Bacterial vaginosis

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Bacterial vaginosis
Other namesAnaerobic vaginositis, non-specific vaginitis, vaginal bacteriosis, Gardnerella vaginitis [1]
Normal vaginal flora versus bacterial vaginosis on Pap stain.jpg
Vaginal squamous cell with normal vaginal flora versus bacterial vaginosis on Pap stain. Normal vaginal flora (left) is predominantly rod-shaped Lactobacilli whereas in bacterial vaginosis (right) there is an overgrowth of bacteria which can be of multiple species.
Specialty Gynecology, infectious disease
Symptoms Vaginal discharge that often smells like fish, burning with urination [2]
Complications Early delivery among pregnant women [3]
CausesImbalance of the naturally occurring bacteria in the vagina [4] [5]
Risk factors Douching, new or multiple sex partners, antibiotics, using an intrauterine device [5]
Diagnostic method Testing the vaginal discharge [6]
Differential diagnosis Vaginal yeast infection, infection with Trichomonas [7]
Prevention Probiotics [6] [8]
Medication Clindamycin, metronidazole, tinidazole, secnidazole, boric acid, probiotics [9] [6] [10]
Frequency~ 5% to 70% of women [11]

Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. [6] [12] Common symptoms include increased vaginal discharge that often smells like fish. [2] The discharge is usually white or gray in color. [2] Burning with urination may occur. [2] Itching is uncommon. [2] [6] Occasionally, there may be no symptoms. [2] Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS. [11] [13] It also increases the risk of early delivery among pregnant women. [3] [14]

Contents

BV is caused by an imbalance of the naturally occurring bacteria in the vagina. [4] [5] There is a change in the most common type of bacteria and a hundred to thousandfold increase in total numbers of bacteria present. [6] Typically, bacteria other than Lactobacilli become more common. [15] Risk factors include douching, new or multiple sex partners, antibiotics, and using an intrauterine device, among others. [5] However, it is not considered a sexually transmitted infection and, unlike gonorrhoea and chlamydia, sexual partners are not treated. [16] 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. [6] BV is often confused with a vaginal yeast infection or infection with Trichomonas. [7]

Usually treatment is with an antibiotic, such as clindamycin or metronidazole. [9] [6] These medications may also be used in the second or third trimesters of pregnancy. [6] The antiseptic boric acid can also be effective. [10] BV often recurs following treatment. [6] Probiotics may help prevent re-occurrence. [6] [8] It is unclear if the use of probiotics or antibiotics affects pregnancy outcomes. [6] [17]

BV is the most common vaginal infection in women of reproductive age. [5] The percentage of women affected at any given time varies between 5% and 70%. [11] BV is most common in parts of Africa and least common in Asia and Europe. [11] In the United States about 30% of women between the ages of 14 and 49 are affected. [18] Rates vary considerably between ethnic groups within a country. [11] While BV-like symptoms have been described for much of recorded history, the first clearly documented case occurred in 1894. [1]

Signs and symptoms

Although about 50% of women with BV are asymptomatic, [19] 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. [2]

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, [20] though others argue that this is often a misdiagnosis. [21]

Complications

Although previously considered a mere nuisance infection, untreated bacterial vaginosis may cause increased susceptibility to sexually transmitted infections, including HIV, and pregnancy complications. [22] [23]

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. [13] There is evidence of an association between BV and increased rates of sexually transmitted infections such as HIV/AIDS. [22] 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). [22] [24]

In addition, bacterial vaginosis as either pre-existing, or acquired, may increase the risk of pregnancy complications, most notably premature birth or miscarriage. [25] [26] Pregnant women with BV have a higher risk of chorioamnionitis, miscarriage, preterm birth, premature rupture of membranes, and postpartum endometritis. [27] Women with BV who are treated with in vitro fertilization have a lower implantation rate and higher rates of early pregnancy loss. [22] [24]

Causes

Healthy vaginal microbiota consists of species that neither cause symptoms or infections, nor negatively affect pregnancy. It is dominated mainly by Lactobacillus species. [15] [28] 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. [29] [12] [30]

One of the main risks for developing BV is douching, which alters the vaginal microbiota and predisposes women to developing BV. [31] Douching is strongly discouraged by the U.S. Department of Health and Human Services and various medical authorities, for this and other reasons. [31]

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. [29] [32] [33] It is possible for sexually inactive persons to develop bacterial vaginosis. [32] [12]

Also, subclinical iron deficiency may correlate with bacterial vaginosis in early pregnancy. [34] 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. [35] Exposure to the spermicide nonoxynol-9 does not affect the risk of developing bacterial vaginosis. [36]

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. [37] [38] [39] TMA is the same compound that is predominantly responsible for the smell of decomposing fish. [37] [38] 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. [37]

Diagnosis

Phase contrast microscopy of clue cells in a vaginal swab Clue cells in bacterial vaginosis.jpg
Phase contrast microscopy of clue cells in a vaginal swab
A pH indicator to detect vaginal alkalinization (here showing approximately pH 8), and a microscope slide to microscopically detect clue cells 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
Gram stain of cells from the vagina (the same magnification) with normal bacterial flora (top) and the bacteria that cause vaginosis (bottom). 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:

Differential diagnosis for bacterial vaginosis includes the following: [42]

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." [44] But the CDC does not specifically identify BV as sexually transmitted infection. [16]

Amsel criteria

In clinical practice BV can be diagnosed using the Amsel criteria: [45]

  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. [46] A modification of the Amsel criteria accepts the presence of two instead of three factors and is considered equally diagnostic. [47]

Gram stain

An alternative is to use a Gram-stained vaginal smear, with the Hay/Ison [48] criteria or the Nugent [27] criteria. The Hay/Ison criteria are defined as follows: [46]

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. [49]

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. [4] A score of 0–10 is generated from combining three other scores. The scores are as follows: [27]

At least 10–20 high power (1000× oil immersion) fields are counted and an average determined. [50]

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

DNA hybridization testing with Affirm VPIII was compared to the Gram stain using the Nugent criteria. [51] 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. [52] 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. [53]

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". [54]

Prevention

Some steps suggested to lower the risk include: not douching, avoiding sex, or limiting the number of sex partners. [55]

Systematic reviews and meta-analyses from 2022 to 2023 have concluded that probiotics may help prevent re-occurrence. [8] [56] [57]

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. [22] 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. [22]

Treatment

Antibiotics

Treatment is typically with the antibiotics metronidazole or clindamycin. [58] They can be either given by mouth or applied inside the vagina with similar efficacy. [19] [58] Other antibiotics related to metronidazole, including tinidazole and the newer secnidazole, are also approved and used to treat BV. [9] [59] [60] 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. [61] Additional antibiotics that are not approved for treatment of BV but might work include macrolides, lincosamides, and penicillins. [22]

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. [24] Recurrence rates are increased with sexual activity with the same pre-/post-treatment partner and inconsistent condom use. [62] Estrogen-containing contraceptives have been found to decrease recurrence. [62]

BV is not considered a sexually transmitted infection, and treatment of a male sexual partner of a woman with BV is not recommended. [63] [64]

Probiotics

A 2009 Cochrane review found tentative but insufficient evidence for probiotics as a treatment for BV. [24] A 2014 review reached the same conclusion. [65] A 2013 review found some evidence supporting the use of probiotics during pregnancy. [66] The preferred probiotics for BV are those containing high doses of lactobacilli (around 109 CFUs Tooltip Colony-forming units) given in the vagina. [67] Intravaginal administration is preferred to taking them by mouth. [67] Prolonged repetitive courses of treatment appear to be more promising than short courses. [67]

The lack of effectiveness of commercially available Lactobacillus probiotics may be because most do not actually contain vaginal lactobacilli strains. [68] 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. [68] [69] [70] It has shown initial effectiveness in considerably reducing recurrence of bacterial vaginosis following antibiotic treatment. [68] [70] LACTIN-V is not yet Food and Drug Administration (FDA)-approved or commercially available. [70] [69]

Antiseptics

Topical antiseptics, for example dequalinium chloride, policresulen, hexetidine, or povidone-iodine 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). [71] 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. [72] Intravaginal boric acid, alone or in conjunction with other medications, may be helpful in the treatment of recurrent BV. [70] [73] [10]

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. [74] [73] [75] [76]

Epidemiology

BV is the most common infection of the vagina in women of reproductive age. [5] The percentage of women affected at any given time varies between 5% and 70%. [11] BV is most common in parts of Africa, and least common in Asia and Europe. [11] In the United States, about 30% of those between the ages of 14 and 49 are affected. [18] Rates vary considerably between ethnic groups within a country. [11]

Related Research Articles

<span class="mw-page-title-main">Pelvic inflammatory disease</span> Infection of uterus, fallopian tubes, ovaries or the inner surface of pelvis

Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be no symptoms. Signs and symptoms, when present, may include lower abdominal pain, vaginal discharge, fever, burning with urination, pain with sex, bleeding after sex, or irregular menstruation. Untreated PID can result in long-term complications including infertility, ectopic pregnancy, chronic pelvic pain, and cancer.

<span class="mw-page-title-main">Trichomoniasis</span> Medical condition

Trichomoniasis (trich) is an infectious disease caused by the parasite Trichomonas vaginalis. About 70% of affected people do not have symptoms when infected. When symptoms occur, they typically begin 5 to 28 days after exposure. Symptoms can include itching in the genital area, a bad smelling thin vaginal discharge, burning with urination, and pain with sex. Having trichomoniasis increases the risk of getting HIV/AIDS. It may also cause complications during pregnancy.

<i>Gardnerella vaginalis</i> Species of bacterium

Gardnerella vaginalis is a species of Gram-variable-staining facultative anaerobic bacteria. The organisms are small non-spore-forming, nonmotile coccobacilli.

Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy.

<span class="mw-page-title-main">Vaginal discharge</span> Medical condition

Vaginal discharge is a mixture of liquid, cells, and bacteria that lubricate and protect the vagina. This mixture is constantly produced by the cells of the vagina and cervix, and it exits the body through the vaginal opening. The composition, amount, and quality of discharge varies between individuals and can vary throughout the menstrual cycle and throughout the stages of sexual and reproductive development. Normal vaginal discharge may have a thin, watery consistency or a thick, sticky consistency, and it may be clear or white in color. Normal vaginal discharge may be large in volume but typically does not have a strong odor, nor is it typically associated with itching or pain. While most discharge is considered physiologic or represents normal functioning of the body, some changes in discharge can reflect infection or other pathological processes. Infections that may cause changes in vaginal discharge include vaginal yeast infections, bacterial vaginosis, and sexually transmitted infections. The characteristics of abnormal vaginal discharge vary depending on the cause, but common features include a change in color, a foul odor, and associated symptoms such as itching, burning, pelvic pain, or pain during sexual intercourse.

<span class="mw-page-title-main">Clue cell</span> Epithelial cell of the human vagina that is covered with bacteria

Clue cells are epithelial cells of the vagina that get their distinctive stippled appearance by being covered with bacteria. The etymology behind the term "clue" cell derives from the original research article from Gardner and Dukes describing the characteristic cells. The name was chosen for its brevity in describing the sine qua non of bacterial vaginosis.

<span class="mw-page-title-main">Aposymbiosis</span>

Aposymbiosis occurs when symbiotic organisms live apart from one another. Studies have shown that the lifecycles of both the host and the symbiont are affected in some way, usually negative, and that for obligate symbiosis the effects can be drastic. Aposymbiosis is distinct from exsymbiosis, which occurs when organisms are recently separated from a symbiotic association. Because symbionts can be vertically transmitted from parent to offspring or horizontally transmitted from the environment, the presence of an aposymbiotic state suggests that transmission of the symbiont is horizontal. A classical example of a symbiotic relationship with an aposymbiotic state is the Hawaiian bobtail squid Euprymna scolopes and the bioluminescent bacteria Vibrio fischeri. While the nocturnal squid hunts, the bacteria emit light of similar intensity of the moon which camouflages the squid from predators. Juveniles are colonized within hours of hatching and Vibrio must outcompete other bacteria in the seawater through a system of recognition and infection.

The Nugent Score is a Gram stain scoring system for vaginal swabs to diagnose bacterial vaginosis (BV). The Nugent score is calculated by assessing for the presence of large Gram-positive rods, small Gram-variable rods, and curved Gram-variable rods. A score of 7 to 10 is consistent with bacterial vaginosis without culture. 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. Bacterial vaginosis diagnosis is done by evaluating the pH, the presences of Lactobacillus spp. versus a mixed flora consisting of Gardnerella vaginalis, Bacteroides spp, Mobiluncus spp, and Mycoplasma hominis. The Amsel Criteria for bacterial vaginosis includes pH, evaluating the presence of clue cells, white discharge and an odor of amines after mixing with KOH.

<span class="mw-page-title-main">Vaginal flora</span> Microorganisms present in the vagina

Vaginal flora, vaginal microbiota or vaginal microbiome are the microorganisms that colonize the vagina. They were discovered by the German gynecologist Albert Döderlein in 1892 and are part of the overall human flora. The amount and type of bacteria present have significant implications for an individual's overall health. The primary colonizing bacteria of a healthy individual are of the genus Lactobacillus, such as L. crispatus, and the lactic acid they produce is thought to protect against infection by pathogenic species.

Female genital disease is a disorder of the structure or function of the female reproductive system that has a known cause and a distinctive group of symptoms, signs, or anatomical changes. The female reproductive system consists of the ovaries, fallopian tubes, uterus, vagina, and vulva. Female genital diseases can be classified by affected location or by type of disease, such as malformation, inflammation, or infection.

<span class="mw-page-title-main">Vaginal yeast infection</span> Medical condition

Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burning with urination, a thick, white vaginal discharge that typically does not smell bad, pain during sex, and redness around the vagina. Symptoms often worsen just before a woman's period.

Lactobacillus crispatus is a common, rod-shaped species of genus Lactobacillus and is a lactic acid producing bacterial species located in both the vagina, through vaginal discharge, and the vertebrate gastrointestinal tract. This species commonly found in vaginal microbiome and is thought to be beneficial to health.

The vaginal flora in pregnancy, or vaginal microbiota in pregnancy, is different from the vaginal flora before sexual maturity, during reproductive years, and after menopause. A description of the vaginal flora of pregnant women who are immunocompromised is not covered in this article. The composition of the vaginal flora significantly differs in pregnancy. Bacteria or viruses that are infectious most often have no symptoms.

<span class="mw-page-title-main">Aerobic vaginitis</span> Medical condition

Aerobic vaginitis (AV) is a form of vaginitis first described by Donders et al. in 2002. It is characterized by a more or less severe disruption of the lactobacillary flora, along with inflammation, atrophy, and the presence of a predominantly aerobic microflora, composed of enteric commensals or pathogens.

<span class="mw-page-title-main">Lactobacillus vaccine</span> Vaccine using an inactivated strain of Lactobacillus

Lactobacillus vaccines are used in the therapy and prophylaxis of non-specific bacterial vaginitis and trichomoniasis. The vaccines consist of specific inactivated strains of Lactobacilli, called "aberrant" strains in the relevant literature dating from the 1980s. These strains were isolated from the vaginal secretions of patients with acute colpitis. The lactobacilli in question are polymorphic, often shortened or coccoid in shape and do not produce an acidic, anti-pathogenic vaginal environment. A colonization with aberrant lactobacilli has been associated with an increased susceptibility to vaginal infections and a high rate of relapse following antimicrobial treatment. Intramuscular administration of inactivated aberrant lactobacilli provokes a humoral immune response. The production of specific antibodies both in serum and in the vaginal secretion has been demonstrated. As a result of the immune stimulation, the abnormal lactobacilli are inhibited, the population of normal, rod-shaped lactobacilli can grow and exert its defense functions against pathogenic microorganisms.

Limosilactobacillus vaginalis is a lactic acid bacterium that is a normal, but infrequent part of the vaginal microbiome.

LACTIN-V, also known as CTV-05 or as Lactobacillus crispatus CTV-05, is a live biopharmaceutical medication containing a strain of Lactobacillus crispatus which is under development for the treatment of urinary tract infections (UTIs) and bacterial vaginosis (BV). It is administered intravaginally and is described as the first vaginal microbiome (VMB)-based live biotherapeutic product (LBP).

<span class="mw-page-title-main">TOL-463</span> Combination drug

TOL-463 is an anti-infective medication which is under development for the treatment of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It is a boric acid-based vaginal anti-infective enhanced with ethylenediaminetetraacetic acid (EDTA) which was designed to have improved activity against vaginal bacterial and fungal biofilms while sparing protective lactobacilli. EDTA enhances the antimicrobial activity of boric acid and improves its efficacy against relevant biofilms.

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