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Clinical focus: bacterial vaginosis

Dr Phillip Hay
MBBS FRCP
Reader in Genitourinary and HIV Medicine
St George's, University of London

Bacterial vaginosis is a common condition with embarrassing symptoms. It is diagnosed by microscopy of vaginal smears, but tests for sexually transmitted infections should also be performed. Although readily treated with antibiotics, recurrence is frequent

Vaginal discharge is a common presentation to genitourinary medicine (GUM) clinics, general practice and other primary care settings. The principal causes are summarised in Table 1. Most women develop an abnormal discharge at some time in their lives. For a few, recurrences are frequent and the condition can dominate their lives. Diagnosis can readily be confirmed by microscopy and culture of appropriate swabs.

[[Tab 1 BV]]

Epidemiology and microbiology
Bacterial vaginosis (BV) is the most common cause of abnormal vaginal discharge in women of childbearing age. Its reported prevalence has varied widely, from as low as 5% in a selected group of asymptomatic college students to 50% of women in rural Uganda. Studies in antenatal clinics and gynaecology clinics show a prevalence of approximately 12% in the UK. It is more common in black women, smokers and those with sexually transmitted infections (STIs). BV often arises spontaneously around the time of menstruation and may resolve spontaneously in mid-cycle.

When BV develops, predominantly anaerobic organisms increase in concentration up to a thousand fold, and overwhelm the lactobacilli (Figure 1). Bacteria found in BV include Gardnerella vaginalis, Mycoplasma hominis, Atopobium vaginae, Mobiluncus species and Prevotella species. Vaginal pH rises to between 4.5 and 7.0.

[[Fig 1 BV]]

Debate continues as to whether BV is sexually transmitted, or just sexually associated. It has some characteristics of an STI: it is more common in women with recent partner change; there tends to be concordance in lesbian couples for both or neither to have BV; and it is more common in those with chlamydia and other STIs. However, it has been reported in women who have never had intercourse, and is not more common in women aged

Physiology
In pre-menarchal girls the vagina is lined with a simple cuboidal epithelium. The pH is neutral and it is colonised by skin commensal bacteria such as Streptococci. Under the influence of oestrogen at puberty, stratified squamous epithelium develops and lactobacilli become the predominant organism. The pH falls to between 3.5 and 4.5. After the menopause, atrophic changes occur with a return to skin flora.
The pH again rises to 7.0.

Normal vaginal discharge is white or yellowish. It consists of epithelial cells, mucus, bacteria and fluid transudate. Lactobacilli and the epithelium metabolise glycogen to lactic acid maintaining a pH below 4.5. Physiological discharge increases mid-cycle, and in pregnancy. A cervical ectropion may be associated with excess mucus production causing persistent discharge.

Clinical features of bacterial vaginosis
Typically, women report offensive, fishy-smelling discharge. It may be white or yellow. The smell is particularly noticeable around the time of menstruation or following intercourse. Remember that semen itself can give off a weak fishy smell. On examination, the discharge is characteristically thin, homogenous and adherent to the walls of the vagina.

Diagnosis
Diagnosis was traditionally made in clinical practice identifying at least three of the composite (Amsel) criteria:

  • Vaginal pH >4.5.
  • Release of a fishy smell on addition of alkali (10% Potassium Hydroxide).
  • A characteristic discharge on examination.
  • Presence of "clue cells" on microscopy.

Clue cells are vaginal epithelial cells so heavily coated with bacteria that the border is obscured (Figure 2). In GUM clinics and microbiology laboratories BV is now diagnosed from a Gram-stained vaginal smear. Large numbers of Gram-positive and Gram-negative cocci are seen, with reduced or absent large Gram-positive bacilli (Lactobacilli). Culture is not useful for diagnosis as, for instance, Gardnerella can be grown from 50% who do not have BV.

[[Fig 2 BV]]

Candida and trichomoniasis can also be diagnosed by microscopy of a saline wet mount and Gram stained vaginal smear. In the absence of microscopy, vaginal pH can be measured simply with narrow range pH paper. BV and trichomoniasis are excluded by a pH 4.5 is not specific for a positive diagnosis of either. Definitive diagnosis may have to await results from swabs sent to microbiology. Full diagnostic evaluation requires a vaginal swab for microscopy and culture, and endocervical swab for chlamydia and gonorrhoea.

Differential diagnosis
Vaginal discharge can originate from anywhere in the upper or lower genital tract. Discharge arising from the vagina itself can be physiological or pathological (Table 2). Other causes are summarised in Table 2. The principal features of the four most common causes of abnormal discharge are summarised in
Table 1.

[[Tab 2 BV]]
 
Itching is the cardinal symptom of candidiasis. There may be increased discharge, which is typically "curdy". Examination may also show soreness and redness of the vagina and vulva, with fissuring and excoriations. Asymptomatic women from whom candida is grown on culture do not require treatment.
Trichomoniasis, at its most severe, presents with a severe vulvo-vaginitis, with inflammation sometimes extending out onto the vulva and adjacent skin. Discharge is purulent, and often offensive because of associated BV. Cervical infection with chlamydia or gonorrhoea may present with pelvic pain, purulent vaginal discharge and intermenstrual or postcoital bleeding.

Treatment
About 50% of women with BV are asymptomatic and do not need treatment. Since it can remit and recur spontaneously, there is little to gain by such treatment, even in terms of reducing complications outside of pregnancy.

Antibiotics with good anti-anaerobic activity are effective. A comprehensive review of treatment studies was used to guide the 2006 US Centers for Disease Control and Prevention (CDC) guidelines.1

Metronidazole 400 mg twice a day for five days is the preferred treatment.
Alternative treatments:

  • 2 g metronidazole as a single dose.
  • Metronidazole vaginal gel 0.75% applied nightly for five nights.
  • Clindamycin cream 2% applied nightly for five to seven nights.

Initial cure rates are greater than 80%, but up to 30% of women relapse within one month of treatment.
No benefit has been shown from treating male partners with metronidazole or clindamycin. BV is, however, associated with non-gonococcal urethritis, so I usually advise testing of partners of women with recurrent BV.

Adverse effects of treatment
Oral metronidazole is associated with nausea, a metallic taste and alcohol intolerance. Allergic rashes occur occasionally. Initial concerns about potential teratogenicity have not been substantiated, and metronidazole can be used in pregnancy.2 It gives breast milk a bitter taste so high doses should be avoided. Clindamycin can induce rashes and occasionally pseudomembranous colitis. About 10% of women develop symptomatic candidiasis following treatment of bacterial vaginosis.

Complications
At its most severe, recurrent BV can be stigmatising and lead to depression. Women with BV are at greater risk of second trimester miscarriage and pre-term delivery during pregnancy. However, 80% of women will have a term delivery. The results of studies treating BV with metronidazole or clindamycin in pregnancy to reduce preterm birth rates have been conflicting, so current guidelines do not recommend routine screening and treatment in pregnancy.

BV should be treated with metronidazole before termination of pregnancy to reduce the incidence of endometritis and pelvic inflammatory disease.

BV is a risk factor for acquisition of STIs, including HIV. However, in a study of mass treatment of men and women in Uganda, three rounds of antibiotic treatment including metronidazole did not reduce the rate of HV acquisition, or even the prevalence of BV.3

Recurrence
In some women the vaginal flora is in a dynamic state, with BV developing and remitting spontaneously. Symptomatic women with recurrent bacterial vaginosis can become frustrated as the condition responds rapidly to treatment with antibiotics but may also relapse rapidly. Our inability to alter this process reflects our current lack of knowledge of the factors that trigger bacterial vaginosis. Regular treatment with 0.75% metronidazole gel twice a week for six months, reduces the rate of recurrence.4 Some women need simultaneous suppressive treatment for candida with fluconazole 150 mg weekly. Alternatively, supply the woman with several courses of treatment so that she can initiate treatment of recurrences herself in a timely manner without having to get an urgent appointment.

Self-help and over-the-counter treatments
Women should be advised to avoid douching and other washing practices that will disturb the endogenous flora. Probiotics and lactic acid gels have not been evaluated sufficiently rigorously in randomised trials to allow a recommendation to be made; but some women derive symptomatic relief from them, and several small studies report improvements in symptoms and efficacy similar to antibiotics.
If a physiological treatment such as lactic acid gel works for a woman it is preferable to repeated course of antibiotics. Some women use it with menstruation and after unprotected intercourse, others regularly, such as twice a week.

Conclusions
BV is a common condition, which can be frustrating for affected women and healthcare practitioners because of frequent recurrences. Repeated treatments with antibiotics may be needed. Lactic acid and probiotics are being researched as alternative treatments. Although associated with adverse outcomes in pregnancy we have not been successful in improving outcomes with antibiotic treatment, except in reducing post-termination of pregnancy endometritis.  

References
1. Koumans EH, Markowitz LE, Hogan V. Indications for therapy and treatment recommendations for bacterial vaginosis in nonpregnant and pregnant women: a synthesis of data. Clin Infect Dis 2002;35(Suppl 2):S152-72.
2. Burtin P, Taddio A, Ariburnu O, Einarson TR, Koren G. Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol 1995;172:525-9.
3. Wawer MJ, Gray RH, Sewankambo NK et al. A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda. AIDS 1998;12(10):1211-25.
4. Sobel JD, Ferris D, Schwebke J et al. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol 2006;194(5):1283-9.

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