Obstetrics & Gynecology:
Higher-Risk Behavioral Practices Associated With Bacterial Vaginosis Compared With Vaginal Candidiasis
Bradshaw, Catriona Susan MD, FAChSHM; Morton, Anna N. MD, FAChSHM; Garland, Suzanne M. MD, FRCPA; Morris, Margaret B. BAppSci, RN; Moss, Lorna M. RN, RM; Fairley, Christopher K. MD, FRACP
From the Melbourne Sexual Health Centre, The Alfred Hospital, Melbourne, Victoria, Australia; School of Population Health, University of Melbourne, Melbourne, Victoria, Australia; Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; and Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.
The principle author, C.S.B., holds a National Medical and Research Council Research Scholarship.
The authors thank Leonie Horvath and Irene Kuzevska for their laboratory expertise and support with this project and all the practitioners at Melbourne Sexual Health Centre for recruitment of participants.
Reprints are not available. Address correspondence to: Catriona Bradshaw, Melbourne Sexual Health Centre, 580 Swanston Street, Carlton, 3053, Victoria, Australia; e-mail: firstname.lastname@example.org.
Objective: Bacterial vaginosis has been associated with hormonal factors and sexual practices; however, the cause is unclear, and the notion that bacterial vaginosis is a sexually transmitted infection is still debated. To investigate whether bacterial vaginosis is associated with specific sexual practices or instead has features in common with a sexually transmitted infection, we compared behavioral associations in women with bacterial vaginosis to women with vaginal candidiasis.
Methods: Women with symptoms of abnormal vaginal discharge or odor who attended Melbourne Sexual Health Centre between July 2003 and August 2004 were eligible for enrollment in the study. Information on demographics and behavioral and contraceptive practices were collected by self-completed questionnaire. Participants were tested for bacterial vaginosis, Candida spp (microscopy and culture), and sexually transmitted infections. Statistical comparisons were made between women with and without bacterial vaginosis and women with and without candidiasis, using univariate and multivariate analysis.
Results: A total of 342 women were enrolled in the study; 157 were diagnosed with bacterial vaginosis, 51 had candidiasis by microscopy, and 95 had candidiasis by culture. Bacterial vaginosis was associated with indicators of high-risk sexual behavior such as a new sexual partner and greater number of male partners in the last year, increased number of lifetime sexual partners, less than 13 years of education, a past history of pregnancy, and smoking (P < .05). Candidiasis was not associated with these risk behaviors and was instead related to practices such as receptive anal and oral sex and douching.
Conclusion: The association between bacterial vaginosis and practices that are associated with sexually transmitted infections, in contrast to those observed with candidiasis, suggests a possible sexually transmitted cause.
Level of Evidence: II-2
Bacterial vaginosis is the commonest cause of abnormal vaginal discharge in women of reproductive age worldwide. It is associated with serious sequelae such as spontaneous abortion,1,2 preterm delivery,1,3 and increased susceptibility to human immunodeficiency virus (HIV) and sexually transmitted infections.4,5 Despite an increasing understanding of the pathogenesis and sequelae, the cause of bacterial vaginosis remains unknown, and recurrence after treatment is common. Bacterial vaginosis has been associated with both hormonal factors and sexual practices; however, it is unclear whether the loss of normal vaginal flora observed with bacterial vaginosis, and the high rate of recurrence after treatment, occurs as a consequence of these factors or is the result of a sexually transmitted agent.
To clarify whether bacterial vaginosis is more likely to be associated with the sexual transmission of an infectious agent or specific practices, we compared behavioral factors associated with bacterial vaginosis with those associated with vaginal candidiasis. Candida spp are common commensals of the genital and gastrointestinal tract and a frequent cause of vaginal symptoms in women of reproductive age. Although sexual transmission may play a role in the pathogenesis of candidiasis, both colonization and symptomatic infection have been associated with specific host and hormonal factors, and candidiasis can occur in the absence of sexual activity. Estimating the contribution of specific sexual practices to bacterial vaginosis may assist in understanding its cause and the role of sexual transmission in disease pathogenesis and may ultimately lead to more effective treatment and prevention of recurrence.
MATERIALS AND METHODS
Women presenting to Melbourne Sexual Health Centre, Melbourne, Victoria, Australia, with symptoms of abnormal vaginal discharge or odor between July 2003 and August 2004 were eligible for enrolment in the study. Melbourne Sexual Health Centre is the principle public sexual health service in Melbourne, a city of 3.5 million people. It provides a free and confidential medical and counseling service for sexually transmitted infection and HIV diagnosis and management. Individuals can self-refer, and the center provides a “walk-in” triaged clinical service to facilitate prompt treatment of symptomatic sexually transmitted infections. Melbourne Sexual Health Centre provided more than 20,000 consultations during the period of the study; the majority (78.3%) of attendees were diagnosed with a clinical condition, whereas (21.7%) attended for an asymptomatic sexually transmitted infection screen. Participants were recruited during sexual health consultations on the basis of symptoms of abnormal vaginal odor or discharge to optimize recruitment of women with bacterial vaginosis. Women who were pregnant, HIV infected, postmenopausal, not fluent in English, menstruating, or had used lubricant or topical vaginal medication within the last 72 hours were excluded.
Considerable effort was made to offer all eligible women participation in the study during this period. A computerized alert system operated to remind clinicians during consultations to offer enrolment in the study, and triage nurses placed labels in files of patients they considered to be potentially eligible for the study. It was not possible to establish the participation rate in this study, because only medical diagnoses and not vaginal symptoms are recorded in the clinic database. However, the number of diagnoses of bacterial vaginosis recorded at Melbourne Sexual Health Centre during the study period was 279, and the number of diagnoses of clinical candidiasis was 348. These figures included women who did not fulfil the eligibility criteria for the following reasons: asymptomatic infection, HIV infection, menstruation on the day of examination, or use of vaginal lubricant or topical vaginal medication within the prior 72 hours. However, the figures did not include recurrent presentations within the study period. Although it is not possible to calculate the participation rate from the data available, 52% (n = 157) of all women diagnosed with bacterial vaginosis during this period entered the study. The diagnosis of vulvovaginal candidiasis in this study was based strictly upon microscopy results and secondarily on culture. The clinic database diagnosis of candidiasis is less restrictive than the study definition and may be entered according to clinical presentation with or without microscopy or culture; it therefore cannot be used to establish participation rate for the study.
Participants completed a questionnaire regarding symptomatology (symptom rating scale 1–5) and sexual and behavioral practices and underwent genital examination. Clinicians performed a speculum examination and recorded the appearance of the vaginal discharge and all clinical and laboratory findings on a standardized data collection sheet. A sample of vaginal secretions from the lateral wall was taken for vaginal pH (Spezialindikator strips pH 2–9, Merck & Co. Inc., NJ), microscopy (wet preparation and Gram stain), and the amine test.6 Evaluation of vaginal Gram-stained smears, wet preparations, and the amine tests was performed on-site by 2 laboratory staff trained in both the Nugent7 and Amsel6 methods, and the presence of yeasts, bacteria, and polymorphonuclear cells was recorded. The Nugent method is a standardized point scoring system (0–10) based on the presence of 3 bacterial morphotypes: large gram-positive rods (Lactobacillus spp), small gram-negative or gram-variable coccobacilli (Gardnerella and anaerobic spp), and curved gram-variable rods (Mobiluncus spp).7 A Nugent score of 0–3 is classed as normal flora, 4–6 as intermediate flora, and 7–10 as bacterial vaginosis. The Amsel method is a combined clinical and laboratory method in which bacterial vaginosis is diagnosed if 3 or more of the following findings are present: a characteristic homogenous white adherent vaginal discharge, a vaginal fluid pH more than 4.5, a positive amine test, and the presence of clue cells.6 Comparison of the diagnosis of bacterial vaginosis in this population using Nugent and Amsel criteria and the rapid diagnostic test, BVBlue, are reported elsewhere.8
Microscopy results and Nugent and Amsel scores were all available during the consultation. Bacterial vaginosis was defined in this study as a Nugent score of 7–10 and a Nugent score of 4–6 with 3 or more Amsel criteria, because the latter reflects women who are diagnosed with bacterial vaginosis and treated in clinical practice. The Nugent method was used as the principle method for diagnosis of bacterial vaginosis in this study as it has least interobserver and intraobserver variability and was able to be rescored by an independent microscopist. Because a considerable proportion of women with intermediate flora have 3 or more Amsel criteria, restricting the diagnosis of bacterial vaginosis to a Nugent score of 7–10 would have resulted in women with intermediate flora and a clinical diagnosis of bacterial vaginosis being regarded as negative.
Treatment for bacterial vaginosis was with 400 mg twice daily of oral metronidazole for 7 days or 2% vaginal clindamycin cream daily for 7 days, if metronidazole was not tolerated. If vaginal yeasts or pseudohyphae were detected on microscopy and symptoms of candidiasis were present, 6 days of intravaginal 1% clotrimazole was prescribed. Women underwent screening for Chlamydia trachomatis by strand displacement amplification (BD ProbeTec ET CT Amplified DNA Assay, Becton Dickinson & Co, Franklin Lakes, NJ), Neisseria gonorrhoeae by culture (modified Thayer-Martin medium), Trichomonas vaginalis by culture (modified Diamonds medium), and Candida spp were cultured in the modified Thayer-Martin and Diamonds media.
Patient samples, questionnaires and clinician checklists were labeled with a unique identifier to ensure confidentiality. The Human Research and Ethics Committee of the Department of Human Services, Victoria, approved this study.
Data were entered and stored in Microsoft Access (Microsoft Corp., Redmond, WA) and analyzed using SPSS 12 (SPSS Inc., Chicago, IL). In the analyses women with bacterial vaginosis were compared with women without bacterial vaginosis; this group included women with and without candidiasis (controls). Because the presence of Candida spp on microscopy was considered most likely to represent symptomatic candidiasis, women with Candida spp on microscopy were compared with women without Candida spp on microscopy; this group included women with and without bacterial vaginosis (controls). An analysis was also performed for women with Candida spp on culture, compared with women without Candida spp on culture. Women with concurrent bacterial vaginosis and candidiasis were treated as both bacterial vaginosis positive and Candida positive and were not excluded from analyses.
With 170 cases of bacterial vaginosis and 170 controls, this study had 80% power to detect an odds ratio of 2 or greater given an exposure rate of 20% in the controls. Proportions were compared using χ2 and Fisher exact tests where appropriate, and 95% confidence intervals were calculated. Univariate analysis was used to calculate crude odds ratios and 95% confidence intervals. A multiple logistic regression model was used to control for confounding factors and to determine which factors remained statistically significant. The variables included in the multivariate model were those significant on the univariate analysis at P < .05 and those considered important based on the published literature. Where factors were highly intercorrelated (eg, sexual partners in last 3 months are also counted in the variable sexual partners in the last 12 months), only 1 variable was included in the model. Patients were excluded from the analysis where clinical information or specimens were not available.
Three hundred forty-two women, presenting with symptoms of either abnormal vaginal odor or discharge were enrolled in the study. Their mean age (± standard deviation) was 28.8 ± 7.7 years. Bacterial vaginosis was diagnosed in 157 (46%) participants. One hundred thirty-eight women had a Nugent score 7–10. One hundred twenty-five (91%) women with a Nugent score of 7–10 had 3 or more Amsel criteria, and 13 women had less than 3 Amsel criteria but were considered positive for bacterial vaginosis in this study. Thirty-five women had intermediate flora (Nugent score 4–6), of whom 19 (54%) had 3 or more Amsel criteria, and 16 had less than 3 Amsel criteria; intermediate flora with less than 3 Amsel criteria was considered negative in this study.
Yeasts (pseudohyphae, budding yeasts, or both) were present on microscopy in 51 (15%) women, and Candida spp were present on culture in 95 (28%). All yeasts identified on microscopy were confirmed to be Candida spp by culture, and all cultured isolates were C albicans except for 2 (2%), which were C glabrata. Nine women (6%) had yeasts on microscopy and concurrent bacterial vaginosis, and 29 women (19%) had Candida spp on culture and bacterial vaginosis. Sexually transmitted infections were uncommon, with 6 cases of Chlamydia trachomatis, 2 cases of Neisseria gonorrhoeae, and 2 cases of Trichomonas vaginalis. All participants were HIV negative.
Table 1 shows the findings of the univariate analysis of demographic and behavioral factors associated with bacterial vaginosis and with candidiasis on microscopy. Women with bacterial vaginosis, compared with women without bacterial vaginosis, were more likely to have had less than 13 years of education, a new sexual partner in the last year, a greater number of male sexual partners in the last year, a greater number of lifetime sexual partners, more frequent vaginal sex, a past history of pregnancy and trichomoniasis, and to be a smoker and Australian (P < .05). There was a positive association between bacterial vaginosis and having a female sexual partner in the prior 3 months (P = .07), having a past history of bacterial vaginosis (P = .07), ever engaging in sex work (P = .07), and currently engaging in sex work (P = .10), but these were of borderline statistical significance. One hundred sixty women were taking oral contraceptives in this study (51%), and use of oral contraception was negatively associated with bacterial vaginosis (P = .03). There was an association between bacterial vaginosis and being in the first 17 days of the menstrual cycle seen in the study group, and in women not taking oral contraception that was of borderline statistical significance, (P = .07). No statistically significant association was seen between bacterial vaginosis and condom use, douching, oral sex, or anal sex.
Women with Candida spp on microscopy, compared with microscopy-negative women, were more likely to be aged less than 28 years, nulliparous, in full-time work or study, and to be more than 17 days from last menses (P < .05). When only women not taking oral contraceptives were examined (n = 148), the association between Candida spp on microscopy and being in the luteal phase of the menstrual phase was slightly greater, crude odds ratio (cOR) 3.7 (95% confidence interval [CI] 1.4–10.1), P < .01. Women with Candida spp on microscopy were more likely to practice receptive anal sex and to have frequent vaginal sex in the prior 3 months, to douche or wash intravaginally, and to have a history of genital herpes and gonorrhea. They were less likely to have had a new sexual partner in the prior 3 months and a history of genital warts (P = .05) and to have fewer male partners in the prior 3 months, although this was not statistically significant.
The demographic and behavioral characteristics in women with Candida spp on culture were compared with women without Candida spp on culture (data not shown). Although the findings were similar to those observed for Candida spp on microscopy, women with Candida spp on culture were more likely to have both given oral sex (cOR 1.9 [95% CI 1.0–3.8], P = .04) and to have received oral sex (2.4[95% CI 1.2–4.6], P = .01) in the last 3 months, to have used condoms inconsistently for vaginal sex (cOR for 100% condom use 0.4[95% CI 0.2–0.8], P < .01), to have had fewer lifetime sexual partners (cOR for > 12 lifetime partners 0.6[95% CI 0.4–1.0], P = .03), and to be more than 17 days from last menses (1.9[95% CI 1.1–3.1], P = .02).
Factors in the univariate analysis that were significantly associated with bacterial vaginosis (P < .05), as well as age and commercial sex work, which have been correlated with bacterial vaginosis in other studies, were entered into a logistic regression model (Table 1). The factors that remained significantly associated with bacterial vaginosis in the multivariate analysis included having a new sexual partner and more than 2 male sexual partners in the last year, more frequent vaginal sex, a past history of trichomoniasis, smoking, and Australian nationality. A negative association between oral contraception and bacterial vaginosis was observed that was of borderline statistical significance (P = .08). It was noted that if days since last menses was included in the logistic regression model, then no significant changes occurred in other variables in the model, but a significant negative association between oral contraception and bacterial vaginosis was seen in the study population, adjusted odds ratio (aOR) 0.6 (95% CI 0.4–1.0), P = .04. However, menstrual phase was not included in the main multivariate model owing to the high numbers of women on oral contraception and the potential interaction between these variables. There were insufficient numbers to examine the associations between bacterial vaginosis and menstrual phase in women not taking oral contraceptives.
All characteristics that were significantly associated in the univariate analysis with Candida spp on microscopy were entered into a logistic regression model (Table 1). Factors that were significantly associated with Candida spp on microscopy included douching or intravaginal washing and a history of gonorrhea (P < .01), although few women in the study had a history of gonorrhea (n = 9). A new sexual partner in the last 3 months and a history of genital warts were negatively associated with Candida spp. on microscopy. We did not include days since last menses in the main multivariate model due to the potential interaction between oral contraception and menstrual phase, which has previously been mentioned. However, if days since last menses was included in the logistic regression model, then no significant change occurred in the other variables in the model, and candidiasis on microscopy was associated with being more than 17 days since last menses in the study population (aOR 2.3 [95% CI 1.1–4.8], P = .03). When factors that had been associated with Candida spp. on culture were entered into a logistic regression model, receptive oral sex in the prior 3 months (aOR 2.4 [95% CI 1.1–5.3], P = .03) and nulliparity (aOR for past pregnancy 0.5 [95% CI 0.3–0.9], P = .03) remained significantly associated with Candida spp. on culture (full data not shown).
To better define risk factors for bacterial vaginosis, we compared demographic and behavioral factors associated with bacterial vaginosis to those associated with vaginal candidiasis. Women with bacterial vaginosis report specific high-risk sexual behaviors that are associated with sexually transmitted infections, whereas women with candidiasis do not. The significant behavioral differences between bacterial vaginosis and vaginal candidiasis support the concept that bacterial vaginosis may be sexually transmitted.
Women with bacterial vaginosis differed from women with candidiasis in this study in both demographics and sexual practices. Bacterial vaginosis was associated with sexual practices that are related to sexually transmitted infections, such as a high number of recent and lifetime sexual partners, a recent change in sexual partner, and a history of sexually transmitted infections and pregnancy. Other studies have reported associations between bacterial vaginosis and risk factors for sexually transmitted infections,9–13 and a study comparing women with chlamydial infection to women with bacterial vaginosis showed that both bacterial vaginosis and Chlamydia were associated with increased number of recent and lifetime sexual partners, a recent change of sexual partner, and higher rates of high-risk sexual behaviors.12
The presence of vaginal Candida spp on microscopy and on culture was associated with specific sexual practices in this study; however, the high-risk behaviors associated with bacterial vaginosis were not seen. Women with vaginal Candida spp were less likely to have had a recent new sexual partner, and were more likely to be nulliparous, to douche, and to practice oral and anal sex. Several studies have reported an association between candidiasis and orogenital sex,14–16 although to our knowledge no association has been shown with receptive anal sex. Higher rates of oral and rectal carriage in women with recurrent vulvovaginal candidiasis17 and concordance in Candida spp. between male and female sexual partners have been reported,18 indicating that inoculation of the vagina after either oral or anal sex could promote colonization and symptomatic infection. Although both conditions were associated with more frequent vaginal sex, inconsistent condom use was only associated with candidiasis and not bacterial vaginosis. Some studies have shown consistent condom use to be protective against candidiasis, and others have shown it to be protective against bacterial vaginosis.11,19,20 However, self-reported condom use can be affected by recall bias, which may explain the lack of consistency between studies.
The hormonal associations for bacterial vaginosis and candidiasis in this study differed. Bacterial vaginosis was negatively associated with oral contraceptive use, and there was a trend toward occurrence in the first 17 days of the menstrual cycle, whereas candidiasis tended to occur in the luteal phase of the cycle. An association between bacterial vaginosis and the follicular phase of the menstrual cycle21 and candidiasis and the luteal phase22 has been previously shown. Several studies have also reported a negative association between oral contraception and bacterial vaginosis,19,21,23 and candidiasis has been associated with higher-dose oral contraceptives.13,22,24 It has been suggested that estrogen increases epithelial cell receptivity and the glycogen content of epithelial cells, promoting growth of candidiasis, whereas glycogen also serves as a substrate for lactobacilli to produce lactic acid, a potent inhibitor of bacterial vaginosis-associated organisms.23
Smoking was associated with bacterial vaginosis in this study, a finding that has previously been reported. The association has been shown to be dose dependent and has persisted after controlling for sexual risk behaviors and alcohol use.9,11,25,26 We did not control for alcohol use in our study; however, the adjusted odds ratio for smoking was similar (2.1, 95% CI 1.2–3.5) to those previously reported (range 1.4–3.0).9,11,25 A variety of chemicals contained in cigarette smoke, including nicotine and cotinine, have been found in the cervical mucous of smokers, and it is postulated that this may produce a change in vaginal flora. However, smoking is associated with high-risk behaviors, and whether there is any true causal relationship between bacterial vaginosis and smoking remains to be established.
Several previously reported associations with bacterial vaginosis were not seen in this study or did not reach statistical significance. There was a positive association between female sexual partners and bacterial vaginosis; however, the low number of lesbians participating in the study limited our ability to detect the significant associations that have been reported by others.9,27 Sex work has been associated with bacterial vaginosis, and although there was a positive association between bacterial vaginosis and sex work in our study, the association did not reach statistical significance. Sex workers who participated in this study were predominantly legal brothel-based workers, who attend our service monthly for sexually transmitted infection screening, have low rates of bacterial sexually transmitted infections and high rates of consistent condom use (David Lee, Melbourne Sexual Health Centre, personal communication). Douching was not associated with bacterial vaginosis, but was significantly associated with candidiasis. Douching has been associated with bacterial vaginosis10,28 and with candidiasis22,29 in other studies.
Our study had a number of limitations. First, it used an observational study design (level of evidence II-2) and therefore it is not possible to rule out unmeasured confounding that may have affected the findings. In addition, the difficultly of clearly separating cases from controls (ie, classification of intermediate flora) could bias the study toward the null and may have accounted for the relatively modest odds ratios. Last, our control group is likely to have been at higher risk of sexually transmitted infections than average for the general community, which would have reduced our ability to detect significant associations. In planning this study, we decided not to use community-based controls because of the difficultly in recruiting women who would require speculum examination. In addition, we decided not to use asymptomatic women attending our service, because they have lower-risk behaviors and may artificially elevate the risks associated with bacterial vaginosis (23% of asymptomatic women attending our service during the study period had > 1 male sexual partner in the last 3 months, whereas 30% of bacterial vaginosis-negative controls had > 1 male sexual partner in the last 3 months, P = .07). We therefore decided upon a clearly defined group of women attending the center with the same specific vaginal symptoms. This meant it would be unlikely that we would overestimate risk, but this may have reduced our ability to detect significant associations. However, despite these limitations, the magnitude of the associations observed in this study is similar to that reported in other observational studies of bacterial vaginosis and candidiasis, and although modest, the odds ratios also fall within the range reported in observational studies of behavioral practices associated with sexually transmitted infections such as Chlamydia.
An association between bacterial vaginosis and sexual risk behaviors has been reported in both heterosexual and homosexual women; however, the notion that bacterial vaginosis is sexually transmitted is still debated. Commonly cited evidence against sexual transmission of bacterial vaginosis includes the failure to prevent recurrence of bacterial vaginosis in women when male sexual partners are concurrently treated. No significant benefit from partner treatment was reported in 5 of 6 trials using regimens containing metronidazole, clindamycin, or tinidazole.30 However, it is difficult to interpret these findings and to use them as evidence to refute sexual transmission in the pathogenesis of bacterial vaginosis, given the relatively high recurrence rates of bacterial vaginosis observed in women after these antibiotic regimens and the absence of a known causative organism for bacterial vaginosis. Additional commonly stated evidence against sexual transmission of bacterial vaginosis is a study that reported the occurrence of bacterial vaginosis in 6 supposedly virginal adolescents.31 It is certainly possible that the sexual risk behaviors associated with bacterial vaginosis in our and other studies may not be indirect evidence for sexual transmission of an infectious agent, but that other factors such as a disturbance in vaginal flora and in local immunity may occur as a consequence of exposure to a new sexual partner, multiple sexual partners, or from increased sexual activity. There appears, however, to be a considerable body of evidence to support sexual transmission of bacterial vaginosis between women.32 In 1955 Gardner and Dukes33 demonstrated transmission of bacterial vaginosis from affected women to unaffected women by transfer of vaginal secretions, and high concordance of bacterial vaginosis between lesbian couples27,32 and an association with insertive unwashed sex toys27 has been reported. Increased numbers of recent and past sexual partners9 have also been associated with bacterial vaginosis among lesbians. With considerable evidence to implicate sexual transmission of bacterial vaginosis between women, it is likely that the pathogenesis in the heterosexual population is similar. Although there are few studies examining bacterial vaginosis-associated organisms and their clinical sequelae in men, these organisms have been isolated from the urethra, the prepuce, and the coronal sulcus,34 Gardnerella vaginalis has been reported as a cause of balanoposthitis,35 and bacterial vaginosis has been shown to be more common in female partners of men with nonspecific urethritis, and nonspecific urethritis as more common in male partners of women with bacterial vaginosis.36
While the precise cause remains unknown, the role of sexual transmission in the pathogenesis of bacterial vaginosis will remain controversial. It is unclear whether the high recurrence rates of bacterial vaginosis after treatment are due to failure to eradicate bacterial vaginosis-associated flora that are resistant to current regimens, failure to treat an as yet unidentified pathogen, reinfection from untreated sexual partners, or a combination of these factors. The recent identification of metronidazole resistant Atopobium vaginae, which appears to be uncommon in women with normal flora but present in the majority of women with bacterial vaginosis,37,38 may prove to be a significant advance in understanding the cause of bacterial vaginosis, and provides further evidence that solely imidazole-based regimens for treatment of bacterial vaginosis are unlikely eradicate infection. Ultimately, only prospective and partner studies and identification of the specific causative factor responsible for bacterial vaginosis, will be able to establish whether bacterial vaginosis is sexually transmitted. However, contrasting the factors associated with bacterial vaginosis compared with vaginal candidiasis has facilitated the identification of high-risk behaviors for bacterial vaginosis, which were not observed with candidiasis. The association between bacterial vaginosis and behaviors that are associated with sexually transmitted infections provides further evidence to support a possible sexually transmitted cause.
1. Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C, Pearson J. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ 1994;308:295–8.
2. McGregor JA, French JI, Parker R, Draper D, Patterson E, Jones W, et al. Prevention of premature birth by screening and treatment for common genital tract infections: results of a prospective controlled evaluation. Am J Obstet Gynecol 1995;173:157–67.
3. Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 1995;333:1737–42.
4. Taha TE, Hoover DR, Dallabetta GA, Kumwenda NI, Mtimavalye LA, Yang LP, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998;12:1699–706.
5. Sewankambo N, Gray RH, Wawer MJ, Paxton L, McNaim D, Wabwire-Mangen F, et al. HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis [published erratum appears in Lancet 1997;350:1036]. Lancet 1997;350:546–50.
6. Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14–22.
7. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 1991;29:297–301.
8. Bradshaw CS, Morton AN, Garland SM, Horvath LB, Kuzevska I, Fairley CK. An evaluation of a point-of-care test, BVBlue, and clinical and laboratory criteria for the diagnosis of bacterial vaginosis (BV). J Clin Microbiol 2005;43:1304–8.
9. Bailey JV, Farquhar C, Owen C. Bacterial vaginosis in lesbians and bisexual women. Sex Transm Dis 2004;31:691–4.
10. Schwebke JR, Desmond RA, Oh MK. Predictors of bacterial vaginosis in adolescent women who douche. Sex Transm Dis 2004;31:433–6.
11. Smart S, Singal A, Mindel A. Social and sexual risk factors for bacterial vaginosis. Sex Transm Infect 2004;80:58–62.
12. Nilsson U, Hellberg D, Shoubnikova M, Nilsson S, Mardh PA. Sexual behavior risk factors associated with bacterial vaginosis and Chlamydia trachomatis infection. Sex Transm Dis 1997;24:241–6.
13. Avonts D, Sercu M, Heyerick P, Vandermeeren I, Meheus A, Piot P. Incidence of uncomplicated genital infections in women using oral contraception or an intrauterine device: a prospective study. Sex Transm Dis 1990;17:23–9.
14. Rylander E, Berglund AL, Krassny C, Petrini B. Vulvovaginal candida in a young sexually active population: prevalence and association with oro-genital sex and frequent pain at intercourse. Sex Transm Infect 2004;80:54–7.
15. de Leon EM, Jacober SJ, Sobel JD, Foxman B. Prevalence and risk factors for vaginal Candida colonization in women with type 1 and type 2 diabetes. BMC Infect Dis 2002;2:1.
16. Geiger AM, Foxman B. Risk factors for vulvovaginal candidiasis: a case-control study among university students. Epidemiology 1996;7:182–7.
17. Mardh PA, Novikova N, Stukalova E. Colonisation of extragenital sites by Candida in women with recurrent vulvovaginal candidosis. BJOG 2003;110:934–7.
18. O'Connor MI, Sobel JD. Epidemiology of recurrent vulvovaginal candidiasis: identification and strain differentiation of Candida albicans. J Infect Dis 1986;154:358–63.
19. Calzolari E, Masciangelo R, Milite V, Verteramo R. Bacterial vaginosis and contraceptive methods. Int J Gynaecol Obstet 2000;70:341–6.
20. Schwebke JR, Richey CM, Weiss HL. Correlation of behaviors with microbiological changes in vaginal flora. J Infect Dis 1999;180:1632–6.
21. Keane FE, Ison CA, Taylor-Robinson D. A longitudinal study of the vaginal flora over a menstrual cycle. Int J STD AIDS 1997;8:489–94.
22. Barousse MM, Van Der Pol BJ, Fortenberry D, Orr D, Fidel PL Jr. Vaginal yeast colonisation, prevalence of vaginitis, and associated local immunity in adolescents. Sex Transm Infect 2004;80:48–53.
23. Shoubnikova M, Hellberg D, Nilsson S, Mardh PA. Contraceptive use in women with bacterial vaginosis. Contraception 1997;55:355–8.
24. Spinillo A, Capuzzo E, Nicola S, Baltaro F, Ferrari A, Monaco A. The impact of oral contraception on vulvovaginal candidiasis. Contraception 1995;51:293–7.
25. Hellberg D, Nilsson S, Mardh PA. Bacterial vaginosis and smoking. Int J STD AIDS 2000;11:603–6.
26. Goldenberg RL, Das A. Fetal fibronectin and bacterial vaginosis in smokers and nonsmokers. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2000;182:164–6.
27. Marrazzo JM, Koutsky LA, Eschenbach DA, Agnew K, Stine K, Hillier SL. Characterization of vaginal flora and bacterial vaginosis in women who have sex with women. J Infect Dis 2002;185:1307–13.
28. Ness RB, Hillier SL, Richter HE, Soper DE, Stamm C, McGregor J, et al. Douching in relation to bacterial vaginosis, lactobacilli, and facultative bacteria in the vagina. Obstet Gynecol 2002;100:765–72.
29. Spinillo A, Pizzoli G, Colonna L, Nicola S, De Seta F, Guaschino S. Epidemiologic characteristics of women with idiopathic recurrent vulvovaginal candidiasis. Obstet Gynecol 1993;81:721–7.
30. Potter J. Should sexual partners of women with bacterial vaginosis receive treatment? Br J Gen Pract 1999;49:913–8.
31. Bump RC, Buesching WJ 3rd. Bacterial vaginosis in virginal and sexually active adolescent females: evidence against exclusive sexual transmission. Am J Obstet Gynecol 1988;158:935–9.
32. Berger BJ, Kolton S, Zenilman JM, Cummings MC, Feldman J, McCormack WM. Bacterial vaginosis in lesbians: a sexually transmitted disease. Clin Infect Dis 1995;21:1402–5.
33. Gardner HL, Dukes CD. Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. Am J Obstet Gynecol 1955;69:962–76.
34. Serour F, Samra Z, Kushel Z, Gorenstein A, Dan M. Comparative periurethral bacteriology of uncircumcised and circumcised males. Genitourin Med 1997;73:288–90.
35. Burdge DR, Bowie WR, Chow AW. Gardnerella vaginalis-associated balanoposthitis. Sex Transm Dis 1986;13:159–62.
36. Keane FE, Thomas BJ, Whitaker L, Renton A, Taylor-Robinson D. An association between non-gonococcal urethritis and bacterial vaginosis and the implications for patients and their sexual partners. Genitourin Med 1997;73:373–7.
37. Verhelst R, Verstraelen H, Claeys G, Verschraegen G, Delanghe J, Van Simaey L, et al. Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol 2004;4:16.
38. Ferris MJ, Masztal A, Aldridge KE, Fortenberry JD, Fidel PL Jr, Martin DH. Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis. BMC Infect Dis 2004;4:5.
Figure. No caption available.
This article has been cited 37 time(s).
Clinical Infectious DiseasesRecurrence of Bacterial Vaginosis Is Significantly Associated With Posttreatment Sexual Activities and Hormonal Contraceptive UseClinical Infectious Diseases
American Journal of Obstetrics and GynecologyPaternal race and bacterial vaginosis during the first trimester of pregnancyAmerican Journal of Obstetrics and Gynecology
Journal of EpidemiologyVaginal Douching in Cambodian Women: Its Prevalence and Association With Vaginal CandidiasisJournal of Epidemiology
Journal of Pediatric and Adolescent GynecologyFindings associated with recurrence of bacterial vaginosis among adolescents attending sexually transmitted diseases clinicsJournal of Pediatric and Adolescent Gynecology
Tropical Medicine & International HealthEffect of consistent condom use on 6-month prevalence of bacterial vaginosis varies by baseline BV statusTropical Medicine & International Health
International Journal of Std & AIDSThe polymicrobial hypothesis of bacterial vaginosis causation: a reassessmentInternational Journal of Std & AIDS
Journal of Womens HealthTreatment Considerations for Bacterial Vaginosis and the Risk of RecurrenceJournal of Womens Health
Journal of Infectious DiseasesDistribution of Genital Lactobacillus Strains Shared by Female Sex PartnersJournal of Infectious Diseases
Clinical Microbiology and InfectionVaginal and endocervical microorganisms in symptomatic and asymptomatic non-pregnant females: risk factors and rates of occurrenceClinical Microbiology and Infection
Archives of Gynecology and ObstetricsInterleukin-6, interleukin-10 and interleukin-12 in vaginal fluid from women with bacterial vaginosisArchives of Gynecology and Obstetrics
Journal of Clinical MicrobiologyHeterogeneity of Vaginal Microbial Communities within IndividualsJournal of Clinical Microbiology
Eukaryotic CellCellular and molecular biology of Candida albicans estrogen responseEukaryotic Cell
Planta MedicaExploratory Study on the Clinical and Mycological Effectiveness of a Herbal Medicinal Product from Solanum chrysotrichum in Patients with Candida Yeast-Associated Vaginal InfectionPlanta Medica
Australian Family Physician
Bacterial vaginosis More questions than answers
Australian Family Physician, 38(6):
Journal of Reproductive Medicine
Factors Associated with Recurrent Bacterial Vaginosis
Journal of Reproductive Medicine, 55():
International Journal of Std & AIDSBacterial vaginosis: a sexually enhanced diseaseInternational Journal of Std & AIDS
Clinical Infectious DiseasesSexual Risk Factors and Bacterial Vaginosis: A Systematic Review and Meta-AnalysisClinical Infectious Diseases
Bmc Infectious DiseasesThe epidemiology of bacterial vaginosis in relation to sexual behaviourBmc Infectious Diseases
Perspectives on Sexual and Reproductive Health
Evidence supporting the notion that bacterial vaginosis can be transmitted sexually continues to accumulate
Perspectives on Sexual and Reproductive Health, 37(4):
Journal of Infectious DiseasesEarly Sexual Experiences and Risk Factors for Bacterial VaginosisJournal of Infectious Diseases
Expert Review of Anti-Infective TherapyBacterial vaginosis: an update on diagnosis and treatmentExpert Review of Anti-Infective Therapy
Indian Journal of Medical Microbiology
Prevalence and Correlates of Bacterial Vaginosis Among Young Women of Reproductive Age in Mysore, India
Indian Journal of Medical Microbiology, 26(2):
International Family Planning Perspectives
Evidence supporting the notion that bacterial vaginosis can be transmitted sexually continues to accumulate
International Family Planning Perspectives, 31(4):
Journal of Infectious Diseases
The association of Atopobium vaginae and Gardnerella vaginalis with bacterial vaginosis and recurrence after oral metronidazole therapy
Journal of Infectious Diseases, 194(6):
Journal of Infectious Diseases
High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence
Journal of Infectious Diseases, 193():
American Journal of EpidemiologyHistologic chorioamnionitis and preterm deliveryAmerican Journal of Epidemiology
Journal of InfectionCigarette smoking and mechanisms of susceptibility to infections of the respiratory tract and other organ systemsJournal of Infection
Plos OneHormonal Contraception Is Associated with a Reduced Risk of Bacterial Vaginosis: A Systematic Review and Meta-AnalysisPlos One
Sexually Transmitted DiseasesBacterial Vaginosis-Race and Sexual Transmission: Issues of CausationSexually Transmitted Diseases
Sexually Transmitted DiseasesVulvovaginal Candidiasis in Women Who Have Sex With WomenSexually Transmitted Diseases
Sexually Transmitted DiseasesRisk Factors for Bacterial Vaginosis Incidence in Young Adult Thai WomenSexually Transmitted Diseases
Sexually Transmitted DiseasesPrevalence of Gardnerella vaginalis and Atopobium vaginae in Virginal WomenSexually Transmitted Diseases
© 2005 The American College of Obstetricians and Gynecologists