future studies of the composition of the vaginal microbiota among women with BV, stratified by symptom status, are also needed to determine if there are any significant differences. If no significant differences are found, it may be difficult to justify not treating asymptomatic BV given its known adverse outcomes and the high likelihood that it is sexually transmitted.