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1Университетская клиника
Том 13, № 2, 2017 © ДонНМУ
ПЕДАГОГИКА ВЫСШЕЙ ШКОЛЫ
УДК 616.523-022.6-06:618
O.Yu. Nikolenko, V.Yu. Nikolenko, Yu.A. Lygina
INFLUENCE OF HSV2 AND CYTOMEGALOVIRUS ON PREGNANCY
(LECTURE FOR INTERN-STUDENTS AND DOCTORS)
Donetsk National Medical University named after M. Gorky
Abstract. Cytomegalovirus and herpetic infections belong to the «TORCH» group and they are capable to damage the placenta, penetrate through it and damage the fetus. Herpes viruses can cause lesions of the genital organs and facilitate the transmission of other infections, including HIV-infection. More than 80 representatives of the herpesvirus family have been discovered, 8 types of them are pathogenic to humans. Herpesviruses belong to the family Herpesviridae and are divided into three subfamilies: a-, p-, y-herpesviruses. The main properties of herpesviruses are: ubiquitarity, universal susceptibility, opportunism, pantropism, the ability to use various transmission mechanisms, a complex strategy of parasitism, immunosuppression and oncogenicity. These are DNA-containing complex viruses. Herpesvirus replication cycle goes through the following stages: adsorption, penetration and disintegration, synthesis of viral particles, complete assembly of in-tracellular virus, release of daughter virions. In these viral agents, genes encoding structural proteins make up only 15 % of DNA, so most of the genome is occupied by genes which are responsible for the synthesis of regulatory proteins and enzymes. This feature allows herpesviruses to realize the possibility of a latent, persistent and reactivated state in the infected organism. Recurrent herpes is recorded in people with isolated or combined immunodeficiency in various parts of the immune system. Reaction of the immune system in herpes viral infections (HVI) in children of the first 3 months of life is accompanied by changes in the cellular immunity. On the lymphocytes of patients with acute and prolonged course ofHVl, there was a significant increase in CD3 + CD95 + expression in the first month of life, indicating an increase in the readiness of lymphocytes for apoptosis. Herpesvirus infection can induce functional damage in nonspecific immune effector cells. In the treatment of herpetic infection, drugs are prescribed depending on the type of herpesvirus and are divided into means of etiotropic and pathogenetic therapy. In infants with an infection caused by HSV1, 2, the appointment of a comprehensive therapy, including the drugs Acyclovir, Immunovenin and Licopid, is the most effective.
Key words: herpesviruses, pregnancy, classification, structure, cycle of reproduction, pathogenesis, treatment
Relevance. Currently, obstetrician-
gynecologists and neonatologists do not doubt inthe
priority and importance of the problems associated with viral infections. Among them, a special place belongs to the herpetic infection, which incidence tends to rapidly increase. In pregnant women, herpes occurs in 7 to 25 % of cases. The causative agent of this infection has a role in the etiology of spontaneous abortion, premature birth and infertility, as well as violation of embryogenesis and congenital pathology of newborns. Particular attention is paid to infectious diseases, the causative agents of which are capable of damaging the placenta, penetrating through it and damaging the fetus — cytomegalovirus (CMV) and herpetic infections (HI), toxoplasmosis and rubella form the basis of the so-called «TORCH» group. Many etiological agents of erosive and ulcerative genital lesions, such as herpes and cytomegalovirus infections, affect the fetus and the newborn, and also facilitate the transmission of other sexually transmitted infections (STIs), including HIV infection (the so-called phenomenon of «epidemiological synergism») [2, 3, 4, 10].
To date, more than 80 representatives of the herpesvirus family have been discovered, of which 8 are pathogenic to humans. According to the modern classification of the type of cells involved in the infectious process, the nature of viral replication, the structure of their genome, herpesviruses are divided into three subfamilies: a-, (3-, and y-herpesviruses. a-herpesviruses include herpes simplex viruses (HSV) of types I and II and varicella zoster virus (VZV), ^-herpesviruses include cytomegalovirus (CMV) and herpesviruses of types VI and VII, y-herpesviruses include Epstein-Barr viruses (EBV) and herpesvirus type VIII [8, 11].
Herpetic viruses belong to the Herpesviridae family. They are DNA(deoxyribonucleic acid)-containing complex viruses, whose virion has an icosahedral type of symmetry and an average size of 250-300 nm. The largest size has a cytomegalovirus virion. Herpesvirus DNA is represented by a double-
stranded linear molecule containing in its composition a short («18 %) and long (« 82 %) components.
From the group of (^-herpesviruses, the leading place is occupied by cytomegalovirus. CMV, like herpes infection, is one of the diseases of the TORCH syndrome, causing intrauterine infection. Thus, CMV is infected with 2.5 to 10 % of all newborns and 49-60 % of infants. It was found that CMV is the most common cause of infection of the fetus — 7 times more often than rubella. CMV is different from other intrauterine infections CMV can be transmitted from mother to fetus, even if the mother has been infected for many months or years, i.e. during pregnancy, CMV activation occurs. CMV is considered one of the main non-genetic causes, which determines the state of health of newborns and even the level of intellectual development of the nation.
Clinical manifestations of CMV are diverse. These include CMV-sialoadenitis, pneumonia, hepatitis, nephrozonephritis, and nervous system damage. Even a «hidden» CMV-syndrome is identified by disorders that, when a child is born, are usually inaccessible to clinical diagnosis, but with careful observation are revealed during the first years of life. They are chorioretinitis, hydrocephalus, episyndrome, periventricular leukomalacia, delayed intellectual development. Pulmonary pathology is expressed by protracted pneumonia, obstructive bronchitis, which is not amenable to antibacterial therapy.
The nature of the central nervous system damaging depends on the timing of infection. When the fetus is infected in utero, hypertension-hydrocephalic syndrome develops with an increasing head volume increase, a convulsive syndrome, and CMV encephalitis. The latter is characterized by necrosis, paraventricular cysts [5].
Childless marriage is a serious social and medical problem. The problem of infertility in women with herpesvirus infection does not have a final solution. Most patients experience one of five causes of fertility decline with herpesvirus infection, such as mechanical factor, peritoneal fluid anomalies, ovulation disorders and other endocrine disorders, involuntary miscarriages, immune disorders. At the present stage of the development of reproductive medicine, scientists, as well as doctors, are attracted to the questions of adequate diagnosis and rational approaches in the treatment of herpesvirus infection, which is called a «silent epidemic», i.e., 20-40 % without clinical manifestations. In Western Europe, the incidence of genital herpes is 80 cases per 100 000 population. The prevalence of the genital herpes virus (type II) significantly exceeds the prevalence of such viruses as human papillomavirus, hepatitis B virus, and even HIV virus [1].
Pathogenesis. In patients with chronic recurrent herpetic infection in severe course of remission, signs of severe immunosuppression for the content of major and small subpopulations of lymphocytes have not been revealed.
AhighercontentofcellswiththeCD3+CD4+CD25+ and CD3-HLA-DR+ phenotype in peripheral blood of patients with a continuously recurring course of the disease was found, compared with patients with a lower relapse rate. The presence of a moderate positive correlation ofthe frequency of exacerbations of herpes infection with the relative amount of CD3+CD4+CD25+ and CD3-HLA-DR+ lymphocytes in peripheral blood has been revealed [7].
The data obtained in recent years indicate that recurrent herpes is recorded in people with isolated or combined immunodeficiency in various parts of the immune system (quantitative and / or functional insufficiency), and first of all this is due to the deficiency of those components that are the «main force» of antiherpetic protection: natural killers (NK), specific IgG-antibodies, gamma-interferon, type-specific T-killers. In this case, against background of insufficient specific immune response, the viruses are able to survive, mutate and latency. The problem of herpetic infection is that the immune system reacts only to free viral parts or antigenic determinants (extracellular location), but it does not react to latent viruses, which are «hidden» in the nerve cells of peripheral nervous system ganglia and in phagocytes. Immune defects are detected only under antigenic load. Along with this, herpesvirus infection can induce functional damage in nonspecific immune effector cells (it alters numerous functions of macrophages, including depression of chemotaxis and inhibition of phagocytosis, and in acute infection, significant inhibition of the blast transformation of lymphocytes and production of cytokines).
Despite the high degree of interest in the problem of studying the features of the interaction of the herpes viruses and the immune system of patients with relapsing forms of herpesvirus infection, there are still unresolved questions regarding the reduction of the frequency of relapses, the unification of diagnostic methods and the treatment of various clinical forms of herpesvirus infection [6].
Treatment. Depending on the type ofherpesvirus certain antiherpetic drugs are prescribed [8].
We offer a scheme for classifying of antiherpetic drugs:
In infants with an infection caused by HSV1, 2, the appointment of a comprehensive therapy, including the drugs Acyclovir, Immunovenin and Licopid, is the most effective. The clinical effects of etiotropic and immunotropic therapy in newborn infants with infection caused by HSV 1, 2 consist in a significant reduction in the duration of conjunctive jaundice, vesicular rash, increased liver size,
hyperbilirubinemia, and hypotrophy compared with the group of children receiving only etiotropic therapy with Acyclovir. The inclusion of Immunovenin and Licopid in the therapy complex, together with etiotropic treatment with Acyclovir, made it possible to reveal their distinct immunomodulatory effects characterized by a significantly higher relative and absolute amount of T-lymphocytes (CD3 +, CD8 +) and decrease in the relative amount of B-lymphocytes (CD20 +) 3 months after completion of treatment compared with a group of children who received only etiotropic therapy with Acyclovir [9].
Conclusions. Herpesviruses can cause spontaneous abortion, premature birth and infertility, as well as a violation of embryogenesis and congenital pathology of newborns.
More than 80 representatives of the herpesvirus family have been discovered, 8 types of which are pathogenic to humans. CMVI and HVI are able to damage the placenta, penetrate through it and affect the fetus.
The reaction of the immune system in children with HVI in the first 3 months oflife is accompanied by changes in the cellular immune system. On the lymphocytes of patients with acute and prolonged course of HVI, there was a significant increase in CD3 + CD95 + expression in the first month of life, indicating an increase in the readiness of lymphocytes for apoptosis.
CD95 + receptor expression on lymphocytes is a favorable prognostic factor has a protective character, prevents disease progression.
Anti-herpetic drugs are prescribed depending on the type of herpesvirus and are divided into drugs for etiotropic and pathogenetic therapy.
О.Ю. Николенко, В.Ю. Николенко, Ю.А. Лыгина ВЛИЯНИЕ ГЕРПЕСВИРУСНОЙ ИНФЕКЦИИ НА БЕРЕМЕННОСТЬ (ЛЕКЦИЯ ДЛЯ ИНТЕРНОВ И ВРАЧЕЙ)
Реферат. Цитомегаловирусная и герпетическая инфекции относятся к «TORCH» группе и способны повреждать плаценту, проникать сквозь нее и поражать плод. Вирусы герпеса могут вызывать поражения половых органов и облегчать передачу других инфекций, в т.ч. ВИЧ-инфекции. Открыто более 80 представителей семейства герпесвиру-сов, из которых 8 типов патогенны для людей. Герпесвирусы относятся к семейству Herpesviridae и делятся на три подсемейства: а-, в-, у-герпе-свирусы. Основными свойствами герпесвирусов являются: убиквитарность, всеобщая восприимчивость, оппортунистичность, пантропизм, способность использовать различные механизмы передачи, сложную стратегию паразитирования, иммуносупрессивность и онкогенность. Это ДНК-содержащие сложные вирусы. Цикл репликации герпесвируса проходит следующие этапы: адсорбцию, проникновение и дезинтеграцию, синтез вирусных частиц, полную сборку внутриклеточного вируса, высвобождение дочерних вирионов. У этих вирусных агентов гены, кодирующие структурные белки, составляют всего лишь 15 % ДНК, поэто-
му большая часть генома занята генами, ответственными за синтез регуляторных протеинов и ферментов. Эта особенность позволяет герпесви-русам реализовывать возможность латентного, персистентного и реактивированного состояния в зараженном организме. Рецидивирующий герпес регистрируется у людей с изолированным или со-четанным иммунодефицитом в различных звеньях иммунной системы. Реакция иммунной системы при герпесвирусных инфекциях у детей первых 3-х месяцев жизни сопровождается изменениями клеточного звена иммунитета. На лимфоцитах больных с острым и затяжным течением герпесвирусных инфекций отмечено достоверное повышение экспрессии CD3+CD95+ на первом месяце жизни, свидетельствующее о нарастании готовности лимфоцитов к апоптозу. Герпесвирусная инфекция может индуцировать функциональные повреждения в неспецифических иммунных эффекторных клетках. При лечении герпетической инфекции назначаются препараты в зависимости от типа герпесви-руса и подразделяются на средства этиотропной и патогенетической терапии. У детей грудного возраста с инфекцией, вызванной ВПГ1, ВПГ2, назначение комплексной терапии, включающей препараты Ацикловир, Иммуноверин и Ликопид, является наиболее эффективным.
Ключевые слова: герпесвирусы, беременность, классификация, строение, цикл репродукции, патогенез, лечение
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