ПРОБЛЕМНЫЕ СТАТЬИ И ОБЗОРЫ
four different antibodies / S. H. Torp // Clin.
Neuropathol. -2002. -Vol. 21 (6). -P. 252-257.
26. WHO Classification of Tumors of the Central
Nervous System / [D.N. Louis, H. Ohgaki, O.D.
Wiestler et al.] -Lyon: IARC, 2007. -312p.
27. Zhu Y. Parada L.E The molecular and genetic
basis of neurological tumors. Nat. Rev. Cancer.
2002: 2: 616 - 626.
УДК: 616.311:616.523-618.3-07
ОСОБЕННОСТИ ДИАГНОСТИКИ И ПРОЯВЛЕНИЙ ГЕРПЕС
ВИРУСНОЙ ИНФЕКЦИИ В ПОЛОСТИ РТА У БЕРЕМЕННЫХ
Н.А. Юлдашева, М.А. Рахимова.
Кафедра госпитальной терапевтической стоматологии ТГСП, Яшнабадский район, улица Махтумкупи, 103, 100047, Ташкент,
http://omd.org/0000-Q003-l689-4443
.
РЕЗЮМЕ
Проблемам диагностики и лечения герпес ви
русной инфекции посвящено большое количество
публикаций, что позволяет считать ее достаточно
изученной.
Таким
образом,
несмотря
на
определенные
успехи в изучении этиологии и патогенеза герпе
тической инфекции в полости рта, сведения у бе
ременных с герпетическим стоматитом малочис
ленны. В связи с этим проведение исследований
по этой проблеме является актуальным.
Эффективность терапии простого герпеса за
висит как от эффективности используемых спец
ифических противовирусных препаратов, так и от
конечного иммунокорригирующего эффекта, что с
одной стороны, вызвало необходимость исследо
вания иммунного статуса пациентов, страдающих
данным заболеванием, с другой - разработку раз
личных схем комбинированного лечения с исполь
зованием различных специфических противови
русных препаратов и иммуномодуляторов, причем
включение физиотерапевтических методов счита
ется наиболее безопасным в данный период.
Ключевые
слова:
Вирус
простого
герпеса
ВПГ-1, беременность, иммуноферментньгй анализ
(ИФА), генитальный герпес (инфекция гениталь
ной или анальной области), гингивостоматит.
FEATURES OF DIAGNOSIS AND MANIFESTATIONS OF HERPES
VIRUS INFECTION IN THE ORAL CAVITY IN PREGNANT WOMEN
N.A. Yuldasheva, M.A. Rakhimova
Department of hospital therapeutic dentistry ofTSDI, Yashnabad district, Makhtumkuli street, 103, 100047, Tashkent, ORCID:
.
org/0000-0003-1689-4443.
ABSTRACT
A large number of publications are devoted to the
problems of diagnosis and treatment of herpes viral
infection, which makes it possible to consider it
sufficiently studied.
Thus, despite certain advances in the study of the
etiology and pathogenesis of herpes infection in the
oral cavity, information in pregnant women with
herpetic stomatitis is scarce. In this regard, research
on this problem is relevant.
The effectiveness of herpes simplex therapy depends
both on the effectiveness of the specific antiviral drugs
used and on the final immune corrective effect, which,
on the one hand, necessitated the study of the immune
status of patients suffering from this disease, on the
other hand, the development of various schemes of
combined treatment using various specific antiviral
drugs and immune modulators, and the inclusion of
physiotherapeutic methods is considered the safest in
this period.
Key
words:
Herpes
simplex
virus
HSV-1,
pregnancy,
enzyme-linked
immune
sorbent
assay
(ELISA), genital herpes (an infection in the genital or
anal area), gingivostomatitis.
RELEVANCE OF THE TOPIC
Currently, there is an increasing interest in the
problem of herpes simplex (HS) on the part of
clinicians of various specialties, which is associated
with a number of objective points: there is an increase
in the infection of the population and a significant
increase in the frequency of clinical manifestations
of viral infections; heterogeneity of the mechanisms
of the formation of immune disorders, which underlie
both relapses of the viral process and leading to
the development of HSV-associated diseases [1];
61
extremely pronounced clinical polymorphism of PG,
from limited lesions of the skin, mucous membranes
and conjunctiva of the eyes to systemic, generalized
forms involving vital internal organs in the viral
process, as well as the development of malignant
neoplasms against the background of chronic HSV
persistence [2].
80 representatives of the Herpes viriolae family
were discovered, of which about eight are pathogenic
for humans and are subdivided, in turn, into a-, |3-,
y-herpes viruses [3].
A large number of publications are devoted to
the problems of diagnosis and treatment of herpes
viral infection, which makes it possible to consider
it sufficiently studied. At the same time, data on the
state of secretory immunity of the oral mucosa and
their influence on the clinical features of the disease
are ambiguous [6]. Viral infections are characterized
by a number of unique pathogenetic features. The
cytopathic effect ofviruses is due to strictly intracellular
parasitism. Viruses start the cellular genetic program
of cell death (apoptosis) [1]. The mechanism of the
cytopathic action of viruses is due to the suppression
of the synthesis of cellular DNA, RNA and proteins,
the destruction of cellular lysosomes and the release
of lysosomal enzymes, which have a detrimental
effect on cellular structures [8]. The virus in saliva in
the absence of signs of damage to the oral mucosa is
detected in 10% of persons infected with HSV [10].
Recurrent herpes is characterized by the appearance
of grouped vesicles on the mucous membrane,
which, merging, form ulcers. In case of relapses,
the localization of the vesicles does not change and
corresponds to the innervation zone of the affected
nerve [11]. When localized on the lip (recurrent
labial herpes), the lesion is more pronounced than
when localized in the oral cavity (recurrent herpetic
stomatitis). Healing of ulcers with recurrent herpes
also occurs without scarring. The spread of infection
to adjacent areas of the skin around the mouth is
observed quite often, especially when lubricating
the lips with a fat ointment [3]. In persons without
pronounced immunity disorders, recurrent herpetic
stomatitis is manifested by the formation of small ulcers
surrounded by a red corolla, in areas of the mucous
membrane, where the epithelium has pronounced
signs of keratinization (fixed part of the gums and
palate). The defeat of the mucous membrane of the
cheeks and tongue in recurrent herpes is observed
rarely and usually in patients with immunodeficiency
[9, 12].
In the pathogenesis of the disease, 4 periods are
distinguished: prodromal, catarrhal, periods of rashes
and extinction of the disease. By severity, there are
mild, moderate and severe forms. Already in the
catarrhal period of the disease, pronounced gingivitis
often occurs, which in the future, especially in severe
form, acquires an erosive and ulcerative character
[20]. There is marked bleeding of the gums and oral
mucosa. In saliva, the pH shift is first determined to
the acidic side, then to the alkaline, while interferon
is usually absent in saliva, and the lysozyme content
is markedly reduced. The manifestation of primary
herpes infection in women during pregnancy is
especially alarming, since the possible effect of herpes
on the embryo or fetus is possible [19, 20].
The modem standards for the etiological diagnosis
of herpes vims infections include a serological method
using enzyme-linked immune sorbent assay (ELISA).
Since herpes simplex viruses have a mechanism of
"escape'’ from the immune system, allowing them
to persist for a long time, non-sterile immunity is
formed in the div [15]. Virus-neutralizing antibodies
that persist throughout life, although they prevent the
spread of the vims by inhibiting its replication, do
not prevent the occurrence of relapses; therefore, the
specific humoral response formed in BBVI reflects the
infection of the organism with the pathogen, but does
not protect it [20].
Detection of IgM antibodies indicates an active
infectious process, the phase of convalescence is
established when testing IgG antibodies, however,
as a result of developing immunosuppression, which
is often observed with prolonged persistence of the
pathogen, IgM and IgG antibodies may be absent
or detected in low titers [11]. This fact reduces the
importance of serological diagnostics in BBVI: it does
not allow differentiating the latent form of infection
from the chronic one, predicting the course of the
disease, and determining the tactics of therapy for sick
children [13].
For
the
greatest
information
content,
it
is
additionally recommended to use ELISA in the study
of paired sera containing IgG antibodies, with an
interval between sampling of 7-10 days, to establish
the fact of an increase in IgG antibodies by 4 times,
which may also serve as an indication of the course of
primary infection [14 ]. To confirm the chronic form
of infection, an enzyme-linked immune sorbent assay
for determining the avidity of IgG antibodies can be
used [5].
Pregnancy leads to a change in a woman's
immunity. And when observing relapses of herpes
lesions, treatment of the triggered process is necessary,
but the action of herpes is not as pathogenic as the
primary introduction of herpes cells [15]. Herpetic
lesions of the oral mucosa have frequent and painful
exacerbations in the form of chronic recurrent herpetic
stomatitis, the treatment of which in women during
pregnancy should be directed without harming the
course of pregnancy [10].
During pregnancy, a suppressive restructuring of
the immune system occurs, aimed at developing and
maintaining immunological tolerance to fetal allo
62
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ПРОБЛЕМНЫЕ СТАТЬИ И ОБЗОРЫ
antigens. An important condition is the switching of
the immune response from type 1 T-helpers (Thl) to
type 2 and 3 T-helpers (Th2, Th3), which leads to the
predominance of the synthesis of anti-inflammatory
cytokines - IL-4, IL- 10 and others [5]. IL-10 plays a
key role in the development of pregnancy, as it inhibits
the production and implementation of the trophoblast
destructive activity of TNF-a [18]. In addition, TGF-B
(transforming growth factor B) secreted by the cells
of the decidual membrane of the uterus blocks
the
development
of
Thl-mediated
reactions
and
simultaneously stimulates differentiation of villi of the
early placenta and cytotrophoblastic invasion [5,6].
The influence of herpes infection on the course of
pregnancy and the condition of the fetus is due to two
main mechanisms. Firstly, infection of the placenta,
amniotic fluid and membranes, as well as the fetus
itself, is possible. This can lead to damage to the
placenta, membranes, teratogenic changes in the tissues
of the embryo and fetus, to the development of local
or generalized lesions, as well as to latent infection
of the fetus, with subsequent clinical manifestations
in the postnatal periodfl8]. Secondly, the influence of
GI with the development of fever in pregnant women,
dysfunctions of the fetoplacental system, homeostasis,
and hormonal balance is possible. These reasons can
lead to early and late miscarriages, delayed pregnancy,
premature
birth,
antenatal
malnutrition,
hypoxia,
fetal malformations and death, the development of
congenital forms of infection in newborns [15, 17].
The variety of clinical manifestations is due to
the duration and form of manifestation of infection
in a pregnant woman, the properties and virulence
of the virus, the state of the placental barrier and the
protective forces of both the mother and the fetus [14].
The study of the influence of herpes infection on the
course of pregnancy, the development of the fetus and
the newborn showed that the most serious danger in
any trimester of pregnancy are generalized forms of
GI in women and primary infection during childbirth
[20]. Herpetic infections in pregnant women are
among the most common diseases that determine
intrauterine infection, embryo and fetopathies, and
obstetric pathology. In recent years, there has been a
trend towards an increase in the infection of pregnant
women with the herpes simplex virus and the ability
of GI, under certain conditions, to endemic spread [14,
16].
Most often, primary herpes is manifested in
the form of herpetic gingivostomatitis. Single or
multiple vesicles appear on the mucous membrane
of the oropharynx, which quickly open up with the
formation of painful erosions, which are then covered
with a whitish coating. The mucous membrane of the
oral cavity, the gums become swollen, hyperemic,
with a cyanotic shade and sharply painful. The pain
syndrome is so pronounced that it makes it difficult
to eat and drink [1]. Gradually, acute inflammatory
phenomena subside and erosion begins to epithelize
from the periphery to the center. Complete regression
of the rash occurs in 2-3 weeks. After the disappearance
of the clinical manifestations of primary herpes or
asymptomatic infection, the herpes viral infection
becomes latent. During this period, HSV is in an
inactive state in the nerve ganglia, and HSV-1 most
often affects the trigeminal ganglia [8]. At the same
time, the production of antibodies to HSV begins.
However, with a decrease in immunity under the
influence of a number of unfavorable factors, relapses
of the disease may occur with varying frequency -
from several days to several months or even years
[19].
HSV-1 is a highly contagious infection, widespread
and endemic throughout the world. Most HSV-1
infections occur during childhood, then the infection
persists throughout life [6]. In the vast majority of
cases, HSV-1 infection develops oral herpes (an
infection in or around the mouth, sometimes called
orolabial or orofacial herpes), but in some cases, the
virus also causes genital herpes (an infection in the
genital or anal area) [7].
The active stage in both asymptomatic and manifest
forms of infection can be detected by laboratory
methods.
Laboratory
markers
of
activation
are
antibodies to ultra-early proteins (anti CMV - IEA
antibodies), IgM to structural proteins (L), low avidity
IgG, an increase in IgG antidiv titers, the appearance
of sero conversion (i.e., the appearance of a positive
antidiv response in previously negative samples ),
an increase in the frequency of detection of viruses in
various clinical material [18].
In the immune genesis of CGS of the oral mucosa
in pregnant women, changes in T- and В-cell and
humoral immunity dominate [7]. For pregnant women
with recurrent herpetic stomatitis of the oral mucosa,
an interferon deficiency state is characteristic, which
is manifested by an increase in serum interferon and
a pronounced decrease in the production of alpha and
gamma interferon. With CGS in pregnant women, the
regulation of the immune response at the level of the
oral mucosa is impaired, which indicates a weakening
of the antiviral defense [16].
Thus, despite certain advances in the study of the
etiology and pathogenesis of herpes infection in the
oral cavity, information in pregnant women with
herpetic stomatitis is scarce. In this regard, research
on this problem is relevant [12].
Conclusion
The effectiveness ofherpes simplex therapy depends
both on the effectiveness of the specific antiviral drugs
used and on the final immune corrective effect, which,
on the one hand, necessitated the study of the immune
status of patients suffering from this disease, on the
other hand, the development of various schemes of
63
combined treatment using various specific antiviral physiotherapeutic methods is considered the safest in
drugs and immune modulators, and the inclusion of this period [11,13].
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