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DOI: 10.17749/2070-4968.2015.9.1.018-030
ISSN 2070-4968
«The significance of immunomodulatory therapy in pregravidal preparation
of the patients with recurrent HSV type 2»
Minaev N.N., Bugrimov D.Ju., Klimovich A.A
Abstract
Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) – is a widespread viruses that can form a
lifelong infection and persistence. Genital herpes in women of childbearing age is a serious risk
of vertical transmission from mother to fetus. Primary HSV infection and the first episode of
genital HSV infections are particularly high risk of infection of the fetus and newborn. [15] The
infection rarely occurs in the uterus. Most often the virus is transmitted during childbirth. The
greatest risk of transmission to the fetus and the newborn in the case of primary maternal
infection occurred during the second half of pregnancy. [1] The risk of transmission from mother
to fetus and newborn, can be reduced or the appointment of antiviral drugs,or in specific cases,
caesarean section. The purpose of this paper is to propose a possible strategy to prevent
transmission of the virus from an infected mother to the fetus.
Key words: recurrent HSV-2, pregravid preparation, maternal antibodies, Toll-like receptors 9,
Ferrovir
The authors declare no possible conflicts of interest.
For citation: Minaev N.N., Bugrimov D.Ju., Klimovich A.A. The significance of
immunomodulatory therapy in pregravidal preparation of the patients with recurrent HSV type
2. Akusherstvo, ginekologiya i reproduktsiya / Obstetrics, gynecology and reproduction. 2015; 1:
18-30 (in Russian).
Received: 20.02.2015; in the revised form: 14.02.2015; accepted: 25.03.2015.
Herpes simplex virus 2 (HSV-2) is classified together with HSV-1 in the subfamily
Alphaherpesvirinae and is one of the very common sexually transmitted infections way around
the world. The prevalence the virus is from 15 to 20% in Europe and the United States, and to
90% in some African populations of Sub-Saharan Africa [14].
Herpes simplex virus (HSV) - is ubiquitous, tunicary, with a double-stranded DNA virus
belonging to the family of herpes viruses transmitted through mucous membranes and damaged
skin. Subsequently, it migrates to the nerve tissue, where stored in a latent state. HSV type 1
(HSV-1) prevails in the orofacial lesions, and usually persists in the trigeminal ganglia, while the
HSV type 2 (HSV 2), the most common in the lumbosacral ganglia [9]. However, this second
serotype may occur at orofacial lesions and at genital area. Changes in sexual behavior of young
people can be partly to explain its high incidence of [9.16]. A distinctive feature of HSV-2
infection is the lack of painful lesions, and the majority of seropositive patients, the disease are
the asymptomatic, so they are unaware of their diagnosis [10.19]. Primary infection is
developing upon contact with the virus in susceptible individuals without HSV-1 and HSV-2
antibodies [8]. The first clinical episode in primary infected individual occurs when a person
with his existing antibodies to HSV type 1 or type 2 the first in contact with the opposite type of
HSV [8]. Due to the protective function of the available antibodies systemic symptoms, during
such episodes, usually shorter and less expressed [17]. The recurrent infection develops in
patients who have antibodies against the same type of HSV, with whom they are in contact [9]. It
is defined as an episode of herpes sores in women with homologous IgG antibodies to HSV the
appropriate type. Recurrent infections are most common during the first three months after the
initial infection, especially with HSV-2. Approximately 15% of all pregnant women with a
history of HSV-2 infection have disease recurrence during childbirth. Acute lesions usually last
for 9 days, and the residual effects - about 4 days. The viral load at relapses is usually lower than
in the primary lesions, and decreased immediately after the prodromal and early of the secondary
clinical episode. IgG level returns to the original value until resolution the incident [17]. Vertical
transmission of HSV-2 can cause eye, skin lesions, widespread meningoencephalitis, and
systemic lesions of the internal organs or fetal malformation. [8] In general, HSV-2 seropositive
women before pregnancy have a reduced risk of neonatal transmission, attributed to
transplacental migration of antibodies to the fetus. But women with recurrent episode of herpes
at childbirth, as a rule, should be delivery by Caesarean section to prevent the transmission of
infection to the newborn [13]. Women, seronegative before pregnancy, have a higher risk of
vertical transmission of HSV-2 and neonatal complications [7]. Maternal age younger than 21
years is a factor of higher risk for vertical transmission of the disease [4]. Approximately 5% of
all cases of neonatal herpes infection occur intrauterine transmission of the virus. During primary
infection there is transient viremia. HSV-2 has a pronounced potential hematogenous spread to
the placenta and fetus. This can lead to a whole range of pathologies typical of the complex
TORCH-infection (toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus), such as
microcephaly, microphthalmia, intracranial calcification and chorioretinitis [17]. Transmission
during childbirth is most cases of neonatal injury and happening during the passage of the fetus
through an infected birth canal. Application of the single spiral scalp electrode increases the risk
of transmission during delivery. [4] From 75 to 90% of children are born with neonatal HSV
from asymptomatic infected mothers who have no history of disease episodes.
The frequency of transmission of HSV-2 in childbirth depends on the type of clinical infection.
Decline in the presence of protective maternal antibodies that cross the placenta:



Primary infection with HSV-2 transmission frequency - 50%;
The first clinical episode in primary infected individuals with antibodies to HSV transmission frequency - 33%;
Recurrent or asymptomatic infection - transmission frequency - 0-4%.
The overall incidence of neonatal infection of the fetus from asymptomatic women infected with
HSV-2 in the laboratory anamnesis is less than 4 per 10,000, or 1% risk of asymptomatic disease
in the mother, multiplied by 4% of risk of vertical transmission [17].
It can thus be generalized as follows:




The frequency of neonatal infection is highest in seronegative women, which confirms
the importance of maternal antibodies in the prevention of vertical transmission;
Presence of mother not only HSV-2 antibodies, but also HSV-1 antibody reduces the
number of infants with HSV-2 virus;
The number of infected infants both with primary and recurrent form are more for HSV-1
versus HSV-2;
Caesarean section is protective surgical intervention to prevent neonatal infection [17].
Diagnosis HSV
1. Study of HSV-culture has long been is the standard criterion of the diagnosis of herpes
infection, with a sensitivity of 70% and a specificity of nearly 100%. The final answer
diagnostics of culture can take up to seven days. The sensitivity of the test of culture is related to
the type of HSV and the place of the fence material. The sensitivity of the test is the highest
during the prodrome and low in a period of recovery, especially in the chronic course of the
process. Sensitivity of culture test below for of HSV-2 then HSV-1. In women with
asymptomatic disease sensitivity is maximal when the material is taken from the cervical canal
and from the place of relapse, even if the lesion is not visualized [17].
2. Currently, more and more widely used for the diagnosis of HSV is polymerase chain reaction
(PCR), is a molecular test, which is easy to use and, ultimately, can replace the study of HSVculture in a standard test [5,6, 18]. As the culture test, PCR can differentiate between HSV-1
from HSV-2. Performing the test takes about one day, and this method has the potential for more
rapid detection of the virus than the test HSV culture. Unfortunately, PCR can`t distinguish
between actively replicating herpes simplex virus from the viral DNA present in a latent state.
3. In the case of asymptomatic herpetic infection or when the results of PCR analysis are
questionable additional information may provide serological testing of antibodies to HSV. Typespecific antibodies of class G to herpes simplex virus 1 and 2 of types indicate previous or
current infection. Type-specific IgG persist throughout life. This phenomenon is called
seropositivity. Recurrent herpes usually proceeds on the background of high levels of IgG,
showing the constant antigenic stimulation of the body [2, 3,15].
Treatment
Acyclovir is the most prescribed medication for the treatment of HSV infection. He was
available for clinical use for nearly three decades and has demonstrated a high level of safety and
efficacy in the treatment of all forms of herpes infections, from mild to very severe, as in
ordinary patients as well as patients with impaired immune response, including and neonates.
Acyclovir is an analogue of deoxyguanosine. After the priority absorption of virus-infected cells
is phosphorylated it is virus-associated thymidine kinase. Then there is preparation of di- and
triphosphorylation of drug, catalyzed enzymes infected cells. The resulting acyclovir
triphosphate terminates viral DNA synthesis by inhibition of viral DNA polymerase by acting as
a terminator of chain fusion. The drug acts selectively on the synthesis of viral DNA. On DNA
replication of the host cell (human cells) acyclovir triphosphate virtually no effect. Valacyclovir
(Valtrex) - preparation of a second generation is identical acyclovir. It was obtained by adding
the side chain of the ester, which increases its bioavailability. After absorption in the body it is
converted to acyclovir. It allows receiving a high serum level of the drug at reducing the
frequency of administration. [17] In view of the above two circumstances can conclude the
following: 1) the incidence of neonatal infection is highest in seronegative women, which
confirms the importance of maternal antibodies in the prevention of vertical transmission; 2) the
presence of the mother, not only HSV-2 antibodies, but also the presence of HSV-1 antibodies
can reduce the number of infants with HSV-2 infection [17].
We hypothesized that the increase in type-specific IgG titer in the blood planning pregnancy
asymptomatic infection or seronegative women will reduce the likelihood of vertical
transmission of the virus in patients with HSV infection. This increase of the titer possible when
used in the background pregravid preparation natural origin drug Ferrovir®, its active substance
is sodium deoxyribonucleat in combination with iron.
Ferrovir® - antiviral drug with immunomodulating and protective action. Ferrovir® is an agonist
of toll-like receptor 9 (Toll-like reseptors 9, TLR 9, CD 289). The preparation contains in its
composition oligonucleotides of salmon DNA, 50% of cases ending nonmethyllated CpG motifs
that are specific ligands of TLR 9. Toll-like reseptors 9 are intracellular, accurately endosomal
localization and expressed by monocytes (macrophages) plasmacytoid dendritic cells and Blymphocytes. Stimulated by Ferrovir through TLR 9 plasmacytoid dendritic cells are able to
influence on the differentiation of Th0 to Th2 (naïve T-helper cells to T-helper type 2). Under
the influence Th 2 happening differentiation of B-cells into plasma cells secreting IgG 2, IgG 4
[1]. A typical and explainable turned out to be fact of the increasing avidity IgG, synthesized at
of the plasma cells. In proliferating centroblasts (activated B-cells) is the process of formation of
additional of antibody diversity in the process of somatic hypermutation in the already
rearranged V-immunoglobulin genes [11]. Thus, increased avidity synthesized antibodies despite
nonspecific antigenic stimulation of B cells of Ferrovir®. It is logical assume that the increase in
the mother's blood type-specific antibody titers, crosses the placental barrier, will provide the
fetus the necessary their number for opsonization viral antigens and their subsequent
phagocytosis of cells mononuclear phagocyte system (MPS).
The aim of the study was to show that the increase in type-specific IgG titer and increasing their
avidity under the influence of the drug Ferrovir® authentically increases the pregnancy rate, and
reduces the number of abortions and premature births in women infected with herpes simplex
virus 1 and / or 2 serotypes.
Materials and methods.
The study included 101 patient of reproductive age from 25 to 31 years with primary or
recurrent, or with a single episode of genital herpes. Most of the patients after the course
antiviral therapy for 12 months successfully conceive a child, carrying of a pregnancy and given
birth the child. All patients had laboratory evidence of infection with HSV 1 or 2 d serotype that
was twice confirmed by PCR by examining scraping from the cervix for 5-7 days of the
menstrual cycle. To establish of the form of infectious process, and most importantly, to
determine the level of seropositivity patients was conducted serological with measurement of
blood levels of type-specific IgG, and their degree of avidity. Under indications them were
performed ultrasound of the pelvic organs, colposcopy, and all the patients were taken smears
from the cervix to oncocytology and pathogenic / opportunistic microflora. It was carried out
dynamic monitoring of, the patients immediately after the treatment through 2 weeks, 1, 3, 6, 9
and 12 months. The main criteria for the inclusion of women in the study had their infection with
HSV-1 and / or 2 d serotype and planning their pregnancy. The main exclusion criteria were the
following: the fact of any patient receiving immunomodulators during at least six months prior to
the study, women planning pregnancy during therapy Ferrovir, that it has an autoimmune
disease. All women participating in the study give written informed consent and were able to, in
our opinion, keep a diary of self-esteem and comply with the requirements of the protocol.
Throughout the existing work evaluated the safety of the drug Ferrovir®, by the criterion of
complications or adverse reactions. Refusal to participate in study could be initiated as a patient,
and by researchers for example in case of compelled reception of by her antiviral or
immunomodulatory drug. Statistical analysis was performed by the method of variation statistics
and correlation analysis using Microsoft Excel 7,0 (Windows 7, Microsoft Office 2007), with the
definition of Student's t test (t) for independent groups. To evaluate the protective effect of
antiviral immunomodulator drug Ferrovir® at the infected of the fetus and habitual loss of
pregnancy and compare of its with the pathogenetic opposite antiviral drug Valtrex, by random
sampling all HSV-infected women, planning pregnancy, (101 patients) were divided into three
representative groups:
- The control group (37 patients) received standard therapy with Valtrex 500 mg 2 times a day.
Within 7 days;
- First study group (32 patients) received therapy with in the injections, (solution for
intramuscular injection of 15 mg / ml). Method of application the drug Ferrovir® consists in
intramuscular injection of 5 ml solution (75 mg), 1 per day after 24 hours within 10 days, 10
injections for the course.
- The second study group (32 patients) received the combined therapy Valtrex + Ferrovir® in
dosages which was applied by the first test group and in the control group, respectively.
Age of the patients of the comparison group (37 women) amounted to 28,8 ± 0,43 years.
Everyone at the beginning of research at the gynecological examination of cervical pathology
was absent. The average age of menarche was 13,3 ± 0,2 years. Beginning sex life was with 16,7
± 0,29 years. In the group had an average 2,5 ± 0,07 pregnancies, 0,9 ± 0,01 birth, 1,3 ± 0,07
abortions, 0,3 ± 0,04 abortions. From gynecological diseases at the clinical examination in the
comparison group before the study accounted for 21 endocervicitis, 8 colpites, 4 adnexitises and
4 patients showed no other gynecologic pathology than HSV. According to the ultrasound (U\S),
2 patients’ diagnosed adnexitis, 5 diagnosed of endometriosis and 29 women in this group was
not determined on the U\S pathology. Oncocytology has identified in the group: the
inflammation in 12 cases, dysplasia in 8 cases and the lack of pathology in 17 cases. According
to the colposcopy, at the beginning of the study 14 the patients showed signs of inflammation
and 23 women had the favorable colposcopic results.
Age of the first patients of the study group (32 female) was 27 ± 0, 36 years. Pathology of the
cervix is absent in all the patients in this group. The mean age of menarche 13,2 ± 0,08 years; the
sexual debut at 17,5 ± 0,22 years. In the group had an average 2, 4 ± 0, 11 pregnancies, 0, 8 ± 0,
33 birth, 1, 4 ± 0, 08 abortions, 0, 2 ± 0, 04 abortions. From gynecological diseases on clinical
examination on the comparison group before the study accounted for 12 endocervicitis, one case
of endometriosis. In 19 patients did not reveal other gynecologic disease other than HSV.
According to the ultrasound, four patients diagnosed adnexitis, four endometriosis and 24
women in this group was not determined on the ultrasound pathology. Oncocytology identified
in a group picture of inflammation in nine cases, dysplasia in six cases and the absence of
pathology in 17 cases. According to the data colposcopy, at the beginning of the study 16
patients revealed the signs of inflammation and 16 women had a favorable colposcopic picture.
Age of the patients of the second study group (32 women) was 27, 8 ± 0, 33 years. Pathology of
the cervix is absent in all the patients in this group. The mean age of menarche 13, 1 ± 0, 1 year;
the sexual debut at 16, 2±0, 34 years. In the group had an average 2, 3 ± 0, 07 pregnancies, 0, 9 ±
0, 03 birth, 1, 1 ± 0, 03 abortions, 0, 3 ± 0, 05 abortions. From gynecological diseases on clinical
examination on the comparison group before the study account for 19 endocervicitis, one
colpitis, four adnexitis, and eight patients did not reveal other gynecologic pathology other than
HSV. According to the data U\S, four patients diagnosed adnexitis, three endometriosis and 25
women in this group was not determined on the ultrasound pathology. Oncocytology revealed in
a group picture of inflammation in 11 cases, dysplasia in six cases and no pathology in 15 cases.
According to the data colposcopy, at the beginning of the study 13 patients revealed the signs of
inflammation and 19 women had a favorable colposcopic picture.
In all three groups there was a similar picture of patients infected with HSV-1 or HSV-2 before
treatment.
There was statistically significant between the groups described clinical parameters. The
confidence level of P ≤ 0, 01-0,05.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
16.7% 18.9%
20.0%
8.1% 5.4%
10.0% 0.0%
1.0% 0.0% 0.0%
0.0%
absence of HSV
HSV1
HSV2
Linear (absence
of HSV) *
Figure 1. There is infection of HSV in the comparison group (Valtrex), according to the ELISA.
(Index of IgG positivity in all patients before treatment by an average is > 1.1).
*Note: P ≤ 0, 05.
In the comparison group (see Fig. 1) draws attention a progredient reduction of the effect of the
standard treatment of Valtrex for a year. After 9 months in the control group of seronegative
patients was not. All indicators type-specific IgG returned to values "before the treatment."
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
12.0%
11.8%12.0%
7.6% 8.9%
3.5% 5.0%
10.0% 0.0%
0.0%
absence of HSV
HSV 1
HSV 2
Linear (absence of
HSV) *
Figure 2. There is infection of HSV in the comparison group (Ferrovir®), according to the
ELISA. (Index of IgG positivity in all patients before treatment by an average is > 1.1).
*Note: P ≤ 0, 05.
In the first test group (see Fig. 2) is seen a distinct trend to increase the number of seronegative
patients by applying Ferrovir®, a solution of 15 mg / ml.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
18.0%
15.5%18.0%
20.0%
9.8% 12.7%
3.0% 5.4%
10.0% 0.0%
0.0%
absence of HSV
HSV1
HSV2
Linear ( absence of
HSV) *
Figure 3. There is infection of HSV in the comparison group (Valtrex + Ferrovir®), according
to the ELISA. (Index of IgG positivity in all patients before treatment by an average is > 1.1).
*Note: P ≤ 0, 05.
In the second study group (see Fig. 3) the trend to maintain the antiviral effects during treatment
of antiviral drug Valtrex with immunomodulating effect Ferrovir® (15 mg / ml) was even more
obvious
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
INDEX avidity <40%
INDEX avidity
41%<x<50%
INDEX avidity
51%<x<60%
INDEX avidity >61%
Linear ( INEX avidity
> 61%) *
Figure 4. IgG avidity index change in the comparison group (Valtrex)
*Note: P≤0, 01.
In the comparison group, which conducted the standard officially recommended therapy of
Valtrex (see Fig. 4) is not marked increase in the number high avidity IgG. This is consistent
with the mechanism of action of the antiviral Valtrex is not related to the impact on B-cells.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
No viral load
<3
48.6%
3<x<5
13.5% 16.2%16.2%
5.4%
0.0% 0.0% 1.7%
5<x<7
>7
Logarithmic (>
7) *
Figure 5. It is viral load in the comparison group (Valtrex), according to the PCR.
*Note: P/≤0,05.
Viral load in the comparison group (Valtrex), (see Fig. 5) is reduced during the first month of
treatment, due to the rapid virucidal and virustatic action of Valtrex. Also, it obligates increases
throughout the remainder of the observation period, as Valtrex has no cumulative effect and
pharmacologically stimulating effect on the immune system. Increased viral load, according to
PCR, explains the decrease of the immune competence of HSV-infected persons or activation of
latent persistent virus under the influence of adverse external influences on the body.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
INDEX avidity
<40%
45.1%45.0%46.1%43.2%41.9%
40.2%
40.2%
INDEX avidity
41%<x<50%
INDEX avidity
51%<x<60%
10.0%
INDEX avidity
>61%
Linear (INDEX
avidity > 61%) *
Figure 6. IgG avidity index change in the first test group (Ferrovir®, 15 mg / ml).
*Note: P ≤ 0, 01.
In the first study group, which was conducted Ferrovir® monotherapy, 15 mg / ml (see Fig. 6),
can be seen a distinct trend of increasing avidity index of type-specific IgG. It is good
explainable an immunomodulatory mechanism of antiviral action Ferrovir®. This includes
stimulating TLR 9 B-lymphocytes (centroblasts). In them there is an active process of somatic
hypermutation, leading to formation of antibody diversity and increase their avidity.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
No viral load
47.0%
<3
3<x<5
12.5%10.2%
12.5%
6.4% 6.0% 7.4% 9.0%
5<x<7
>7
Polynominal (>7) *
Figure 7. It is viral load in the first test group (Ferrovir®, 15 mg / ml), according to PCR.
*Note: P ≤ 0, 05.
Viral load in the first study group patients on background of therapy with Ferrovir®, 15 mg / ml
(see Fig. 7) decreases is gradually and reaches the minimum values of the third month of
treatment. This can be explained by an immunomodulating character of antiviral action of
Ferrovir which requires certain time for antigen-positive selection of B – cells, and their
transformation into plasma cells, and the synthesis of the latest, a sufficient number of typespecific IgG. But on the other hand, create a clone of plasma cells synthesizing high-avidity,
type-specific antibody IgG, provides long-term control over the foci of latent persistence
of HSV.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
INDEX avidity <40%
INDEX avidity
41%<x<50%
INDEX avidity
51%<x<60%
INDEX avidity >61%
Linear (INDEX avidity
> 61%) *
Figure 8. Change of index avidity IgG in a second treatment group (Valtrex + Ferrovir® + 15
mg / ml).
*Note: P ≤ 0, 01.
Women in the second treatment group receiving Valtrex and Ferrovir® + 15 mg / ml (see Fig. 8),
increase in titer high-avidity, type-specific IgG is somewhat less pronounced than in the first
group. This can be explained by the presence in the scheme of pregravid preparation of Valtrex,
provider virustatic action which in its turn, reduces antigenic diversity HSV, and accordingly
reduced the ability of antigen-positive selection of B-cells in the germentativnyh centers of the
lymph nodes, that provides somatic hypermutation and increased avidity antibodies.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
No viral load
38.0%
<3
0.0% 0.0%
12.0%12.0%10.0%
6.3%
3<x<5
2.6%
5<x<7
>7
logarithmic
(>7) *
Figure 9. It is viral load in the first test group (Valtrex + Ferrovir®, 15 mg / ml), according to
PCR.
*Note: P ≤ 0, 05.
Dynamics of viral load in the second study group (Valtrex and Ferrovir® + 15 mg / ml) (see Fig.
9) was similar to the comparison group in terms of its sharp drop in the first month of treatment
due to the rapid effect of Valtrex. And, at the same time, the curve indicator of viral load at the
end of the observation period reaches a low value, as in the first study group, that is caused by
prolonged immunomodulating effect of Ferrovir, 15 mg / ml.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
No pathology
50% 50%
38%
48%
45% 42% 44%
40%
bacterial vaginosis
vaginal candidiasis
non-specific
inflammation
linear (non-specific
inflammation)*
Figure 10. Indicators smear in the comparison group (Valtrex) during pregravid preparation.
*Note: P ≤ 0, 05.
In this group (see Fig. 10) the trend at reducing the non-specific inflammation is minimal, it is
easily explained the specific selective antiviral mechanism of action of Valtrex, has no effect on
eukaryotic vaginal flora.
100.0%
90.0%
80.0% 68.8%
70.0%
60.0%
50.0%
40.0%
25.0%
30.0%
21.9%
18.8%
15.6%
15.6%
20.0%
10.0%
0.0% 0.0%
0.0%
No pathology
non-specific
inflammation
bacterial vaginosis
vaginal candidiasis
Linear (non-specific
inflammation)*
Figure 11. Indicators smear in the first study group (Ferrovir®, 15 mg / ml) during pregravid
preparation.
*Note: P≤ 0, 05.
In women who received only therapy Ferrovir (see. Fig. 11) can be seen a distinct trend in the
reduction of non-specific inflammation, which is obligate, caused an
immunomodulating character effect of this drug.
100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
No pathology
non-specific
inflammation
vaginal candidiasis
bacterial vaginosis
Linear(non-specific
inflammation) *
Figure 12. Indicators smear in the first study group (Valtrex +Ferrovir®, 15 mg / ml) during
pregravid preparation.
*Note: P≤ 0, 05.
Similar tendency of decrease the level of non-specific inflammation, provided by Ferrovir®,
noted in the second study group (see Fig. 12).
There is frequency of the pregnancy.
28.10%
31.30%
Ferrovir®,
Valtrex
Valtrex + Ferrovir®,
13.50%
*Note: P≤ 0, 05.
We noted a higher pregnancy rate in the groups where in pregravid of preparation was included
Ferrovir®. This, in our opinion, is explained an immunomodulating character effects of the
drug Ferrovir®, reduces the manifestations of PID, and accordingly improves the quality of the
smear on the pathogenic and / or conditionally pathogenic flora.
There is frequency of pregnancy loss.
5.60%
7%
Ferrovir®,
Valtrex
Valtrex + Ferrovir®,
7.90%
*Note: P≤ 0, 05.
The frequencies of pregnancy loss from various causes (miscarriages in the early stages, in cases
of undiagnosed pregnancy, miscarriages till 8 weeks, after the 8 weeks), was significantly lower
in group’s pregravid preparation, are included in the program Ferrovir ®. We attribute this to an
immunomodulating character effect of the drug, which reduces symptoms of PID. It is also
probable that a significant role in preserving of pregnancy plays a sufficient level of maternal
type-specific, high-avidity IgG in the blood of fetus from the first weeks of pregnancy.
The conclusions:
1. Use in pregravidal preparing standard officially recommended the treatment regimen of
Valtrex has obvious disadvantages manifested in the exclusion out the epidemiological
situation "virus - host" of the immune system of the patient. They, in
particular, expressed in the principle impossibility of the organism to involve the innate
and the acquired immune response to antigens of HSV-2.
2. These deficiencies are well compensated for inclusion in the scheme pregravid
preparation antiviral drug immunomodulatory effects Ferrovir®
3. Observed the distinct increase of the index type-specific, high-avidity IgG against HSV-2
in the group of patients treated with Ferrovir®.
4. The pregnancy rate for patients in the groups with preparation of Ferrovir® significantly
higher than in the monotherapy group of Valtrex.
5. The frequency of fetal loss syndrome in patients with high index type-specific, highavidity IgG, generated application of Ferrovir, significantly lower than women in the
comparison group with fixed rates IgG titer and the avidity index.
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About the authors:
Minaev Nikolai Nikolaevich − PhD, MD, professor, Head of the Department of
Obstetrics and Gynecology. The Institute of Advanced Training. Voronezh State Medical
Academy named after NN Burdenko Russian Ministry of Health. Address: 394036, Russian
Federation, Voronezh, Studencheskaya str. 10. Тел.: +79036502044. E-mail: [email protected].
Bugrimov Daniil Yur'evich − PhD, advisor RAE master MANEB, Senior Researcher,
Director of the Institute of Experimental Biology and Medicine (EBM Research Institute),
Voronezh State Medical Academy named after NN Burdenko Russian Ministry of Health,
Address: 394036, Russian Federation, Voronezh, Studencheskaya str. 10. Тел.: +9515512557;
+791923490 49. E-mail: [email protected].
Klimovich Andrew Alekseevich − researcher of the Institute of Experimental Biology
and Medicine (EBM Research Institute), Voronezh State Medical Academy named after NN
Burdenko Russian Ministry of Health. Address: 394036, Russian Federation, Voronezh,
Studencheskaya str. 10. Тел.: +7906590529410. E-mail: [email protected].