Bacterial vaginosis

Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria.<ref name=Don2014/><ref name="ClarkTal2014">Template:Cite journal</ref> Common symptoms include increased vaginal discharge that often smells like fish.<ref name=NIH2013S/> The discharge is usually white or gray in color.<ref name=NIH2013S/> Burning with urination may occur.<ref name=NIH2013S/> Itching is uncommon.<ref name=NIH2013S/><ref name=Don2014/> Occasionally, there may be no symptoms.<ref name=NIH2013S>Template:Cite web</ref> Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS.<ref name=Ken2013>Template:Cite journal</ref><ref name=Bradshaw2015>Template:Cite journal</ref> It also increases the risk of early delivery among pregnant women.<ref name=Queenan2012>Template:Cite book</ref><ref>Template:Cite web</ref>

BV is caused by an imbalance of the naturally occurring bacteria in the vagina.<ref name=Bennett2015>Template:Cite book</ref><ref name=NIH2013O/> There is a change in the most common type of bacteria and a hundred to thousandfold increase in total numbers of bacteria present.<ref name=Don2014/> Typically, bacteria other than Lactobacilli become more common.<ref name=Nardis2013>Template:Cite journal</ref> Risk factors include douching, new or multiple sex partners, antibiotics, and using an intrauterine device, among others.<ref name=NIH2013O/> However, it is not considered a sexually transmitted infection and, unlike gonorrhoea and chlamydia, sexual partners are not treated.<ref name="cdc.gov">Template:Cite web</ref> Diagnosis is suspected based on the symptoms, and may be verified by testing the vaginal discharge and finding a higher than normal vaginal pH, and large numbers of bacteria.<ref name=Don2014/> BV is often confused with a vaginal yeast infection or infection with Trichomonas.<ref name=Mash2006>Template:Cite journal</ref>

Usually treatment is with an antibiotic, such as clindamycin or metronidazole.<ref name="FaughtReyes2019">Template:Cite journal</ref><ref name=Don2014/> These medications may also be used in the second or third trimesters of pregnancy.<ref name=Don2014/> The antiseptic boric acid can also be effective.<ref name="LærkeholmMüllerDamstedPetersenSaunte2024" /> BV often recurs following treatment.<ref name=Don2014/> Probiotics may help prevent re-occurrence.<ref name=Don2014>Template:Cite journal</ref><ref name="ChiengAbdulJalalBedi2022">Template:Cite journal</ref> It is unclear if the use of probiotics or antibiotics affects pregnancy outcomes.<ref name=Don2014/><ref>Template:Cite journal</ref>

BV is the most common vaginal infection in women of reproductive age.<ref name=NIH2013O>Template:Cite web</ref> The percentage of women affected at any given time varies between 5% and 70%.<ref name=Ken2013/> BV is most common in parts of Africa and least common in Asia and Europe.<ref name=Ken2013/> In the United States about 30% of women between the ages of 14 and 49 are affected.<ref name=CDC2010Stats>Template:Cite web</ref> Rates vary considerably between ethnic groups within a country.<ref name=Ken2013/> While BV-like symptoms have been described for much of recorded history, the first clearly documented case occurred in 1894.<ref name=History1997>Template:Cite book</ref>

Signs and symptoms

Although about 50% of women with BV are asymptomatic,<ref name="Tidbury Langhart Weidlinger Stute 2021 pp. 37–45">Template:Cite journal</ref> 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.

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 two weeks before the period starts. Some practitioners claim that BV can be asymptomatic in almost half of affected women,<ref name="pmid11120507">Template:Cite journal</ref> though others argue that this is often a misdiagnosis.<ref>Template:Cite journal</ref>

Complications

Although previously considered a mere nuisance infection, untreated bacterial vaginosis may cause increased susceptibility to sexually transmitted infections, including HIV, and pregnancy complications.<ref name=Amaya2015/><ref name=CDC>Template:Cite web</ref>

It has been shown that HIV-infected women with bacterial vaginosis (BV) are more likely to transmit HIV to their sexual partners than those without BV.<ref name=Bradshaw2015/> There is evidence of an association between BV and increased rates of sexually transmitted infections such as HIV/AIDS.<ref name=Amaya2015/> BV is associated with up to a six-fold increase in HIV shedding. BV is a risk factor for viral shedding and herpes simplex virus type 2 infection. BV may increase the risk of infection with or reactivation of human papillomavirus (HPV).<ref name=Amaya2015/><ref name="SenokVerstraelen2009"/>

In addition, bacterial vaginosis as either pre-existing, or acquired, may increase the risk of pregnancy complications, most notably premature birth or miscarriage.<ref>Template:Cite web</ref><ref name="HillierNugent1995">Template:Cite journal</ref> Pregnant women with BV have a higher risk of chorioamnionitis, miscarriage, preterm birth, premature rupture of membranes, and postpartum endometritis.<ref name="Nugent1991" /> Women with BV who are treated with in vitro fertilization have a lower implantation rate and higher rates of early pregnancy loss.<ref name=Amaya2015/><ref name="SenokVerstraelen2009"/>

Causes

Template:Main Healthy vaginal microbiota consists of species that neither cause symptoms or infections, nor negatively affect pregnancy. It is dominated mainly by Lactobacillus species.<ref name=Nardis2013/><ref name="PetrovaLievens2015">Template:Cite journal</ref> BV is defined by the disequilibrium in the vaginal microbiota, with decline in the number of lactobacilli. While the infection involves a number of bacteria, it is believed that most infections start with Gardnerella vaginalis creating a biofilm, which allows other opportunistic bacteria, such as Prevotella and Bacteroides, to thrive.<ref name=":0">Template:Cite journal</ref><ref name="ClarkTal2014"/><ref>Template:Cite journal</ref>

One of the main risks for developing BV is douching, which alters the vaginal microbiota and predisposes women to developing BV.<ref name="Cottrell">Template:Cite journal</ref> Douching is strongly discouraged by the U.S. Department of Health and Human Services and various medical authorities, for this and other reasons.<ref name="Cottrell" />

BV is a risk factor for pelvic inflammatory disease, HIV, sexually transmitted infections (STIs), endometriosis, and reproductive and obstetric disorders or negative outcomes. Although BV can be associated with sexual activity, there is no clear evidence of sexual transmission.<ref name=":0" /><ref name="pmid35509673">Template:Cite journal</ref><ref name="Bradshaw2006">Template:Cite journal</ref> It is possible for sexually inactive persons to develop bacterial vaginosis.<ref name="pmid35509673"/><ref name="ClarkTal2014"/>

Also, subclinical iron deficiency may correlate with bacterial vaginosis in early pregnancy.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> Exposure to the spermicide nonoxynol-9 does not affect the risk of developing bacterial vaginosis.<ref>Template:Cite journal</ref>

The cause of the fishy smell of BV is mainly due to reduction of trimethylamine oxide (TMAO) to trimethylamine (TMA) by bacteria in vaginal secretion.<ref name="Spiegel1991">Template:Cite journal</ref><ref name="BrandGalask1986">Template:Cite journal</ref><ref name="WolrathBorénHallén2002">Template:Cite journal</ref> TMA is the same compound that is predominantly responsible for the smell of decomposing fish.<ref name="Spiegel1991" /><ref name="BrandGalask1986" /> The diamines putrescine and cadaverine, which are the decarboxylation products of arginine and lysine amino acid metabolism, respectively, are also present in BV and may contribute to the fishy smell of the condition as well.<ref name="Spiegel1991" />

Diagnosis

File:Clue cells in bacterial vaginosis.jpg

Phase contrast microscopy of clue cells in a vaginal swab

File:Bacterial vaginosis workup.jpg

A pH indicator to detect vaginal alkalinization (here showing approximately pH 8), and a microscope slide to microscopically detect clue cells

File:Normal and BV flora.jpg

Gram stain of cells from the vagina (the same magnification) with normal bacterial flora (top) and the bacteria that cause vaginosis (bottom).

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

• Gram stain which shows the depletion of lactobacilli and overgrowth of Gardnerella vaginalis bacteria. Bacterial vaginosis is usually confirmed by a Gram stain of vaginal secretions.<ref name="pmid32235174">Template:Cite journal</ref>
• 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 microscope slide containing the vaginal discharge. A characteristic fishy odor is considered a positive whiff test and is suggestive of bacterial vaginosis.<ref>Template:Citation</ref> Addition of a base to vaginal secretion with the diamines putrescine and cadaverine causes them to become volatile and thereby produce a more intense fishy smell.<ref name="Spiegel1991" />
• 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.Template:Citation needed
• 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.

Differential diagnosis for bacterial vaginosis includes the following:<ref name=diagnosis>Template:Cite web</ref>

• Normal vaginal discharge.
• Candidiasis (thrush, or a yeast infection).
• Trichomoniasis, an infection caused by Trichomonas vaginalis.
• Aerobic vaginitis<ref name="pmid11845812">Template:Cite journal</ref>

The Center for Disease Control (CDC) defines STIs as "a variety of clinical syndromes and infections caused by pathogens that can be acquired and transmitted through sexual activity."<ref name="pmid26042815">Template:Cite journal</ref> But the CDC does not specifically identify BV as sexually transmitted infection.<ref name="cdc.gov"/>

Amsel criteria

In clinical practice BV can be diagnosed using the Amsel criteria:<ref name = Amsel>Template:Cite journal</ref>

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.<ref name=GCH>Template:Cite web</ref> A modification of the Amsel criteria accepts the presence of two instead of three factors and is considered equally diagnostic.<ref>Template:Cite journal</ref>

Gram stain

An alternative is to use a Gram-stained vaginal smear, with the Hay/Ison<ref name = HayIson>Template:Cite journal</ref> criteria or the Nugent<ref name="Nugent1991">Template:Cite journal</ref> criteria. The Hay/Ison criteria are defined as follows:<ref name=GCH/>

• Grade 1 (Normal): Lactobacillus morphotypes predominate.
• Grade 2 (Intermediate): 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)

Gardnerella vaginalis is the main culprit in BV. Gardnerella vaginalis is a short, Gram-variable rod (coccobacillus). Hence, the presence of clue cells and gram variable coccobacilli are indicative or diagnostic of bacterial vaginosis.<ref>Template:Cite journal</ref>

Nugent score

The Nugent score is now rarely used by physicians due to the time it takes to read the slides and requires the use of a trained microscopist.<ref name=Bennett2015/> A score of 0–10 is generated from combining three other scores. The scores are as follows:<ref name="Nugent1991" />

• 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.<ref name="pmid31077161">Template:Cite journal</ref>

Lactobacillus morphotypes – average per high powered (1000× oil immersion) field. View multiple fields.	Gardnerella / Bacteroides morphotypes – average per high powered (1000× oil immersion) field. View multiple fields.	Curved Gram variable rods – average per high powered (1000× oil immersion) field. View multiple fields (note that this factor is less important – scores of only 0–2 are possible)
Score 0 for >30 Score 1 for 15–30 Score 2 for 14 Score 3 for <1 (this is an average, so results can be >0, yet <1) Score 4 for 0	Score 0 for 0 Score 1 for <1 (this is an average, so results can be >0, yet <1) Score 2 for 1–4 Score 3 for 5–30 Score 4 for >30	Score 0 for 0 Score 1 for <5 Score 2 for 5+Template:Citation needed

DNA hybridization testing with Affirm VPIII was compared to the Gram stain using the Nugent criteria.<ref name="pmid17078859">Template:Cite journal</ref> The Affirm VPIII test may be used for the rapid diagnosis of BV in symptomatic women but uses expensive proprietary equipment to read results, and does not detect other pathogens that cause BV, including Prevotella spp, Bacteroides spp, and Mobiluncus spp.<ref>Template:Cite journal</ref> The cervicovaginal microbiome measured using 16S rRNA sequencing has the capacity to increase throughput of the Nugent Score and has demonstrate to be directly comparable to clinical Nugent Score measurement.<ref>Template:Cite journal</ref>

Screening

Screening during pregnancy is not recommended in the United States as of 2020 because " the US Preventive Services Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis in pregnant persons at increased risk for preterm delivery".<ref>Template:Cite journal</ref>

Prevention

Some steps suggested to lower the risk include: not douching, avoiding sex, or limiting the number of sex partners.<ref name=CDCbv2014>Template:Cite web</ref>

Systematic reviews and meta-analyses from 2022 to 2023 have concluded that probiotics may help prevent re-occurrence.<ref name="ChiengAbdulJalalBedi2022" /><ref name="ChenLiQing2022">Template:Cite journal</ref><ref name="MaWangSu2023">Template:Cite journal</ref>

Early evidence suggested that antibiotic treatment of male partners could re-establish the normal microbiota of the male urogenital tract and prevent the recurrence of infection.<ref name=Amaya2015>Template:Cite journal</ref> However, a 2016 Cochrane review found high-quality evidence that treating the sexual partners of women with bacterial vaginosis had no effect on symptoms, clinical outcomes, or recurrence in the affected women. It also found that such treatment may lead treated sexual partners to report increased adverse events.<ref name=Amaya2015/>

Treatment

Antibiotics

Treatment is typically with the antibiotics metronidazole or clindamycin.<ref name=Od2009/> They can be either given by mouth or applied inside the vagina with similar efficacy.<ref name="Tidbury Langhart Weidlinger Stute 2021 pp. 37–45"/><ref name=Od2009>Template:Cite journal</ref> Other antibiotics related to metronidazole, including tinidazole and the newer secnidazole, are also approved and used to treat BV.<ref name="FaughtReyes2019" /><ref name="AdisInsight-Tinidazole">Template:Cite web</ref><ref name="AdisInsight-Secnidazole">Template:Cite web</ref> When clindamycin is given to pregnant women symptomatic with BV before 22 weeks of gestation the risk of pre-term birth before 37 weeks of gestation is lower.<ref name="LamontNhan-Chang">Template:Cite journal</ref> Additional antibiotics that are not approved for treatment of BV but might work include macrolides, lincosamides, and penicillins.<ref name="Amaya2015"/>

Although antibiotics are effective, about 10% to 15% of people do not improve with the first course of antibiotics and recurrence rates of up to 80% have been documented.<ref name="SenokVerstraelen2009">Template:Cite journal</ref> Recurrence rates are increased with sexual activity with the same pre-/post-treatment partner and inconsistent condom use.<ref name="BradshawVodstrcilHocking2013">Template:Cite journal</ref>

BV is not considered a sexually transmitted infection, and antibiotic treatment of a male sexual partner of a woman with BV is not recommended.<ref>Template:Cite journal</ref><ref name="pmid10818662">Template:Cite journal</ref>

Antiseptics

Topical antiseptics, for example dequalinium chloride, policresulen, hexetidine, povidone-iodine, or boric acid vaginal suppositories may be applied, if the risk of ascending infections is low (outside of pregnancy and in immunocompetent people without histories of upper genital tract infections).<ref name=Schaefer2008>Template:Cite book</ref><ref name="AbbeMitchell2023" />

Dequalinium chloride is available as a prescription vaginal tablet, for instance in Europe and Canada, is given as a 6-day course, and is non-inferior to metronidazole in the treatment of bacterial vaginosis.<ref name="CarterTuddenhamBrotman2024">Template:Cite journal</ref><ref name="MendlingWeissenbacherGerber2016">Template:Cite journal</ref><ref name="Slawson2024">Template:Cite journal</ref><ref name="AdisInsight-Dequalinium">Template:Cite web</ref> Povidone-iodine is approved as a vaginal gel to treat bacterial vaginosis under the brand name Astrodimer, among others.<ref name="AdisInsight-Astrodimer">Template:Cite web</ref><ref name="AbbeMitchell2023">Template:Cite journal</ref><ref name="ISIDOG2023">Template:Cite web</ref> One study found that vaginal irrigations with hydrogen peroxide (3%) resulted in a slight improvement, but this was much less than with the use of oral metronidazole.<ref>Template:Cite journal</ref> Dequalinium chloride and povidone-iodine (as Astrodimer) have the best evidence of effectiveness.<ref name="AbbeMitchell2023" /> Neither of these are available in the United States, though they are available in other countries.<ref name="AbbeMitchell2023" /> Intravaginal boric acid, alone or in conjunction with other medications, may be helpful in the treatment of recurrent BV.<ref name="CDC2021" /><ref name="UpToDate" /><ref name="LærkeholmMüllerDamstedPetersenSaunte2024">Template:Cite journal</ref>

TOL-463, an experimental formulation of boric acid enhanced with ethylenediaminetetraacetic acid (EDTA), is under development as an intravaginal medication for the treatment of BV and has shown preliminary effectiveness in clinical trials.<ref name="AdisInsight-TOL-463">Template:Cite web</ref><ref name="UpToDate">Template:Cite web</ref><ref name="pmid33750246">Template:Cite journal</ref><ref name="pmid30184181">Template:Cite journal</ref>

Probiotics

A 2009 Cochrane review found tentative but insufficient evidence for probiotics as a treatment for BV.<ref name="SenokVerstraelen2009"/> A 2014 review reached the same conclusion.<ref>Template:Cite journal</ref> A 2013 review found some evidence supporting the use of probiotics during pregnancy.<ref>Template:Cite journal</ref> The preferred probiotics for BV are those containing high doses of lactobacilli (around 10⁹ Template:Abbrlink) given in the vagina.<ref name="pmid23912864">Template:Cite journal</ref> Intravaginal administration is preferred to taking them by mouth.<ref name="pmid23912864" /> Prolonged repetitive courses of treatment appear to be more promising than short courses.<ref name="pmid23912864" />

The lack of effectiveness of commercially available Lactobacillus probiotics may be because most do not actually contain vaginal lactobacilli strains.<ref name="pmid33330916">Template:Cite journal</ref> LACTIN-V is a live biopharmaceutical medication containing the vaginally important Lactobacillus crispatus which is under development for the treatment of bacterial vaginosis and recurrent urinary tract infections.<ref name="pmid33330916" /><ref name="AdisInsight-LACTIN-V">Template:Cite web</ref><ref name="CDC2021">Template:Cite web</ref> It has shown initial effectiveness in considerably reducing recurrence of bacterial vaginosis following antibiotic treatment.<ref name="pmid33330916" /><ref name="CDC2021" /> LACTIN-V is not yet Food and Drug Administration (FDA)-approved or commercially available.<ref name="CDC2021" /><ref name="AdisInsight-LACTIN-V" />

Miscellaneous

Estrogen-containing contraceptives have been found to decrease recurrence of BV.<ref name="BradshawVodstrcilHocking2013" />

Epidemiology

BV is the most common infection of the vagina in women of reproductive age.<ref name=NIH2013O/> The percentage of women affected at any given time varies between 5% and 70%.<ref name=Ken2013/> BV is most common in parts of Africa, and least common in Asia and Europe.<ref name=Ken2013/> In the United States, about 30% of those between the ages of 14 and 49 are affected.<ref name=CDC2010Stats/> Rates vary considerably between ethnic groups within a country.<ref name=Ken2013/>

External links

• WHO fact sheet on bacterial vaginosis