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Sexually Transmitted Diseases:
doi: 10.1097/OLQ.0b013e318073bd82
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Natural History of Asymptomatic Bacterial Vaginosis in a High-Risk Group of Women

Schwebke, Jane R. MD; Desmond, Renee PhD

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From the Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

This work was supported by NIH grant Therapy and Prevention of Bacterial Vaginosis, R01 AI048044.

Correspondence: Jane R. Schwebke, MD, University of Alabama at Birmingham, 703 19th Street South, ZRB 239, Birmingham, AL 35233. E-mail: schwebke@uab.edu.

Received for publication December 28, 2007, and accepted April 6, 2007.

BACTERIAL VAGINOSIS (BV) IS the most common vaginal infection worldwide and has been associated with complications including preterm birth and acquisition of STD/HIV.1–3 Despite its prevalence, BV is very poorly understood in terms of its microbiologic etiology and pathogenesis. Treatment of BV remains suboptimal with cure rates of 60% to 80% and high recurrence rates.4 In addition, women with BV are often asymptomatic, and controversy exists as to the appropriate management of these women. Little is known with regard to the natural history of asymptomatic BV: does it resolve, remain stable, or evolve into symptomatic BV? Using a data derived from a clinical trial of the treatment of symptomatic BV, we were able to describe vaginal flora changes over a three-month period of time and specifically examine the natural history of asymptomatic BV during this time frame among women recently treated for symptomatic BV.

Women attending the Jefferson County Department of Health STD Clinic with symptomatic BV were enrolled into a clinical trial examining the effect of duration of therapy with metronidazole as well as dual therapy with metronidazole and azithromycin on cure rates for BV.5 All women received at least 7 days of oral metronidazole. Women were reexamined at 7 days after completion of therapy (day 21) and 21 days after completion of therapy (days 35–40). Cure was evaluated using Nugent and Amsel criteria. At follow-up, women were questioned specifically about intercurrent behaviors and the presence of vaginal discharge and/or odor. Women with persistent symptomatic BV were retreated with standard therapy and discontinued from the study. Women with asymptomatic BV at follow-up were not retreated and continued to be observed.

Five hundred sixty-eight women were entered into the study. The demographics have been previously presented.5 In brief, for the current substudy of 49 women, 100% were black, 69.4% reported a history of STD, and the mean number of sexual partners in the prior 3 months was 1.6. There were no significant differences in these characteristics of the women in the substudy when compared with the larger cohort.

Of the 568 women entered into the study, 49 (8.6%) had asymptomatic BV, defined by Nugent score of 7 to 10, and absence of symptoms of vaginal discharge and/or odor, at the first follow-up visit. Of these, 41 had no coexisting genital infection and returned for subsequent visits. Table 1 shows the outcome of these women at their second follow-up visit (days 35–40). The majority, 46.3%, continued to have asymptomatic BV; 14.6% of women were asymptomatic with Nugent scores of 0 to 3; and 26.8% were asymptomatic with intermediate Nugent scores of 4 to 6. Twelve percent of women developed symptoms of BV within this follow-up period. Overall, 18/41 (43.9%; 95% CI, 29–59) of women with asymptomatic BV redeveloped symptoms by day 95 to 100 after treatment for symptomatic BV.

Table 1
Table 1
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Table 2 shows the outcomes of women with asymptomatic BV at the first follow-up visit defined by Amsel criteria (vaginal pH >4.5, positive whiff test, presence of clue cells). Thirty-nine women met these criteria. The distribution of women at the second follow-up visit by Amsel criteria (no BV, asymptomatic BV, and symptomatic BV) was very similar to the classification by Nugent score. Forty-two percent continued with asymptomatic BV, whereas 15.2% became symptomatic. By the final study visit, 18/39 (36.7%) developed symptomatic BV. In a multinomial model predicting the likelihood of symptomatic BV, an increased vaginal pH was a significant risk factor whereas a normal Nugent score was protective (P <0.05). Neither douching nor recent sexual activity was predictive of developing symptomatic as opposed to asymptomatic BV.

Table 2
Table 2
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Symptomatic BV is characterized by vaginal discharge and/or odor. However, half of all women who meet the diagnostic criteria for BV are asymptomatic.6 The microbiologic changes that occur in women with symptomatic and asymptomatic BV appear by culture techniques to be identical. The natural history of asymptomatic BV has not been well studied. There are some data on the persistence of vaginal flora changes in pregnant women. Hillier et al. reported that among women with intermediate Nugent scores, one-third reverted to normal flora at 8 to 10 weeks follow-up and one-third had progressed to BV. Symptom data were not presented. Among women with BV flora at enrollment, 19% were intermediate at follow-up, and 12% had normal vaginal flora. None of the women had received treatment for BV.7 In a small, prospective study of women with asymptomatic BV, 81% of women who received placebo had persistent BV by Nugent score, 11% had intermediate scores, and 8% had normal scores of 0 to 3 at 5 weeks after enrollment. About 18.5% of women with BV by Nugent score developed symptomatic BV characterized by patient self-report of vaginal discharge and/or odor at day 28 of the study.8 The patient population in our current study may not be equivalent to that in the studies cited above because these women initially presented with symptomatic BV and developed asymptomatic BV after treatment. However, the development of symptomatic BV at around 4 weeks after treatment is remarkably similar at 12% to 15%.

In summary, approximately 40% of women overall who had asymptomatic BV at the first follow-up visit after treatment for symptomatic BV redeveloped symptoms by 3 to 4 months. The findings of this study may not be able to be generalized to all women with asymptomatic BV because these women were recently treated for symptomatic BV and also represent a group of women at high risk for BV/STD. However, certainly women such as these are encountered frequently in clinical practice. Such high rates of recurrent symptomatic BV pose the question of whether women who have persistent BV, albeit asymptomatic, would benefit from repeat treatment to attempt to prevent development of symptomatic BV. Alternatively, our inability to microbiologically cure these women may simply reflect the inadequacies of current treatment regimens.

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References

1. Hillier SL, Nugent RP, Eschenbach DA, et al. Association between bacterial vaginosis and preterm delivery of a low-birth weight infant. N Engl J Med 1995; 333:1737–1742.

2. Hillier S. The vaginal microbial ecosystem and resistance to HIV. AIDS 1998; 14:17–21.

3. Wiesenfeld H, Hillier S, Krohn MA, et al. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 2003; 36:663–668.

4. Joesoef MR, Schmid GP, Hillier SL. Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. Clin Infect Dis 1999; 28:S57–S65.

5. Schwebke J, Desmond RA. A randomized trial of metronidazole duration plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Inf Dis 2007; 44:213–219.

6. Amsel R, Totten PA, Spiegel CA, et al. Non-specific vaginitis: diagnostic and microbial and epidemiological associations. Am J Med 1983; 74:14–22.

7. Hillier SL, Krohn MA, Nugent RP, et al. Characteristics of three vaginal flora patterns assessed by Gram stain among pregnant women. Am J Obstet Gynecol 1992; 166:938–944.

8. Schwebke J. Asymptomatic bacterial vaginosis: Response to therapy. Am J Obstet Gynecol 2000; 183:1434–1439.

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