Bacterial vaginosis

Bacterial vaginosis
Micrograph of bacterial vaginosis — cells of the cervix covered with rod-shaped bacteria, Gardnerella vaginalis (arrows).
Classification and external resources
ICD-10	B96, N76
ICD-9	616.1
Patient UK	Bacterial vaginosis
MeSH	D016585

Bacterial vaginosis (BV), also known as vaginal bacteriosis or Gardnerella vaginitis,^[1] is a disease of the vagina caused by excessive bacteria.^[2] Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urination may occur.^[3] Itching is uncommon.^[2][3] Occasionally there may be no symptoms.^[3] Having BV increases the risk of infection by a number of other sexually transmitted infections including HIV/AIDS.^[4] It also increases the risk of early delivery among pregnant women.^[5]

BV is caused by an imbalance of the naturally occurring bacteria in the vagina.^[6] There is a change in the most common type of bacteria and a hundred to thousand fold increase in total numbers of bacteria present.^[2] Risk factors include douching, new or multiple sex partners, antibiotics, and using an intrauterine device among others.^[6] However, it is not considered a sexually transmitted infection.^[7] Diagnosis is suspected based on the symptom and may be verified by testing the vaginal discharge and finding a higher than normal vaginal pH and large numbers of bacteria.^[2] BV is often confused with a vaginal yeast infection or infection with Trichomonas.^[8]

Usually treatment is with the antibiotic, clindamycin or metronidazole. These medications may also be used in the second or third trimesters of pregnancy. Often the condition; however, re-occurs following treatment. Probiotic may help prevent re-occurrence.^[2] It is unclear if the use of probiotics or antibiotics affects pregnancy outcomes.^[2][9]

BV is the most common vaginal infection in women of reproductive age.^[6] The percentage of women affected at any given time varies between 5% and 70%.^[4] BV is most common in parts of Africa and least common in Asia and Europe.^[4] In the United States about 30% of women between the ages of 14 and 49 are affected.^[10] Rates vary considerably between ethnic groups within a country.^[4] While BV like symptoms have been described for much of recorded history, the first clearly documentation case occurred in 1894.^[1]

Signs and symptoms

Common symptoms include increased vaginal discharge that usually smells like fish. The discharge is often white or gray in color. There may be burning with urination. Occasionally there may be no symptoms.^[3]

The discharge coats the walls of the vagina, and is usually without significant irritation, pain, or erythema (redness), although mild itching can sometimes occur. By contrast, the normal vaginal discharge will vary in consistency and amount throughout the menstrual cycle and is at its clearest at ovulation—about 2 weeks before the period starts. Some practitioners claim that BV can be asymptomatic in almost half of affected women,^[11] though others argue that this is often a misdiagnosis.^[12]

Causes

A healthy vagina normally contains many microorganisms; some of the most common ones are Lactobacillus species, including L. crispatus, L. gasseri, L. jensenii, and L. iners. Lactobacilli, particularly hydrogen peroxide-producing species, appear to help prevent other vaginal microorganisms from multiplying to a level where they cause symptoms. The microorganisms involved in BV are very diverse, and include Gardnerella vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, and species of the genera Peptostreptococcus and Mobiluncus, as well as anaerobic Gram-negative rod-shaped species such as Prevotella and Bacteroides. A change in normal bacterial flora including the reduction of Lactobacilli, which may be due to the use of antibiotics or pH imbalance, allows more resistant bacteria to gain a foothold and multiply.

One of the most direct causes of BV is douching, which alters the vaginal flora and predisposes women to developing BV.^[13][14] Douching is strongly discouraged by the U.S. Department of Health and Human Services and various medical authorities, for this and other reasons.^[13]

Although BV can be associated with sexual activity, there is no clear evidence of sexual transmission.^[15][16] It is possible for sexually inactive persons to get infected with bacterial vaginosis. Rather, BV is a disordering of the chemical and biological balance of the normal flora. Recent research is exploring the link between sexual partner treatment and eradication of recurrent cases of BV. Pregnant women and women with sexually transmitted infections are especially at risk for getting this infection.

Bacterial vaginosis may sometimes affect women after menopause. A 2005 study by researchers at Ghent University in Belgium showed that subclinical iron deficiency (anemia) was a strong predictor of bacterial vaginosis in pregnant women.^[17] A longitudinal study published in February 2006 in the American Journal of Obstetrics and Gynecology showed a link between psychosocial stress and bacterial vaginosis persisted even when other risk factors were taken into account.^[18]

Diagnosis

Workup of suspected bacterial vaginosis, with a pH indicator to detect vaginal alkalinization (here showing approximately pH 8), and a microscope slide to microscopically detect clue cells.

To make a diagnosis of bacterial vaginosis, a swab from inside the vagina should be obtained. These swabs should be tested for:

• A characteristic "fishy" odor on wet mount. This test, called the whiff test, is performed by adding a small amount of potassium hydroxide to a microscopic slide containing the vaginal discharge. A characteristic fishy odor is considered a positive whiff test and is suggestive of bacterial vaginosis.
• Loss of acidity. To control bacterial growth, the vagina is normally slightly acidic with a pH of 3.8–4.2. A swab of the discharge is put onto litmus paper to check its acidity. A pH greater than 4.5 is considered alkaline and is suggestive of bacterial vaginosis.
• The presence of clue cells on wet mount. Similar to the whiff test, the test for clue cells is performed by placing a drop of sodium chloride solution on a slide containing vaginal discharge. If present, clue cells can be visualized under a microscope. They are so-named because they give a clue to the reason behind the discharge. These are epithelial cells that are coated with bacteria.

Two positive results in addition to the discharge itself are enough to diagnose BV. If there is no discharge, then all three criteria are needed.^[19] Differential diagnosis for bacterial vaginosis includes the following:^[20]

• Normal discharge.
• Candidiasis (thrush, or a yeast infection).
• Trichomoniasis, an infection caused by Trichomonas vaginalis.

In clinical practice

In clinical practice BV can be diagnosed using the Amsel criteria:^[19]

1. Thin, white, yellow, homogeneous discharge
2. Clue cells on microscopy
3. pH of vaginal fluid >4.5
4. Release of a fishy odor on adding alkali—10% potassium hydroxide (KOH) solution.

At least three of the four criteria should be present for a confirmed diagnosis.^[21] The modified Amsel Criteria is equally diagnostic of BV as the Amsel's. The modified Amsel Criteria says two instead of the three out of the four criteria is diagnostic of BV.

BV can also be diagnosed with BVBLUE, a CLIA-waived rapid diagnostic that tests for sialidase enzyme activity. Studies have shown this test to be more accurate, specific, and comprehensive than the Amsel criteria.

Gram stain

An alternative is to use a Gram-stained vaginal smear, with the Hay/Ison^[22] criteria or the Nugent^[23] criteria. The Hay/Ison criteria are defined as follows:^[21]

• Grade 1 (Normal): Lactobacillus morphotypes predominate.
• Grade 2 (Intermediate): Mixed flora with some Lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present.
• Grade 3 (Bacterial Vaginosis): Predominantly Gardnerella and/or Mobiluncus morphotypes. Few or absent Lactobacilli. (Hay et al., 1994)

NB: Gardnerella vaginalis is the main culprit in BV. Gardnerella vaginalis is a short rod, therefore, it is a coccobacillus. The bacteria that have covered the squamous epithelial cells making the epithelial cells have obsured ends are not bacilli, they are coccobacilli. Hence, the presence of clue cells and gram variable coccobacilli are indicative or diagnostic of Bacterial Vaginosis.

The standards for research are the Nugent^[23] Criteria. In this scale, a score of 0-10 is generated from combining three other scores. This method is time consuming and requires trained staff, but it has high interobserver reliability. The scores are as follows:

• 0–3 is considered negative for BV
• 4–6 is considered intermediate
• 7+ is considered indicative of BV.

At least 10–20 high power (1000× oil immersion) fields are counted and an average determined.

A recent study ^[24] compared the Gram stain using the Nugent criteria and the DNA hybridization test Affirm VPIII in diagnosing BV. The Affirm VPIII test detected Gardnerella in 107 (93.0%) of 115 vaginal specimens positive for BV diagnosed by Gram stain. The Affirm VPIII test has a sensitivity of 87.7% and specificity of 96% and may be used for the rapid diagnosis of BV in symptomatic women. However Affirm VPIII does have some drawbacks: 1) It requires a very expensive proprietary piece of equipment to read results, and 2) it does not detect other pathogens that cause BV, including Prevotella spp, Bacteroides spp, & Mobiluncus spp.

Treatment

Antibiotics

Metronidazole or clindamycin either orally or vaginally are effective treatment.^[25] However, there is a high rate of recurrence.^[15] Recurrence rates are increased with sexual activity with the same pre-/posttreatment partner and inconsistent condom use although estrogen-containing contraceptives decrease recurrence.^[26]

The usual medical regimen for treatment is the antibiotic metronidazole (500 mg twice a day, once every 12 hours) for 7 days.^[27] A one-time 2g dose is no longer recommended by the CDC because of low efficacy. Extended release metronidazole is an alternative recommendation.

Alternatively, antibiotics may be applied topically (vaginally).^[14]

Bacterial vaginosis is not considered a sexually transmitted infection, and treatment of a male sexual partner of a woman with bacterial vaginosis is not recommended.^[28][29]

Probiotics

The term probiotic is used for a nutrient that stimulates the growth of microorganisms that make up the healthy vaginal flora. The term is generally used for food components that improve human health by selectively stimulating the growth and/or activity of existing bacteria in the intestine.^[30] The concept of prebiotics assumes that the imbalance in vaginal micro-flora is influenced by a depletion of nutrient and substrate needed for the lactobacilli to multiply and produce lactic acid. The natural substrate for acid production is glycogen, which is deposited in epithelial cells.^[31] Lactose is the preferred compound, as it is generally fermented by lactobacilli, and it is not assimilated by Gardnerella vaginalis and Candida spp. (C. albicans, C. glabrata, C. krusei).^[32][33][34] The beneficial effect on several vaginal nuisances was indicated by a user survey.^[35] The clinical trial is still pending, but the concept was proven by a Chinese study using sucrose^[36] Several studies have found probiotics (containing Lactobacillus bacteria species, including L. rhamnosus, L. reuteri, L. acidophilus, and L. fermentum) to be highly effective (88–90% cure rate at 1 month) either alone or in combination with antibiotics,^[25] either taken orally or applied topically (vaginally), and significantly superior to antibiotics alone.^{[14][37][38][39]}

Some studies have also found probiotics useful in maintenance therapy, preventing recurrence. One Italian study found that once-weekly application of probiotics for 6 months almost completely prevented recurrence at 6 months (96%), and was still effective at 12 months.^[14][40]

In 2009 one Cochrane review was neutral about the role of probiotics usefulness in the treatment of BV.^[37]

Complications

Although previously considered a mere nuisance infection, untreated bacterial vaginosis may cause complications, such as increased susceptibility to sexually transmitted infections including HIV and pregnancy complications.^[41]

It has been shown that HIV-infected women with bacterial vaginosis (BV) have higher HIV concentrations in their vaginal secretions.^[42] Diagnostic criteria for BV have also been associated with a female genital tract factor that induces expression of HIV.^[43] The elevated HIV copy number in vaginal secretions of women with BV has been associated with an increased risk of heterosexual transmission of HIV.^[44]

Also, clinical studies have shown that BV-associated bacterial microbiota can activate HIV replication leading to significant increase in HIV production in the female genital tract, as detected in the vaginal secretions.^[45] Moreover, bacterial extracts of the leading causes of BV (i.e. Gardnerella vaginalis and some vaginal anareobic bacteria) may increase HIV production. Extracts from these bacterial cultures increased HIV production by more than 100 fold, as measured by HIV antigen (p24) production.^[46][47] Interestingly, pathogenic strains of G vaginalis were shown to be stronger inducers of HIV production, than the less pathogenic G vaginalis strains, which have weaker association with BV.^[48]

In addition, Bacterial vaginosis an intercurrent disease in pregnancy may increase the risk of pregnancy complications, most notably premature birth or miscarriage.^[49]

Epidemiology

BV is the most common infection of the vagina in women of reproductive age.^[6] The percentage of women affected at any given time vary between 5% and 70%.^[4] BV is most common in parts of Africa and least common in Asia and Europe.^[4] In the United States about 30% of those between the ages of 14 and 49 are affected.^[10] Rates vary considerably between ethnic groups within a country.^[4]

References