INTRODUCTION — Bacterial vaginosis (BV) is a clinical condition characterized by a shift in vaginal microbiota away from Lactobacillus species toward more diverse bacterial species, including facultative anaerobes. The altered microbiome causes a rise in vaginal pH and symptoms that range from none to very bothersome. Future health implications of BV include, but are not limited to, increased susceptibility to other sexually transmitted infections and preterm birth.
This topic will discuss the pathogenesis, clinical presentation, and treatment of BV. Related topics on the treatment of BV, evaluation of vaginitis, and cervicitis are presented separately.
●(See "Bacterial vaginosis: Treatment".)
●(See "Acute cervicitis".)
DEFINITION — BV is characterized by three alterations in the vaginal environment :
●A shift in vaginal microbiota from Lactobacillus species to one of high bacterial diversity, including facultative anaerobes.
●Production of volatile amines by the new bacterial microbiota.
●Resultant rise in vaginal pH to >4.5 (normal vaginal pH of estrogenized women ranges from 4.0 to 4.5). (See "Approach to females with symptoms of vaginitis", section on 'Vaginal pH'.)
EPIDEMIOLOGY — BV is the most common cause of vaginal discharge in women of childbearing age, accounting for 40 to 50 percent of cases [2-4]. In the United States, the National Health and Nutrition Examination Survey (NHANES), which included results from self-collected vaginal swabs from over 3700 women, estimated the prevalence of BV was 29 percent in the general population of women aged 14 to 49 years and 50 percent in African American women . This included both symptomatic and asymptomatic infection. Worldwide, a meta-analysis of studies from seven regions of the world found that the prevalence of Nugent-diagnosed BV was 23 to 29 percent among women of reproductive age, with small variations according to the population studied [6,7]. The health consequences of BV infection are presented below. (See 'Consequences of infection' below.)
PATHOGENESIS AND MICROBIOLOGY
●Altered vaginal microbiota and dysbiosis – BV represents a complex change in the vaginal microbiota characterized by a reduction in concentration of the normally dominant hydrogen peroxide-producing lactobacilli and an increase in concentration of other organisms, especially anaerobic Gram-negative rods [8-12]. Ethnicity and age are additional factors that appear to impact the vaginal microbial community . The absence of inflammation is the basis for the term "vaginosis" rather than "vaginitis." Some authors use the term "dysbiosis" to reflect the microbial imbalance in the vaginal microbiota that can ultimately impact vaginal function and lead to negative health consequences [14,15]. (See 'Consequences of infection' below.)
The major bacteria detected in women with BV are Gardnerella vaginalis, Prevotella species, Porphyromonas species, Bacteroides species, Peptostreptococcus species, Mycoplasma hominis, and Ureaplasma urealyticum, as well as Mobiluncus, Megasphaera, Sneathia, and Clostridiales species [8,16]. Fusobacterium species and Atopobium vaginae are also common.
The difference in vaginal microbiota between women with and without BV was illustrated in a study that used broad range DNA probes to determine the vaginal microbiota of 27 women with BV and 46 controls . Overall, 35 bacterial phylotypes were identified in women with BV, including 16 which were newly recognized. Women with BV had a mean of 12.6 phylotypes (range 9 to 17) per sample compared with 3.3 phylotypes (range 1 to 6) per sample in women without BV. The organisms newly identified by polymerase chain reaction include fastidious bacteria termed "BV-associated bacteria 1, 2 and 3" in the Clostridiales order, which appear to be specific indicators of BV . Subsequent studies have documented several other bacterial species in the human vagina, including the novel strains Peptoniphilaceae DNF01163 and Prevotellaceae DNF00733 [18-21].
●Production of amines – Hydrogen peroxide-producing lactobacilli appear to be important in preventing overgrowth of the anaerobes normally present in the vaginal microbiota. With the loss of lactobacilli, pH rises and massive overgrowth of vaginal anaerobes occurs. These anaerobes produce large amounts of proteolytic carboxylase enzymes, which break down vaginal peptides into a variety of amines that are volatile, malodorous, and associated with increased vaginal transudation and squamous epithelial cell exfoliation, resulting in the typical clinical features observed in patients with BV (see 'Clinical features' below). The rise in pH also facilitates adherence of G. vaginalis to the exfoliating epithelial cells.
●Role of biofilm – Increasing evidence suggests that G. vaginalis is the key player in the pathogenesis of BV and the development of a biofilm may be an essential component of this process, in addition to the gradual overgrowth of resident anaerobic vaginal microbiota [22-28]. In this model, a cohesive form of G. vaginalis adheres to the vaginal epithelium and then becomes the scaffolding to which other species adhere . This hypothesis is supported by a study of microbiota on the epithelial surfaces of vaginal biopsy specimens from women with BV that showed a biofilm adhered to part or all of the epithelium, and G. vaginalis comprised 90 percent of bacteria in the biofilm, while Atopobium vaginae accounted for most of the remainder . Subsequent desquamation of these epithelial cells would result in the classic clue cells diagnostic of the disorder (see 'Diagnosis' below). By contrast, most healthy controls had unstructured accumulations of bacteria within secretions loosely attached to epithelial surfaces.
Extracellular DNA (eDNA) is a factor in the structural stability of biofilms in a variety of bacterial species and appears to play an important role in the establishment and maintenance of the G. vaginalis biofilm in BV . The presence of a biofilm may make it difficult to eradicate BV and increase the rate of recurrence, but discovery of the role of eDNA has led to the hypothesis that a DNase might be able to destroy the eDNA that helps to maintain the BV biofilm.
●Sexual activity – While the majority of epidemiologic data support the hypothesis that BV is a sexually transmitted infection, it is not yet classified as such because of lack of a single causative agent and absence of a clear disease counterpart in males [16,31-35]. In addition, early studies reported mixed results on the impact of treatment of the male sexual partner [36-41]. However, a subsequent review of early negative or inconclusive studies reported that these studies lacked sufficient power to detect reasonable effect sizes, had deficient or inadequately reported randomization methods, and lacked information on adherence to therapy .
Sexual activity is a risk factor for BV, and most experts believe that BV does not occur in women who have never had sexual contact of any type, including receptive oral sex [43,44]. Epidemiologic studies are strongly supportive of sexual transmission of BV pathogens. In a systematic review and meta-analysis of 43 observational studies, sexual contact with new and multiple male and female partners was associated with an increased risk of BV, while condom use was associated with a decreased risk . Many BV-associated species have been isolated from the male penile skin, semen, urethra, and urine specimens, and the penile microbiome has been reported to correlate with incident BV infections [45-47].
BV is highly prevalent (25 to 50 percent) in women who have sex with women (WSW), and is associated with increasing numbers of female sexual partners, a female partner with symptomatic BV, and various sexual practices, suggesting sexual transmission is an important factor [48-53]. However, in one study, sexually active monogamous WSW partnerships over six months tended to have concordant, stable, vaginal microbiota, which was most concordant for normal microbiota . This suggests that longer duration, sexually active partnerships led to stability and alignment of a favorable vaginal microbiota in WSW couples. Accordingly, the majority of investigators believe that BV, as an original or first infection or occurrence, is sexually transmitted. However, in contrast to trichomoniasis, chlamydial, or gonococcal infection, there is also a high rate of symptomatic recurrence of BV in the absence of sexual activity or reinfection.
●Sexually transmitted infections – The presence of other sexually transmitted infections appears to be associated with an increased prevalence of BV. In a systematic review and meta-analysis of studies evaluating the association between BV infection and herpes simplex virus (HSV) type 2 infection, women infected with HSV-2 had a 55 percent higher risk of BV infection compared with women who were HSV-2 uninfected . Similarly, a five-year prospective cohort study reported that BV was both more prevalent and more persistent among HIV-infected women compared with those without HIV . Conversely, BV may also be a risk factor for HIV acquisition . (See "HIV and women", section on 'Bacterial vaginosis, genital ulcers, and pelvic inflammatory disease'.)
●Race and ethnicity – While higher rates of BV have been reported in minority populations, it is not clear if this finding reflects genetic, socioeconomic, behavioral, or other differences [5,13,57,58]. In the United States NHANES 2001 to 2004 study, the rates of BV based on self-collected swabs were 51 percent for African-American women, 32 percent for Mexican-American women, and 23 percent for women of European ancestry . By contrast, in a small study comparing the vaginal microbiota of White women and Black women by both cultivation-dependent and cultivation-independent methods, there were no differences in colonization and density of bacterial species by race once women with BV by Nugent criteria were removed .
●Other – In addition to sexual and infectious risk factors, most studies indicate that douching and cigarette smoking are risk factors for acquisition of BV among sexually active women [2,3,50,60-65]. Although some degree of genetic susceptibility to BV is likely, no association between a gene polymorphism and BV has been established . One questionnaire study reported an association between high fat diets and BV as well as an inverse relationship for BV with the intakes of folate, vitamin E, and calcium . While these dietary factors were associated with BV, further studies are needed to determine causality. One study that evaluated Nugent scores for nearly 6000 women reported that overweight (body mass index [BMI] 25.0 to 29.9 kg/m2) and obese (BMI ≥30 kg/m2) women had higher Nugent scores and rates of BV compared with women of normal BMI (BMI 18.5 to 24.9 kg/m2) . The prevalence rates of BV were 21, 30, and 35 percent for lean, overweight, and obese BMIs, respectively. Black women had a greater prevalence of BV, independent of body mass. Of note, BV is not associated with chronic medical conditions (eg, diabetes) or immunosuppressive states.
CLINICAL FEATURES — Fifty to 75 percent of women with BV are asymptomatic [43,68,69]. Symptomatic women typically present with vaginal discharge and/or vaginal odor [43,68,69]. The discharge is off-white, thin, and homogeneous; the odor is an unpleasant "fishy smell" that may be more noticeable after sexual intercourse and during menses [70,71].
BV alone typically does not cause dysuria, dyspareunia, pruritus, burning, or vaginal inflammation (erythema, edema) [68,69]. The presence of these symptoms suggests mixed vaginitis (symptoms due to two pathogens) . However, symptoms are poorly predictive of diagnosis; thus, all symptomatic women should undergo examination and evaluation .
CONSEQUENCES OF INFECTION
●Pregnant women with BV are at higher risk of preterm delivery [75-78]. (See "Bacterial vaginosis: Treatment", section on 'Pregnant persons'.)
●BV is a risk factor for [79-81]:
•Endometrial bacterial colonization
•Posthysterectomy vaginal cuff cellulitis
●BV is a risk factor for HIV acquisition and transmission [56,82,83].
●BV is a risk factor for acquisition of herpes simplex virus type 2, gonorrhea, chlamydia, and trichomonas infection [84-86].
It has been hypothesized that the increased risk of acquisition of sexually transmitted infections in women with BV may be due to lack of hydrogen peroxide-producing lactobacilli in the vaginal microbiota of affected women; other factors associated with BV infection, such as local cytokine production, may also play a role.
●BV is more common among women with pelvic inflammatory disease (PID). While it is not clear whether it is a causal factor or an independent risk factor for this disease [87,88], BV-associated organisms have been found in the endometrium in women with PID who do not have any other causes identified .
●BV may be a factor in development of precancerous cervical lesions. In a systematic review and meta-analysis of primarily cross-sectional studies, the risk of cervical intraepithelial neoplasia (CIN) or squamous intraepithelial lesions (SIL) was increased in women with BV (odds ratio 1.51, 95% CI 1.24-1.83); however, there was considerable heterogeneity among these studies and both CIN 1 and low-grade SIL, which do not usually progress to cancer, were included as outcomes . BV appears conducive to the persistence of human papillomavirus infection [91,92], which is necessary but not sufficient for development of high-grade cervical lesions and cancer. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention", section on 'Role of human papillomavirus'.)
DIAGNOSIS — The general diagnostic approach to women with vaginal discharge is reviewed separately. (See "Approach to females with symptoms of vaginitis".)
In clinical practice, the diagnosis of BV in premenopausal women is usually based upon the presence of at least three Amsel criteria (characteristic vaginal discharge, elevated pH, clue cells, fishy odor) if microscopy is available (figure 1) [93,94]. Use of Nugent or Hay/Ison criteria to evaluate a Gram-stained smear of vaginal discharge is the diagnostic standard in research studies, but doing so requires more time, resources, and expertise . If microscopy is not available, the diagnosis should be based upon findings on clinical examination (characteristic vaginal discharge, elevated vaginal pH, fishy odor). In one study of eight clinics affiliated with an academic medical center, even these simple tests were infrequently used to assess the 303 symptomatic women enrolled: pH was assessed in 15 percent of cases and whiff test in 21 percent . Although the presence of discharge was evaluated in 100 percent of cases, 30 percent of participants with BV diagnosed by the study gold standard received inadequate treatment, and 23 percent of participants without BV received inappropriate treatment.
Commercial tests approved by the US Food and Drug Administration (FDA) that have acceptable performance compared with Gram stain include a DNA probe-based test for high concentrations of G. vaginalis (BD Affirm VPIII), vaginal fluid sialidase activity test (OSOM BVBlue test), and two polymerase chain reaction (PCR)-based assays that target several BV-associated species (BD Max, Aptima BV). Use of the proline-aminopeptidase test card (Pip Activity TestCard) is no longer recommended because of low sensitivity and specificity.
Amsel criteria — The diagnosis of BV is usually based on Amsel criteria, which are simple and useful in an office practice where microscopy is available [68,71]. The first three findings are sometimes also present in patients with trichomoniasis (table 1).
Amsel criteria for diagnosis of BV (at least three criteria must be present) :
●Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls.
●Vaginal pH >4.5.
●Positive whiff-amine test, defined as the presence of a fishy odor when a drop of 10 percent potassium hydroxide (KOH) is added to a sample of vaginal discharge.
●Clue cells on saline wet mount (picture 1A-B and figure 1). Clue cells are vaginal epithelial cells studded with adherent coccobacilli that are best appreciated at the edge of the cell (picture 2). For a positive result, at least 20 percent of the epithelial cells on wet mount should be clue cells. The presence of clue cells diagnosed by an experienced microscopist is the single most reliable predictor of BV .
Mobiluncus species may be noted on microscopy as well (movie 1).
Using Gram stain as the standard for diagnosing BV, the sensitivity of Amsel criteria for diagnosis of BV is over 90 percent and specificity is 77 percent .
Gram stain — Gram stain of vaginal discharge is the gold standard for diagnosis of BV (picture 3A-B) , but is mostly performed in research studies because it requires more time, resources, and expertise than Amsel criteria [99-101]. The Gram-stained smear is evaluated using Nugent criteria (table 2) or Hay/Ison criteria (table 3). If clinical criteria are used to define infection, then reported sensitivity ranges from 62 to 100 percent .
Cytology — The Papanicolaou smear is not reliable for diagnosis of BV (sensitivity 49 percent, specificity 93 percent) . No information is available on the sensitivity and specificity of liquid-based cervical cytology screening methods. If a cytology smear suggests BV (ie, shift in microbiota from predominantly lactobacilli to predominantly coccobacilli with or without clue cells), the patient should be asked about symptoms, and if symptomatic, she should undergo standard diagnostic testing for BV and treatment, if appropriate. Treatment of asymptomatic women is not routinely indicated. (See "Bacterial vaginosis: Treatment", section on 'Nonpregnant asymptomatic females'.)
Culture — Because BV represents complex changes in the vaginal microbiota, vaginal culture has no role in diagnosis. Although cultures for G. vaginalis are positive in almost all women with symptomatic infection, the organism is detected in up to 50 to 60 percent of healthy asymptomatic women; thus, its presence alone, no matter how identified, is not diagnostic of BV.
Commercial tests — Commercial tests for diagnosis of BV are now increasingly used, given increase in availability and the failure of clinicians to efficiently utilize microscopy and pH measurement.
The Affirm VPIII test is an automated DNA probe assay for detecting G. vaginalis when present at a high concentration . It takes less than one hour to perform and is a fast option when findings on physical examination suggest BV (characteristic vaginal discharge and results of pH and whiff test, if available) but microscopy cannot be performed to look for clue cells. In one study, for example, the combination of a positive DNA probe (concentration of G. vaginalis ≥2 times 107 CFU/mL) and vaginal pH >4.5 had a sensitivity and specificity of 95 and 99 percent, respectively, for diagnosis of BV when clinical criteria were used as the diagnostic standard . Not all studies have reproduced these initial excellent results, and overdiagnosis is possible. Moreover, superior sensitivity and specificity are now reported for PCR testing .
The OSOM BVBlue system is a chromogenic diagnostic test based on the presence of elevated sialidase enzyme activity in vaginal fluid samples. This enzyme is produced by bacterial pathogens associated with BV including Gardnerella, Bacteroides, Prevotella, and Mobiluncus. The test can be performed at the point of care, and results are available in 10 minutes (Clinical Laboratory Improvement Amendments [CLIA]-waived). Sensitivity ranging from 88 to 94 percent and specificity ranging from 91 to 98 percent have been reported when compared with Amsel and Nugent criteria [107-109]. This test is now infrequently performed.
Molecular tests that assay the vaginal microbiome for evidence of BV, vaginal candidiasis, and trichomonas have shown promise in clinical studies, and two assays have been approved by the FDA for use [110-112]. The vaginal specimen swab can be collected by a clinician or the patient.
The BD Max system uses quantitative PCR measurement of G. vaginalis, Atopobium vaginae, Megasphaera-1, BV-associated bacteria 2, L. crispatus, L. jensenii, and a proprietary algorithm to provide a positive/negative assessment for the presence of BV. In a study of 1763 symptomatic women, the sensitivity of the assay compared with a combination of Nugent score and Amsel criteria was 90.5 percent (95% CI 88.3-92.2) and specificity was 85.8 percent (95% CI 83.0-88.3) . The Aptima BV is a nucleic acid amplification test that measures the presence of Lactobacillus, G. vaginalis, and A. vaginae. In a study that included 1501 symptomatic women, the sensitivity compared with a combination of Nugent score and Amsel criteria was 95 percent (95% CI 93.1-96.4) and specificity was 89.6 percent (95% CI 87.1-91.6) . Although these tests have good sensitivity and specificity compared with standard clinical tests , cost may be prohibitive .
Lastly, a urine test that uses fluorescence in situ hybridization to identify the BV biofilm on desquamated vaginal epithelial cells in urine sediment appears promising and is also under investigation .
Diagnosis without speculum examination — BV has been diagnosed using a swab of vaginal discharge obtained by the patient or clinician without physical examination. However, omission of the speculum examination results in under-diagnosis and should be avoided. Additionally, a speculum examination facilitates evaluation for alternative or concurrent diagnoses, such as cervicitis, pelvic inflammatory disease, or retained objects.
●In one study, young women with or without vaginitis symptoms self-tested for BV using a pH or sialidase test and results were compared with clinician-performed examination with clinical diagnosis of BV by modified Amsel criteria . Compared with diagnosis by clinician examination, self-pH was 73 percent sensitive and 67 percent specific and self-sialidase was 40 percent sensitive and 90 percent specific.
●In another study of the diagnostic accuracy for BV among women presenting with vaginal discharge to a sexually transmitted diseases (STD) clinic, all women provided self-obtained vaginal swabs for examination, completed a questionnaire, and then were examined by a clinician . A nonexamining clinician reviewed the findings of the questionnaire and self-obtained vaginal swab and diagnosed BV if at least two of three Amsel criteria were positive (pH >4.5, >20 percent clue cells, positive Whiff test). Examining clinicians diagnosed BV if at least three of the four standard Amsel criteria were positive (characteristic discharge, pH >4.5, >20 percent clue cells, positive Whiff test). In all cases, Gram-stained slides for diagnosis of BV by Nugent criteria were made, but the results were not disclosed, and 125 were positive. The investigators found that clinical examination with a speculum examination was more likely to result in a correct diagnosis of BV than just examination of a self-obtained vaginal swab (90/125 versus 68/125), but also resulted in over-diagnosis/over-treatment in 15 patients (105 positive diagnoses versus 61 positive diagnoses).
●In studies of both PCR-based diagnostic platforms, self-collected swabs had a similar sensitivity and specificity for diagnosis of BV as clinician-collected swabs [110,113]. However, as noted above, we advise a complete examination, especially at first presentation or in cases of recurrent symptoms, to evaluate for alternative diagnoses.
DIFFERENTIAL DIAGNOSIS — Although supporting data are lacking, in our experience, in the absence of microscopy, a lack of fishy odor (negative whiff test) makes the diagnosis of BV unlikely. BV is usually suspected because of high vaginal pH (>4.5). Other causes of increased pH include trichomoniasis, atrophic vaginitis, and desquamative inflammatory vaginitis. These four entities are easily distinguishable by clinical and microscopic features.
●Women with BV do not have dyspareunia or signs of vaginal inflammation; by contrast, women with atrophic vaginitis, desquamative inflammatory vaginitis, and trichomoniasis usually have these signs and symptoms.
●Both atrophic vaginitis and desquamative inflammatory vaginitis are associated with an increased number of parabasal cells on microscopy, which is not observed in women with BV.
●A large number of polymorphonuclear leukocytes on microscopy are characteristic of desquamative inflammatory vaginitis, trichomoniasis, and atrophic vaginitis with infection, but not BV.
●Visualization of trichomonads readily makes the diagnosis of trichomoniasis in the setting of an elevated pH; however, in other cases, we suggest using more sensitive and specific diagnostic tests to diagnose or exclude trichomoniasis. (See "Trichomoniasis", section on 'Diagnosis'.)
●Mixed infections with BV and a second pathogen, either T. vaginalis or Candida species, are not infrequent, with clinical and laboratory findings reflecting features of both entities.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial vaginosis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Bacterial vaginosis (The Basics)")
●Beyond the Basics topics (see "Patient education: Bacterial vaginosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Bacterial vaginosis (BV) is characterized by a shift in vaginal microbiota, production of volatile amines, and resultant rise in vaginal pH. BV is the most common cause of vaginitis in women of childbearing age. (See 'Definition' above and 'Epidemiology' above.)
●BV represents a complex change in the vaginal microbiota characterized by a reduction in concentration of the normally dominant hydrogen peroxide- and lactic acid-producing lactobacilli and an increase in concentration of other organisms, particularly anaerobic and highly specific fastidious BV-associated bacteria. Vaginal wall biofilms, comprised predominantly of Gardnerella vaginalis, appear to play a role in pathogenesis. (See 'Pathogenesis and microbiology' above.)
●Approximately 50 to 75 percent of women with BV are asymptomatic. Those with symptoms often present with an off-white, thin, and homogeneous "fishy smelling" discharge that is more noticeable after coitus and during menses. (See 'Clinical features' above.)
●Sequelae of BV can include an increased risk of preterm birth, plasma-cell endometritis, postpartum fever, posthysterectomy vaginal cuff cellulitis, postabortal infection, pelvic inflammatory disease, and acquisition of other sexually transmitted infections. (See 'Consequences of infection' above.)
●When microscopy is available, the diagnosis of BV is based on the presence of at least three of the following four Amsel criteria (see 'Diagnosis' above):
•Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls.
•Vaginal pH greater than 4.5.
•Positive whiff-amine test, defined as the presence of a fishy odor when 10 percent potassium hydroxide (KOH) is added to a sample of vaginal discharge.
●If microscopy is not available, we suggest using physical examination, pH testing, whiff-amine test, and commercial tests based upon polymerase chain reaction measurement of several bacterial species to make the diagnosis of BV. (See 'Commercial tests' above.)
●Vaginal culture is not useful for diagnosing BV. (See 'Culture' above.)