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BACTERIAL VAGINOSIS
Hamidova M.G.
hamidova.mushtaribegim@bsmi.uz
+998906135513
Assistant of the Department of Normal Physiology of Bukhara State Medical Instituti named
after Abu Ali ibn Sino
ANNOTATION:
Bacterial vaginosis (BV) is one of the most common infectious
pathologies of women of childbearing age. Bacterial vaginosis is a condition in which the
normal vaginal microflora, represented mainly by lactobacilli, is replaced by numerous
anaerobic and other opportunistic flora. Dysbiosis has been linked to complications such as
rupture of the membranes, premature birth, infections of the chorion, amnion, and amniotic
fluid., intrauterine fetal death. This suggests the need for screening for bacterial vaginosis
and its treatment before pregnancy.
Key words:
Bacterial vaginosis; vaginal microbiocenosis; immune defense mechanisms;
cytokines.
Bacterial vaginosis (BV) is a polymicrobial disease in which the normal vaginal microbiota
(protective lactobacilli) is replaced by microaerophilic (Gardnerella vaginalis) and obligate
anaerobic (
Bacteroides spp., Prevotella spp., Mobiluncus spp., Veillonella spp.,
Medasphaega spp., Leptotrichia spp., Atopobium vaginae
and others) by microorganisms
[1]. There is a generally accepted opinion that there is no inflammatory leukocyte reaction in
BV.
According to world statistics, BV occupies one of the first places among diseases of the
vagina. Its prevalence in the population ranges from 12% to 80% and depends on the
number of women surveyed [1]. BV is detected in 80-87% of women with abnormal vaginal
discharge, in 37-40% of pregnant women, and in 25% of adolescent girls. However, it is not
possible to determine the true incidence of BV due to the fact that approximately 50% of
women have an asymptomatic condition. At the same time, BV is found in 15-19% of
patients in outpatient gynecological practice, in 10-40% of pregnant women, in 24-40% of
women with STIs, and in 35% of women with PID (pelvic inflammatory disease).
BV is not an STI and does not pose a danger to life, however, it becomes a risk factor for
pregnancy complications, as well as a cause of the development of PID [2].
Important components of the vaginal indigenous (resident, obligate, predominant in the
biotope) microflora are lactobacilli, bifidobacteria and propionic acid bacteria, which must
be at least 95% in this biotope in order for the protection of the vagina to be effective. The
evolution of the vaginal biotope has led to the development of adaptive mechanisms that
allow these indigenous microorganisms to actively develop in the vaginal environment,
adhere to the epithelium, forming strong symbiotic bonds with it, and successfully compete
with facultative and transient opportunistic and pathogenic microflora.
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The first place among the indigenous flora is occupied by lactobacilli.
Lactobacillus
сrisраtus
,
L. inеrs
,
L. jеnsеnii
and
L. gаssеri
are most often isolated. The dominant species
is
L. сrisраtus
— they are found in 72% of women with normocenosis.
Lactobacilli are capable of:
• actively reproduce in the vaginal environment;
• adhere to the surface of epitheliocytes, leaving no room for infectious agents;
• Ferment glycogen with accumulation of organic acids;
• synthesize hydrogen peroxide, which is practically the only bactericidal factor that can be
produced in the human div;
• produce lysozyme, bacteriocins;
• Stimulate local immunity.
Lactobacilli are the most adapted to colonize the vagina and protect it from colonization by
opportunistic and pathogenic microorganisms [3].
Bifidobacteria are the second main component of the native flora. Five species are most
common:
Bifidobacterium bifidum
,
B. lоngum
,
B. infаntis
,
B. brеvе
and
B. аdоlеsсеntis
.
They are able to ferment glycogen to form organic acids, thus creating an optimal pH
environment for themselves; adhere to the surface of the epithelium, synthesize
antimicrobial metabolites, and stimulate local immunity. Effectively inhibit the growth of
Gardnerella, Staphylococcus, Escherichia, Klebsiella and other opportunistic
microorganisms. In healthy non-pregnant women, bifidobacteria are contained in lower
concentrations than lactobacilli (up to 107 CFU/ml). During pregnancy (especially in the
prenatal period), their titer increases sharply, which is a powerful factor in protecting the
newborn's div from colonization by pathogenic microorganisms during passage through
the birth canal [4].
The third type of indigenous flora is propionic acid bacteria. These are gram-positive
asporogenic polymorphic small rods that compete well for nutrients with anaerobes. They
are characterized by strict anaerobism, actively ferment glycogen to form propionic and
acetic acids, and inhibit the growth of opportunistic bacteria. They have antioxidant,
antimutagenic, anticarcinogenic and immunostimulating properties.
In general, the normocenosis in the vagina is characterized by a dynamic relationship
between
Lасtоbасillus асidорhilus
(produces hydrogen peroxide, which has a toxic effect on
pathogenic microorganisms and maintains the pH of the vagina) and other endogenous flora.
It depends on the levels of estrogens in the blood plasma; the amount of glycogen in the
epithelium, because acidic environment is produced from it; pH; products of metabolism of
endogenous flora and pathogenic microorganisms.
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Summing up, we can say that two main factors of protection are decisive — an acidic
environment (pH of the vagina in the range from 3.8 to 4.5) and colonization resistance.
Colonization resistance is understood as a set of mechanisms that ensure the ability of a
microbiota and a macroorganism to cooperatively protect an ecosystem from pathogenic
microflora. Microorganisms within communities come into contact with each other in
different planes and have a minimal free surface for contact with the matrix. Many
microcolonies and similar isolated communities are combined into a common structure — a
biofilm [5].
The colonization properties of native flora depend on its adhesive properties. By attaching to
the surface of epitheliocytes, a biofilm is formed on the vaginal mucosa, consisting of
vaginal mucus, colonies of indigenous microflora and its metabolites. This is one of the
most powerful protective factors, as it prevents adhesion and excessive development of
opportunistic microorganisms.
The causes of disruption of normal microflora can be endogenous and exogenous factors.
Endogenous factors include various hormonal changes during puberty, pregnancy, childbirth,
and abortion; neuroendocrine diseases, hypothyroidism, and diabetes; and disorders in the
local immune system.
Exogenous factors: use of tampons, spermicides; frequent excessive vaginal showering and
douching; change of sexual partner; use of broad-spectrum vaginal pills; therapy with
antibiotics, cytostatic, glucocorticoid, antiviral drugs.
There are five main nosological forms of pathological vaginal discharge: BV, aerobic
vaginitis (AV), vulvovaginal candidiasis (VVC), trichomoniasis vaginitis (TV) and mixed
vaginitis [6].
Exogenous factors: use of tampons, spermicides; frequent excessive vaginal showering and
douching; change of sexual partner; use of broad-spectrum vaginal pills; therapy with
antibiotics, cytostatic, glucocorticoid, antiviral drugs.
There are five main nosological forms of pathological vaginal discharge: BV, aerobic
vaginitis (AV), vulvovaginal candidiasis (VVC), trichomoniasis vaginitis (TV) and mixed
vaginitis [6].
BV is understood as the dysbiotic state of the vaginal flora caused by a sharp increase in the
number of opportunistic pathogens and a sharp decrease in the concentration of lactobacilli,
mainly producing hydrogen peroxide. It affects all areas of a woman's activity and reduces
her quality of life.
The most common complications of BV [7]:
• development of chorionamnionitis;
• premature birth, premature discharge of amniotic fluid (increases by 2.6–3.8 times);
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• endometritis;
• postpartum sepsis;
• recultivitis after hysterectomy;
• persistence of a latent viral infection;
• creating conditions for colonization of genitourinary organs by STI pathogens;
• tubal infertility (32%), PID (35%).
BV may become a cofactor for the development of papillomavirus infection.
Further studies have shown that, taking into account the similar cytokine gene expression
profile in BV and vaginitis, the traditional view of BV as a non-inflammatory disease is not
entirely correct. Vaginitis and BV are accompanied by a significant increase in the level of
mRNA expression of the IL-6, IL-8, IL-10 genes and a decrease in the content of IL-12a and
IL-18 compared with the control group. Vaginitis also significantly increases the level of
mRNA expression of the IL-1b, TNF, IFN-γ, and CD45 genes.
BV significantly reduces the number of lactobacilli producing hydrogen peroxide, and
polymicrobial, mainly anaerobic, microflora prevails. The primary causative agents of BV
are anaerobic bacteria:
G. vаginаlis
,
Mobiluncus
sрр.,
Bасtеrоidеs
sрр.,
Аtороbium vаginае
.
Currently, progressive researchers identify 2 groups of BV markers [8-10]. Low-specific
ones (defined in both healthy women and BV patients) include
G. vаginаlis
,
Mоbilunсus
sрр.,
Megasphаera
spp.,
Leptotrichia
spp., to the highly specific (detectable only in women
with BV) —
A. vaginae
, vaginosis-associated bacteria
Clostridium phylum
,
Muсinаsе
,
Siаlidаsе
.
Pathogenesis.
The number of lactobacilli producing hydrogen peroxide decreases in the
vagina, while the pH of the vagina increases (pH ≥ 4.5), the growth of anaerobic bacteria
and the release of amines (the smell of rotting fish).
The so—called "key cells" (glue cells) are formed - epithelial cells of the vagina, densely
covered with gram-variable rods (in 70-80% of women with BV).
The clinical picture.
In 50% of patients, the disease is asymptomatic in the presence of
laboratory signs. Patients with BV complain of copious white or gray discharge, often with
an unpleasant odor (rotting fish), especially after unprotected sexual intercourse or during
menstruation. Seminal fluid has a pH of 7.0, so after ejaculation, the pH of the vagina
increases, the amines become free, and being volatile, they cause this odor. Its
intensification in connection with sexual intercourse is a pathognomonic ghost of BV.
As the process progresses, the discharge foams, becomes yellowish-green, thick, slightly
stringy, sticky; 25-30% of women feel burning and itching. Dyspareunia and dysuria occur
[13]. The duration of these symptoms can last for years.
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Diagnostics.
BV is diagnosed on the basis of the "golden diagnostic standard" — the clinical
and laboratory criteria proposed by R. Amsel [5]:
• homogeneous vaginal discharge;
• pH of vaginal discharge > 4.5;
• positive aminotest result;
• the presence of "key cells" in Gram-stained vaginal discharge smears or in a native
preparation.
The diagnosis is considered confirmed if there are any 3 criteria out of the 4 suggested.
In addition to screening tests, microscopy of a Gram-stained vaginal smear is used to
diagnose BV. The sensitivity and specificity of the method are close to 100%. In addition to
the "key cells", additional signs of BV include the predominance of epithelial cells over
leukocytes and the detection of less than 5 lactobacilli in the visual field when magnified
with immersion.
Treatment.
The requirements for the drug of choice for the treatment of BV are etiotropicity,
a minimum percentage of relapses, convenience of forms and patient compliance, safety,
optimal pharmacoeconomic indicators. The drug of choice should not inhibit the growth of
lactoflora, but contribute to the normalization of microbiocenosis. It is necessary to note
such advantages of local therapy as the absence of systemic action, minimal risk of adverse
reactions, simplicity and convenience of use, absence of contraindications (except for
individual intolerance to the drug), the possibility of use in women with extragenital
pathology (especially in localized forms of the infectious process: acute vulvitis, vaginitis,
cervicitis or exacerbations of chronic processes of the vagina and cervix), rapid entry into
the focus of infection and rapid exposure.
Approaches to the treatment of BV have recently synchronized in the USA (MMVR — STD
treatment Guidelines), Europe (European STD Guidelines) and Russia.
• Clindamycin cream 2% — 5 g in an applicator (single dose) intravaginally once a day (at
night) for 7 days;
• metronidazole gel 0.75% — 5 g (single dose) intravaginally once a day (overnight) for 5
days;
• Metronidazole 500 mg orally 2 times a day for 7 days.
1 g of Metrogil vaginal gel contains 10 mg of the active ingredient metronidazole. It is an
antimicrobial and antiprotozoal agent, a derivative of 5-nitromidazole. The drug is active
against
Triсhоmоnаs vаginаlis
,
Entamoeba histolytica
,
G. vаginаlis
,
Giаrdiа intеstinаlis
,
Lаmbliа
sрр., obligate anaerobes
Bасtеrоidеs
sрр.,
Fusоbасtеrium
sрр.,
Vеillоnеllа
sрр.,
Рrеvоtеllа
. Indications for use are BV and urogenital trichomoniasis.
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Alcohol and alcohol-containing products should be avoided both during metronidazole
therapy and for 24 hours after its end. If oral metronidazole is intolerant, its intravaginal
administration is also contraindicated.
Metronidazole intravaginal in therapeutic concentration does not inhibit the growth of
vaginal lactobacillus colonies and has a high penetrating ability into the vaginal fluid. The
relative bioavailability of the vaginal gel is 2 times higher than the bioavailability of a single
dose (500 mg) of metronidazole vaginal tablets. It quickly (within 5 days) eliminates clinical
manifestations and provides clinical efficacy reaching 90%. Due to the low concentration in
the blood serum, the risk of side effects is reduced. Finally, and most importantly, the acidic
environment of the Metrogil vaginal gel contributes to the rapid normalization of the vaginal
ecosystem.
When bacteria switch to the growth mode in the biofilm, significant changes occur in the
expression of dozens of bacterial genes in accordance with the stage of colony development
[28]. Potent antibiotics do not affect
G. vаginаlis
films, which contribute to the survival of
most of the pathogenic microflora after the end of antibiotic treatment [27, 29], which leads
to the development of chronic and recurrent forms of the disease.
The first biofilm bacteria synthesize special adhesion proteins to build a matrix. When they
are fixed, they emit signaling molecules that "recruit" new bacteria, in addition, the division
of bacteria already fixed in the biofilm is stimulated.
CONCLUSION
Vaginal metronidazole preparations promote the eradication of pathogenic planktonic
microorganisms, do not have a systemic effect, and the applicator ensures its rapid entry into
the infection site. The use of metronidazole is accompanied by a minimal number of adverse
reactions.
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